Atypical teratoid rhabdoid tumor pathophysiology: Difference between revisions

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Latest revision as of 17:24, 16 May 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

Atypical teratoid rhabdoid tumor is comprised of rhabdoid tumor cells and varying amounts of small undifferentiated primitive neuroectodermal tumor (PNET)-like mesenchymal, and/or epithelial differentiated tumor cells. Gene involved in the pathogenesis of atypical teratoid rhabdoid tumor include SMARCB1 (hSNF5/INI-1), a tumor suppressor gene. Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome. On gross pathology, atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately vascular. On microscopic histopathological analysis, atypical teratoid rhabdoid tumor is characterized by round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures. Atypical teratoid rhabdoid tumor is demonstrated by positivity to tumor markers such as epithelial membrane antigen, vimentin, and smooth muscle actin.

Pathophysiology

Pathogenesis

Atypical teratoid rhabdoid tumor is comprised of rhabdoid tumor cells and varying amounts of small undifferentiated primitive neuroectodermal tumor (PNET)-like mesenchymal, and/or epithelial differentiated tumor cells.^[1]

Genetics

Gene involved in the pathogenesis of atypical teratoid rhabdoid tumor include SMARCB1 (hSNF5/INI-1), a tumor suppressor gene.^[2]
Atypical teratoid rhabdoid tumor is characterized by loss of the long arm of chromosome 22, which results in loss of the hSNF5/INI-1 gene.
INI1, a member of the SWI/SNF chromatin remodeling complex, is important in the maintenance of the mitotic spindle and cell cycle control.

Associated Conditions

Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome.^[1]

Gross Pathology

On gross pathology, atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately vascular.^[3]
Common intracranial sites associated with atypical teratoid rhabdoid tumor include:^[4]


Infratentorial	Supratentorial

Cerebellum Brain stem	Cerebral hemispheres Pineal gland Septum pellucidum Hypothalamus

Microscopic Pathology

On microscopic histopathological analysis, atypical teratoid rhabdoid tumor is characterized by the round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures.^[1]
According to the WHO classification of tumors of the central nervous system, atypical teratoid rhabdoid tumor is classified into a WHO grade IV tumor.

Immunohistochemistry

Atypical teratoid rhabdoid tumor is demonstrated by positivity to tumor markers, such as:^[5]^[6]

References

↑ ^1.0 ^1.1 ^1.2 Slavc, Irene; Chocholous, Monika; Leiss, Ulrike; Haberler, Christine; Peyrl, Andreas; Azizi, Amedeo A.; Dieckmann, Karin; Woehrer, Adelheid; Peters, Christina; Widhalm, Georg; Dorfer, Christian; Czech, Thomas (2014). "Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012". Cancer Medicine. 3 (1): 91–100. doi:10.1002/cam4.161. ISSN 2045-7634.
↑ Ginn, Kevin F.; Gajjar, Amar (2012). "Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions". Frontiers in Oncology. 2. doi:10.3389/fonc.2012.00114. ISSN 2234-943X.
↑ Chan KH, Mohammed Haspani MS, Tan YC, Kassim F (2011). "A case report of atypical teratoid/rhabdoid tumour in a 9-year-old girl". Malays J Med Sci. 18 (3): 82–6. PMC 3216225. PMID 22135607.
↑ Location of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015
↑ Markers of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015
↑ Meyers SP, Khademian ZP, Biegel JA, Chuang SH, Korones DN, Zimmerman RA (2006). "Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes". AJNR Am J Neuroradiol. 27 (5): 962–71. PMID 16687525.

Template:WH Template:WS

[SlavcChocholous2014-1] 1.0 ^1.1 ^1.2 Slavc, Irene; Chocholous, Monika; Leiss, Ulrike; Haberler, Christine; Peyrl, Andreas; Azizi, Amedeo A.; Dieckmann, Karin; Woehrer, Adelheid; Peters, Christina; Widhalm, Georg; Dorfer, Christian; Czech, Thomas (2014). "Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012". Cancer Medicine. 3 (1): 91–100. doi:10.1002/cam4.161. ISSN 2045-7634.

