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Myxoma pathophysiology

2019-04-03T13:52:25Z

Fahad AlKhalfan: /* Microscopic Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as having a gelatinous, irregular surface.<ref name="pmid25297937" />
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid7477198" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid7477198" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

{|
|
[[Image:800px-Atrial myxoma edge high mag.jpg|200px|thumb|none|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage. [https://upload.wikimedia.org/wikipedia/commons/7/74/Atrial_myxoma_edge_high_mag.jpg Source:Case courtesy by Nephron, via Wikimedia Commons]]]
|
[[Image:Cardiac myxoma mic 2.jpg|200px|thumb|none|'''Gamna Bodies:''' A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image:Cardiac myxoma mic 3.jpg|200px|thumb|none|'''Cardiac myxoma:''' Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image:Cardiac myxoma mic 4.jpg|200px|thumb|none|'''Cardiac myxoma:''' The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image:Cardiac myxoma mic 5.jpg|200px|thumb|none|'''Cardiac myxoma:''' Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma. [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|}

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma pathophysiology

2019-04-03T13:39:48Z

Fahad AlKhalfan: /* Microscopic Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as having a gelatinous, irregular surface.<ref name="pmid25297937" />
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid7477198" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid7477198" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

{|
|
[[Image:800px-Atrial myxoma edge high mag.jpg|200px|thumb|none|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage. [https://upload.wikimedia.org/wikipedia/commons/7/74/Atrial_myxoma_edge_high_mag.jpg Source:Case courtesy by Nephron, via Wikimedia Commons]]]
|
[[Image:Cardiac myxoma mic 2.jpg|200px|thumb|none|'''Gamna Bodies:''' A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.[http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image:Cardiac myxoma mic 3.jpg|200px|thumb|none|'''Cardiac myxoma:''' Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.[http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image:Cardiac myxoma mic 4.jpg|200px|thumb|none|'''Cardiac myxoma:''' The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.[http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|
[[Image:Cardiac myxoma mic 5.jpg|200px|thumb|none|'''Cardiac myxoma:''' Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.[http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]]]
|}

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma pathophysiology

2019-04-02T20:20:57Z

Fahad AlKhalfan: /* Microscopic Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as having a gelatinous, irregular surface.<ref name="pmid25297937" />
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid7477198" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid7477198" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage. Case courtesy of Nephron [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)]
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T20:17:40Z

Fahad AlKhalfan: /* Gross Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as having a gelatinous, irregular surface.<ref name="pmid25297937" />
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid7477198" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid7477198" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T20:11:20Z

Fahad AlKhalfan: /* Pathogenesis */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as having a gelatinous, irregular surface.<ref name="pmid25297937" />
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid7477198" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma pathophysiology

2019-04-02T20:10:10Z

Fahad AlKhalfan: /* Gross Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as having a gelatinous, irregular surface.<ref name="pmid25297937" />
*Myxomas that have an irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T20:07:31Z

Fahad AlKhalfan: /* Gross Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Myxomas are usually described as gelatinous, irregular surface that fills the [[left atrium]].
*Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T20:02:34Z

Fahad AlKhalfan: /* Gross Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma.
*Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid25900256">{{cite journal| author=He DK, Zhang YF, Liang Y, Ye SX, Wang C, Kang B et al.| title=Risk factors for embolism in cardiac myxoma: a retrospective analysis. | journal=Med Sci Monit | year= 2015 | volume= 21 | issue= | pages= 1146-54 | pmid=25900256 | doi=10.12659/MSM.893855 | pmc=4418206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25900256 }} </ref>
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma pathophysiology

2019-04-02T19:56:30Z

Fahad AlKhalfan: /* Gross Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma.
*Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid12208428" />
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T19:53:38Z

Fahad AlKhalfan:

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid12208428" />
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

*Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref>

*Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T19:51:47Z

Fahad AlKhalfan:

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid12208428" />
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
*On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

*They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

*The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma pathophysiology

2019-04-02T19:50:14Z

Fahad AlKhalfan: /* Microscopic Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid12208428" />
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages).

The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications.

In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor.

The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T19:49:33Z

Fahad AlKhalfan: /* Microscopic Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid12208428" />
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref>

They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-02T19:47:38Z

Fahad AlKhalfan: /* Gross Pathology */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
* On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma.<ref name="pmid25297937" />
* Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>
* Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize.<ref name="pmid12208428" />
* Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk.<ref name="pmid12208428" />
* In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile.<ref name="pmid12208428" />
* Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.<ref name="pmid12208428" />
* Cardiac myxomas are intracavitary tumors.<ref name="pmid12208428" />
* The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%).<ref name="pmid12208428" />
* However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* Large cardiac myxomas are usually located in [[fossa ovalis]].<ref name="pmid10903697" />
* The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* [http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref> They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-01T21:26:46Z

Fahad AlKhalfan: /* Genetics */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
* Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.<ref name="pmid26416542" />
* Inherited myxomas are usually present in [[Carney complex]].<ref name="pmid26416542" />
* The development of [[Carney complex]] is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3.<ref name="pmid26416542" />
* The gene 17q24.2-q24.3 plays an important role in cardiac development and myxomagenesis. The expression of [[PRKAR1A]] causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>
* The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A.<ref name=":0" />
* Inactivating germline mutations of this gene are found in 70% of people with Carney complex.<ref name=":0" />
* Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16.<ref name=":0" />
* Both types of Carney complex are [[autosomal dominant]].<ref name=":0" />
* Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref name=":0">Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==
* The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref>
* Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>

==Gross Pathology==
On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma. Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref> Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize. Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk. In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile. Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.

Cardiac myxomas are intracavitary tumors. The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%). However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> Large cardiac myxomas are usually located in [[fossa ovalis]]. The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref> They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-01T19:46:41Z

Fahad AlKhalfan: /* Pathogenesis */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
===Pathogenesis===
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.
Inherited myxomas are usually presented in the [[Carney complex]]. The development of this syndrome is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3. This gene plays an important role in cardiac development and myxomagenesis. The expression of PRKAR1A causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>

The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex. Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16. Both types of Carney complex are [[autosomal dominant]]. Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref>Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==

The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref> Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>
==Gross Pathology==
On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma. Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref> Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize. Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk. In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile. Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.

Cardiac myxomas are intracavitary tumors. The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%). However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> Large cardiac myxomas are usually located in [[fossa ovalis]]. The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref> They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma pathophysiology

2019-04-01T19:41:24Z

Fahad AlKhalfan: /* Pathogenesis */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
===Pathogenesis===
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.
Inherited myxomas are usually presented in the [[Carney complex]]. The development of this syndrome is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3. This gene plays an important role in cardiac development and myxomagenesis. The expression of PRKAR1A causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>

The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex. Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16. Both types of Carney complex are [[autosomal dominant]]. Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref>Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==

The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref> Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>
==Gross Pathology==
On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma. Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref> Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize. Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk. In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile. Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.

Cardiac myxomas are intracavitary tumors. The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%). However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> Large cardiac myxomas are usually located in [[fossa ovalis]]. The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref> They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-01T19:40:41Z

Fahad AlKhalfan: /* Pathogenesis */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
* The site of tumor attachment, normally the foramen ovale, is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.
Inherited myxomas are usually presented in the [[Carney complex]]. The development of this syndrome is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3. This gene plays an important role in cardiac development and myxomagenesis. The expression of PRKAR1A causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>

The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex. Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16. Both types of Carney complex are [[autosomal dominant]]. Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref>Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==

The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref> Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>
==Gross Pathology==
On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma. Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref> Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize. Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk. In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile. Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.

Cardiac myxomas are intracavitary tumors. The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%). However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> Large cardiac myxomas are usually located in [[fossa ovalis]]. The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref> They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma pathophysiology

2019-04-01T19:32:22Z

Fahad AlKhalfan: /* Overview */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}} {{MV}}{{CZ}}{{AAM}}
==Overview==

Cardiac myxoma is a benign intracavitary endocardial mass that represents the most common primary tumor of the heart.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Myxoma cells are characterized by undifferentiated mesenchymal cells, which potentially differentiate into many [[tissues]] such as [[blood vessels]], [[glandular]] structures, and [[bones]].<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref> The primary distribution of cardiac myxoma is the [[left atrium]] (75%) of the heart, regularly they tend to be located in the [[fossa ovalis]] and endocardium of the [[atrial septum]].<ref name="pmid109036972">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Pathogenesis==
Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref> The exact pathogenesis of cardiac myxoma is not fully understood.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697|doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> It is thought that cardiac myxoma is produced by the neoplastic theory, dysembryoplastic theory, histopathogenesis of glandular cells in myxoma or the thrombotic theory.<ref name="pmid16508920">{{cite journal |vauthors=Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli LG, Gabbiani G |title=Cardiac myxoma cells exhibit embryonic endocardial stem cell features |journal=J. Pathol. |volume=209 |issue=2 |pages=231–9 |year=2006 |pmid=16508920 |doi=10.1002/path.1959 |url=}}</ref><ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
The site of tumor attachment, normally foramen ovale is considered to be consistent with an origin from multipotent mesenchymal cells or from embryonic rests.<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

==Genetics==
Sporadic cardiac myxomas and familial forms are related with several chromosome and gene alterations which involve cardiac development.
Inherited myxomas are usually presented in the [[Carney complex]]. The development of this syndrome is a result of [[PRKAR1A]] gene inactivation mutation that is associated with [[chromosome]] 17q24.2-q24.3. This gene plays an important role in cardiac development and myxomagenesis. The expression of PRKAR1A causes myxomatous changes in the endocardium.<ref name="pmid26416542">{{cite journal |vauthors=Sun Y, Chen X, Sun J, Wen X, Liu X, Zhang Y, Hoffman AR, Hu JF, Gao Y |title=A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family |journal=Can J Cardiol |volume=31 |issue=11 |pages=1393–401 |year=2015 |pmid=26416542 |doi=10.1016/j.cjca.2015.05.018 |url=}}</ref>

The encoded protein of [[PRKAR1A]] is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex. Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2p16. Both types of Carney complex are [[autosomal dominant]]. Despite dissimilar genetics, there appears to be no [[phenotype|phenotypic]] difference between PRKAR1A and chromosome 2p16 mutations.<ref>Carney Complex. Wikipedia. https://en.wikipedia.org/wiki/Carney_complex Accessed on November 24, 2015</ref>

==Associated Conditions==

The [[Carney complex]] is characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous, and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue [[nevus]].<ref>Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. ''Medicine'' (Baltimore). 1985;64(4):270-83.</ref><ref>Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. ''British Journal of Dermatology'' 2005;152:391-393.</ref><ref>Gaissmaier et al. (letter and response) Carney Complex. ''Circulation'' 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150</ref> Approximately 7% of all cardiac myxomas are associated with Carney complex.<ref name="Reynen1995">{{Cite journal | last1 = Reynen | first1 = K. | title = Cardiac Myxomas | journal = New England Journal of Medicine | volume = 333 | issue = 24 | pages = 1610–1617 | year = 1995 | pmid = 7477198 | doi = 10.1056/NEJM199512143332407}}</ref>
==Gross Pathology==
On gross pathology, external appearance, consistency size, and weight are extremely variable findings of cardiac myxoma. Tumor consistency depends on the quantity and distribution of fibrous tissue and calcification (it can be smooth, lobulated, friable or gelatinous).<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref> Usually a macroscopic gelatinous, irregular surface that fills the [[left atrium]] is a characteristic finding of myxoma. Myxomas that have irregular consistency are more likely to form surface [[thrombi]] and embolize. Morphologically, these lesions tend to be attached to the endocardium by a broad-based pedunculated stalk. In some cases, the attachment to the endocardium can also be without a clear stalk, or sessile. Cardiac myxomas are non-invasive tumors, thus there is no infiltration to underlying tissues.

Cardiac myxomas are intracavitary tumors. The distribution is normally within the [[interatrial septum]] or adjacent to foramen ovale (75%). However, they can also be found in other cardiac chambers, such as [[right atrium]] (15%), ventricles (2%) or cardiac valves (rare).<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> Large cardiac myxomas are usually located in [[fossa ovalis]]. The size of the tumor varies from 0.6 to 12 cm, with a mean weight of 40 g.<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left">
<gallery heights="225" widths="225">
Image:Atrial myxoma 1.jpg|A gelatinous tumor is attached by a narrow pedicle to the atrial septum. The myxoma has an irregular surface and nearly fills the left atrium
Image:Left atrial myxoma 1.jpg|Left atrial myxoma
Image:Gross myxoma.jpg|Gross pathology atrial myxoma: myxomas are brownish or white and are frequently covered with thrombus</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>
<div align="left">
<gallery heights="225" widths="225">
</gallery>
</div>

==Microscopic Pathology==
On microscopic histopathological analysis, myxoma cells have an ovoid nucleus with large nucleoli, abundant eosinophilic cytoplasm, and indistinct cell borders.<ref name="pmid18350919">{{cite journal |vauthors=Vaideeswar P, Butany JW |title=Benign cardiac tumors of the pluripotent mesenchyme |journal=Semin Diagn Pathol |volume=25 |issue=1 |pages=20–8 |year=2008 |pmid=18350919 |doi= |url=}}</ref> They are usually arranged in perivascular ring structures (typically, infiltrated by lymphocytes and macrophages). The '''Gamna-Bodies''' which consist of [[fibrosis]] and deposition of [[pigments|iron pigments]] are a characteristic finding of myxoma tumors.

Other frequent histological findings, are hemosiderin within the histiocytes, thrombosis, fibrosis and calcifications. In some cases, extramedular hematopoises is present and mucin-producing glands can be also seen in the base of the tumor. The extracellular matrix forms an alcian blue-positive myxoid stroma, composed of variable amounts of proteoglycans, elastin and collagen.<ref name="pmid25297937">{{cite journal |vauthors=Di Vito A, Mignogna C, Donato G |title=The mysterious pathways of cardiac myxomas: a review of histogenesis, pathogenesis and pathology |journal=Histopathology |volume=66 |issue=3 |pages=321–32 |year=2015 |pmid=25297937 |doi=10.1111/his.12531 |url=}}</ref>

<div align="center">
<gallery heights="225" widths="225">
Image:800px-Atrial myxoma edge high mag.jpg|'''Black arrow (top)''': Endothelium '''Black arrow (bottom)''': Hemosiderin macrophage <ref> Cardiac Myxoma. Libre Pathology URL http://librepathology.org/wiki/index.php/Cardiac_myxoma Accessed on November 19,2015 </ref>
</gallery>
</div>

[http://www.peir.net Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="150" widths="150">
Image:Cardiac myxoma mic 2.jpg|Cardiac myxoma: Gamna Bodies: A peculiar form of fibrosis with deposition of iron pigment, identical to that seen in the spleens of patients with sickle cell anemia, is not uncommon in myxoma.
Image:Cardiac myxoma mic 3.jpg|Cardiac myxoma: Common features at the interface with the atrial septum include lymphoid aggregates, smooth muscle bundles, and thick walled vessels which angiographically may look like neovascularization.
Image:Cardiac myxoma mic 4.jpg|Cardiac myxoma: The extramedullary hematopoiesis seen here is present in about 7 percent of cardiac myxomas.
Image:Cardiac myxoma mic 5.jpg|Cardiac myxoma: Glandular structures are seen in less than 5 percent of cases. In this example, they were limited to the base of the myxoma.
</gallery>
</div>

==Immunohistochemistry==

Cardiac myxoma cells exhibit immuno-reactivity mainly for [[calretinin]] (75–100%) followed by vimentin (>50%), NOTCH1, alpha-1 antichymotrypsin and plakophilin- 2.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Calretinin plays an important role in the discrimination of mural thrombi and papillary fibroelastoma.<ref name="pmid11642722">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Roman JJ |title=Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma |journal=Histol. Histopathol. |volume=16 |issue=4 |pages=1031–6 |year=2001 |pmid=11642722 |doi= |url=}}</ref> Another immunohistochemical marker, [[survivin]] (an apoptosis inhibitor) has been detected to play an important role in the development and growth of cardiac myxomas.<ref name="pmid21880190">{{cite journal |vauthors=Lin YS, Jung SM, Wu HH, Shiu TF, Tzai FC, Chu JJ, Lin PJ, Chu PH |title=Survivin expression in cardiac myxoma |journal=Chang Gung Med J |volume=34 |issue=4 |pages=360–6 |year=2011 |pmid=21880190 |doi= |url=}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px"
| valign="center" |
|+ '''Cardiac Myxoma Summary'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Features'''

! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''

|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''General aspects'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Isolated cells with irregular cellular borders, mild or no atypia, absence of mitosis
:*Myxoma requires the presence of lepidic cells
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Genetics'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[PRKAR1A]] gene plays an important role in cardiac development and myxomagenesis
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gross Pathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Smooth, lobulated mass can be friable or gelatinous
:*No infiltration to underlying tissues
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Micropathology'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Inflammatory infiltrate with [[hemosiderin]], [[calcification]]s, and extramedullary hemopoyesis.
:*Scattered thin-walled vessels
|-

| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Inmunohistochemistry'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Calretinin (75–100%)
:*Vimentin (>50%)

|}

==References==
{{Reflist|2}}

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Myxoma classification

2019-04-01T19:27:54Z

Fahad AlKhalfan: /* Classification */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}}{{MV}}

==Overview==

Cardiac myxomas are classified by the World Health Organization ([[WHO]]) histological classification of tumors of the heart, as "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] mesenchymal tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Classification==

* Based on the location and biological behavior of symptoms, cardiac myxomas may be classified into two groups: '''typical''' and '''atypical'''. In typical cases, cardiac myxomas are almost always single, and there is a striking predilection for the left atrium, with approximately 75-86% occurring there.<ref name="pmid10903697" />

* In atypical cases, presentation is usually early and multicentricity is more common. They are more frequently located on the right side of the heart (38%), or in the [[left ventricle]] (5%). There is also recurrence after [[surgical]] excision (12%–22%) and an association with other conditions, such as the [[Carney complex]].<ref name="pmid10903697" />

* Cardiac myxomas are anatomically distributed, as following:<ref name="pmid10903697" />
** Atria (95%)
***Left (75%)
***Right (20%)
** Ventricles (5%)

* There is no established histological differentiation between both type of cardiac myxomas (typical and atypical).<ref name="pmid3951243">{{cite journal |vauthors=McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet HJ, Carney JA |title=The significance of multiple, recurrent, and "complex" cardiac myxomas |journal=J. Thorac. Cardiovasc. Surg. |volume=91 |issue=3 |pages=389–96 |year=1986 |pmid=3951243 |doi= |url=}}</ref>

==References==

{{Reflist|2}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma classification

2019-04-01T18:18:59Z

Fahad AlKhalfan: /* Classification */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}}{{MV}}

==Overview==

Cardiac myxomas are classified by the World Health Organization ([[WHO]]) histological classification of tumors of the heart, as "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] mesenchymal tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Classification==

* Based on the location and biological behavior of symptoms, cardiac myxomas may be classified into two groups: '''typical''' and '''atypical'''. In typical cases, cardiac myxomas are almost always single, and there is a striking predilection for the left atrium, with approximately 75-86% occurring there.<ref name="pmid10903697" />

* In atypical cases, presentation is usually early and multicentricity is more common. They are more frequently located on the right side of the heart (38%), or in the [[left ventricle]] (5%). There is also recurrence after [[surgical]] excision (12%–22%) and an association with other conditions, such as the [[Carney complex]].<ref name="pmid10903697" />

* Cardiac myxomas are anatomically distributed, as following:
** Atria (95%)
***Left (75%)
***Right (20%)
** Ventricles (5%)

* There is no established histological differentiation between both type of cardiac myxomas (typical and atypical).<ref name="pmid3951243">{{cite journal |vauthors=McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet HJ, Carney JA |title=The significance of multiple, recurrent, and "complex" cardiac myxomas |journal=J. Thorac. Cardiovasc. Surg. |volume=91 |issue=3 |pages=389–96 |year=1986 |pmid=3951243 |doi= |url=}}</ref>

==References==

{{Reflist|2}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma classification

2019-04-01T18:16:34Z

Fahad AlKhalfan: /* Classification */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}}{{MV}}

==Overview==

Cardiac myxomas are classified by the World Health Organization ([[WHO]]) histological classification of tumors of the heart, as "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] mesenchymal tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Classification==

* Based on the location and biological behavior of symptoms, cardiac myxomas may be classified into two groups: '''typical''' and '''atypical'''. In typical cases, cardiac myxomas are almost always single, and there is a striking predilection for the left atrium, with approximately 75-86% occurring there.<ref name="pmid10903697" />

* In atypical cases, presentation is usually early and multicentricity is more common. They are more frequently located on the right side of the heart (38%), or in the [[left ventricle]] (5%).<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> There is also recurrence after [[surgical]] excision (12%–22%) and an association with other conditions, such as the [[Carney complex]].

* Cardiac myxomas are anatomically distributed, as following:
** Atria (95%)
***Left (75%)
***Right (20%)
** Ventricles (5%)

* There is no established histological differentiation between both type of cardiac myxomas (typical and atypical).<ref name="pmid3951243">{{cite journal |vauthors=McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet HJ, Carney JA |title=The significance of multiple, recurrent, and "complex" cardiac myxomas |journal=J. Thorac. Cardiovasc. Surg. |volume=91 |issue=3 |pages=389–96 |year=1986 |pmid=3951243 |doi= |url=}}</ref>

==References==

{{Reflist|2}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma classification

2019-04-01T18:15:02Z

Fahad AlKhalfan: /* Classification */

__NOTOC__
{{Myxoma}}
{{CMG}} {{AE}}{{MV}}

==Overview==

Cardiac myxomas are classified by the World Health Organization ([[WHO]]) histological classification of tumors of the heart, as "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] mesenchymal tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>

==Classification==

* Based on the location and biological behavior of symptoms, cardiac myxomas may be classified into two groups: '''typical''' and '''atypical'''. In typical cases, cardiac myxomas are almost always single, and there is a striking predilection for the left atrium, with approximately 75-86% occurring there.

* In atypical cases, presentation is usually early and multicentricity is more common. They are more frequently located on the right side of the heart (38%), or in the [[left ventricle]] (5%).<ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> There is also recurrence after [[surgical]] excision (12%–22%) and an association with other conditions, such as the [[Carney complex]].

* Cardiac myxomas are anatomically distributed, as following:
** Atria (95%)
***Left (75%)
***Right (20%)
** Ventricles (5%)

* There is no established histological differentiation between both type of cardiac myxomas (typical and atypical).<ref name="pmid3951243">{{cite journal |vauthors=McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet HJ, Carney JA |title=The significance of multiple, recurrent, and "complex" cardiac myxomas |journal=J. Thorac. Cardiovasc. Surg. |volume=91 |issue=3 |pages=389–96 |year=1986 |pmid=3951243 |doi= |url=}}</ref>

==References==

{{Reflist|2}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma overview

2019-04-01T17:46:24Z

Fahad AlKhalfan: /* Surgery */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

*Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>
*In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
*Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>
*Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>
*In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
* Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].
* Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref>
* On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma.
* A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
* The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref>
* However, in some cases like inherited myxomatosis, there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
* Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==
* Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref>
* The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected.
* Females are more commonly affected with cardiac myxoma than men.
** The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==
* Common risk factors in the development of myxoma are female gender and genetic predisposition.
* In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==
* If left untreated, cardiac myxoma progression occurs slowly.
* The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref>
* Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]].
* [[Metastases]] are uncommon in cardiac myxoma.
* Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]].
* Right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]].
* Approximately 20% of patients with cardiac myxoma are asymptomatic.
* Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
* There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===
* Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers.
* Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref>
* General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>
* Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position.
* Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===
* There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>
* The auscultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>
* Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
* Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===
* On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
* On CT scan, a cardiac myxoma may be characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref>
* A CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography.
* A CT scan can also differentiate between calcification and fat, and may allow the diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===
* On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]].
* This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===
* The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma.
* On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]].
* Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps.
* As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===
* Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===
* There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
* Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref>
* The feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref>
* Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref>
* The short and long-term prognosis is generally regarded as excellent.<ref name="pmid25797902" />

==References==
{{Reflist|2}}

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Myxoma overview

2019-04-01T17:36:46Z

Fahad AlKhalfan: /* Surgery */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

*Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>
*In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
*Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>
*Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>
*In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
* Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].
* Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref>
* On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma.
* A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
* The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref>
* However, in some cases like inherited myxomatosis, there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
* Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==
* Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref>
* The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected.
* Females are more commonly affected with cardiac myxoma than men.
** The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==
* Common risk factors in the development of myxoma are female gender and genetic predisposition.
* In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==
* If left untreated, cardiac myxoma progression occurs slowly.
* The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref>
* Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]].
* [[Metastases]] are uncommon in cardiac myxoma.
* Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]].
* Right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]].
* Approximately 20% of patients with cardiac myxoma are asymptomatic.
* Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
* There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===
* Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers.
* Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref>
* General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>
* Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position.
* Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===
* There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>
* The auscultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>
* Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
* Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===
* On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
* On CT scan, a cardiac myxoma may be characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref>
* A CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography.
* A CT scan can also differentiate between calcification and fat, and may allow the diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===
* On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]].
* This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===
* The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma.
* On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]].
* Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps.
* As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===
* Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===
* There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
* Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref>
* The feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref>
* Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref>
* The short and long-term prognosis is generally regarded as excellent.

==References==
{{Reflist|2}}

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[[Category:Cardiology]]
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Myxoma overview

2019-04-01T17:36:06Z

Fahad AlKhalfan: /* Medical Therapy */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

*Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>
*In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
*Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>
*Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>
*In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
* Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].
* Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref>
* On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma.
* A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
* The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref>
* However, in some cases like inherited myxomatosis, there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
* Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==
* Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref>
* The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected.
* Females are more commonly affected with cardiac myxoma than men.
** The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==
* Common risk factors in the development of myxoma are female gender and genetic predisposition.
* In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==
* If left untreated, cardiac myxoma progression occurs slowly.
* The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref>
* Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]].
* [[Metastases]] are uncommon in cardiac myxoma.
* Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]].
* Right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]].
* Approximately 20% of patients with cardiac myxoma are asymptomatic.
* Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
* There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===
* Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers.
* Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref>
* General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>
* Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position.
* Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===
* There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>
* The auscultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>
* Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
* Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===
* On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
* On CT scan, a cardiac myxoma may be characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref>
* A CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography.
* A CT scan can also differentiate between calcification and fat, and may allow the diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===
* On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]].
* This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===
* The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma.
* On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]].
* Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps.
* As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===
* Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===
* There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
* Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref> T
* he feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref>
* Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref>
* The short and long-term prognosis is generally regarded as excellent.

==References==
{{Reflist|2}}

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[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma overview

2019-04-01T17:32:59Z

Fahad AlKhalfan: /* Natural History, Complications and Prognosis */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

*Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>
*In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
*Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>
*Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>
*In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
* Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].
* Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref>
* On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma.
* A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
* The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref>
* However, in some cases like inherited myxomatosis, there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
* Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==
* Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref>
* The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected.
* Females are more commonly affected with cardiac myxoma than men.
** The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==
* Common risk factors in the development of myxoma are female gender and genetic predisposition.
* In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==
* If left untreated, cardiac myxoma progression occurs slowly.
* The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref>
* Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]].
* [[Metastases]] are uncommon in cardiac myxoma.
* Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]].
* Right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]].
* Approximately 20% of patients with cardiac myxoma are asymptomatic.
* Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
* There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===
* Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers.
* Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref>
* General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>
* Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position.
* Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===
* There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>
* The auscultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>
* Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
* Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===
* On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
* On CT scan, a cardiac myxoma may be characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref>
* A CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography.
* A CT scan can also differentiate between calcification and fat, and may allow the diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===
* On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]].
* This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===
* The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma.
* On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]].
* Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps.
* As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===
* Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===

There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref> The feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref> Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref> The short and long-term prognosis is generally regarded as excellent.

==References==
{{Reflist|2}}

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Myxoma overview

2019-04-01T17:09:57Z

Fahad AlKhalfan: /* Classification */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

*Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>
*In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
*Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>
*Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>
*In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
* Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==
* Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref>
* Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]].
* Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref>
* On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma.
* A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
* The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref>
* However, in some cases like inherited myxomatosis, there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
* Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==
* Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref>
* The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref>
* The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected.
* Females are more commonly affected with cardiac myxoma than men.
** The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref>
* Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==
* Common risk factors in the development of myxoma are female gender and genetic predisposition.
* In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==

If left untreated, cardiac myxoma progression occurs slowly. The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref> Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]]. [[Metastases]] are uncommon in cardiac myxoma.

Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]]. Whereas, right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]]. Approximately 20% of patients with cardiac myxoma are asymptomatic. Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===

Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers. Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref> General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref> Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position. Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===

There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref> The ascultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref> Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===

On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
On cardiac myxoma, CT scan is characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref> CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography, and it can also differentiate calcification and fat, and may allow tissue diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===

On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]]. This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===

The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma. On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]]. Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps. As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===

Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===

There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref> The feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref> Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref> The short and long-term prognosis is generally regarded as excellent.

==References==
{{Reflist|2}}

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[[Category:Cardiology]]
[[Category:Up-To-Date]]
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Myxoma overview

2019-04-01T17:05:52Z

Fahad AlKhalfan: /* Historical Perspective */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

*Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>
*In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>
*Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>
*Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>
*In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==

Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref> Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]]

Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref> On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma. A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref> However, in some cases like inherited myxomatosis there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==

Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref> The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected. Females are more commonly affected with cardiac myxoma than men. The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==

Common risk factors in the development of myxoma are female gender and genetic predisposition. In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==

If left untreated, cardiac myxoma progression occurs slowly. The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref> Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]]. [[Metastases]] are uncommon in cardiac myxoma.

Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]]. Whereas, right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]]. Approximately 20% of patients with cardiac myxoma are asymptomatic. Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===

Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers. Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref> General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref> Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position. Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===

There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref> The ascultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref> Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===

On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
On cardiac myxoma, CT scan is characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref> CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography, and it can also differentiate calcification and fat, and may allow tissue diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===

On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]]. This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===

The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma. On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]]. Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps. As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===

Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===

There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref> The feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref> Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref> The short and long-term prognosis is generally regarded as excellent.

==References==
{{Reflist|2}}

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{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Cardiology]]
[[Category:Surgery]]

Myxoma overview

2019-04-01T17:05:12Z

Fahad AlKhalfan: /* Historical Perspective */

{{Myxoma}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MV}}{{CZ}}{{AAM}}

==Overview==
A '''myxoma''' (''Myxo-'' = Latin for [[mucus]]) is the most common primary [[tumor]] of the [[heart]]. Cardiac myxomas are usually located in either the [[left atrium|left]] or [[right atrium]] of the heart; about 86 percent occur in the [[left atrium]].<ref>Knepper LE, Biller J, Adams HP Jr, Bruno A. Neurologic manifestations of atrial myxoma. A 12-year experience and review. Stroke. 1988 Nov;19(11):1435-40. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3188128 Medline abstract])</ref>
Myxomas are typically [[peduncle (anatomy)|pedunculate]]d, with a stalk that is attached to the [[interatrial septum]]. The most common location for attachment of the stalk is the [[fossa ovalis]] region of the interatrial septum. The phrase "myxomatous degeneration" refers to the process in which [[connective tissue]] becomes filled with [[mucus]]. About 71% of myxomas occur in the heart, 41% on the skin, and 7% in the oral cavity (usually on the palate). Common [[physical examination]] findings of cardiac myxoma include murmur and abnormal heart sounds that change when the patient changes positions. Complications that can develop as a result of myxoma are: [[arrhythmias]], [[pulmonary edema]], [[peripheral emboli]], [[metastasis]], [[blockage of the mitral heart valve]]. Surgery is the mainstay of treatment for myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

==Historical Perspective==

Cardiac myxoma was first described in 1845.<ref name="history">King TW. On simple vascular growths in the left auricle of the heart. Lancet 1845; 2:428-9</ref>

In 1951, Prichard described a kind of microscopic endocardial structure of the atrial septum, which was suggested to be associated with cardiac myxoma.<ref>{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref>

Clarence Crafoord, a Swedish cardiovascular surgeon successfully removed a cardiac myxoma for the first time in 1954.<ref>{{cite journal |vauthors=Chitwood WR |title=Clarence Crafoord and the first successful resection of a cardiac myxoma |journal=Ann. Thorac. Surg. |volume=54 |issue=5 |pages=997–8 |year=1992 |pmid=1417305 |doi= |url=}}</ref>

Before 1951, cardiac myxoma diagnosis was made only at post-mortem examination.<ref name="pmid14789340">{{cite journal |vauthors=PRICHARD RW |title=Tumors of the heart; review of the subject and report of 150 cases |journal=AMA Arch Pathol |volume=51 |issue=1 |pages=98–128 |year=1951 |pmid=14789340 |doi= |url=}}</ref>

In 1959, the first M-mode [[echocardiogram]] of a left atrial myxoma was reported.<ref name="pmid11388092">{{cite journal |vauthors=Pinede L, Duhaut P, Loire R |title=Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases |journal=Medicine (Baltimore) |volume=80 |issue=3 |pages=159–72 |year=2001 |pmid=11388092 |doi= |url=}}</ref>

==Classification==
Cardiac myxomas are classified by the WHO histological classification of tumors of the heart "[[Benign tumors]] and tumor-like lesions" and categorized into a type of [[pluripotent]] [[mesenchymal]] tumor.<ref name="pmid23460447">{{cite journal |vauthors=Amano J, Nakayama J, Yoshimura Y, Ikeda U |title=Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences |journal=Gen Thorac Cardiovasc Surg |volume=61 |issue=8 |pages=435–47 |year=2013 |pmid=23460447 |pmc=3732772 |doi=10.1007/s11748-013-0214-8 |url=}}</ref><ref name="pmid7446701">{{cite journal |vauthors=Wold LE, Lie JT |title=Cardiac myxomas: a clinicopathologic profile |journal=Am. J. Pathol. |volume=101 |issue=1 |pages=219–40 |year=1980 |pmid=7446701 |pmc=1903582 |doi= |url=}}</ref>

==Pathophysiology==

Cardiac myxoma arises from remnants of subendocardial vasoformative reserve cells, which are primitive [[mesenchymal]] cells that are normally involved in the supportive structure of the [[endocardium]].<ref name="pmid10064365">{{cite journal |vauthors=Roscher AA, Kato NS, Quan H, Padmanabhan M |title=Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review |journal=J Cardiovasc Surg (Torino) |volume=37 |issue=6 Suppl 1 |pages=131–7 |year=1996 |pmid=10064365 |doi= |url=}}</ref><ref name="pmid11737312">{{cite journal |vauthors=Acebo E, Val-Bernal JF, Gómez-Román JJ |title=Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma |journal=Histopathology |volume=39 |issue=5 |pages=529–35 |year=2001 |pmid=11737312 |doi= |url=}}</ref> Myxomas are usually located in the [[fossa ovalis]] and [[endocardium]] of the [[atrial septum]]

Some symptoms of myxoma may be associated with the release of [[interleukin 6]] (IL-6).<ref name="Seino-IL6">{{cite journal | author=Seino Y, Ikeda U, Shimada K. | title=Increased expression of interleukin 6 mRNA in cardiac myxomas. | journal=Br Heart J | year=1993 | volume=69 | issue=6 | pages=565-7 | id=PMID 8343326}}</ref><ref name="Jourdan-IL6">{{cite journal | author=Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B | title=Constitutive production of interleukin-6 and immunologic features in cardiac myxomas.| journal=Arthritis Rheum | year=1990 | volume=33 | issue=3 | pages=398-402 | id=PMID 1690543}}</ref> On [[gross pathology]], a gelatinous, irregular surface that fills the [[left atrium]] is characteristic finding of myxoma. A common hystopathological finding is the ''Gamna-Gandy Bodies'' that consist of fibrosis and deposition of [[pigments|iron pigments]].

==Causes==
The main cause of cardiac myxoma remains unknown.<ref name="pmid13129418">{{cite journal |vauthors=Amano J, Kono T, Wada Y, Zhang T, Koide N, Fujimori M, Ito K |title=Cardiac myxoma: its origin and tumor characteristics |journal=Ann Thorac Cardiovasc Surg |volume=9 |issue=4 |pages=215–21 |year=2003 |pmid=13129418 |doi= |url=}}</ref><ref name="pmid26442965">{{cite journal |vauthors=Messina F, Romano P, Crosca S |title=Atrial myxomas and different clinical presentations |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2015 |pmid=26442965 |doi=10.1016/j.ijcard.2015.08.063 |url=}}</ref> However, in some cases like inherited myxomatosis there is a strong relation with genetic mutations of PRKAR1A gene.

==Differentiating Myxoma from other Diseases==
Cardiac myxoma should be differentiated from other benign and malignant primary heart tumors including [[papillary fibroelastoma]], [[lipoma]], [[rhabdomyoma]], and cardiac [[metastasis]].<ref name="pmid24599357">{{cite journal |vauthors=Hartig I, Kraatz EG, Beurich HW, Moosig F |title=[Atrial myxoma with clinical signs of systemic inflammatory disease.] |journal=Z Rheumatol |volume= |issue= |pages= |year=2014 |pmid=24599357 |doi=10.1007/s00393-013-1347-y |url=}}</ref>

==Epidemiology and Demographics==

Cardiac myxomas are the most common primary cardiac tumor in adults, with a reported prevalence of 0.03% in general [[population]].<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref> The [[incidence]] of cardiac myxoma is about 1/ 100,000 per year.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdp</ref> The majority of patients with cardiac myxoma are diagnosed between 30 to 60 years; children are rarely affected. Females are more commonly affected with cardiac myxoma than men. The female-to-male ratio is approximately 1.8 to 1.<ref name="pmid12208428">{{cite journal |vauthors=Yoon DH, Roberts W |title=Sex distribution in cardiac myxomas |journal=Am. J. Cardiol. |volume=90 |issue=5 |pages=563–5 |year=2002 |pmid=12208428 |doi= |url=}}</ref><ref name="pmid10903697">{{cite journal |vauthors=Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR |title=Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation |journal=Radiographics |volume=20 |issue=4 |pages=1073–103; quiz 1110–1, 1112 |year=2000 |pmid=10903697 |doi=10.1148/radiographics.20.4.g00jl081073 |url=}}</ref> Cardiac myxomas represent 78% of heart tumors.

==Risk Factors==

Common risk factors in the development of myxoma are female gender and genetic predisposition. In some cases, right atrial myxoma has been associated with tricuspid stenosis and atrial fibrillation.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref>

==Natural History, Complications and Prognosis==

If left untreated, cardiac myxoma progression occurs slowly. The overlap of various phenomena such as [[thrombosis]], [[hemorrhage]], or fragmentation may influence tumor growth, detachment, and consequently [[embolism]].<ref name="pmid3547010">{{cite journal |vauthors=Markel ML, Waller BF, Armstrong WF |title=Cardiac myxoma. A review |journal=Medicine (Baltimore) |volume=66 |issue=2 |pages=114–25 |year=1987 |pmid=3547010 |doi= |url=}}</ref> Constitutional symptoms, such as: [[weight loss]], [[fatigue]], [[weakness]] are often the initial clinical onset of cardiac myxoma, and may resemble those from [[endocarditis]]. [[Metastases]] are uncommon in cardiac myxoma.

Since the majority of the cardiac myxomas are left sided, it may progress to develop mitral valve obstruction or systemic embolic events, such as [[stroke]]. Whereas, right atrial myxomas may obstruct the [[tricuspid valve]] and can present as [[right sided heart failure]]. Approximately 20% of patients with cardiac myxoma are asymptomatic. Overall, clinical features of cardiac myxoma are associated with the size of the tumor, location, size, and mobility.<ref>Burke A, Virmani R. Tumors of the Heart and Great Vessels. Amer Registry of Pathology; 1996.</ref>

==Diagnosis==
===Staging===
There is no established system for the staging of myxoma.<ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 30, 2015</ref>

===History and Symptoms===

Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal blood flow within the heart chambers. Left atrial myxoma symptoms may mimic [[mitral stenosis]], while right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm wide.<ref name="pmid20834208">{{cite journal |vauthors=Ramchandani M |title=Less invasive surgery for cardiac tumors |journal=Methodist Debakey Cardiovasc J |volume=6 |issue=3 |pages=27–31 |year=2010 |pmid=20834208 |doi= |url=}}</ref> General symptoms may also mimic those of [[infective endocarditis]]. <ref name="wiki">Atrial Myxoma.Wikipedia URL https://en.wikipedia.org/wiki/Atrial_myxoma Accessed November 13, 2015</ref> Cardiac myxoma symptoms may occur at any time, but most often they tend to occur with changes in body position. Common symptoms include: [[chest pain]], [[palpitation]], [[dizziness]], [[syncope]] and [[dyspnea on exertion]].

===Physical Examination===

There are no specific physical findings for cardiac myxoma.<ref name="pmid433739">{{cite journal |vauthors=Bulkley BH, Hutchins GM |title=Atrial myxomas: a fifty year review |journal=Am. Heart J. |volume=97 |issue=5 |pages=639–43 |year=1979 |pmid=433739 |doi= |url=}}</ref><ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref><ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref> The ascultatory presence of a "tumor plop" (which is caused by the obstruction of the mitral valve orifice by the tumor) on physical examination is highly suggestive of cardiac myxoma.<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref> Common physical examination findings of cardiac myxoma include [[systolic]] or [[diastolic murmurs]] (depending on size, mobility, and location of the tumor).<ref name="pmid9578352">{{cite journal |vauthors=Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS |title=Cardiac myxomas: clinical and echocardiographic profile |journal=Int. J. Cardiol. |volume=63 |issue=3 |pages=251–9 |year=1998 |pmid=9578352 |doi= |url=}}</ref>

===Laboratory Findings===
Laboratory findings consistent with cardiac myxoma are generally non-specific, results often demonstrate [[anemia]], [[leukocytosis]] and elevated [[erythrocyte sedimentation rate]].<ref name="pmid7477198">{{cite journal |vauthors=Reynen K |title=Cardiac myxomas |journal=N. Engl. J. Med. |volume=333 |issue=24 |pages=1610–7 |year=1995 |pmid=7477198 |doi=10.1056/NEJM199512143332407 |url=}}</ref>

===Chest X-ray===

On [[chest x-ray]], cardiac myxoma is characterized by normal results and in some cases a [[calcification]] overlying the heart.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===CT Scan===
On cardiac myxoma, CT scan is characterized by low attenuation and areas of [[dystrophic calcification]] in cardiac chambers.<ref>Schoepf UJ. CT of the Heart, Principles and Applications.Springer Science & Business Media; 2007</ref> CT scan may be helpful in the diagnosis of cardiac myxoma, because it provides better soft-tissue contrast than echocardiography, and it can also differentiate calcification and fat, and may allow tissue diagnosis of some masses such as lipomas.<ref name="pmid10555666">{{cite journal |vauthors=Araoz PA, Eklund HE, Welch TJ, Breen JF |title=CT and MR imaging of primary cardiac malignancies |journal=Radiographics |volume=19 |issue=6 |pages=1421–34 |year=1999 |pmid=10555666 |doi=10.1148/radiographics.19.6.g99no031421 |url=}}</ref>

===MRI===

On Magnetic Resonance Imaging (MRI) or ''Cardiac Magenetic Resonance (CMR)'', cardiac myxoma is characterized by a [[soft tissue]] mass within the [[cardiac chambers]] isointense to [[skeletal muscle]]. This imaging modality, plays an important role in the evaluation of cardiac masses and is of great value when echocardiographic findings are suboptimal or when the lesion has an atypical location or appearance.<ref name="pmid12006696">{{cite journal |vauthors=Grebenc ML, Rosado-de-Christenson ML, Green CE, Burke AP, Galvin JR |title=Cardiac myxoma: imaging features in 83 patients |journal=Radiographics |volume=22 |issue=3 |pages=673–89 |year=2002 |pmid=12006696 |doi=10.1148/radiographics.22.3.g02ma02673 |url=}}</ref>

===Echocardiography===

The [[echocardiogram]] is the initial modality and most useful diagnostic imaging study in cardiac myxoma. On cardiac [[ultrasound]], cardiac myxoma is characterised by the presence of a [[heterogeneous]] pedunculated mass that is commonly located in the [[left atrium]]. Echocardiography allows for evaluation assessment of tumor mobility, as it often protrudes through valve flaps. As a test modality, [[two-dimensional echocardiography]] is often coupled with other modalities (such as, Doppler echocardiography) to detect vascular abnormalities that frequently occur in cardiac myxomas.<ref name="pmid2605587">{{cite journal |vauthors=Bentivoglio M, Savino K, Corea L, Verdecchia P, Porcellati C |title=[Doppler echocardiography in atrial myxoma] |language=Italian |journal=Cardiologia |volume=34 |issue=9 |pages=783–6 |year=1989 |pmid=2605587 |doi= |url=}}</ref>

===Other Diagnostic Studies===

Other diagnostic study for cardiac myxoma is cardiac angiography, which often demonstrates contrast media-enhanced tumor vasculature.<ref name="pmid16450793">{{cite journal |vauthors=Huang CY, Yu WC, Chen KC, Lin SJ |title=Coronary angiography of cardiac myxoma |journal=Clin Cardiol |volume=28 |issue=11 |pages=505–9 |year=2005 |pmid=16450793 |doi= |url=}}</ref>

==Treatment==
===Medical Therapy===

There is no known medical therapy for cardiac myxomas.<ref name="radiopedia">Cardiac Myxoma. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30, 2015</ref>

===Surgery===
Surgery is the mainstay of treatment for cardiac myxoma. <ref>Cardiac Myxoma. Radiopedia. http://radiopaedia.org/articles/cardiac-myxoma Accessed on November 30,2015</ref> The feasibility of surgery depends on the patient hemodynamic stability at diagnosis.<ref>Berdajs DA, Ferrari E. Surgical treatment for heart myxomas. Multimed Man Cardiothorac Surg. 2012;2012:mms016.</ref> Cardiac myxoma surgery has an operative mortality around 0 to 3%, depending on risk factors or mechanical damage to a heart valve, as well as adhesion of the tumor to valve leaflets.<ref name="pmid25797902">{{cite journal |vauthors=Jain S, Maleszewski JJ, Stephenson CR, Klarich KW |title=Current diagnosis and management of cardiac myxomas |journal=Expert Rev Cardiovasc Ther |volume=13 |issue=4 |pages=369–75 |year=2015 |pmid=25797902 |doi=10.1586/14779072.2015.1024108 |url=}}</ref> The short and long-term prognosis is generally regarded as excellent.

==References==
{{Reflist|2}}

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Sandbox:Fahad

2019-03-29T19:06:17Z

Fahad AlKhalfan:

__NOTOC__

{{CMG}}; {{AE}} {{Fahad}}

==Overview==

==Pathohysiology==
===Pathogenesis===
====Director====

Hello my name is <br> Fahad.

# Numbered lists are also good
## very organized
## easy to follow
### easier still
# I did not break the list

# I just broke the list

; Definition list : list of definitions
; item : the item's definition
; another item: the other item's definition
----
IF a line starts with a space THEN <br />
it will be formatted exactly
as typed;
in a fixed-width font;
lines will not wrap;
ENDIF

*# and nest them
*#* like this
*#*; can I mix definition list as well?
*#*: yes
*#*; how?
*#*: it's easy as
*#** a
*#*:* b
*#**; c

efawfewafewa <div style="display:inline;
width:220px; float:right;">
[[Image:humanbody.jpg|frame|Anatomy]] </div>efaefwa

{|
|<ol start="125"><li>a<li>bb<li> ccc</ol>
|<ol start="128"><li>ddd<li>ee<li>f</ol>
|}

{|
|<ol start="125"><li>a<li>bb<li>ccc</ol>
|<ol start="128"><li>ddd<li>ee<li>f</ol>
|}
==References==
{{Reflist|2}}

Coronary artery calcium scoring

2018-11-02T15:12:34Z

Fahad AlKhalfan: /* Role of CAC score in Clinical Practice */

__NOTOC__
{{SI}}
{{CMG}}; {{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]],{{TarekNafee}}
==Overview==
The presence of [[Coronary artery calcification|coronary artery calcification]] indicates underlying [[Coronary heart disease|CHD]].<ref name="pmid22740742">{{cite journal| author=Shah NR, Coulter SA| title=An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. | journal=Tex Heart Inst J | year= 2012 | volume= 39 | issue= 2 | pages= 240-2 | pmid=22740742 | doi= | pmc=3384065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22740742 }} </ref> The coronary artery calcium (CAC) scan is a non-contrast [[Computed tomography|CT]] scan used to visualize the extent of calcification in the [[Coronary arteries|coronary vessels]].<ref name="pmid25937196">{{cite journal| author=Hecht HS| title=Coronary artery calcium scanning: past, present, and future. | journal=JACC Cardiovasc Imaging | year= 2015 | volume= 8 | issue= 5 | pages= 579-96 | pmid=25937196 | doi=10.1016/j.jcmg.2015.02.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25937196 }} </ref> While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture and therefore may not be a good predictor of luminal obstruction. <ref name="pmid22740742" />

The role of CAC in patients with low or intermediate risk of developing a CHD event is uncertain. However, it is not indicated for patients at high risk of CHD as aggressive preventative measures would have already been initiated.