[GinnGajjar2012-2] Ginn, Kevin F.; Gajjar, Amar (2012). "Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions". Frontiers in Oncology. 2. doi:10.3389/fonc.2012.00114. ISSN 2234-943X.

[pmid22135607-3] Chan KH, Mohammed Haspani MS, Tan YC, Kassim F (2011). "A case report of atypical teratoid/rhabdoid tumour in a 9-year-old girl". Malays J Med Sci. 18 (3): 82–6. PMC 3216225. PMID 22135607.

[locationatrt1-4] Location of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015

[ihcatrt1-5] Markers of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015

[pmid16687525-6] Meyers SP, Khademian ZP, Biegel JA, Chuang SH, Korones DN, Zimmerman RA (2006). "Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes". AJNR Am J Neuroradiol. 27 (5): 962–71. PMID 16687525.

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[6]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Atypical teratoid rhabdoid tumor}}
-{{CMG}}
+{{CMG}}{{AE}}{{SR}}
 ==Overview==
-==Pathophysiology==
+Atypical teratoid rhabdoid tumor is comprised of [[Malignant rhabdoid tumor|rhabdoid tumor]] [[Cell (biology)|cells]] and varying amounts of small undifferentiated [[Primitive neuroectodermal tumor|primitive neuroectodermal tumor (PNET)]]-like [[Mesenchymal stem cell|mesenchymal]], and/or [[Epithelium|epithelial]] differentiated [[tumor]] [[Cell (biology)|cells]]. [[Gene]] involved in the [[pathogenesis]] of atypical teratoid rhabdoid tumor include ''[[SMARCB1]]'' (''hSNF5/INI-1''), a [[tumor suppressor gene]]. Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome. On [[gross pathology]], atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately [[vascular]]. On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], atypical teratoid rhabdoid tumor is characterized by round blue [[tumor]] [[Cell (biology)|cells]] of high [[Cell (biology)|cellularity]] composed of atypical [[cells]] with eccentric [[Cell nucleus|nuclei]], small [[Nucleolus|nucleoli]], and abundant amounts of [[eosinophilic]] [[cytoplasm]] with frequent [[mitotic]] figures. Atypical teratoid rhabdoid tumor is demonstrated by positivity to [[tumor markers]] such as [[Epithelium|epithelial]] [[membrane]] [[antigen]], [[vimentin]], and [[actin|smooth muscle actin]].
+== Pathophysiology ==
+===Pathogenesis===
+*Atypical teratoid rhabdoid tumor is comprised of [[Malignant rhabdoid tumor|rhabdoid tumor]] [[Cell (biology)|cells]] and varying amounts of small undifferentiated [[Primitive neuroectodermal tumor|primitive neuroectodermal tumor (PNET)]]-like [[Mesenchymal stem cell|mesenchymal]], and/or [[Epithelium|epithelial]] differentiated [[tumor]] [[Cell (biology)|cells]].<ref name="SlavcChocholous2014">{{cite journal|last1=Slavc|first1=Irene|last2=Chocholous|first2=Monika|last3=Leiss|first3=Ulrike|last4=Haberler|first4=Christine|last5=Peyrl|first5=Andreas|last6=Azizi|first6=Amedeo A.|last7=Dieckmann|first7=Karin|last8=Woehrer|first8=Adelheid|last9=Peters|first9=Christina|last10=Widhalm|first10=Georg|last11=Dorfer|first11=Christian|last12=Czech|first12=Thomas|title=Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012|journal=Cancer Medicine|volume=3|issue=1|year=2014|pages=91–100|issn=20457634|doi=10.1002/cam4.161}}</ref>
+==Genetics==
+*[[Gene]] involved in the [[pathogenesis]] of atypical teratoid rhabdoid tumor include ''[[SMARCB1]]'' (''hSNF5/INI-1''), a [[tumor suppressor gene]].<ref name="GinnGajjar2012">{{cite journal|last1=Ginn|first1=Kevin F.|last2=Gajjar|first2=Amar|title=Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions|journal=Frontiers in Oncology|volume=2|year=2012|issn=2234-943X|doi=10.3389/fonc.2012.00114}}</ref>
+*Atypical teratoid rhabdoid tumor is characterized by loss of the long arm of [[chromosome 22]], which results in loss of the ''hSNF5/INI-1'' [[gene]].
+*''INI1'', a member of the [[SWI/SNF]] [[chromatin]] remodeling complex, is important in the maintenance of the [[Spindle apparatus|mitotic spindle]] and [[cell cycle]] control.
-===Mircoscopic Pathology===
+==Associated Conditions==
-AT/RT and rhabdoid tumor share the term "rhabdoid" because under a microscope both tumors resemble [[rhabdomyosarcoma]].
+*Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition [[syndrome]].<ref name="SlavcChocholous2014">{{cite journal|last1=Slavc|first1=Irene|last2=Chocholous|first2=Monika|last3=Leiss|first3=Ulrike|last4=Haberler|first4=Christine|last5=Peyrl|first5=Andreas|last6=Azizi|first6=Amedeo A.|last7=Dieckmann|first7=Karin|last8=Woehrer|first8=Adelheid|last9=Peters|first9=Christina|last10=Widhalm|first10=Georg|last11=Dorfer|first11=Christian|last12=Czech|first12=Thomas|title=Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012|journal=Cancer Medicine|volume=3|issue=1|year=2014|pages=91–100|issn=20457634|doi=10.1002/cam4.161}}</ref>
-The tumor [[histology]] is jumbled small and large cells.  The [[Tissue (biology)|tissue]] of this tumor contains many different types of cells including the rhabdoid cells, large spindled cell, [[Epithelial reticular cells|epithelial]] and mesencymal cells and areas resembling [[primitive neuroectodermal tumor]] (PNET).  As much as 70% of the tumor may be made up of PNET-likw cells.  [[Ultrastructure]] characteristic whorls of [[intermediate filament]]s in the rhabdoid tumors (as with rhabdoid tumors in any area of the body).  Ho and associates found sickle shaped embracing cells, previously unreported, in all of 11 cases of AT/RT.
-===Immunohistochemistry===
+==Gross Pathology==
+*On [[gross pathology]], atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately [[vascular]].<ref name="pmid22135607">{{cite journal| author=Chan KH, Mohammed Haspani MS, Tan YC, Kassim F| title=A case report of atypical teratoid/rhabdoid tumour in a 9-year-old girl. | journal=Malays J Med Sci | year= 2011 | volume= 18 | issue= 3 | pages= 82-6 | pmid=22135607 | doi= | pmc=PMC3216225 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22135607  }} </ref>
+*Common [[Cranium|intracranial]] sites associated with atypical teratoid rhabdoid tumor include:<ref name="locationatrt1">Location of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015</ref>
-[[Immunohistochemistry]] refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically to antigens in biological tissues.  A tissue sample is stained to identify specific cellular proteins.  Immunohistochemical staining is widely used in the diagnosis and treatment of cancer. Specific molecular markers are characteristic of particular cancer types. Immunohistochemistry is also widely used in basic research to understand the distribution and localization of biomarkers in different parts of a tissue.  Below are proteins found in an Atypical Teratoid Rhaboid Tumor.
+{| style="border: 0px; font-size: 90%; margin: 3px; width:1000px align=center"
+| valign="top" |
+|+
+! style="background: #4479BA; width: 800px;" | {{fontcolor|#FFF|Infratentorial}}
+! style="background: #4479BA; width: 800px;" | {{fontcolor|#FFF|Supratentorial}}
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |
+*[[Cerebellum]]
+*[[Brain stem]]
+| style="padding: 5px 5px; background: #DCDCDC;" |
+*[[cerebrum|Cerebral hemispheres]]
+*[[Pineal gland]]
+*[[Septum pellucidum]]
+*[[Hypothalamus]]
+|}
-*[[Vimentin]]-positive
+==Microscopic Pathology==
-*[[Cytokeratin]]-positive