==Coronary Artery Calcium Scoring Systems==
===Agatston Method===
{| align="right"
|
[[Image:Lesionspecificcalciumscore.png|thumb|200px|Lesion Specific Calcium Score - By Cardiomed - Own work, CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)]]
|}
* The Agatston score is a scoring system that uses images obtained from a non-contrast CT.
* It is determined by the number of calcific lesions, the area of each lesion and the peak [[Hounsfield scale|HU]] of each lesion detected. The score for every calcific lesion is based on its density score and area (mm<sup>2</sup>).<ref name="pmid2407762">{{cite journal| author=Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R| title=Quantification of coronary artery calcium using ultrafast computed tomography. | journal=J Am Coll Cardiol | year= 1990 | volume= 15 | issue= 4 | pages= 827-32 | pmid=2407762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2407762 }} </ref>
* The density score is determined by the peak HU and is as follows:

** 1 = 130 - 199 HU
** 2 = 200 - 299 HU
** 3 = 300 - 399 HU
** 4 = >399 HU

* If a lesion had a peak HU of 250 and an area of 4 mm<sup>2</sup>, it would receive a score of 8.
* The CAC is the sum of the scores assigned to each calcific lesion.
* The degree of calcification has also been shown to vary depending on certain demographic factors including age, gender and ethnicity.
* Taking this into consideration, the CAC score using the Agatston method can either be presented as an absolute value or as a percentile after adjusting for these three factors.<ref name="pmid28670030" /> Percentiles can be obtained from the [https://www.mesa-nhlbi.org/Calcium/input.aspx Multi-Ethnic Study of Atherosclerosis (MESA) website].
The CAC can be stratified as the following:<ref name="pmid28670030" /><ref name="pmid21098187">{{cite journal| author=van der Bijl N, Joemai RM, Geleijns J, Bax JJ, Schuijf JD, de Roos A et al.| title=Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 195 | issue= 6 | pages= 1299-305 | pmid=21098187 | doi=10.2214/AJR.09.3734 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21098187 }} </ref>
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Coronary Artery Calcium Score
! style="background:#4479BA; color: #FFFFFF;" align="center" + |CAC Score Percentile
(after adjustment)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Calcification Grade
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Interpretation
|-
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |None
| style="background:#DCDCDC;" align="center" + |Very low risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |1-10
| rowspan="2" style="background:#DCDCDC;" align="center" + |≤75
| style="background:#DCDCDC;" align="center" + |Minimum
| rowspan="2" style="background:#DCDCDC;" align="center" + |Low risk of future CHD event, low probability of MI
|-
| style="background:#DCDCDC;" align="center" + |11-100
| style="background:#DCDCDC;" align="center" + |Mild
|-
| style="background:#DCDCDC;" align="center" + |101-400
| style="background:#DCDCDC;" align="center" + |76-90
| style="background:#DCDCDC;" align="center" + |Moderate
| style="background:#DCDCDC;" align="center" + |Increased risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |>400
| style="background:#DCDCDC;" align="center" + |>90
| style="background:#DCDCDC;" align="center" + |Severe
| style="background:#DCDCDC;" align="center" + |Increased probability of MI
|}
'''Calcium Volume Score'''
* The calcium volume score is calculated by multiply the number of [[voxel|voxels]] with calcification by the volume of each voxel. This would include all voxels with a HU score of greater than 130.<ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>
'''Relative Calcium Mass Score'''
* The relative calcium mass score is calculated by multiplying the mean attenuation of the calcified plaque by the plaque volume in each image. <ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>

==Role of CAC score in Clinical Practice==
* The presence of CAC indicates underlying CHD.
* While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture. Therefore, CAC is not a good predictor of luminal obstruction.<ref name="pmid22740742" />
* CAC scores have been shown to improve upon the current [[Framingham Risk Score|Framingham Risk Score]], providing a significant increase in the accuracy of risk stratification.<ref name="pmid28670030" /><ref name="pmid22740742" /> However, there is no prospective data that indicates that CAC screening results in a reduction of coronary events.<ref name="pmid22740742" />
* CAC has also been demonstrated to be an independent predictor of major cardiovascular events.<ref name="pmid28670030" />
'''CAC Scores in Asymptomatic Patients'''
* Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of CHD event in the long term.<ref name="pmid28670030" />
* The use of the CAC score is not indicated in asymptomatic high risk patients as aggressive preventive measures would have already been initiated.<ref name="pmid28670030" />
* Guidelines regarding the use of CAC in low and intermediate risk individuals have not been consistent.
* In 2010, the American College of Cardiology stated that the use of CAC is appropriate in asymptomatic, low risk individuals with a family history of CHD and in individuals with an intermediate risk of CHD (10%-20% 10 year risk of CHD).<ref name="pmid21144964">{{cite journal| author=Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al.| title=2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2010 | volume= 56 | issue= 25 | pages= e50-103 | pmid=21144964 | doi=10.1016/j.jacc.2010.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21144964 }} </ref> However, this has changed in the 2013 guidelines.
* The latest recommendation by the ACC is that CAC can be used to guide risk based decision making if after quantitative risk assessment, a risk based decision is uncertain.<ref name="pmid24222018" />
* Due to concerns related to cumulative radiation exposure, routine serial CAC scans are not currently recommended.<ref name="pmid22740742" />
'''CAC Scores in Symptomatic Patients'''
* The use of the CAC score alone is limited in symptomatic patients.
* The pretest probability of a CHD event should always be considered when interpreting a CAC score.<ref name="pmid28670030" />
* The ACCF/AHA Expert Consensus suggests that the CAC score can be used to help rule out obstructive coronary disease in low risk patients presenting with atypical chest pain.<ref name="pmid17239724">{{cite journal| author=Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM et al.| title=ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. | journal=J Am Coll Cardiol | year= 2007 | volume= 49 | issue= 3 | pages= 378-402 | pmid=17239724 | doi=10.1016/j.jacc.2006.10.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17239724 }} </ref>
* The National Institute for Health and Care Excellence (NICE) recommends that a CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD (based on the modified Diamond and Forrester Criteria).<ref name="pmid20538674">{{cite journal| author=Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, Chest Pain Guideline Development Group| title=NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. | journal=Heart | year= 2010 | volume= 96 | issue= 12 | pages= 974-8 | pmid=20538674 | doi=10.1136/hrt.2009.190066 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538674 }} </ref> If the CAC is:
** 0: Consider other causes of chest pain
** 1-400: Offer CT coronary angiography
** >400: Offer invasive coronary angiography.

==Latest Guidelines ==
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Guideline
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Recommendation
! style="background:#4479BA; color: #FFFFFF;" align="center" | '''Class'''
! style="background:#4479BA; color: #FFFFFF;" align="center" | '''Level of Evidence'''
|-
| 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk <ref name="pmid24222018">{{cite journal| author=Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al.| title=2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2014 | volume= 129 | issue= 25 Suppl 2 | pages= S49-73 | pmid=24222018 | doi=10.1161/01.cir.0000437741.48606.98 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24222018 }} </ref>
| If after quantitative risk assessment, a risk-based decision is uncertain, one or more of the following tools may be used to aid in decision making: family history, hs-CRP, CAC score or ABI.
| IIb
| B
|-
| 2016 European Guidelines on Cardiovascular Disease Prevention In Clinical Practice <ref name="pmid27222591">{{cite journal| author=Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.| title=2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). | journal=Eur Heart J | year= 2016 | volume= 37 | issue= 29 | pages= 2315-81 | pmid=27222591 | doi=10.1093/eurheartj/ehw106 | pmc=4986030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27222591 }} </ref>
| CAC may be considered as a risk factor in CV risk assessment in patients with a calculated SCORE risk between 5% to 10%.
| IIb
| B
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Guideline
! style="background:#4479BA; color: #FFFFFF;" align="center" + colspan="3" | '''Recommendation'''
|-
| rowspan="4" | ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR
2010 Appropriate Use Criteria
for Cardiac Computed Tomography <ref name="pmid21232696">{{cite journal| author=Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P et al.| title=ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. | journal=J Cardiovasc Comput Tomogr | year= 2010 | volume= 4 | issue= 6 | pages= 407.e1-33 | pmid=21232696 | doi=10.1016/j.jcct.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21232696 }} </ref>
| CAC would be appropriate in patients with a 10-20% 10-year risk of CHD.
| colspan="2" | Appropriate
|-
| CAC would be appropriate in low risk patients (<10% 10-year risk of CHD) with a family history of premature CHD.
| colspan="2" | Appropriate
|-
| The usefulness of CAC is uncertain in patients with peripheral arterial disease or other coronary risk equivalents, or have a 10-year CHD risk greater than 20%, or who are 40 or older with diabetes.
| colspan="2" | Uncertain
|-
| CAC would be inappropriate in low risk patients (<10% 10-year risk of CHD).
| colspan="2" | Inappropriate
|-
|National Institute for Health and Care Excellence (NICE) Guidance.
Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. (2010)<ref name="pmid20538674" />
| colspan="3" |The CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD.
|}

==References==
{{Reflist|2}}

{{WH}}{{WS}}

Coronary artery calcium scoring

2018-11-02T15:11:43Z

Fahad AlKhalfan: /* Latest Guidelines */

__NOTOC__
{{SI}}
{{CMG}}; {{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]],{{TarekNafee}}
==Overview==
The presence of [[Coronary artery calcification|coronary artery calcification]] indicates underlying [[Coronary heart disease|CHD]].<ref name="pmid22740742">{{cite journal| author=Shah NR, Coulter SA| title=An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. | journal=Tex Heart Inst J | year= 2012 | volume= 39 | issue= 2 | pages= 240-2 | pmid=22740742 | doi= | pmc=3384065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22740742 }} </ref> The coronary artery calcium (CAC) scan is a non-contrast [[Computed tomography|CT]] scan used to visualize the extent of calcification in the [[Coronary arteries|coronary vessels]].<ref name="pmid25937196">{{cite journal| author=Hecht HS| title=Coronary artery calcium scanning: past, present, and future. | journal=JACC Cardiovasc Imaging | year= 2015 | volume= 8 | issue= 5 | pages= 579-96 | pmid=25937196 | doi=10.1016/j.jcmg.2015.02.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25937196 }} </ref> While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture and therefore may not be a good predictor of luminal obstruction. <ref name="pmid22740742" />

The role of CAC in patients with low or intermediate risk of developing a CHD event is uncertain. However, it is not indicated for patients at high risk of CHD as aggressive preventative measures would have already been initiated.

==Coronary Artery Calcium Scoring Systems==
===Agatston Method===
{| align="right"
|
[[Image:Lesionspecificcalciumscore.png|thumb|200px|Lesion Specific Calcium Score - By Cardiomed - Own work, CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)]]
|}
* The Agatston score is a scoring system that uses images obtained from a non-contrast CT.
* It is determined by the number of calcific lesions, the area of each lesion and the peak [[Hounsfield scale|HU]] of each lesion detected. The score for every calcific lesion is based on its density score and area (mm<sup>2</sup>).<ref name="pmid2407762">{{cite journal| author=Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R| title=Quantification of coronary artery calcium using ultrafast computed tomography. | journal=J Am Coll Cardiol | year= 1990 | volume= 15 | issue= 4 | pages= 827-32 | pmid=2407762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2407762 }} </ref>
* The density score is determined by the peak HU and is as follows:

** 1 = 130 - 199 HU
** 2 = 200 - 299 HU
** 3 = 300 - 399 HU
** 4 = >399 HU

* If a lesion had a peak HU of 250 and an area of 4 mm<sup>2</sup>, it would receive a score of 8.
* The CAC is the sum of the scores assigned to each calcific lesion.
* The degree of calcification has also been shown to vary depending on certain demographic factors including age, gender and ethnicity.
* Taking this into consideration, the CAC score using the Agatston method can either be presented as an absolute value or as a percentile after adjusting for these three factors.<ref name="pmid28670030" /> Percentiles can be obtained from the [https://www.mesa-nhlbi.org/Calcium/input.aspx Multi-Ethnic Study of Atherosclerosis (MESA) website].
The CAC can be stratified as the following:<ref name="pmid28670030" /><ref name="pmid21098187">{{cite journal| author=van der Bijl N, Joemai RM, Geleijns J, Bax JJ, Schuijf JD, de Roos A et al.| title=Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 195 | issue= 6 | pages= 1299-305 | pmid=21098187 | doi=10.2214/AJR.09.3734 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21098187 }} </ref>
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Coronary Artery Calcium Score
! style="background:#4479BA; color: #FFFFFF;" align="center" + |CAC Score Percentile
(after adjustment)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Calcification Grade
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Interpretation
|-
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |None
| style="background:#DCDCDC;" align="center" + |Very low risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |1-10
| rowspan="2" style="background:#DCDCDC;" align="center" + |≤75
| style="background:#DCDCDC;" align="center" + |Minimum
| rowspan="2" style="background:#DCDCDC;" align="center" + |Low risk of future CHD event, low probability of MI
|-
| style="background:#DCDCDC;" align="center" + |11-100
| style="background:#DCDCDC;" align="center" + |Mild
|-
| style="background:#DCDCDC;" align="center" + |101-400
| style="background:#DCDCDC;" align="center" + |76-90
| style="background:#DCDCDC;" align="center" + |Moderate
| style="background:#DCDCDC;" align="center" + |Increased risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |>400
| style="background:#DCDCDC;" align="center" + |>90
| style="background:#DCDCDC;" align="center" + |Severe
| style="background:#DCDCDC;" align="center" + |Increased probability of MI
|}
'''Calcium Volume Score'''
* The calcium volume score is calculated by multiply the number of [[voxel|voxels]] with calcification by the volume of each voxel. This would include all voxels with a HU score of greater than 130.<ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>
'''Relative Calcium Mass Score'''
* The relative calcium mass score is calculated by multiplying the mean attenuation of the calcified plaque by the plaque volume in each image. <ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>

==Role of CAC score in Clinical Practice==
* The presence of CAC indicates underlying CHD.
* While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture. Therefore, CAC is not a good predictor of luminal obstruction.<ref name="pmid22740742" />
* CAC scores have been shown to improve upon the current [[Framingham Risk Score|Framingham Risk Score]], providing a significant increase in the accuracy of risk stratification.<ref name="pmid28670030" /><ref name="pmid22740742" /> However, there is no prospective data that indicates that CAC screening results in a reduction of coronary events.<ref name="pmid22740742" />
* CAC has also been demonstrated to be an independent predictor of major cardiovascular events.<ref name="pmid28670030" />
'''CAC Scores in Asymptomatic Patients'''
* Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of CHD event in the long term.<ref name="pmid28670030" />
* The use of the CAC score is not indicated in asymptomatic high risk patients as aggressive preventive measures would have already been initiated.<ref name="pmid28670030" />
* Guidelines regarding the use of CAC in low and intermediate risk individuals have not been consistent.
* In 2010, the American College of Cardiology stated that the use of CAC is appropriate in asymptomatic, low risk individuals with a family history of CHD and in individuals with an intermediate risk of CHD (10%-20% 10 year risk of CHD).<ref name="pmid21144964">{{cite journal| author=Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al.| title=2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2010 | volume= 56 | issue= 25 | pages= e50-103 | pmid=21144964 | doi=10.1016/j.jacc.2010.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21144964 }} </ref> However, this has changed in the 2013 guidelines.
* The latest recommendation by the ACC is that CAC can be used to guide risk based decision making if after quantitative risk assessment, a risk based decision is uncertain.<ref name="pmid24222018" />
* Due to concerns related to cumulative radiation exposure, routine serial CAC scans are not currently recommended.<ref name="pmid22740742" />
'''CAC Scores in Symptomatic Patients'''
* The use of the CAC score alone is limited in symptomatic patients.
* The pretest probability of a CHD event should always be considered when interpreting a CAC score.<ref name="pmid28670030" />
* The ACCF/AHA Expert Consensus suggests that the CAC score can be used to help rule out obstructive coronary disease in low risk patients presenting with atypical chest pain.<ref name="pmid17239724">{{cite journal| author=Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM et al.| title=ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. | journal=J Am Coll Cardiol | year= 2007 | volume= 49 | issue= 3 | pages= 378-402 | pmid=17239724 | doi=10.1016/j.jacc.2006.10.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17239724 }} </ref>
* The National Institute for Health and Care Excellence (NICE) recommends that a CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD (based on the modified Diamond and Forrester Criteria).<ref name="pmid20538674">{{cite journal| author=Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, Chest Pain Guideline Development Group| title=NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. | journal=Heart | year= 2010 | volume= 96 | issue= 12 | pages= 974-8 | pmid=20538674 | doi=10.1136/hrt.2009.190066 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538674 }} </ref> If the CAC is:

** 0: Consider other causes of chest pain
** 1-400: Offer CT coronary angiography
** >400: Offer invasive coronary angiography.

==Latest Guidelines ==
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Guideline
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Recommendation
! style="background:#4479BA; color: #FFFFFF;" align="center" | '''Class'''
! style="background:#4479BA; color: #FFFFFF;" align="center" | '''Level of Evidence'''
|-
| 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk <ref name="pmid24222018">{{cite journal| author=Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al.| title=2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2014 | volume= 129 | issue= 25 Suppl 2 | pages= S49-73 | pmid=24222018 | doi=10.1161/01.cir.0000437741.48606.98 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24222018 }} </ref>
| If after quantitative risk assessment, a risk-based decision is uncertain, one or more of the following tools may be used to aid in decision making: family history, hs-CRP, CAC score or ABI.
| IIb
| B
|-
| 2016 European Guidelines on Cardiovascular Disease Prevention In Clinical Practice <ref name="pmid27222591">{{cite journal| author=Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.| title=2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). | journal=Eur Heart J | year= 2016 | volume= 37 | issue= 29 | pages= 2315-81 | pmid=27222591 | doi=10.1093/eurheartj/ehw106 | pmc=4986030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27222591 }} </ref>
| CAC may be considered as a risk factor in CV risk assessment in patients with a calculated SCORE risk between 5% to 10%.
| IIb
| B
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Guideline
! style="background:#4479BA; color: #FFFFFF;" align="center" + colspan="3" | '''Recommendation'''
|-
| rowspan="4" | ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR
2010 Appropriate Use Criteria
for Cardiac Computed Tomography <ref name="pmid21232696">{{cite journal| author=Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P et al.| title=ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. | journal=J Cardiovasc Comput Tomogr | year= 2010 | volume= 4 | issue= 6 | pages= 407.e1-33 | pmid=21232696 | doi=10.1016/j.jcct.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21232696 }} </ref>
| CAC would be appropriate in patients with a 10-20% 10-year risk of CHD.
| colspan="2" | Appropriate
|-
| CAC would be appropriate in low risk patients (<10% 10-year risk of CHD) with a family history of premature CHD.
| colspan="2" | Appropriate
|-
| The usefulness of CAC is uncertain in patients with peripheral arterial disease or other coronary risk equivalents, or have a 10-year CHD risk greater than 20%, or who are 40 or older with diabetes.
| colspan="2" | Uncertain
|-
| CAC would be inappropriate in low risk patients (<10% 10-year risk of CHD).
| colspan="2" | Inappropriate
|-
|National Institute for Health and Care Excellence (NICE) Guidance.
Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. (2010)<ref name="pmid20538674" />
| colspan="3" |The CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD.
|}

==References==
{{Reflist|2}}

{{WH}}{{WS}}

Coronary artery calcium scoring

2018-11-02T15:08:53Z

Fahad AlKhalfan: /* Latest Guidelines */

__NOTOC__
{{SI}}
{{CMG}}; {{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]],{{TarekNafee}}
==Overview==
The presence of [[Coronary artery calcification|coronary artery calcification]] indicates underlying [[Coronary heart disease|CHD]].<ref name="pmid22740742">{{cite journal| author=Shah NR, Coulter SA| title=An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. | journal=Tex Heart Inst J | year= 2012 | volume= 39 | issue= 2 | pages= 240-2 | pmid=22740742 | doi= | pmc=3384065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22740742 }} </ref> The coronary artery calcium (CAC) scan is a non-contrast [[Computed tomography|CT]] scan used to visualize the extent of calcification in the [[Coronary arteries|coronary vessels]].<ref name="pmid25937196">{{cite journal| author=Hecht HS| title=Coronary artery calcium scanning: past, present, and future. | journal=JACC Cardiovasc Imaging | year= 2015 | volume= 8 | issue= 5 | pages= 579-96 | pmid=25937196 | doi=10.1016/j.jcmg.2015.02.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25937196 }} </ref> While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture and therefore may not be a good predictor of luminal obstruction. <ref name="pmid22740742" />

The role of CAC in patients with low or intermediate risk of developing a CHD event is uncertain. However, it is not indicated for patients at high risk of CHD as aggressive preventative measures would have already been initiated.

==Coronary Artery Calcium Scoring Systems==
===Agatston Method===
{| align="right"
|
[[Image:Lesionspecificcalciumscore.png|thumb|200px|Lesion Specific Calcium Score - By Cardiomed - Own work, CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)]]
|}
* The Agatston score is a scoring system that uses images obtained from a non-contrast CT.
* It is determined by the number of calcific lesions, the area of each lesion and the peak [[Hounsfield scale|HU]] of each lesion detected. The score for every calcific lesion is based on its density score and area (mm<sup>2</sup>).<ref name="pmid2407762">{{cite journal| author=Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R| title=Quantification of coronary artery calcium using ultrafast computed tomography. | journal=J Am Coll Cardiol | year= 1990 | volume= 15 | issue= 4 | pages= 827-32 | pmid=2407762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2407762 }} </ref>
* The density score is determined by the peak HU and is as follows:

** 1 = 130 - 199 HU
** 2 = 200 - 299 HU
** 3 = 300 - 399 HU
** 4 = >399 HU

* If a lesion had a peak HU of 250 and an area of 4 mm<sup>2</sup>, it would receive a score of 8.
* The CAC is the sum of the scores assigned to each calcific lesion.
* The degree of calcification has also been shown to vary depending on certain demographic factors including age, gender and ethnicity.
* Taking this into consideration, the CAC score using the Agatston method can either be presented as an absolute value or as a percentile after adjusting for these three factors.<ref name="pmid28670030" /> Percentiles can be obtained from the [https://www.mesa-nhlbi.org/Calcium/input.aspx Multi-Ethnic Study of Atherosclerosis (MESA) website].
The CAC can be stratified as the following:<ref name="pmid28670030" /><ref name="pmid21098187">{{cite journal| author=van der Bijl N, Joemai RM, Geleijns J, Bax JJ, Schuijf JD, de Roos A et al.| title=Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 195 | issue= 6 | pages= 1299-305 | pmid=21098187 | doi=10.2214/AJR.09.3734 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21098187 }} </ref>
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Coronary Artery Calcium Score
! style="background:#4479BA; color: #FFFFFF;" align="center" + |CAC Score Percentile
(after adjustment)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Calcification Grade
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Interpretation
|-
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |None
| style="background:#DCDCDC;" align="center" + |Very low risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |1-10
| rowspan="2" style="background:#DCDCDC;" align="center" + |≤75
| style="background:#DCDCDC;" align="center" + |Minimum
| rowspan="2" style="background:#DCDCDC;" align="center" + |Low risk of future CHD event, low probability of MI
|-
| style="background:#DCDCDC;" align="center" + |11-100
| style="background:#DCDCDC;" align="center" + |Mild
|-
| style="background:#DCDCDC;" align="center" + |101-400
| style="background:#DCDCDC;" align="center" + |76-90
| style="background:#DCDCDC;" align="center" + |Moderate
| style="background:#DCDCDC;" align="center" + |Increased risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |>400
| style="background:#DCDCDC;" align="center" + |>90
| style="background:#DCDCDC;" align="center" + |Severe
| style="background:#DCDCDC;" align="center" + |Increased probability of MI
|}
'''Calcium Volume Score'''
* The calcium volume score is calculated by multiply the number of [[voxel|voxels]] with calcification by the volume of each voxel. This would include all voxels with a HU score of greater than 130.<ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>
'''Relative Calcium Mass Score'''
* The relative calcium mass score is calculated by multiplying the mean attenuation of the calcified plaque by the plaque volume in each image. <ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>

==Role of CAC score in Clinical Practice==
* The presence of CAC indicates underlying CHD.
* While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture. Therefore, CAC is not a good predictor of luminal obstruction.<ref name="pmid22740742" />
* CAC scores have been shown to improve upon the current [[Framingham Risk Score|Framingham Risk Score]], providing a significant increase in the accuracy of risk stratification.<ref name="pmid28670030" /><ref name="pmid22740742" /> However, there is no prospective data that indicates that CAC screening results in a reduction of coronary events.<ref name="pmid22740742" />
* CAC has also been demonstrated to be an independent predictor of major cardiovascular events.<ref name="pmid28670030" />
'''CAC Scores in Asymptomatic Patients'''
* Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of CHD event in the long term.<ref name="pmid28670030" />
* The use of the CAC score is not indicated in asymptomatic high risk patients as aggressive preventive measures would have already been initiated.<ref name="pmid28670030" />
* Guidelines regarding the use of CAC in low and intermediate risk individuals have not been consistent.
* In 2010, the American College of Cardiology stated that the use of CAC is appropriate in asymptomatic, low risk individuals with a family history of CHD and in individuals with an intermediate risk of CHD (10%-20% 10 year risk of CHD).<ref name="pmid21144964">{{cite journal| author=Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al.| title=2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2010 | volume= 56 | issue= 25 | pages= e50-103 | pmid=21144964 | doi=10.1016/j.jacc.2010.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21144964 }} </ref> However, this has changed in the 2013 guidelines.
* The latest recommendation by the ACC is that CAC can be used to guide risk based decision making if after quantitative risk assessment, a risk based decision is uncertain.<ref name="pmid24222018" />
* Due to concerns related to cumulative radiation exposure, routine serial CAC scans are not currently recommended.<ref name="pmid22740742" />
'''CAC Scores in Symptomatic Patients'''
* The use of the CAC score alone is limited in symptomatic patients.
* The pretest probability of a CHD event should always be considered when interpreting a CAC score.<ref name="pmid28670030" />
* The ACCF/AHA Expert Consensus suggests that the CAC score can be used to help rule out obstructive coronary disease in low risk patients presenting with atypical chest pain.<ref name="pmid17239724">{{cite journal| author=Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM et al.| title=ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. | journal=J Am Coll Cardiol | year= 2007 | volume= 49 | issue= 3 | pages= 378-402 | pmid=17239724 | doi=10.1016/j.jacc.2006.10.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17239724 }} </ref>
* The National Institute for Health and Care Excellence (NICE) recommends that a CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD (based on the modified Diamond and Forrester Criteria).<ref name="pmid20538674">{{cite journal| author=Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, Chest Pain Guideline Development Group| title=NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. | journal=Heart | year= 2010 | volume= 96 | issue= 12 | pages= 974-8 | pmid=20538674 | doi=10.1136/hrt.2009.190066 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538674 }} </ref> If the CAC is:

** 0: Consider other causes of chest pain
** 1-400: Offer CT coronary angiography
** >400: Offer invasive coronary angiography.

==Latest Guidelines ==
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Guideline
! style="background:#4479BA; color: #FFFFFF;" align="center" + | Recommendation
! style="background:#4479BA; color: #FFFFFF;" align="center" | '''Class'''
! style="background:#4479BA; color: #FFFFFF;" align="center" | '''Level of Evidence'''
|-
| 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk <ref name="pmid24222018">{{cite journal| author=Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al.| title=2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2014 | volume= 129 | issue= 25 Suppl 2 | pages= S49-73 | pmid=24222018 | doi=10.1161/01.cir.0000437741.48606.98 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24222018 }} </ref>
| If after quantitative risk assessment, a risk-based decision is uncertain, one or more of the following tools may be used to aid in decision making: family history, hs-CRP, CAC score or ABI.
| IIb
| B
|-
| 2016 European Guidelines on Cardiovascular Disease Prevention In Clinical Practice <ref name="pmid27222591">{{cite journal| author=Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.| title=2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). | journal=Eur Heart J | year= 2016 | volume= 37 | issue= 29 | pages= 2315-81 | pmid=27222591 | doi=10.1093/eurheartj/ehw106 | pmc=4986030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27222591 }} </ref>
| CAC may be considered as a risk factor in CV risk assessment in patients with a calculated SCORE risk between 5% to 10%.
| IIb
| B
|-
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + colspan="2" |
! style="background:#4479BA; color: #FFFFFF;" align="center" + colspan="2" | '''Recommendation'''
|-
| rowspan="4" | ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR
2010 Appropriate Use Criteria
for Cardiac Computed Tomography <ref name="pmid21232696">{{cite journal| author=Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P et al.| title=ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. | journal=J Cardiovasc Comput Tomogr | year= 2010 | volume= 4 | issue= 6 | pages= 407.e1-33 | pmid=21232696 | doi=10.1016/j.jcct.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21232696 }} </ref>
| CAC would be appropriate in patients with a 10-20% 10-year risk of CHD.
| colspan="2" | Appropriate
|-
| CAC would be appropriate in low risk patients (<10% 10-year risk of CHD) with a family history of premature CHD.
| colspan="2" | Appropriate
|-
| The usefulness of CAC is uncertain in patients with peripheral arterial disease or other coronary risk equivalents, or have a 10-year CHD risk greater than 20%, or who are 40 or older with diabetes.
| colspan="2" | Uncertain
|-
| CAC would be inappropriate in low risk patients (<10% 10-year risk of CHD).
| colspan="2" | Inappropriate
|-
|National Institute for Health and Care Excellence (NICE) Guidance.
Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. (2010)<ref name="pmid20538674" />
| colspan="3" |The CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD.
|}

==References==
{{Reflist|2}}

{{WH}}{{WS}}

Coronary artery calcium scoring

2018-11-01T20:22:01Z

Fahad AlKhalfan: /* Agatston Method */

__NOTOC__
{{SI}}
{{CMG}}; {{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]],{{TarekNafee}}
==Overview==
The presence of [[Coronary artery calcification|coronary artery calcification]] indicates underlying [[Coronary heart disease|CHD]].<ref name="pmid22740742">{{cite journal| author=Shah NR, Coulter SA| title=An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. | journal=Tex Heart Inst J | year= 2012 | volume= 39 | issue= 2 | pages= 240-2 | pmid=22740742 | doi= | pmc=3384065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22740742 }} </ref> The coronary artery calcium (CAC) scan is a non-contrast [[Computed tomography|CT]] scan used to visualize the extent of calcification in the [[Coronary arteries|coronary vessels]].<ref name="pmid25937196">{{cite journal| author=Hecht HS| title=Coronary artery calcium scanning: past, present, and future. | journal=JACC Cardiovasc Imaging | year= 2015 | volume= 8 | issue= 5 | pages= 579-96 | pmid=25937196 | doi=10.1016/j.jcmg.2015.02.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25937196 }} </ref> While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture and therefore may not be a good predictor of luminal obstruction. <ref name="pmid22740742" />

The role of CAC in patients with low or intermediate risk of developing a CHD event is uncertain. However, it is not indicated for patients at high risk of CHD as aggressive preventative measures would have already been initiated.

==Coronary Artery Calcium Scoring Systems==
===Agatston Method===
{| align="right"
|
[[Image:Lesionspecificcalciumscore.png|thumb|200px|Lesion Specific Calcium Score - By Cardiomed - Own work, CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)]]
|}
* The Agatston score is a scoring system that uses images obtained from a non-contrast CT.
* It is determined by the number of calcific lesions, the area of each lesion and the peak [[Hounsfield scale|HU]] of each lesion detected. The score for every calcific lesion is based on its density score and area (mm<sup>2</sup>).<ref name="pmid2407762">{{cite journal| author=Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R| title=Quantification of coronary artery calcium using ultrafast computed tomography. | journal=J Am Coll Cardiol | year= 1990 | volume= 15 | issue= 4 | pages= 827-32 | pmid=2407762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2407762 }} </ref>
* The density score is determined by the peak HU and is as follows:

** 1 = 130 - 199 HU
** 2 = 200 - 299 HU
** 3 = 300 - 399 HU
** 4 = >399 HU

* If a lesion had a peak HU of 250 and an area of 4 mm<sup>2</sup>, it would receive a score of 8.
* The CAC is the sum of the scores assigned to each calcific lesion.
* The degree of calcification has also been shown to vary depending on certain demographic factors including age, gender and ethnicity.
* Taking this into consideration, the CAC score using the Agatston method can either be presented as an absolute value or as a percentile after adjusting for these three factors.<ref name="pmid28670030" /> Percentiles can be obtained from the [https://www.mesa-nhlbi.org/Calcium/input.aspx Multi-Ethnic Study of Atherosclerosis (MESA) website].
The CAC can be stratified as the following:<ref name="pmid28670030" /><ref name="pmid21098187">{{cite journal| author=van der Bijl N, Joemai RM, Geleijns J, Bax JJ, Schuijf JD, de Roos A et al.| title=Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 195 | issue= 6 | pages= 1299-305 | pmid=21098187 | doi=10.2214/AJR.09.3734 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21098187 }} </ref>
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Coronary Artery Calcium Score
! style="background:#4479BA; color: #FFFFFF;" align="center" + |CAC Score Percentile
(after adjustment)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Calcification Grade
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Interpretation
|-
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |None
| style="background:#DCDCDC;" align="center" + |Very low risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |1-10
| rowspan="2" style="background:#DCDCDC;" align="center" + |≤75
| style="background:#DCDCDC;" align="center" + |Minimum
| rowspan="2" style="background:#DCDCDC;" align="center" + |Low risk of future CHD event, low probability of MI
|-
| style="background:#DCDCDC;" align="center" + |11-100
| style="background:#DCDCDC;" align="center" + |Mild
|-
| style="background:#DCDCDC;" align="center" + |101-400
| style="background:#DCDCDC;" align="center" + |76-90
| style="background:#DCDCDC;" align="center" + |Moderate
| style="background:#DCDCDC;" align="center" + |Increased risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |>400
| style="background:#DCDCDC;" align="center" + |>90
| style="background:#DCDCDC;" align="center" + |Severe
| style="background:#DCDCDC;" align="center" + |Increased probability of MI
|}
'''Calcium Volume Score'''
* The calcium volume score is calculated by multiply the number of [[voxel|voxels]] with calcification by the volume of each voxel. This would include all voxels with a HU score of greater than 130.<ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>
'''Relative Calcium Mass Score'''
* The relative calcium mass score is calculated by multiplying the mean attenuation of the calcified plaque by the plaque volume in each image. <ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>