+*On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], atypical teratoid rhabdoid tumor is characterized by the round blue [[tumor]] [[Cell (biology)|cells]] of high [[Cellular|cellularity]] composed of atypical [[Cell (biology)|cells]] with eccentric [[Cell nucleus|nuclei]], small [[Nucleolus|nucleoli]], and abundant amounts of [[eosinophilic]] [[cytoplasm]] with frequent [[Mitosis|mitotic]] figures.<ref name="SlavcChocholous2014">{{cite journal|last1=Slavc|first1=Irene|last2=Chocholous|first2=Monika|last3=Leiss|first3=Ulrike|last4=Haberler|first4=Christine|last5=Peyrl|first5=Andreas|last6=Azizi|first6=Amedeo A.|last7=Dieckmann|first7=Karin|last8=Woehrer|first8=Adelheid|last9=Peters|first9=Christina|last10=Widhalm|first10=Georg|last11=Dorfer|first11=Christian|last12=Czech|first12=Thomas|title=Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012|journal=Cancer Medicine|volume=3|issue=1|year=2014|pages=91–100|issn=20457634|doi=10.1002/cam4.161}}</ref>
-*Neuron specific enolase-positive
+*According to the ''[[World Health Organization|WHO]] [[classification]]'' ''of [[Tumor|tumors]] of the [[central nervous system]]'', atypical teratoid rhabdoid tumor is [[Classification|classified]] into a [[World Health Organization|WHO]] [[Grading (tumors)|grade]] IV [[tumor]].
-*Epitelial membrane antigen-positive
-*[[Glial fibrillary acidic protein]]- positive
-*[[Synaptophysin]]
-*[[Chromogranin]]
-*Smooth muscle [[actin]]
-*[[Desmin]]
-*Carcinoembrionary [[antigen]]
-*CD99
-*[[S-100 protein|S-100]]
-*[[neurofilament]]s
-*[[Alpha-fetoprotein|AFP]]- not found
-*[[Human chorionic gonadotropin|HCG]] – negative
-====Genetics====
+==Immunohistochemistry==
-[[Cytogenetics]] is the study of the tumor’s genetic make-up.  A technique called [[Fluorescent in situ hybridization|fluoresecene in situ hybridization (FISH)]] has been gaining attention in the literature because it may be able to help locate a mutation or abnormality that may be allowing tumor growth.  Also, this technique has been shown to be useful in identifying some tumors and distinguishing two histologically similar tumors from each other (such as AT/RTs and PNETs). In particular, medulloblastmas/PNETs may possibly be differentiated cytogenetically from AT/RTs as chromosomal deletions of 17p are relatively common with medulloblastoma and abnormalities of [[22q11.2 deletion syndrome|22q11.2]] are not seen.  On the other hand, chromosomal 22 deletions are very comomon in AT/RTs.
+*Atypical teratoid rhabdoid tumor is demonstrated by positivity to [[tumor markers]], such as:<ref name="ihcatrt1">Markers of Atypical teratoid/rhabdoid tumour. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/atypical-teratoidrhabdoid-tumour. Accessed on December 14, 2015</ref><ref name="pmid16687525">{{cite journal| author=Meyers SP, Khademian ZP, Biegel JA, Chuang SH, Korones DN, Zimmerman RA| title=Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes. | journal=AJNR Am J Neuroradiol | year= 2006 | volume= 27 | issue= 5 | pages= 962-71 | pmid=16687525 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16687525  }} </ref>
+:*[[Epithelium|Epithelial]] [[membrane]] [[antigen]]
+:*[[Vimentin]]
+:*[[actin|Smooth muscle actin]]
+:*[[GFAP]]
+:*[[Cytokeratin]]
+:*[[Neurofilament]]
+:*[[Desmin]]
-In importance of the [[SWI/SNF|hSNF5/INI1]] gene located on chromosomal band [[22q11.2 deletion syndrome|22q11.2]] is highlighted in the summary paper form the Workshop on Childhood Atypical Teratoid Rhabdoid Tumors as the mutation’s presence is sufficient to change the diagnosis from a medulloblastoma or PNET to the more aggressive AT/RT classification. However, it should be noted that this mutation is not present in 100% of cases.  Therefore, if the mutation is not present in an otherwise classic AT/RT immunohistochemical and morphologic pattern then the diagnosis remains an AT/RT.
 ==References==
 {{reflist|2}}
-{{WH}}
-{{WS}}
-[[Category:Oncology]]
 [[Category:Types of cancer]]
 [[Category:Rare cancers]]
@@ Line 46: / Line 64: @@
 [[Category:Pediatric cancers]]
 [[Category:Disease]]
+[[Category:Oncology]]
+{{WH}}
+{{WS}}