==Role of CAC score in Clinical Practice==
* The presence of CAC indicates underlying CHD.
* While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture. Therefore, CAC is not a good predictor of luminal obstruction.<ref name="pmid22740742" />
* CAC scores have been shown to improve upon the current [[Framingham Risk Score|Framingham Risk Score]], providing a significant increase in the accuracy of risk stratification.<ref name="pmid28670030" /><ref name="pmid22740742" /> However, there is no prospective data that indicates that CAC screening results in a reduction of coronary events.<ref name="pmid22740742" />
* CAC has also been demonstrated to be an independent predictor of major cardiovascular events.<ref name="pmid28670030" />
'''CAC Scores in Asymptomatic Patients'''
* Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of CHD event in the long term.<ref name="pmid28670030" />
* The use of the CAC score is not indicated in asymptomatic high risk patients as aggressive preventive measures would have already been initiated.<ref name="pmid28670030" />
* Guidelines regarding the use of CAC in low and intermediate risk individuals have not been consistent.
* In 2010, the American College of Cardiology stated that the use of CAC is appropriate in asymptomatic, low risk individuals with a family history of CHD and in individuals with an intermediate risk of CHD (10%-20% 10 year risk of CHD).<ref name="pmid21144964">{{cite journal| author=Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al.| title=2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2010 | volume= 56 | issue= 25 | pages= e50-103 | pmid=21144964 | doi=10.1016/j.jacc.2010.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21144964 }} </ref> However, this has changed in the 2013 guidelines.
* The latest recommendation by the ACC is that CAC can be used to guide risk based decision making if after quantitative risk assessment, a risk based decision is uncertain.<ref name="pmid24222018" />
* Due to concerns related to cumulative radiation exposure, routine serial CAC scans are not currently recommended.<ref name="pmid22740742" />
'''CAC Scores in Symptomatic Patients'''
* The use of the CAC score alone is limited in symptomatic patients.
* The pretest probability of a CHD event should always be considered when interpreting a CAC score.<ref name="pmid28670030" />
* The ACCF/AHA Expert Consensus suggests that the CAC score can be used to help rule out obstructive coronary disease in low risk patients presenting with atypical chest pain.<ref name="pmid17239724">{{cite journal| author=Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM et al.| title=ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. | journal=J Am Coll Cardiol | year= 2007 | volume= 49 | issue= 3 | pages= 378-402 | pmid=17239724 | doi=10.1016/j.jacc.2006.10.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17239724 }} </ref>
* The National Institute for Health and Care Excellence (NICE) recommends that a CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD (based on the modified Diamond and Forrester Criteria).<ref name="pmid20538674">{{cite journal| author=Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, Chest Pain Guideline Development Group| title=NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. | journal=Heart | year= 2010 | volume= 96 | issue= 12 | pages= 974-8 | pmid=20538674 | doi=10.1136/hrt.2009.190066 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538674 }} </ref> If the CAC is:

** 0: Consider other causes of chest pain
** 1-400: Offer CT coronary angiography
** >400: Offer invasive coronary angiography.

==Latest Guidelines ==
{| class="wikitable"
! Guideline
! colspan="3" | Recommendation
|-
| colspan="2" |
! '''[[ACC AHA guidelines classification scheme|Class]]'''
! '''[[ACC AHA guidelines classification scheme|Level of Evidence]]'''
|-
| 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk <ref name="pmid24222018">{{cite journal| author=Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al.| title=2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2014 | volume= 129 | issue= 25 Suppl 2 | pages= S49-73 | pmid=24222018 | doi=10.1161/01.cir.0000437741.48606.98 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24222018 }} </ref>
| If after quantitative risk assessment, a risk-based decision is uncertain, one or more of the following tools may be used to aid in decision making: family history, hs-CRP, CAC score or ABI.
| IIb
| B
|-
| 2016 European Guidelines on Cardiovascular Disease Prevention In Clinical Practice <ref name="pmid27222591">{{cite journal| author=Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.| title=2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). | journal=Eur Heart J | year= 2016 | volume= 37 | issue= 29 | pages= 2315-81 | pmid=27222591 | doi=10.1093/eurheartj/ehw106 | pmc=4986030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27222591 }} </ref>
| CAC may be considered as a risk factor in CV risk assessment in patients with a calculated SCORE risk between 5% to 10%.
| IIb
| B
|-
| colspan="2" |
! colspan="2" | '''Recommendation'''
|-
| rowspan="4" | ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR
2010 Appropriate Use Criteria
for Cardiac Computed Tomography <ref name="pmid21232696">{{cite journal| author=Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P et al.| title=ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. | journal=J Cardiovasc Comput Tomogr | year= 2010 | volume= 4 | issue= 6 | pages= 407.e1-33 | pmid=21232696 | doi=10.1016/j.jcct.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21232696 }} </ref>
| CAC would be appropriate in patients with a 10-20% 10-year risk of CHD.
| colspan="2" | Appropriate
|-
| CAC would be appropriate in low risk patients (<10% 10-year risk of CHD) with a family history of premature CHD.
| colspan="2" | Appropriate
|-
| The usefulness of CAC is uncertain in patients with peripheral arterial disease or other coronary risk equivalents, or have a 10-year CHD risk greater than 20%, or who are 40 or older with diabetes.
| colspan="2" | Uncertain
|-
| CAC would be inappropriate in low risk patients (<10% 10-year risk of CHD).
| colspan="2" | Inappropriate
|-
|National Institute for Health and Care Excellence (NICE) Guidance.
Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. (2010)<ref name="pmid20538674" />
| colspan="3" |The CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD.
|}

==References==
{{Reflist|2}}

{{WH}}{{WS}}

Coronary artery calcium scoring

2018-11-01T20:19:52Z

Fahad AlKhalfan: /* Agatston Method */

__NOTOC__
{{SI}}
{{CMG}}; {{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]],{{TarekNafee}}
==Overview==
The presence of [[Coronary artery calcification|coronary artery calcification]] indicates underlying [[Coronary heart disease|CHD]].<ref name="pmid22740742">{{cite journal| author=Shah NR, Coulter SA| title=An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. | journal=Tex Heart Inst J | year= 2012 | volume= 39 | issue= 2 | pages= 240-2 | pmid=22740742 | doi= | pmc=3384065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22740742 }} </ref> The coronary artery calcium (CAC) scan is a non-contrast [[Computed tomography|CT]] scan used to visualize the extent of calcification in the [[Coronary arteries|coronary vessels]].<ref name="pmid25937196">{{cite journal| author=Hecht HS| title=Coronary artery calcium scanning: past, present, and future. | journal=JACC Cardiovasc Imaging | year= 2015 | volume= 8 | issue= 5 | pages= 579-96 | pmid=25937196 | doi=10.1016/j.jcmg.2015.02.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25937196 }} </ref> While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture and therefore may not be a good predictor of luminal obstruction. <ref name="pmid22740742" />

The role of CAC in patients with low or intermediate risk of developing a CHD event is uncertain. However, it is not indicated for patients at high risk of CHD as aggressive preventative measures would have already been initiated.

==Coronary Artery Calcium Scoring Systems==
===Agatston Method===
{| align="right"
|
[[Image:Lesionspecificcalciumscore.png|thumb|200px|Lesion Specific Calcium Score - By Cardiomed - Own work, CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)]]
|}
* The Agatston score is a scoring system that uses images obtained from a non-contrast CT.
* It is determined by the number of calcific lesions, the area of each lesion and the peak [[Hounsfield scale|HU]] of each lesion detected. The score for every calcific lesion is based on its density score and area (mm<sup>2</sup>).<ref name="pmid2407762">{{cite journal| author=Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R| title=Quantification of coronary artery calcium using ultrafast computed tomography. | journal=J Am Coll Cardiol | year= 1990 | volume= 15 | issue= 4 | pages= 827-32 | pmid=2407762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2407762 }} </ref>
* The density score is determined by the peak HU and is as follows:

** 1 = 130 - 199 HU
** 2 = 200 - 299 HU
** 3 = 300 - 399 HU
** 4 = >399 HU

* If a lesion had a peak HU of 250 and an area of 4 mm<sup>2</sup>, it would receive a score of 8.
* The CAC is the sum of the scores assigned to each calcific lesion.
* The degree of calcification has also been shown to vary depending on certain demographic factors including age, gender and ethnicity.
* Taking this into consideration, the CAC score using the Agatston method can either be presented as an absolute value or as a percentile after adjusting for these three factors.<ref name="pmid28670030" /> Percentiles can be obtained from the [https://www.mesa-nhlbi.org/Calcium/input.aspx Multi-Ethnic Study of Atherosclerosis (MESA) website].
The CAC can be stratified as the following:<ref name="pmid28670030" /><ref name="pmid21098187">{{cite journal| author=van der Bijl N, Joemai RM, Geleijns J, Bax JJ, Schuijf JD, de Roos A et al.| title=Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 195 | issue= 6 | pages= 1299-305 | pmid=21098187 | doi=10.2214/AJR.09.3734 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21098187 }} </ref>
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Coronary Artery Calcium Score
! style="background:#4479BA; color: #FFFFFF;" align="center" + |CAC Score Percentile
(after adjustment)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Calcification Grade
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Interpretation
|-
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |0
| style="background:#DCDCDC;" align="center" + |None
| style="background:#DCDCDC;" align="center" + |Very low risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |1-10
| style="background:#DCDCDC;" align="center" + rowspan="2" |≤75
| style="background:#DCDCDC;" align="center" + |Minimum
| style="background:#DCDCDC;" align="center" + rowspan="2" |Low risk of future CHD event, low probability of MI
|-
| style="background:#DCDCDC;" align="center" + |11-100
| style="background:#DCDCDC;" align="center" + |Mild
|-
| style="background:#DCDCDC;" align="center" + |101-400
| style="background:#DCDCDC;" align="center" + |76-90
| style="background:#DCDCDC;" align="center" + |Moderate
| style="background:#DCDCDC;" align="center" + |Increased risk of future CHD event
|-
| style="background:#DCDCDC;" align="center" + |>400
| style="background:#DCDCDC;" align="center" + |>90
| style="background:#DCDCDC;" align="center" + |Severe
| style="background:#DCDCDC;" align="center" + |Increased probability of MI
|}
'''Calcium Volume Score'''
* The calcium volume score is calculated by multiply the number of [[voxel|voxels]] with calcification by the volume of each voxel. This would include all voxels with a HU score of greater than 130.<ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>
'''Relative Calcium Mass Score'''
* The relative calcium mass score is calculated by multiplying the mean attenuation of the calcified plaque by the plaque volume in each image. <ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>

==Role of CAC score in Clinical Practice==
The presence of CAC indicates underlying CHD. While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture. Therefore, CAC is not a good predictor of luminal obstruction.<ref name="pmid22740742" />

CAC scores have been shown to improve upon the current [[Framingham Risk Score|Framingham Risk Score]], providing a significant increase in the accuracy of risk stratification.<ref name="pmid28670030" /><ref name="pmid22740742" /> However, there is no prospective data that indicates that CAC screening results in a reduction of coronary events.<ref name="pmid22740742" /> CAC has also been demonstrated to be an independent predictor of major cardiovascular events.<ref name="pmid28670030" />

'''CAC Scores in Asymptomatic Patients'''

Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of CHD event in the long term.<ref name="pmid28670030" />

The use of the CAC score is not indicated in asymptomatic high risk patients as aggressive preventive measures would have already been initiated.<ref name="pmid28670030" />

Guidelines regarding the use of CAC in low and intermediate risk individuals have not been consistent. In 2010, the American College of Cardiology stated that the use of CAC is appropriate in asymptomatic, low risk individuals with a family history of CHD and in individuals with an intermediate risk of CHD (10%-20% 10 year risk of CHD).<ref name="pmid21144964">{{cite journal| author=Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al.| title=2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2010 | volume= 56 | issue= 25 | pages= e50-103 | pmid=21144964 | doi=10.1016/j.jacc.2010.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21144964 }} </ref> However, this has changed in the 2013 guidelines. The latest recommendation by the ACC is that CAC can be used to guide risk based decision making if after quantitative risk assessment, a risk based decision is uncertain.<ref name="pmid24222018" />

Due to concerns related to cumulative radiation exposure, routine serial CAC scans are not currently recommended.<ref name="pmid22740742" />

'''CAC Scores in Symptomatic Patients'''

The use of the CAC score alone is limited in symptomatic patients. The pretest probability of a CHD event should always be considered when interpreting a CAC score.<ref name="pmid28670030" /> The ACCF/AHA Expert Consensus suggests that the CAC score can be used to help rule out obstructive coronary disease in low risk patients presenting with atypical chest pain.<ref name="pmid17239724">{{cite journal| author=Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM et al.| title=ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. | journal=J Am Coll Cardiol | year= 2007 | volume= 49 | issue= 3 | pages= 378-402 | pmid=17239724 | doi=10.1016/j.jacc.2006.10.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17239724 }} </ref>

The National Institute for Health and Care Excellence (NICE) recommends that a CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD (based on the modified Diamond and Forrester Criteria).<ref name="pmid20538674">{{cite journal| author=Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, Chest Pain Guideline Development Group| title=NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. | journal=Heart | year= 2010 | volume= 96 | issue= 12 | pages= 974-8 | pmid=20538674 | doi=10.1136/hrt.2009.190066 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538674 }} </ref> If the CAC is:
* 0: Consider other causes of chest pain
* 1-400: Offer CT coronary angiography
* >400: Offer invasive coronary angiography.

==Latest Guidelines ==
{| class="wikitable"
! Guideline
! colspan="3" | Recommendation
|-
| colspan="2" |
! '''[[ACC AHA guidelines classification scheme|Class]]'''
! '''[[ACC AHA guidelines classification scheme|Level of Evidence]]'''
|-
| 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk <ref name="pmid24222018">{{cite journal| author=Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al.| title=2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2014 | volume= 129 | issue= 25 Suppl 2 | pages= S49-73 | pmid=24222018 | doi=10.1161/01.cir.0000437741.48606.98 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24222018 }} </ref>
| If after quantitative risk assessment, a risk-based decision is uncertain, one or more of the following tools may be used to aid in decision making: family history, hs-CRP, CAC score or ABI.
| IIb
| B
|-
| 2016 European Guidelines on Cardiovascular Disease Prevention In Clinical Practice <ref name="pmid27222591">{{cite journal| author=Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.| title=2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). | journal=Eur Heart J | year= 2016 | volume= 37 | issue= 29 | pages= 2315-81 | pmid=27222591 | doi=10.1093/eurheartj/ehw106 | pmc=4986030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27222591 }} </ref>
| CAC may be considered as a risk factor in CV risk assessment in patients with a calculated SCORE risk between 5% to 10%.
| IIb
| B
|-
| colspan="2" |
! colspan="2" | '''Recommendation'''
|-
| rowspan="4" | ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR
2010 Appropriate Use Criteria
for Cardiac Computed Tomography <ref name="pmid21232696">{{cite journal| author=Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P et al.| title=ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. | journal=J Cardiovasc Comput Tomogr | year= 2010 | volume= 4 | issue= 6 | pages= 407.e1-33 | pmid=21232696 | doi=10.1016/j.jcct.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21232696 }} </ref>
| CAC would be appropriate in patients with a 10-20% 10-year risk of CHD.
| colspan="2" | Appropriate
|-
| CAC would be appropriate in low risk patients (<10% 10-year risk of CHD) with a family history of premature CHD.
| colspan="2" | Appropriate
|-
| The usefulness of CAC is uncertain in patients with peripheral arterial disease or other coronary risk equivalents, or have a 10-year CHD risk greater than 20%, or who are 40 or older with diabetes.
| colspan="2" | Uncertain
|-
| CAC would be inappropriate in low risk patients (<10% 10-year risk of CHD).
| colspan="2" | Inappropriate
|-
|National Institute for Health and Care Excellence (NICE) Guidance.
Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. (2010)<ref name="pmid20538674" />
| colspan="3" |The CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD.
|}

==References==
{{Reflist|2}}

{{WH}}{{WS}}

Coronary artery calcium scoring

2018-11-01T20:16:36Z

Fahad AlKhalfan: /* Agatston Method */

__NOTOC__
{{SI}}
{{CMG}}; {{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]],{{TarekNafee}}
==Overview==
The presence of [[Coronary artery calcification|coronary artery calcification]] indicates underlying [[Coronary heart disease|CHD]].<ref name="pmid22740742">{{cite journal| author=Shah NR, Coulter SA| title=An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. | journal=Tex Heart Inst J | year= 2012 | volume= 39 | issue= 2 | pages= 240-2 | pmid=22740742 | doi= | pmc=3384065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22740742 }} </ref> The coronary artery calcium (CAC) scan is a non-contrast [[Computed tomography|CT]] scan used to visualize the extent of calcification in the [[Coronary arteries|coronary vessels]].<ref name="pmid25937196">{{cite journal| author=Hecht HS| title=Coronary artery calcium scanning: past, present, and future. | journal=JACC Cardiovasc Imaging | year= 2015 | volume= 8 | issue= 5 | pages= 579-96 | pmid=25937196 | doi=10.1016/j.jcmg.2015.02.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25937196 }} </ref> While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture and therefore may not be a good predictor of luminal obstruction. <ref name="pmid22740742" />

The role of CAC in patients with low or intermediate risk of developing a CHD event is uncertain. However, it is not indicated for patients at high risk of CHD as aggressive preventative measures would have already been initiated.

==Coronary Artery Calcium Scoring Systems==
===Agatston Method===
{| align="right"
|
[[Image:Lesionspecificcalciumscore.png|thumb|200px|Lesion Specific Calcium Score - By Cardiomed - Own work, CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)]]
|}
* The Agatston score is a scoring system that uses images obtained from a non-contrast CT.
* It is determined by the number of calcific lesions, the area of each lesion and the peak [[Hounsfield scale|HU]] of each lesion detected. The score for every calcific lesion is based on its density score and area (mm<sup>2</sup>).<ref name="pmid2407762">{{cite journal| author=Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R| title=Quantification of coronary artery calcium using ultrafast computed tomography. | journal=J Am Coll Cardiol | year= 1990 | volume= 15 | issue= 4 | pages= 827-32 | pmid=2407762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2407762 }} </ref>
* The density score is determined by the peak HU and is as follows:

** 1 = 130 - 199 HU
** 2 = 200 - 299 HU
** 3 = 300 - 399 HU
** 4 = >399 HU

* If a lesion had a peak HU of 250 and an area of 4 mm<sup>2</sup>, it would receive a score of 8.
* The CAC is the sum of the scores assigned to each calcific lesion.
* The degree of calcification has also been shown to vary depending on certain demographic factors including age, gender and ethnicity.
* Taking this into consideration, the CAC score using the Agatston method can either be presented as an absolute value or as a percentile after adjusting for these three factors.<ref name="pmid28670030" /> Percentiles can be obtained from the [https://www.mesa-nhlbi.org/Calcium/input.aspx Multi-Ethnic Study of Atherosclerosis (MESA) website].
The CAC can be stratified as the following:<ref name="pmid28670030" /><ref name="pmid21098187">{{cite journal| author=van der Bijl N, Joemai RM, Geleijns J, Bax JJ, Schuijf JD, de Roos A et al.| title=Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. | journal=AJR Am J Roentgenol | year= 2010 | volume= 195 | issue= 6 | pages= 1299-305 | pmid=21098187 | doi=10.2214/AJR.09.3734 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21098187 }} </ref>
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Coronary Artery Calcium Score
! style="background:#4479BA; color: #FFFFFF;" align="center" + |CAC Score Percentile
(after adjustment)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Calcification Grade
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Interpretation
|-
|0
|0
|None
|Very low risk of future CHD event
|-
|1-10
| rowspan="2" |≤75
|Minimum
| rowspan="2" |Low risk of future CHD event, low probability of MI
|-
|11-100
|Mild
|-
|101-400
|76-90
|Moderate
|Increased risk of future CHD event
|-
|>400
|>90
|Severe
|Increased probability of MI
|}
'''Calcium Volume Score'''
* The calcium volume score is calculated by multiply the number of [[voxel|voxels]] with calcification by the volume of each voxel. This would include all voxels with a HU score of greater than 130.<ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>
'''Relative Calcium Mass Score'''
* The relative calcium mass score is calculated by multiplying the mean attenuation of the calcified plaque by the plaque volume in each image. <ref name="pmid28670030">{{cite journal| author=Neves PO, Andrade J, Monção H| title=Coronary artery calcium score: current status. | journal=Radiol Bras | year= 2017 | volume= 50 | issue= 3 | pages= 182-189 | pmid=28670030 | doi=10.1590/0100-3984.2015.0235 | pmc=5487233 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28670030 }} </ref>

==Role of CAC score in Clinical Practice==
The presence of CAC indicates underlying CHD. While there is a strong correlation between CAC burden and coronary plaque area, CAC scans do not identify noncalcified plaques that are capable of erosion or rupture. Therefore, CAC is not a good predictor of luminal obstruction.<ref name="pmid22740742" />

CAC scores have been shown to improve upon the current [[Framingham Risk Score|Framingham Risk Score]], providing a significant increase in the accuracy of risk stratification.<ref name="pmid28670030" /><ref name="pmid22740742" /> However, there is no prospective data that indicates that CAC screening results in a reduction of coronary events.<ref name="pmid22740742" /> CAC has also been demonstrated to be an independent predictor of major cardiovascular events.<ref name="pmid28670030" />

'''CAC Scores in Asymptomatic Patients'''

Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of CHD event in the long term.<ref name="pmid28670030" />

The use of the CAC score is not indicated in asymptomatic high risk patients as aggressive preventive measures would have already been initiated.<ref name="pmid28670030" />

Guidelines regarding the use of CAC in low and intermediate risk individuals have not been consistent. In 2010, the American College of Cardiology stated that the use of CAC is appropriate in asymptomatic, low risk individuals with a family history of CHD and in individuals with an intermediate risk of CHD (10%-20% 10 year risk of CHD).<ref name="pmid21144964">{{cite journal| author=Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al.| title=2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2010 | volume= 56 | issue= 25 | pages= e50-103 | pmid=21144964 | doi=10.1016/j.jacc.2010.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21144964 }} </ref> However, this has changed in the 2013 guidelines. The latest recommendation by the ACC is that CAC can be used to guide risk based decision making if after quantitative risk assessment, a risk based decision is uncertain.<ref name="pmid24222018" />

Due to concerns related to cumulative radiation exposure, routine serial CAC scans are not currently recommended.<ref name="pmid22740742" />

'''CAC Scores in Symptomatic Patients'''

The use of the CAC score alone is limited in symptomatic patients. The pretest probability of a CHD event should always be considered when interpreting a CAC score.<ref name="pmid28670030" /> The ACCF/AHA Expert Consensus suggests that the CAC score can be used to help rule out obstructive coronary disease in low risk patients presenting with atypical chest pain.<ref name="pmid17239724">{{cite journal| author=Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM et al.| title=ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. | journal=J Am Coll Cardiol | year= 2007 | volume= 49 | issue= 3 | pages= 378-402 | pmid=17239724 | doi=10.1016/j.jacc.2006.10.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17239724 }} </ref>

The National Institute for Health and Care Excellence (NICE) recommends that a CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD (based on the modified Diamond and Forrester Criteria).<ref name="pmid20538674">{{cite journal| author=Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, Chest Pain Guideline Development Group| title=NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. | journal=Heart | year= 2010 | volume= 96 | issue= 12 | pages= 974-8 | pmid=20538674 | doi=10.1136/hrt.2009.190066 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538674 }} </ref> If the CAC is:
* 0: Consider other causes of chest pain
* 1-400: Offer CT coronary angiography
* >400: Offer invasive coronary angiography.

==Latest Guidelines ==
{| class="wikitable"
! Guideline
! colspan="3" | Recommendation
|-
| colspan="2" |
! '''[[ACC AHA guidelines classification scheme|Class]]'''
! '''[[ACC AHA guidelines classification scheme|Level of Evidence]]'''
|-
| 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk <ref name="pmid24222018">{{cite journal| author=Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al.| title=2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2014 | volume= 129 | issue= 25 Suppl 2 | pages= S49-73 | pmid=24222018 | doi=10.1161/01.cir.0000437741.48606.98 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24222018 }} </ref>
| If after quantitative risk assessment, a risk-based decision is uncertain, one or more of the following tools may be used to aid in decision making: family history, hs-CRP, CAC score or ABI.
| IIb
| B
|-
| 2016 European Guidelines on Cardiovascular Disease Prevention In Clinical Practice <ref name="pmid27222591">{{cite journal| author=Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.| title=2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). | journal=Eur Heart J | year= 2016 | volume= 37 | issue= 29 | pages= 2315-81 | pmid=27222591 | doi=10.1093/eurheartj/ehw106 | pmc=4986030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27222591 }} </ref>
| CAC may be considered as a risk factor in CV risk assessment in patients with a calculated SCORE risk between 5% to 10%.
| IIb
| B
|-
| colspan="2" |
! colspan="2" | '''Recommendation'''
|-
| rowspan="4" | ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR
2010 Appropriate Use Criteria
for Cardiac Computed Tomography <ref name="pmid21232696">{{cite journal| author=Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P et al.| title=ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. | journal=J Cardiovasc Comput Tomogr | year= 2010 | volume= 4 | issue= 6 | pages= 407.e1-33 | pmid=21232696 | doi=10.1016/j.jcct.2010.11.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21232696 }} </ref>
| CAC would be appropriate in patients with a 10-20% 10-year risk of CHD.
| colspan="2" | Appropriate
|-
| CAC would be appropriate in low risk patients (<10% 10-year risk of CHD) with a family history of premature CHD.
| colspan="2" | Appropriate
|-
| The usefulness of CAC is uncertain in patients with peripheral arterial disease or other coronary risk equivalents, or have a 10-year CHD risk greater than 20%, or who are 40 or older with diabetes.
| colspan="2" | Uncertain
|-
| CAC would be inappropriate in low risk patients (<10% 10-year risk of CHD).
| colspan="2" | Inappropriate
|-
|National Institute for Health and Care Excellence (NICE) Guidance.
Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. (2010)<ref name="pmid20538674" />
| colspan="3" |The CAC score can be used in patients with chest pain and a 10% to 29% estimated likelihood of CAD.
|}

==References==
{{Reflist|2}}

{{WH}}{{WS}}

Atrial fibrillation pharmacological cardioversion

2018-09-17T20:20:46Z

Fahad AlKhalfan: /* 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation[1] */

__NOTOC__
{| class="infobox" style="float:right;"
| [[File:Siren.gif|30px|link=Atrial fibrillation resident survival guide]]|| <br> || <br>
| [[Atrial fibrillation resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{Atrial fibrillation}}
{{CMG}}; '''Associate Editor(s)-In-Chief:''' {{CZ}}; [[Varun Kumar, M.B.B.S.]]

==Overview==

Chemical cardioversion refers to restoring the heart's rhythm to normal through pharmacological agents such as [[amiodarone]], [[propafenone]], and [[flecainide]]. Such medications work by altering the heart’s electrical properties to suppress the abnormal heart rhythms and restore a normal rhythm, and can be administered orally or intravenously. The treatment can be carried either in an in-patient or out-patient setting.

==2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation<ref name="JanuaryWann2014">{{cite journal|last1=January|first1=C. T.|last2=Wann|first2=L. S.|last3=Alpert|first3=J. S.|last4=Calkins|first4=H.|last5=Cleveland|first5=J. C.|last6=Cigarroa|first6=J. E.|last7=Conti|first7=J. B.|last8=Ellinor|first8=P. T.|last9=Ezekowitz|first9=M. D.|last10=Field|first10=M. E.|last11=Murray|first11=K. T.|last12=Sacco|first12=R. L.|last13=Stevenson|first13=W. G.|last14=Tchou|first14=P. J.|last15=Tracy|first15=C. M.|last16=Yancy|first16=C. W.|title=2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society|journal=Circulation|year=2014|issn=0009-7322|doi=10.1161/CIR.0000000000000041}}</ref> (DO NOT EDIT)==

===Rhythm Control===

====Electrical and Pharmacological Cardioversion of AF and Atrial Flutter====

=====Pharmacological Cardioversion=====

{| class="wikitable" style="width: 80%;"
|-
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' [[Flecainide]], [[dofetilide]], [[propafenone]], and [[intravenous]] [[ibutilide]] are useful for pharmacological [[cardioversion]] of [[AF]] or [[atrial flutter]] provided contraindications to the selected drug are absent. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}

{| class="wikitable" style="width: 80%;"
|-
| colspan="1" style="text-align:center; background:LightCoral" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III: Harm]]
|-
| bgcolor="LightCoral" |<nowiki>"</nowiki>'''1.''' [[Dofetilide]] therapy should not be initiated out of hospital owing to the risk of excessive [[QT prolongation]] that can cause [[torsades de pointes]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}

{| class="wikitable" style="width: 80%;"
|-
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' Administration of oral [[amiodarone]] is a reasonable option for pharmacological [[cardioversion]] of [[AF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' [[Propafenone]] or [[flecainide]] (“pill-in-the-pocket”) in addition to a [[beta blocker]] or [[Calcium channel blocker#Non-dihydropyridine|nondihydropyridine calcium channel antagonist]] is reasonable to terminate [[AF]] outside the hospital once this treatment has been observed to be safe in a monitored setting for selected patients. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}

==Sources==

* [http://circ.ahajournals.org/content/early/2014/03/27/CIR.0000000000000041 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation]<ref name="JanuaryWann2014">{{cite journal|last1=January|first1=C. T.|last2=Wann|first2=L. S.|last3=Alpert|first3=J. S.|last4=Calkins|first4=H.|last5=Cleveland|first5=J. C.|last6=Cigarroa|first6=J. E.|last7=Conti|first7=J. B.|last8=Ellinor|first8=P. T.|last9=Ezekowitz|first9=M. D.|last10=Field|first10=M. E.|last11=Murray|first11=K. T.|last12=Sacco|first12=R. L.|last13=Stevenson|first13=W. G.|last14=Tchou|first14=P. J.|last15=Tracy|first15=C. M.|last16=Yancy|first16=C. W.|title=2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society|journal=Circulation|year=2014|issn=0009-7322|doi=10.1161/CIR.0000000000000041}}</ref>

* [http://circ.ahajournals.org/content/123/10/e269.full.pdf ACCF/AHA/HRS 2011 Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation]<ref name="pmid21382897">Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2011) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=21382897 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.] ''Circulation'' 123 (10):e269-367. [http://dx.doi.org/10.1161/CIR.0b013e318214876d DOI:10.1161/CIR.0b013e318214876d] PMID: [http://pubmed.gov/21382897 21382897]</ref>

* [http://circ.ahajournals.org/content/122/24/2619 ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines]<ref name="pmid21060077">{{cite journal| author=Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB et al.| title=ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. | journal=Circulation | year= 2010 | volume= 122 | issue= 24 | pages= 2619-33 | pmid=21060077 | doi=10.1161/CIR.0b013e318202f701 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21060077 }}</ref>

* [http://circ.ahajournals.org/content/117/8/1101.full.pdf ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults With Nonvalvular Atrial Fibrillation or Atrial Flutter]<ref name="pmid18283199">Estes NA, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS et al. (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18283199 ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society.] ''Circulation'' 117 (8):1101-20. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.187192 DOI:10.1161/CIRCULATIONAHA.107.187192] PMID: [http://pubmed.gov/18283199 18283199]</ref>

* [http://content.onlinejacc.org/cgi/reprint/48/4/e149.pdf ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation]<ref name="pmid16908781">Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16908781 ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.] ''Circulation'' 114 (7):e257-354. [http://dx.doi.org/10.1161/CIRCULATIONAHA.106.177292 DOI:10.1161/CIRCULATIONAHA.106.177292] PMID: [http://pubmed.gov/16908781 16908781]</ref>

==References==

{{reflist|2}}

{{Electrocardiography}}
{{Circulatory system pathology}}

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[[Category:Arrhythmia]]
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[[Category:Primary care]]
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[[Category:Up-To-Date Cardiology]]

Atrial fibrillation pharmacological cardioversion

2018-09-17T20:19:16Z

Fahad AlKhalfan: /* 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)[1] */

__NOTOC__
{| class="infobox" style="float:right;"
| [[File:Siren.gif|30px|link=Atrial fibrillation resident survival guide]]|| <br> || <br>
| [[Atrial fibrillation resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{Atrial fibrillation}}
{{CMG}}; '''Associate Editor(s)-In-Chief:''' {{CZ}}; [[Varun Kumar, M.B.B.S.]]

==Overview==

Chemical cardioversion refers to restoring the heart's rhythm to normal through pharmacological agents such as [[amiodarone]], [[propafenone]], and [[flecainide]]. Such medications work by altering the heart’s electrical properties to suppress the abnormal heart rhythms and restore a normal rhythm, and can be administered orally or intravenously. The treatment can be carried either in an in-patient or out-patient setting.

==2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation<ref name="JanuaryWann2014">{{cite journal|last1=January|first1=C. T.|last2=Wann|first2=L. S.|last3=Alpert|first3=J. S.|last4=Calkins|first4=H.|last5=Cleveland|first5=J. C.|last6=Cigarroa|first6=J. E.|last7=Conti|first7=J. B.|last8=Ellinor|first8=P. T.|last9=Ezekowitz|first9=M. D.|last10=Field|first10=M. E.|last11=Murray|first11=K. T.|last12=Sacco|first12=R. L.|last13=Stevenson|first13=W. G.|last14=Tchou|first14=P. J.|last15=Tracy|first15=C. M.|last16=Yancy|first16=C. W.|title=2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society|journal=Circulation|year=2014|issn=0009-7322|doi=10.1161/CIR.0000000000000041}}</ref>==

===Rhythm Control===

====Electrical and Pharmacological Cardioversion of AF and Atrial Flutter====

=====Pharmacological Cardioversion=====

{| class="wikitable" style="width: 80%;"
|-
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' [[Flecainide]], [[dofetilide]], [[propafenone]], and [[intravenous]] [[ibutilide]] are useful for pharmacological [[cardioversion]] of [[AF]] or [[atrial flutter]] provided contraindications to the selected drug are absent. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}

{| class="wikitable" style="width: 80%;"
|-
| colspan="1" style="text-align:center; background:LightCoral" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III: Harm]]
|-
| bgcolor="LightCoral" |<nowiki>"</nowiki>'''1.''' [[Dofetilide]] therapy should not be initiated out of hospital owing to the risk of excessive [[QT prolongation]] that can cause [[torsades de pointes]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}

{| class="wikitable" style="width: 80%;"
|-
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' Administration of oral [[amiodarone]] is a reasonable option for pharmacological [[cardioversion]] of [[AF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' [[Propafenone]] or [[flecainide]] (“pill-in-the-pocket”) in addition to a [[beta blocker]] or [[Calcium channel blocker#Non-dihydropyridine|nondihydropyridine calcium channel antagonist]] is reasonable to terminate [[AF]] outside the hospital once this treatment has been observed to be safe in a monitored setting for selected patients. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}

==Sources==

* [http://circ.ahajournals.org/content/early/2014/03/27/CIR.0000000000000041 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation]<ref name="JanuaryWann2014">{{cite journal|last1=January|first1=C. T.|last2=Wann|first2=L. S.|last3=Alpert|first3=J. S.|last4=Calkins|first4=H.|last5=Cleveland|first5=J. C.|last6=Cigarroa|first6=J. E.|last7=Conti|first7=J. B.|last8=Ellinor|first8=P. T.|last9=Ezekowitz|first9=M. D.|last10=Field|first10=M. E.|last11=Murray|first11=K. T.|last12=Sacco|first12=R. L.|last13=Stevenson|first13=W. G.|last14=Tchou|first14=P. J.|last15=Tracy|first15=C. M.|last16=Yancy|first16=C. W.|title=2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society|journal=Circulation|year=2014|issn=0009-7322|doi=10.1161/CIR.0000000000000041}}</ref>

* [http://circ.ahajournals.org/content/123/10/e269.full.pdf ACCF/AHA/HRS 2011 Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation]<ref name="pmid21382897">Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2011) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=21382897 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.] ''Circulation'' 123 (10):e269-367. [http://dx.doi.org/10.1161/CIR.0b013e318214876d DOI:10.1161/CIR.0b013e318214876d] PMID: [http://pubmed.gov/21382897 21382897]</ref>

* [http://circ.ahajournals.org/content/122/24/2619 ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines]<ref name="pmid21060077">{{cite journal| author=Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB et al.| title=ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. | journal=Circulation | year= 2010 | volume= 122 | issue= 24 | pages= 2619-33 | pmid=21060077 | doi=10.1161/CIR.0b013e318202f701 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21060077 }}</ref>

* [http://circ.ahajournals.org/content/117/8/1101.full.pdf ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults With Nonvalvular Atrial Fibrillation or Atrial Flutter]<ref name="pmid18283199">Estes NA, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS et al. (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18283199 ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society.] ''Circulation'' 117 (8):1101-20. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.187192 DOI:10.1161/CIRCULATIONAHA.107.187192] PMID: [http://pubmed.gov/18283199 18283199]</ref>

* [http://content.onlinejacc.org/cgi/reprint/48/4/e149.pdf ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation]<ref name="pmid16908781">Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16908781 ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.] ''Circulation'' 114 (7):e257-354. [http://dx.doi.org/10.1161/CIRCULATIONAHA.106.177292 DOI:10.1161/CIRCULATIONAHA.106.177292] PMID: [http://pubmed.gov/16908781 16908781]</ref>

==References==

{{reflist|2}}

{{Electrocardiography}}
{{Circulatory system pathology}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[CME Category::Cardiology]]

[[Category:Arrhythmia]]
[[Category:Cardiology]]
[[Category:Electrophysiology]]
[[Category:Emergency medicine]]
[[Category:Primary care]]
[[Category:Up-To-Date]]
[[Category:Up-To-Date Cardiology]]

Sandbox:Fahad

2018-09-17T18:29:14Z

Fahad AlKhalfan:

==Overview ==
== Atrial fibrillation (AF or afib) is a [https://www.wikidoc.org/index.php/Cardiac_arrhythmia cardiac arrhythmia] (abnormal heart rhythm) that involves the two upper chambers ([https://www.wikidoc.org/index.php/Atrium_(anatomy) atria]) of the [https://www.wikidoc.org/index.php/Heart heart]. Atrial fibrillation is an irregularly irregular heart beat due to chaotic firing of the impulses in the atrium. In this rhythm, the atrium is stimulated chaotically by a wide number of ectopic foci of electrical activity. ==
==Classification==
== Although several clinical classification plans and protocols have been proposed, none of them fully account for all aspects of atrial fibrillation. The [https://www.wikidoc.org/index.php/American_Heart_Association American Heart Association], [https://www.wikidoc.org/index.php/American_College_of_Cardiology American College of Cardiology], and the [https://www.wikidoc.org/index.php/European_Society_of_Cardiology European Society of Cardiology] have proposed a classification system based on simplicity and clinical relevance.<ref name="pmid16908781">{{cite journal |author=Fuster V, Rydén LE, Cannom DS, ''et al'' |title=ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society |journal=Circulation |volume=114 |issue=7 |pages=e257-354 |year=2006 |pmid=16908781 |doi=10.1161/CIRCULATIONAHA.106.177292}}</ref> This classification system contains four main categories which are: first detected or diagnosed, paroxysmal, persistent, and permanent atrial fibrillation. ==

Sandbox:Fahad

2018-09-17T18:28:48Z

Fahad AlKhalfan: /* Epidemiology and Demographics */

==Overview Atrial fibrillation (AF or afib) is a [https://www.wikidoc.org/index.php/Cardiac_arrhythmia cardiac arrhythmia] (abnormal heart rhythm) that involves the two upper chambers ([https://www.wikidoc.org/index.php/Atrium_(anatomy) atria]) of the [https://www.wikidoc.org/index.php/Heart heart]. Atrial fibrillation is an irregularly irregular heart beat due to chaotic firing of the impulses in the atrium. In this rhythm, the atrium is stimulated chaotically by a wide number of ectopic foci of electrical activity. ==
==Classification Although several clinical classification plans and protocols have been proposed, none of them fully account for all aspects of atrial fibrillation. The [https://www.wikidoc.org/index.php/American_Heart_Association American Heart Association], [https://www.wikidoc.org/index.php/American_College_of_Cardiology American College of Cardiology], and the [https://www.wikidoc.org/index.php/European_Society_of_Cardiology European Society of Cardiology] have proposed a classification system based on simplicity and clinical relevance.<ref name="pmid16908781">{{cite journal |author=Fuster V, Rydén LE, Cannom DS, ''et al'' |title=ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society |journal=Circulation |volume=114 |issue=7 |pages=e257-354 |year=2006 |pmid=16908781 |doi=10.1161/CIRCULATIONAHA.106.177292}}</ref> This classification system contains four main categories which are: first detected or diagnosed, paroxysmal, persistent, and permanent atrial fibrillation. ==

Sandbox:Fahad

2018-09-17T17:34:56Z

Fahad AlKhalfan:

==Epidemiology and Demographics==
===Incidence===
Research has shown that the incidence of AF increased from less than 0.1% per year in those under 40 years of age to greater than 1.5% per year in women over 80 age and greater than 2% per year in men over 80 years of age. The age-adjusted incidence in the [[Framingham Heart Study]] found that in 38 years of follow-up, 20.6% of men and 26.0% of women who had developed AF had [[congestive heart failure]] at inclusion versus 3.2% and 2.9%, respectively, of those without AF. Among patients referred for treatment of [[heart failure]], the 2-to-3-year incidence of AF was 5% to 10%. There was some evidence to suggest that incidence of AF may be lower in heart failure patients with pharmacologic intervention.<ref name="pmid16908781">{{cite journal| author=Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al.| title=ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. | journal=Circulation | year= 2006 | volume= 114 | issue= 7 | pages= e257-354 | pmid=16908781 | doi=10.1161/CIRCULATIONAHA.106.177292 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16908781 }}</ref>
===Prevalence===
It should be noted that the prevalence of atrial fibrillation increases with increasing age, and its prevalence is increased among Caucasians, patients with [[hypertension]] and [[valvular heart disease]].<ref name="pmid11601835">{{cite journal |author=Fuster V, Rydén LE, Asinger RW, ''et al'' |title=ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology |journal=Eur. Heart J. |volume=22 |issue=20 |pages=1852–923 |year=2001 |month=October |pmid=11601835 |doi=10.1053/euhj.2001.2983 |url=}}</ref> The prevalence in the general population is 0.4%.<ref name="pmid14297523">{{cite journal |author=OSTRANDER LD, BRANDT RL, KJELSBERG MO, EPSTEIN FH |title=ELECTROCARDIOGRAPHIC FINDINGS AMONG THE ADULT POPULATION OF A TOTAL NATURAL COMMUNITY, TECUMSEH, MICHIGAN |journal=Circulation |volume=31 |issue= |pages=888–98 |year=1965 |month=June |pmid=14297523 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14297523}}</ref>
===United States===
Approximately 2.2 million individuals in the United States and 4.5 million in the European Union have AF.<ref name="pmid16908781" /><ref>{{cite journal |author=Go AS, Hylek EM, Phillips KA, ''et al'' |title=Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study |journal=JAMA |volume=285 |issue=18 |pages=2370–5 |year=2001 |pmid=11343485|doi=10.1001/jama.285.18.2370}}</ref>

Crohn's disease surgery

2018-09-14T19:20:44Z

Fahad AlKhalfan: /* Recommendations of the American Society of Colon and Rectal Surgeons (2015) */

__NOTOC__
{{Crohn's disease}}
{{CMG}};{{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]]

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015) ==
The American Society of Colon and Rectal Surgeons updated their guidelines on the role of surgical intervention in patients with Crohn's disease based on more recent evidence.<ref name="pmid26445174">{{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disease. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 11 | pages= 1021-36 | pmid=26445174 | doi=10.1097/DCR.0000000000000450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26445174 }}</ref>

The guidelines are as follows:
{| class="wikitable"
!Operative Indication
!Description
!Recommendation
![[ACCP guidelines classification scheme|Quality of Evidence]]
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-14T19:19:51Z

Fahad AlKhalfan: /* Recommendations of the American Society of Colon and Rectal Surgeons (2015){{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disea...

__NOTOC__
{{Crohn's disease}}
{{CMG}};{{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]]

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015) ==
The American Society of Colon and Rectal Surgeons updated their guidelines on the role of surgical intervention in patients with Crohn's disease based on more recent evidence.<ref name="pmid26445174">{{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disease. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 11 | pages= 1021-36 | pmid=26445174 | doi=10.1097/DCR.0000000000000450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26445174 }}</ref>
The guidelines are as follows:
{| class="wikitable"
!Operative Indication
!Description
!Recommendation
![[ACCP guidelines classification scheme|Quality of Evidence]]
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-14T19:16:10Z

Fahad AlKhalfan:

__NOTOC__
{{Crohn's disease}}
{{CMG}};{{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]]

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015)<ref name="pmid26445174">{{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disease. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 11 | pages= 1021-36 | pmid=26445174 | doi=10.1097/DCR.0000000000000450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26445174 }} </ref>==

{| class="wikitable"
!Operative Indication
!Description
!Recommendation
![[ACCP guidelines classification scheme|Quality of Evidence]]
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-14T19:14:54Z

Fahad AlKhalfan:

__NOTOC__
{{Crohn's disease}}
{{CMG}},{{AE}}[[User: Fahad Alkhalfan|Fahad AlKhalfan, M.D.]]

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015)<ref name="pmid26445174">{{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disease. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 11 | pages= 1021-36 | pmid=26445174 | doi=10.1097/DCR.0000000000000450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26445174 }} </ref>==

{| class="wikitable"
!Operative Indication
!Description
!Recommendation
![[ACCP guidelines classification scheme|Quality of Evidence]]
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-11T02:24:35Z

Fahad AlKhalfan:

__NOTOC__
{{Crohn's disease}}
{{CMG}}

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015)<ref name="pmid26445174">{{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disease. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 11 | pages= 1021-36 | pmid=26445174 | doi=10.1097/DCR.0000000000000450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26445174 }} </ref>==

{| class="wikitable"
!Operative Indication
!Description
!Recommendation
![[ACCP guidelines classification scheme|Quality of Evidence]]
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-11T02:11:42Z

Fahad AlKhalfan: /* Recommendations of the American Society of Colon and Rectal Surgeons (2015) */

__NOTOC__
{{Crohn's disease}}
{{CMG}}

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015)<ref name="pmid26445174">{{cite journal| author=Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al.| title=Clinical Practice Guideline for the Surgical Management of Crohn's Disease. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 11 | pages= 1021-36 | pmid=26445174 | doi=10.1097/DCR.0000000000000450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26445174 }} </ref>==

{| class="wikitable"
!Operative Indication
!Description
!Recommendation
!Quality of evidence
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-11T02:08:26Z

Fahad AlKhalfan: /* Recommendations of the American Society of Colon and Rectal Surgeons */

__NOTOC__
{{Crohn's disease}}
{{CMG}}

==Overview==
Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

==Surgery==
Two-thirds to three-quarters of patients with Crohn’s disease will require [[surgery]] at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, [[perforation]], [[abscess]], or [[bleeding]] in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.
===Colectomy===
*Colectomy is the method of surgery employed.
*Some people who have Crohn’s disease in the [[large intestine]] need to have their entire colon removed in an operation called a [[colectomy]].
*A small opening is made in the front of the [[abdominal wall]], and the tip of the [[ileum]], which is located at the end of the [[small intestine]], is brought to the skin’s surface.
*This opening, called a [[stoma]], is where waste exits the body.
*The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline.
*A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives.
*Rarely only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected.
*Because Crohn’s disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments.

==Recommendations of the American Society of Colon and Rectal Surgeons (2015)==

{| class="wikitable"
!Operative Indication
!Description
!Recommendation
!Quality of evidence
|-
| rowspan="2" |Failed Medical Therapy
|Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
| Patients receiving therapy with anti-TNFs, high-dose glucocorticoids, and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient's risk stratiffication, overal clinical status, and surgeon judgement.
|Weak recommendation
| 2C
|-
|Inflammation
|Patients with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery.
|Strong recommendation
|1C
|-
| rowspan="3" |Stricture
|Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy.
|Strong recommendation
|1C
|-
|Surgery is indicated for patients with symptomatic small-bowel or anastomotic structures that are not amenable to medical therapy and/or dilation.
|Strong recommendation
|1C
|-
|Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection.
|Strong recommendation
|1C
|-
| rowspan="3" |Penetrating Disease
|Patients with a free perforation should undergo surgery.
|Strong recommendation
|1B
|-
|Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful.
|Weak recommendation
|2B
|-
|Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persists despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1C
|-
|Hemorrhage
|Stable patients with significant GI hemorrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patietns should typically undergo operative exploration.
|Strong recommendation
|1C
|-
|Growth Retardation
|Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery.
|Strong recommendation
|1B
|-
| rowspan="3" |Neoplasia
|Patients with long-standing Crohn's disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel.
|Strong recommendation
|1B
|-
|Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasia-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum.
|Strong recommendation
|1B
|-
|Suspicious lesions (i.e. mass, ulcer) identified in patients with Crohn's disease should typically be biopsied, especially when considering a small-bowel strictureplasty.
|Strong recommendation
|1C
|}

==References==
{{reflist|2}}
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Autoimmune diseases]]
[[Category:Digestive diseases]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Inflammations]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Abdominal pain]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Crohn's disease surgery

2018-09-11T01:59:15Z

Fahad AlKhalfan: