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{{Leiomyoma}}
{{SI}}
'''For patient information, click [[{{PAGENAME}} (patient information)|here]].'''


'''For patient information, click [[Uterine fibroids (patient information)|here]]'''
{{CMG}} {{AE}} {{RAK}}; {{CZ}}; {{SC}}; {{Ammu}}
 
{{CMG}}; {{AE}} {{CZ}} {{SC}}
 
{{SK}}
 
==[[Leiomyoma overview|Overview]]==
 
==[[Leiomyoma historical perspective|Historical Perspective]]==
 
==[[Leiomyoma classification|Classification]]==
 
==[[Leiomyoma pathophysiology|Pathophysiology]]==
 
==[[Leiomyoma differential diagnosis|Differentiating Leiomyoma from other Diseases]]==
 
==[[Leiomyoma epidemiology and demographics|Epidemiology and Demographics]]==
 
==[[Leiomyoma risk factors|Risk Factors]]==
 
==[[Leiomyoma screening|Screening]]==
 
==[[Leiomyoma natural history|Natural History, Complications and Prognosis]]==
 
==Diagnosis==
[[Leiomyoma staging|Staging]] | [[Leiomyoma history and symptoms|History and Symptoms]] | [[Leiomyoma physical examination|Physical Examination]] | [[Leiomyoma laboratory findings|Laboratory Findings]] | [[Leiomyoma X ray|X Ray]] | [[Leiomyoma CT|CT]] | [[Leiomyoma MRI|MRI]] | [[Leiomyoma ultrasound|Ultrasound]] | [[Leiomyoma other imaging findings|Other Imaging Findings]] | [[Leiomyoma other diagnostic studies|Other Diagnostic Studies]] | [[Leiomyoma biopsy|Biopsy]]
 
==Treatment==
[[Leiomyoma medical therapy|Medical Therapy]] | [[Leiomyoma surgery|Surgery]] | [[Leiomyoma primary prevention|Primary Prevention]] | [[Leiomyoma secondary prevention|Secondary Prevention]] | [[Leiomyoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Leiomyoma future or investigational therapies|Future or Investigational Therapies]]
 
==Related Chapters==
* [[Myosarcoma]]


{{SK}} Uterine myoma; Fibroid; Fibroids; Uterine; Fibroid Tumor; Fibroid Uterus; Uterine fibromyoma; Leiomyomata
==Overview==
Uterine leiomyoma was first discovered by Hippocrates in 460-375 B.C and called it  “[[uterine]] stone”. [[Uterine]] leiomyoma  may be classified according to their location into 3 subtypes: [[submucosal]], [[subserous]], and intramural. The [[pathogenesis]] of leiomyoma is characterized by [[benign]] [[smooth muscle]] [[neoplasm]]. They can occur in any [[Organ (biology)|organ]], but the most common forms occur in the [[uterus]], [[small bowel]] and the [[esophagus]]. [[Chromosome]] aberrations such as t(12; 14)(q14-q15;q23–24), del(7)(q22q32), [[Rearrangement|rearrangements]] involving 6p21, 10q, [[trisomy 12]], and deletions of 1p3q has been associated with the development of leiomyoma. Uterine leiomyoma must be differentiated from other diseases that cause uterine mass, such as: uterine [[adenomyoma]], [[pregnancy]], [[hematometra]], [[uterine sarcoma]], uterine carcinosarcoma, and [[metastasis]]. Leiomyoma is more commonly observed among patients aged 40 years and older. Common [[risk factors]] in the development of uterine leiomyoma include African-American race, early [[menarche]], [[prenatal]] exposure to [[diethylstilbestrol]], having one or more [[pregnancies]] extending beyond 20 weeks, [[obesity]], significant consumption of [[beef]] and other red meats, [[hypertension]], [[family history]], and [[alcohol]] consumption. [[Physical examination]] may be remarkable for enlarged, mobile [[uterus]] with an irregular contour on [[Pelvic examination|bimanual pelvic examination]]. The mainstay of [[therapy]] for uterine leiomyoma is [[oral contraceptive pills]], either combination pills or [[Progestin-only oral contraceptives (patient information)|progestin-only]], [[Gonadotropin-releasing hormone analog]]s. Surgery is also part of mainstay therapy for uterine leiomyoma.
==Historical Perspective==
*Uterine leiomyoma was first discovered by Hippocrates, an ancient Greek [[physician]], in 460-375 B.C and called it  “[[uterine]] stone”.
*In the second century AD, Galen described the lesion as "scleromas".
*In 1860 and 1863, Rokitansky and Klob coined the term [[fibroid]].
*In 1854, Virchow, a German [[pathologist]], demonstrated that those [[tumors]] originated from the [[uterine]] [[smooth muscle]].
*In 1809, the first [[laparotomy]] was conducted by Ephraim McDowell to treat leiomyoma in Danville, USA.<ref name="BoziniBaracat2007">{{cite journal|last1=Bozini|first1=Nilo|last2=Baracat|first2=Edmund C|title=The history of myomectomy at the Medical School of University of São Paulo|journal=Clinics|volume=62|issue=3|year=2007|issn=1807-5932|doi=10.1590/S1807-59322007000300002}}</ref>
==Classification==
*[[Uterine]] leiomyoma may be classified according to the [[International Federation of Gynecology and Obstetrics]] ([[FIGO]]) [[classification]] system, based on their location in the uterus, into 8 subtypes:<ref name="pmid21496802">{{cite journal| author=Munro MG, Critchley HO, Fraser IS, FIGO Menstrual Disorders Working Group| title=The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. | journal=Fertil Steril | year= 2011 | volume= 95 | issue= 7 | pages= 2204-8, 2208.e1-3 | pmid=21496802 | doi=10.1016/j.fertnstert.2011.03.079 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21496802  }} </ref>
**[[Intramural]] [[Myoma|myomas]]
***[[FIGO]] types 3, 4, and 5
***Located within the uterine wall
**[[Submucosal]] myomas
***Derived from [[Myometrium|myometrial]] [[cells]] below the [[endometrium]] and may protrude into the [[uterine cavity]]
***May be subclassified according to this protrusion:
****Type 0: [[pedunculated]] intracavitary
****Type 1: < 50% intramural
****Type 2: ≥ 50% intramural
**Subserosal myomas
***[[FIGO]] types 6 and 7
***Derived from [[myometrium]] at the at the [[serous]] surface of the [[uterus]]
**[[Cervical]] myomas
***[[FIGO]] type 8
***Usually located in the [[cervix]]
*Leiomyoma may be classified according to histology features into two subtypes of bening and malignant:<ref name="pmid20179432">{{cite journal |vauthors=Ip PP, Tse KY, Tam KF |title=Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy |journal=Adv Anat Pathol |volume=17 |issue=2 |pages=91–112 |date=March 2010 |pmid=20179432 |doi=10.1097/PAP.0b013e3181cfb901 |url=}}</ref><ref name="pmid2307449">{{cite journal |vauthors=O'Connor DM, Norris HJ |title=Mitotically active leiomyomas of the uterus |journal=Hum. Pathol. |volume=21 |issue=2 |pages=223–7 |date=February 1990 |pmid=2307449 |doi= |url=}}</ref><ref name="pmid3337336">{{cite journal |vauthors=Perrone T, Dehner LP |title=Prognostically favorable "mitotically active" smooth-muscle tumors of the uterus. A clinicopathologic study of ten cases |journal=Am. J. Surg. Pathol. |volume=12 |issue=1 |pages=1–8 |date=January 1988 |pmid=3337336 |doi= |url=}}</ref><ref name="pmid21659347">{{cite journal |vauthors=Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW |title=Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features |journal=J. Med. Genet. |volume=48 |issue=8 |pages=505–12 |date=August 2011 |pmid=21659347 |doi=10.1136/jmg.2011.088807 |url=}}</ref><ref name="pmid11283798">{{cite journal |vauthors=Alam NA, Bevan S, Churchman M, Barclay E, Barker K, Jaeger EE, Nelson HM, Healy E, Pembroke AC, Friedmann PS, Dalziel K, Calonje E, Anderson J, August PJ, Davies MG, Felix R, Munro CS, Murdoch M, Rendall J, Kennedy S, Leigh IM, Kelsell DP, Tomlinson IP, Houlston RS |title=Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43 |journal=Am. J. Hum. Genet. |volume=68 |issue=5 |pages=1264–9 |date=May 2001 |pmid=11283798 |pmc=1226106 |doi=10.1086/320124 |url=}}</ref><ref name="pmid16223449">{{cite journal |vauthors=Halama N, Grauling-Halama SA, Daboul I |title=Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome? |journal=BMC Gastroenterol |volume=5 |issue= |pages=33 |date=October 2005 |pmid=16223449 |pmc=1266363 |doi=10.1186/1471-230X-5-33 |url=}}</ref><ref name="pmid11865300">{{cite journal |vauthors=Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomäki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA |title=Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer |journal=Nat. Genet. |volume=30 |issue=4 |pages=406–10 |date=April 2002 |pmid=11865300 |doi=10.1038/ng849 |url=}}</ref>
**Bening
***Mitotically active leiomyomas
***Myxoid leiomyomas
***[[Epithelioid]] leiomyomas
***Dissecting leiomyomas
**Neoplasm with uncertain clinical behavior
***[[Smooth muscle]] tumors of uncertain malignant potential
***Leiomyoma with bizarre nuclei
***Cellular leiomyomas
**[[Neoplasm]] with extrauterine disease
***Leiomyomatosis peritonealis disseminata
***Intravenous leiomyomatosis
***Benign [[metastasizing]] leiomyomas
**Multiorgan or primary extrauterine neoplasms
***Hereditary leiomyomatosis and [[renal cell carcinoma]] syndrome
***[[Lymphangioleiomyomatosis]]
***[[Cowden syndrome]]
***Vulvar and [[esophageal]] leiomyomatosis


==Pathophysiology==
==Pathophysiology==
===Uterine Leiomyomata===
*The [[pathogenesis]] of leiomyoma is characterized by [[benign]] [[smooth muscle]] [[neoplasm]]. They can occur in any [[Organ (biology)|organ]], but the most common forms occur in the [[uterus]], [[small bowel]] and the [[esophagus]].
{{main|Uterine fibroids}}
*It is thought that leiomyoma is the result of either transformation of normal uterine [[muscle cells]] into abnormal cells through [[somatic]] [[Mutation|mutations]], or through the growth of abnormal [[uterine]] muscle cells into tumors.<ref name="pmid8529956">{{cite journal| author=Hashimoto K, Azuma C, Kamiura S, Kimura T, Nobunaga T, Kanai T et al.| title=Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene. | journal=Gynecol Obstet Invest | year= 1995 | volume= 40 | issue= 3 | pages= 204-8 | pmid=8529956 | doi=10.1159/000292336 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8529956  }} </ref><ref name="pmid7529041">{{cite journal| author=Mashal RD, Fejzo ML, Friedman AJ, Mitchner N, Nowak RA, Rein MS et al.| title=Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata. | journal=Genes Chromosomes Cancer | year= 1994 | volume= 11 | issue= 1 | pages= 1-6 | pmid=7529041 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7529041  }} </ref>
Uterine fibroids are leiomyomata of the [[uterus|uterine]] smooth muscle. As other leiomyomata, they are [[benign]], but may lead to excessive menstrual bleeding ([[menorrhagia]]), often cause [[anemia]] and may lead to [[infertility]]. Enucleation is removal of fibroids without removing the uterus ([[hysterectomy]]), which is also commonly performed. [[Laser]] surgery (called myolysis) is increasingly used, and provides a viable alternative to surgery.
*[[Genetic mutations]] involved in the [[pathogenesis]] of leiomyoma include: <ref name=":0">Genetics of Uterine Leiomyomas. glowm (2016). http://www.glowm.com/section_view/heading/Genetics%20of%20Uterine%20Leiomyomas/item/363 Accessed on April 19, 2016</ref>
**t(12;14)(q14-q15;q23–24)
**del(7)(q22q32)
**[[Rearrangement|Rearrangements]] involving 6p21, 10q, trisomy 12
**[[Deletion (genetics)|Deletions]] of 1p3q
*On [[gross pathology]], round, well circumscribed, non-encapsulated, solid white or tan [[nodules]], and whorled are characteristic findings of leiomyoma.<ref name="pmid26137094">{{cite journal| author=Zhu X, Fei J, Zhang W, Zhou J| title=Uterine leiomyoma mimicking a gastrointestinal stromal tumor with chronic spontaneous hemorrhage: A case report. | journal=Oncol Lett | year= 2015 | volume= 9 | issue= 6 | pages= 2481-2484 | pmid=26137094 | doi=10.3892/ol.2015.3083 | pmc=4473300 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26137094  }} </ref>
*On [[microscopic]] [[Histopathology|histopathological]] analysis, elongated and spindle-shaped cells with a cigar-shaped nucleus are characteristic findings of leiomyoma.


Uterine leiomyomas originate in the [[myometrium]] and are classified by location:  
==Causes==
*Sub[[mucosal]] – lie just beneath the [[endometrium]].
* [[Chromosome]] aberrations in uterine leiomyoma include:<ref name="pmid23926501">{{cite journal |vauthors=Medikare V, Kandukuri LR, Ananthapur V, Deenadayal M, Nallari P |title=The genetic bases of uterine fibroids; a review |journal=J Reprod Infertil |volume=12 |issue=3 |pages=181–91 |date=July 2011 |pmid=23926501 |pmc=3719293 |doi= |url=}}</ref>
*[[wiktionary:Intramural|Intramural]] – lie within the uterine wall.
**T(12;14)(q14-q15;q23–24)
*Sub[[serous]] – lies at the serosal surface of the uterus or may bulge out from the [[myometrium]] and can become pedunculated.
**Deletion of (7)(q22q32)
**[[Rearrangement|Rearrangements]] involving 6p21, 10q
**Trisomy 12
**Deletion of 1p3q have been associated with the development of leiomyoma


Estrogen and progesterone usually stimulate their growth, and hormone suppression may hence decrease their size.
==Differentiating Leiomyoma from other Diseases==
{| class="wikitable"
|+Differentiating Leiomyoma from Other Diseases
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease entity
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Etiology (Genetic or others)
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Histopathological findings
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Immunohistochemical staining
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Risk factors
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Common site of involvement
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Clinical manifestations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other associated features
|-
| style="background:#DCDCDC;" align="center" + |'''[[Leiomyoma]]'''<ref name="pmid7611533" /><ref name="pmid8635024" /><ref name="pmid8847061" /><ref name="pmid12673560" /><ref name="pmid16160478" /><ref name="pmid16967468" /><ref name="pmid9606802" /><ref name="pmid6336632" /><ref name="pmid8635024" /><ref name="pmid16160478" /><ref name="pmid17414097" />
|
* Loss of normal [[chromosome]] 1q ([[hereditary]][[leiomyomatosis]])
* [[Renal cell cancer]](HLRCC) [[gene mutation]]
|
* Prominent [[cellular]] [[atypia]]
* [[Nuclear]] [[atypia]], including [[nuclear]]  [[pleomorphism]], hyperchromatism, irregularity in [[nuclear|nucle]]<nowiki/>[[nuclear|ar]]  [[Membrane|membranes]], high [[nuclear]] size, and prominent [[nucleoli]]
* [[Cigar]]-shaped [[nuclei]]
* Abundant [[mitoses]], [[mitotic index]] higher than 10 or more per 10 <nowiki/>high-power fields
* [[Area]]<nowiki/>s of [[coagulative necrosis]] ([[tumor cell]][[necrosis]])
* Pali<nowiki/>sading and extensive [[degenerative]] [[Change|changes]] in the form of hyalinization, [[calcification]], and myxoid changes
* Elon<nowiki/>gated [[Cells (biology)|cells]] with [[eosinophilic]] or occasional [[Fibrillarin|fibrillar]] [[cytoplasm]] with [[Distinctive feature|distinct]] [[cell membranes]]
|Positive for:
* HHF35 (90%)
* Alpha-[[smooth muscle]] [[actin]] (90%)
* [[Vimentin]]
* [[Desmin]] (75%)
* H-[[caldesmon]]
* [[Phosphotungstic acid hematoxylin|PTAH]] ([[Stain|stains]][[myofibrils]])
* [[Keratin]] (30%)
* [[ER]] (usually in [[uterine]] and [[female]][[retroperitoneal]][[tumors]])
* [[S100A1|S100]] (occasionally weak [[staining]])
* EMA (may be focal)
* [[CD34]]
Negative for:
* [[CD117]]
|
* Immundeficiency ([[HIV]])
* [[Dioxin|Digoxin]] [[Exposure assessment|exposure]]
* [[HHV-8|Human herpes virus type-8 (HHV-8)]]
* [[Epstein barr virus mononucleosis|Epstein barr virus]]
* Long term [[tamoxifen]] use
* [[History and Physical examination|History]] of [[pelvic]][[Radiation|radiations]]
* [[Hereditary]] [[breast carcinoma]] with [[BRCA1]][[mutation]]
* [[Hereditary nonpolyposis colorectal cancer|Hereditary nonpolyposis colorectal carcinoma]] with [[MSH2]] [[mutation]]
* [[Li-Fraumeni syndrome]]
* [[Malignant]] [[melanoma]]
* [[Retinoblastoma]]
|
* [[Uterus]]
* [[Abdomen]]
* [[Esophagus]]
* [[Rectum]]
* [[Skin]] / [[subcutis]]
* [[Retroperitoneum]]
* [[Extremities]]
* Large [[vessels]] ([[inferior vena cava]], [[saphenous vein]], [[femoral vein]], [[pulmonary artery]], [[femoral artery]])
* [[Superficial]] or deep [[Soft tissue|soft tissues]]
* [[Bone]]
* [[Breast]]
* [[Colon]]
* [[Epididymis]]
* [[Mediastinum]]
* [[Lungs]]
|
* [[Asymptomatic]]
* [[Uterine|(uterine]] [[leiomyosarcoma]]<nowiki/>may be associated with:
** Irregular [[vaginal bleeding]](intermenstrual or [[postmenopausal]])
** New [[lump]] or a [[mass]]<nowiki/>protruding into [[vagina]]<nowiki/>or growing [[mass]] in [[abdomen]] or [[pelvis]]
** [[Abdominal pain]]
** [[Abdominal distension]]
** [[Pelvic pain]]
** [[Urinary system|Urinary]] [[symptoms]]
* [[Esophageal]][[leiomyosarcoma]] may cause:
** [[Dysphagia]]
** [[Hematemesis]]
* [[rectal]] [[leiomyosarcoma]]<nowiki/>may cause:
** [[Black]], [[tarry stools]]
** [[Rectal bleeding]]
|_
|-
| style="background:#DCDCDC;" align="center" + |'''[[Neurofibroma]]'''<ref name="RodriguezFolpe2012">{{cite journal|last1=Rodriguez|first1=Fausto J.|last2=Folpe|first2=Andrew L.|last3=Giannini|first3=Caterina|last4=Perry|first4=Arie|title=Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems|journal=Acta Neuropathologica|volume=123|issue=3|year=2012|pages=295–319|issn=0001-6322|doi=10.1007/s00401-012-0954-z}}</ref><ref name="ChoiKomurov2017">{{cite journal|last1=Choi|first1=Kwangmin|last2=Komurov|first2=Kakajan|last3=Fletcher|first3=Jonathan S.|last4=Jousma|first4=Edwin|last5=Cancelas|first5=Jose A.|last6=Wu|first6=Jianqiang|last7=Ratner|first7=Nancy|title=An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system|journal=Scientific Reports|volume=7|issue=1|year=2017|issn=2045-2322|doi=10.1038/srep43315}}</ref><ref name="LiaoBooker2018">{{cite journal|last1=Liao|first1=Chung-Ping|last2=Booker|first2=Reid C.|last3=Brosseau|first3=Jean-Philippe|last4=Chen|first4=Zhiguo|last5=Mo|first5=Juan|last6=Tchegnon|first6=Edem|last7=Wang|first7=Yong|last8=Clapp|first8=D. Wade|last9=Le|first9=Lu Q.|title=Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis|journal=Journal of Clinical Investigation|volume=128|issue=7|year=2018|pages=2848–2861|issn=0021-9738|doi=10.1172/JCI99424}}</ref><ref name="StaserYang2010">{{cite journal|last1=Staser|first1=K.|last2=Yang|first2=F.-C.|last3=Clapp|first3=D. W.|title=Mast cells and the neurofibroma microenvironment|journal=Blood|volume=116|issue=2|year=2010|pages=157–164|issn=0006-4971|doi=10.1182/blood-2009-09-242875}}</ref><ref name="MuirNeubauer2001">{{cite journal|last1=Muir|first1=David|last2=Neubauer|first2=Debbie|last3=Lim|first3=Ingrid T.|last4=Yachnis|first4=Anthony T.|last5=Wallace|first5=Margaret R.|title=Tumorigenic Properties of Neurofibromin-Deficient Neurofibroma Schwann Cells|journal=The American Journal of Pathology|volume=158|issue=2|year=2001|pages=501–513|issn=00029440|doi=10.1016/S0002-9440(10)63992-2}}</ref><ref name="WilkinsonManson2004">{{cite journal|last1=Wilkinson|first1=Lana M.|last2=Manson|first2=David|last3=Smith|first3=Charles R.|title=Best Cases from the AFIP|journal=RadioGraphics|volume=24|issue=suppl_1|year=2004|pages=S237–S242|issn=0271-5333|doi=10.1148/rg.24si035170}}</ref><ref name="BernthalJones2013">{{cite journal|last1=Bernthal|first1=Nicholas|last2=Jones|first2=Kevin|last3=Monument|first3=Michael|last4=Liu|first4=Ting|last5=Viskochil|first5=David|last6=Randall|first6=R.|title=Lost in Translation: Ambiguity in Nerve Sheath Tumor Nomenclature and Its Resultant Treatment Effect|journal=Cancers|volume=5|issue=4|year=2013|pages=519–528|issn=2072-6694|doi=10.3390/cancers5020519}}</ref><ref name="StaserYang2010">{{cite journal|last1=Staser|first1=K.|last2=Yang|first2=F.-C.|last3=Clapp|first3=D. W.|title=Mast cells and the neurofibroma microenvironment|journal=Blood|volume=116|issue=2|year=2010|pages=157–164|issn=0006-4971|doi=10.1182/blood-2009-09-242875}}</ref><ref name="MautnerFriedrich2003">{{cite journal|last1=Mautner|first1=V. F.|last2=Friedrich|first2=R. E.|last3=von Deimling|first3=A.|last4=Hagel|first4=C.|last5=Korf|first5=B.|last6=Knöfel|first6=M. T.|last7=Wenzel|first7=R.|last8=Fünsterer|first8=C.|title=Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma|journal=Neuroradiology|volume=45|issue=9|year=2003|pages=618–625|issn=0028-3940|doi=10.1007/s00234-003-0964-6}}</ref><ref name="ShenHarper1996">{{cite journal|last1=Shen|first1=M H|last2=Harper|first2=P S|last3=Upadhyaya|first3=M|title=Molecular genetics of neurofibromatosis type 1 (NF1).|journal=Journal of Medical Genetics|volume=33|issue=1|year=1996|pages=2–17|issn=1468-6244|doi=10.1136/jmg.33.1.2}}</ref><ref name="RubinGutmann2005">{{cite journal|last1=Rubin|first1=Joshua B.|last2=Gutmann|first2=David H.|title=Neurofibromatosis type 1 — a model for nervous system tumour formation?|journal=Nature Reviews Cancer|volume=5|issue=7|year=2005|pages=557–564|issn=1474-175X|doi=10.1038/nrc1653}}</ref><ref name="Gray1990">{{cite journal|last1=Gray|first1=Mark H.|title=Immunohistochemical Demonstration of Factor XIIIa Expression in Neurofibromas|journal=Archives of Dermatology|volume=126|issue=4|year=1990|pages=472|issn=0003-987X|doi=10.1001/archderm.1990.01670280056009}}</ref>
|
Can be sporadic or as a part of [[Neurofibromatosis 1]] and 2
* ''[[Neurofibromatosis type I|NF1]] [[gene]] located at [[chromosomal]] region [[CCL7|17q11.2]], [[Code|codes]] for''[[neurofibromin]]
* Functional part of [[neurofibromin]] GAP (or [[GTPase-activating proteins|GTPase-activating protein]]) accelerates the [[Conversion (logic)|conversion]] of the active [[GTP-binding protein|GTP]]-bound [[RAS]] to its inactive GDP-[[Bound state|bound]] form
* Loss of ''[[RAS]]'' [[control]]<nowiki/>leads to increased [[Activity (chemistry)|activity]] of other [[Signaling pathway|signaling pathways]]<nowiki/>including ''[[C-Raf|RAF]]'', ''[[Extracellular signal-regulated kinases|ERK1/2]]'', ''[[Phosphoinositide 3-kinase|PI3K]]'', ''[[PAK1|PAK]], [[MAPK]], [[SCF-complex|SCF]]/[[c-kit]]'' and ''[[Mammalian target of rapamycin|mTOR-S6 kinase]]''
|
* Uniphasic, low to moderate cellularity
* No peripheral perineural [[capsule]]
* [[Random]] [[pattern]], only [[rare]] palisading
* No well formed verocy bodies
* Hypocellular with abundant [[mucinous]]/myxoid [[matrix]] without hypercellular [[Area|areas]]
* Frequent [[mast cells]]
* Contains [[neural]] [[fibroblasts]] and fibrillary or shredded carrot [[collagen]]
* [[Random]] [[proliferation]] of [[Schwann cells]] and scattered admixed [[axons]]
* No [[Nevi|nevoid cells]]
* No [[epithelial]] component
* [[Diffuse]] [[growth]] [[pattern]]
* Scant [[cytoplasm]]
* Wavy [[spindle cells]] with buckled [[nuclei]]
* Pseudomeissnerian [[Body|bodies]] representing specific [[differentiation]] may be present
* Lacks storiform [[pattern]]
[[Neurofibroma]] with [[degenerative]] [[atypia]] ("ancient [[Change detection|change]]") has following [[microscopic]] [[Features (pattern recognition)|features]]:
* [[Localized disease|Localized]] [[Cells (biology)|cells]] with large [[pleomorphic]] [[nuclei]], [[cytoplasmic]] [[nuclear]] [[inclusions]], smudgy [[chromatin]], and inconspicuous [[nuclei]]
* Absent or very low [[Mitotic|mitotic activity]]
* Low to moderate cellularity
|Positive for:
* [[S100A12|S100]] (weaker)
* [[SOX10]]
* [[Neurofilament]] (and Bielshowsky)
* [[GFAP]]
* [[CD34]] (stronger)
* Factor XIIIa
* [[Calretinin]] (focal)
* MBP ([[myelin]]-[[Basic (chemistry)|basic]] [[protein]])


===Esophageal===
Negative for:
They are also the most common [[benign]] [[esophagus|esophageal]] [[tumour]], though this accounts for less than 1% of esophageal neoplasms. The remainder consists mainly of carcinomas. Although the vast majority of benign esophageal tumors are clinically silent and go undetected, large or strategically located tumors may become symptomatic. <ref name=AMN>{{cite web | author = James C. Chou, MD & Frank G. Gress, MD | title =Benign Esophageal Tumors | work =Esophageal Cancer Overview (Cancer of the Esophagus) | url=http://www.health.am/cr/benign-esophageal-tumors/ | publsiher=Armenian Health Network, Health.am | accessdate=2007-03-21}}</ref>
* EMA (except in plexiform [[Neurofibroma|neurofibromas]])
|
* [[Neurofibromatosis type I|Neurofibromatosis 1]]
* [[Neurofibromatosis 2]](multiple [[Neurofibroma|neurofibromas]], [[meningiomas]] of the [[brain]]<nowiki/>or [[spinal cord]], and [[ependymomas]] of the [[spinal cord]])
|
* Can occur anywhere
* [[Diffuse]] [[Neurofibroma|neurofibromas]] commonly involve [[scalp]]
|
*
* Soft [[Mass|masses]]/[[Bumps on skin|bumps on or under skin]] ([[internal]] or [[superficial]])
* [[Transient]] [[itching]] ([[mast cells]] release [[histamine]])
* [[Transient]] [[pain]]
* [[Numbness]] and [[tingling]] in the affected [[area]]
* Severe [[bleeding]] (sign of [[tumor]] [[growth]])
* [[Physical therapy|Physical]] disfiguration
* [[Cognitive]] [[disability]]
* [[Stinging in the eye|Stinging]]
* [[Neurological]] [[Deficits in Attention, Motor control and Perception|deficits]]
* [[Change detection|Changes]] in [[Movement disorder|movement]] ([[clumsiness]] in [[hands]], trouble [[walking]])
* [[Bowel]] [[incontinence]]
* [[Scoliosis]] (an [[abnormal]] [[Curvature of spine|curvature of the spine]], if the [[tumor]] creates [[muscular]] [[imbalance]] or erodes [[bones]] of the [[spine]])
* Following [[symptoms]] may occur with [[genitourinary tract]] involvement (rarely):
** [[Urinary tract infection]] (most common [[clinical]] manifestation)
** [[Urinary retention]]
** [[Urinary frequency]]
** [[Urgency]]
** [[Hematuria]]
** Pelvic mass
** [[Hydronephrosis)|Hydronephrosis]]
** [[Urinary incontinence]] (decreased [[Urinary bladder|bladder]] capacity or [[compliance]])
** [[Appearance|Appears]] as a focal [[mass]] or [[diffuse]] [[Urinary bladder|bladder]] wall thickening in case of a [[plexiform neurofibroma]]
|
* [[Nerve]] often not identified, incorporates [[nerve]], [[axons]] often present in [[lesion]]
* Seldom [[cystic]]
* Frequently multiple
* Widespread [[soft tissue]] [[Infiltration (medical)|infiltration]]
* Tends to displace [[Adnexal and skin appendage neoplasms|adnexa]]
* <2cm in [[diameter]]
* [[Lack (manque)|Lacks]] [[Distinctive feature|distinct]] [[Lobule|lobulation]]
* [[Lack (manque)|Lacks]] [[fat]]
* Affects [[Individual growth|individuals]] between 20-40 [[Year|years]] of [[age]]
* Men and women are [[Equalism|equally]] affected
* [[Plexiform neurofibroma]] are thought to be [[Congenital disorder|congenital]] and occur earlier in [[life]]
|-
| style="background:#DCDCDC;" align="center" + |'''[[Schwannoma]]'''<ref>Schwannoma. Dr Tim Luijkx and Dr Sara Wein et al. http://radiopaedia.org/articles/schwannoma</ref><ref name="wiki">Vestibular Schwannoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Vestibular_schwannoma Accessed on October 2 2015</ref><ref name="pmid2612565">{{cite journal |vauthors=Giordano J, Rogers LV |title=Peripherally administered serotonin 5-HT3 receptor antagonists reduce inflammatory pain in rats |journal=[[European Journal of Pharmacology]] |volume=170 |issue=1-2 |pages=83–6 |year=1989 |pmid=2612565 |doi= |url= |issn= |accessdate=2015-11-20}}</ref><ref name="pmid2588243">{{cite journal |vauthors=Kolvenbach H, Lauven PM, Schneider B, Kunath U |title=Repetitive intercostal nerve block via catheter for postoperative pain relief after thoracotomy |journal=[[The Thoracic and Cardiovascular Surgeon]] |volume=37 |issue=5 |pages=273–6 |year=1989 |pmid=2588243 |doi=10.1055/s-2007-1020331 |url=http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-1020331 |issn= |accessdate=2015-11-20}}</ref><ref name="pmid3735913">{{cite journal |vauthors=Opaleva-Stegantseva VA, Ivanov AG, Gavrilina IA, Khar'kov EI, Ratovskaia VI |title=[Incidence of sudden death cases in acute coronary insufficiency and acute myocardial infarction at the pre-hospital stage in Krasnoyarsk] |language=Russian |journal=[[Kardiologiia]] |volume=26 |issue=5 |pages=23–6 |year=1986 |pmid=3735913 |doi= |url= |issn= |accessdate=2015-11-20}}</ref>
|
* Loss of [[Function (biology)|function]] of the [[tumor suppressor gene]] '''[[Merlin (protein)|merlin]]''' (schwannomin)
* Direct [[Genetics (journal)|genetic]] [[Change detection|change]] involving the ''[[NF2 gene|NF2]]'' [[gene]] on [[chromosome 22]]
* Can occur spontaneously
* [[Mutations]] and biallelic inactivation of ''[[SMARCB1]] ([[Spinal cord|spinal]] [[schwannomas]])''
|
* [[Encapsulated organisms|Encapsulated]]
* Aggregates of [[Spindle cells|spindled cells]] with indistinct [[cytoplasm]] and elongated [[nuclei]] with [[Blunt end|blunt]] pointed ends
* Ancient changes may show [[nuclear]] [[pleomorphism]] and occasionally [[nuclear]] [[inclusions]] as well
* Infrequent [[extracellular]] [[collagen]]
* [[Biphasic]]: majority entirely, and  compactly hypercellular '''Antoni A''' & myxoid hypocellular '''Antoni B''' [[Area|areas]] (may be absent in small [[tumors]])
* [[Nuclear]] palisading evident around fibrillary [[Process (anatomy)|process]] ('''Verocay bodies''') in [[cellular]] [[Area|areas]]
* Large, irregularly [[Spaced out|spaced]] [[vessels]] prominent in Antoni B [[Area|areas]]
* Narrow, elongated and wavy [[Cells (biology)|cells]] with tapered ends, [[Interspersed repeat|interspersed]] with [[Collagen|collagen fibers]]
* [[Tumor cell|Tumor cells]] with ill defined [[cytoplasm]], [[dense]] [[chromatin]]
* Often displays [[degenerative]] [[nuclear]] [[atypia]] (ancient [[Change detection|change]])
* [[Rare]] [[Mitotic|mitotic figures]]
* [[Blood vessels]] may show gaping [[tortuous]] [[Luminal|lumina]] having thickened hyalinized walls; may have [[thrombi]]
* Dilated [[vessels]] surrounded/invested by [[hemorrhage]]
* Foamy [[macrophages]]
* [[Lymphoid]] aggregates
* Amianthoid [[Fiber|fibers]] or [[collagenous]] spherules: large [[nodular]] [[Mass|masses]] of [[collagen]] with [[Radiating fibers|radiating]] [[Edge detection|edges]]
* No [[axons]] except where [[nerve]] is attached
* [[Malignant]] [[transformation]] may have [[malignant]] [[Epithelioid cell|epithelioid cells]] and rarely shows [[Divergent evolution|divergent]] [[differentiation]] as [[angiosarcoma]]-like [[Area|areas]]
|Positive for:
* [[S-100]]
* [[SOX10]]
* [[CD56]]
* Podoplanin
* [[CD34]] (weak)
* [[Neurofilament]] (and Bielshowsky)
* Factor XIIIa (focal)
* [[Calretinin]]
* [[GFAP]]
* EMA ([[capsule]]) highlights the perineural [[fibroblasts]]
* [[Laminin]]
* [[Type IV collagen]]
* [[Vimentin]]
* [[CD68]]
Negative for:
* [[Cytokeratin]]
* [[Desmin]]
* [[SMA]]
|
* [[Neurofibromatosis type II|NF-2]] associated
* [[Schwannomatosis]]
* [[Carney complex]]
|
* [[Upper limbs]]
* [[Head]] and [[neck]] [[area]] ([[oral cavity]], [[Orbit (anatomy)|orbit]] and [[salivary glands]])
* Deeply seated [[tumors]] are mainly in:
** [[Posterior mediastinum]]
** [[Retroperitoneum]]
* [[Posterior]] [[Spine|spinal]] roots
* [[Bone]]
* [[Gastrointestinal tract]]
* [[Pancreas]]
* [[Liver]]
* [[Thyroid]]
* [[Adrenal glands]]
* [[Lymph nodes]]
* [[Penis]] (rarely)
* [[Vulva]] (rarely)
|
[[Symptoms]] of [[schwannoma]] depend on the [[Location parameter|location]] of the [[tumor]]:
*Intracranial [[schwannoma]]:
**[[Acoustic neuroma]] (most common):
***[[Sensorineural]] [[hearing]] loss
***[[Vertigo]]
***[[Tinnitus]]
***[[Facial weakness]]
***[[Facial]] [[numbness]] and [[tingling]]
***[[Headaches]]
***[[Dizziness]]
***[[Difficulty swallowing]] and [[hoarseness]]
***[[Taste]] changes
***[[Confusion]]
**[[Trigeminal]] [[schwannoma]]:
***[[Trigeminal nerve]] [[dysfunction]]
**[[Facial nerve]] [[schwannoma]]:
***[[Facial nerve]] [[dysfunction]]
**[[Jugular foramen]] [[schwannoma]]:
***[[Hearing loss]]
***[[Tinnitus]]
***[[Dysphagia]]
***[[Ataxia]]
***[[Hoarseness]]
**[[Hypoglossal nerve|Hypoglossal]] [[schwannomas]]:
***[[Hypoglossal nerve]] [[dysfunction]]
*[[Spine|Spinal]] [[Schwannoma|schwannoma:]]
**[[Back pain]]
**[[Urinary incontinence]]
**[[Urinary retention]]
**[[Clumsiness]]
**[[Weakness]]
**[[Paresthesias]]
*[[Intercostal nerve]] [[schwannoma]]:
**Usually [[asymptomatic]]
*[[Intramuscular]] [[schwannoma]]:
**Painless [[mass]]
|
* [[Nerve]] often identifiable
* [[Eccentric Lesion|Eccentric]] to [[nerve]], [[axons]] generally absent within [[lesion]]
* Occasionally [[cystic]]
* Can [[Causes|cause]] other [[neoplasms]] including:
**[[Meningioma]]
**[[Mesothelioma]]
**[[Glioma|Glioma multiforme]]
**[[Breast Cancer|Breast cancer]]
**[[Colorectal Cancer|Colorectal cancer]]
**[[Renal cell carcinoma|Kidney (clear cell type) carcinoma]]
**[[Hepatocellular carcinoma]]
**[[Prostatic cancer]]
**[[Dermal]] [[cancer]]


===Leiomyoma of Jejunum===
* [[Affect|Affects]] individuals between 20-50 years of [[age]]
Leiomyoma is the most common benign tumor of small bowel. Approximately 50% of cases are found in the jejunum, followed by the ileum in 31% of cases. Almost one half of all lesions are less than 5 centimeters. <ref name=ARO>{{cite web | author = By Michael P. Buetow, M.D. | title =Leiomyoma of Jejunum | url=http://www.appliedradiology.com/case/case.asp?ID=88&SubCatID=97&CatID=43&ThreadID= | publsiher=Applied Radiology Online | accessdate=2007-03-21}}</ref>
* [[Men]] and women are equally [[Affect|affected]]
|-
| style="background:#DCDCDC;" align="center" + |'''Palisaded encapsulated [[neuroma]] (PEN) /[[solitary]] circumscribed [[neuroma]]'''<ref name="pmid17414438">{{cite journal| author=Misago N, Inoue T, Narisawa Y| title=Unusual benign myxoid nerve sheath lesion: myxoid palisaded encapsulated neuroma (PEN) or nerve sheath myxoma with PEN/PEN-like features? | journal=Am J Dermatopathol | year= 2007 | volume= 29 | issue= 2 | pages= 160-4 | pmid=17414438 | doi=10.1097/01.dad.0000256688.91974.09 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17414438  }} </ref>
|
* Spontaneous [[development]]
* [[RET gene|RET]] [[proto-oncogene]] [[genetic mutations]] ([[inherited]] PEN)
|
* [[Solitary]] [[dermal]] or [[subcutaneous]] [[tumor]]
* [[Encapsulated organisms|Encapsulated]] by [[perineurium]]
* Club-like [[extension]] in the [[subcutaneous tissue]]
* Moderately [[cellular]] [[lesion]] with [[proliferation]] of [[schwann cells]] and [[axons]]
* [[Nuclear]] palisading may be present
* Rare [[mast cells]]
* [[Silver staining|'''Silver''' stains]] show the [[axons]] traversing the [[Schwann cells]]
|Positive for:
* EMA
* [[S100A1|S100]] ([[schwann cells]])
* [[Neurofilament]] ([[axons]])
* [[Collagen, type IV, alpha 1|Collagen type IV]]
* EMA ([[perineurium]])
* [[Neuron-Specific Enolase (NSE)|Neuron-specific Enolase]]
* [[CD57]] (Leu-7)
* [[Myelin basic protein|Myelin basic proteins]]
Negative for:
* [[GFAP]]
|
* Positive [[family history]] of [[tumor]] occurrence
* [[Multiple mucosal neuroma syndrome]]
* [[Multiple endocrine neoplasia syndrome]] ([[MEN 2B]])
|90% [[lesions]] affect the [[face]] involving:
* [[Eyelid]]
* [[Nose]]
* [[Oral mucosa]]
Remaining 10% can occur anywhere in [[body]] involving:
* [[Shoulder]]
* [[Arm]]
* [[Hand]]
* [[Foot]]
* [[Glans penis|Glans of penis]]
|
* Small, [[solitary]], raised, [[Domes|dome-shaped]], firm, flesh-colored painless [[nodule]] on [[skin]]
* Cosmetic issues due to [[facial]] involvement
* [[Scar]] after [[surgery]]
|
* [[Benign]] [[tumor]] of the [[nerve fibers]]
* [[Affect|Affects]] middle [[Age|aged]] people (40-60 years)
* No known [[familial]] [[Association (statistics)|association]]
* [[Affect|Affects]] [[females]] more frequently than [[males]]
|-
| style="background:#DCDCDC;" align="center" + |'''[[Traumatic neuroma]]'''<ref name="pmid9745184">{{cite journal| author=Lee EJ, Calcaterra TC, Zuckerbraun L| title=Traumatic neuromas of the head and neck. | journal=Ear Nose Throat J | year= 1998 | volume= 77 | issue= 8 | pages= 670-4, 676 | pmid=9745184 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9745184  }} </ref><ref name="pmid27179535">{{cite journal| author=Hanna SA, Catapano J, Borschel GH| title=Painful pediatric traumatic neuroma: surgical management and clinical outcomes. | journal=Childs Nerv Syst | year= 2016 | volume= 32 | issue= 7 | pages= 1191-4 | pmid=27179535 | doi=10.1007/s00381-016-3109-z | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27179535  }} </ref><ref name="pmid18599222">{{cite journal| author=Foltán R, Klíma K, Spacková J, Sedý J| title=Mechanism of traumatic neuroma development. | journal=Med Hypotheses | year= 2008 | volume= 71 | issue= 4 | pages= 572-6 | pmid=18599222 | doi=10.1016/j.mehy.2008.05.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18599222  }} </ref><ref name="pmid28915703">{{cite journal| author=Yao C, Zhou X, Zhao B, Sun C, Poonit K, Yan H| title=Treatments of traumatic neuropathic pain: a systematic review. | journal=Oncotarget | year= 2017 | volume= 8 | issue= 34 | pages= 57670-57679 | pmid=28915703 | doi=10.18632/oncotarget.16917 | pmc=5593675 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28915703  }} </ref>
|
* Tangle of [[neural]] [[Fiber|fibers]] and [[connective tissue]] that [[Development|develops]] following a [[peripheral nerve]] [[injury]]
* Interruption in [[Continuity correction|continuity]] of [[nerve]] [[Causality|causing]] [[wallerian degeneration]] (loss of [[axons]] in [[proximal]] stump and [[retraction]] of [[axons]] in [[distal]] [[Segment (linguistics)|segment]]), followed by exuberant [[regeneration]] of [[nerve]] and [[Formation matrix|formation]] of [[mass]] of [[Schwann cells]], [[axons]] and [[fibrous]] [[Cells (biology)|cells]]
|
* Numerous well formed small [[nerve]] twigs
* Limited [[soft tissue]] [[Infiltration (medical)|infiltration]]
* Contains [[axons]] in haphazardly arranged [[nerves]] within mature [[collagenous]] [[scar]] with entrapped [[smooth muscle]]
|Positive for:
* [[S100A1|S100]]
|
* History of [[trauma]] to a [[nerve]] (especially during a [[surgery]])
* [[Cone biopsy]] ([[rare]] [[Complications|complication]])
* 55% of [[hysterectomy]] [[patients]] have microneuromas, associated with [[childbirth]]
|Most common [[oral]] [[Location parameter|locations]] are:
* [[Tongue]]
* Near [[mental foramen]] of [[mouth]]
[[Rare|Rarely]] involves:
* [[Head]]
* [[Neck]]
|
* Firm, [[oval]], whitish, [[Slow|slowly]] [[Growth|growing]], [[palpable]] [[nodule]] on [[skin]] (no discoloration of [[skin]] on the top of [[nodule]])
* </=2cm in [[Size consistency|size]]
* [[Trauma|Traumatic]] [[neuropathic]] [[pain]] with the presence of a [[Typical set|typical]] [[trigger point]] in the [[area]] of a [[neuroma]]  (especially with the [[pressure]] application) [[Causality|causing]] the [[patient]] to feel burning, stabbing, [[raw]], gnawing or sickening [[sensations]]
* [[Paresthesias|Paresthesia]] over the [[Injured reserve list|injured]] [[area]]
* [[Dysesthesia]] ([[painful]] [[hypersensitivity]] to normal [[light]] [[tactile]] [[Stimulants|stimuli]])
* [[Function (biology)|Functional]] [[impairment]]
* [[Psychological]] [[distress]] (severely decreasing the [[quality of life]])
|Also known as:
* [[Amputation]] [[neuroma]]
* [[Traumatic neuroma|Pseudoneuroma]]
|-
| style="background:#DCDCDC;" align="center" + |'''Neurotized [[melanocytic nevus]]'''<ref name="pmid1693815">{{cite journal| author=Gray MH, Smoller BR, McNutt NS, Hsu A| title=Neurofibromas and neurotized melanocytic nevi are immunohistochemically distinct neoplasms. | journal=Am J Dermatopathol | year= 1990 | volume= 12 | issue= 3 | pages= 234-41 | pmid=1693815 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1693815  }} </ref><ref name="pmid22742554">{{cite journal| author=Chen Y, Klonowski PW, Lind AC, Lu D| title=Differentiating neurotized melanocytic nevi from neurofibromas using Melan-A (MART-1) immunohistochemical stain. | journal=Arch Pathol Lab Med | year= 2012 | volume= 136 | issue= 7 | pages= 810-5 | pmid=22742554 | doi=10.5858/arpa.2011-0335-OA | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22742554  }} </ref><ref name="pmid25657396">{{cite journal| author=Singh N, Chandrashekar L, Kar R, Sylvia MT, Thappa DM| title=Neurotized congenital melanocytic nevus resembling a pigmented neurofibroma. | journal=Indian J Dermatol | year= 2015 | volume= 60 | issue= 1 | pages= 46-50 | pmid=25657396 | doi=10.4103/0019-5154.147789 | pmc=4318062 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25657396  }} </ref><ref name="pmid1690969">{{cite journal| author=Gray MH, Smoller BR, McNutt NS, Hsu A| title=Immunohistochemical demonstration of factor XIIIa expression in neurofibromas. A practical means of differentiating these tumors from neurotized melanocytic nevi and schwannomas. | journal=Arch Dermatol | year= 1990 | volume= 126 | issue= 4 | pages= 472-6 | pmid=1690969 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1690969  }} </ref>
|
* [[Melanin|Melan]]-A (Mart-1) [[gene]]
* [[Defect]] in [[embryologic]] [[development]] [[Causes|causing]] fast [[proliferation]] [[rate]] of [[melanocytes]] (during first twelve weeks of [[pregnancy]])
|
* Neurotized [[Nevus]] is a type of [[mole]] in which  [[melanocytes]] are in the [[dermis]] with accompanying [[fibrosis]]
* [[Biphasic]] consisting of [[malignant melanoma]] and mature appearing [[neural]] component
* [[Superficial]] classic [[Nevoid melanoma|nevoid]] [[melanocytes]] (i.e. [[melanocytes]] appear like [[spindle cells]] resembling a [[nerve]]; and hence, called a neurotized [[nevus]])
* [[Congenital]] and nested [[growth]] [[Pattern|patterns]]
* More abundant [[cytoplasm]]
* Tends to surround [[adnexa]]
* Scattered nests of type A or B [[nevus]] [[Cells (biology)|cells]], surrounded by [[basement membrane]], present in the [[papillary]] [[dermis]] of [[lesions]] (otherwise indistinguishable from [[Neurofibroma|neurofibromas]])
|Positive for:
* [[S100A1|S-100]]
* MelanA (MART-1)
Negative for:
* Factor XIIIa
* Leu-7
* [[Glial fibrillary acidic protein|GFAP]]
* [[Myelin basic protein|MBP]]
|
* [[Sun exposure]] ([[Ultraviolet light|ultraviolet light)]]
* [[Hormonal]] [[Change detection|changes]] during:
** [[Pregnancy]]
** [[Diabetes]]


===Gross Pathology===
* Fair-[[Skin|skinned]] individuals (Caucasians of America and Europe)
* Positive [[family history]] of [[mole]]
|Can occur anywhere in [[body]], mostly involving following [[Area|areas]]:
* [[Head]]
* [[Neck]]
|
* Slowly growing, [[benign]], [[oval]] or round, well-circumscribed [[macule]], [[papule]] or [[Nodule (medicine)|nodule]]
* [[Color]] varies from [[skin]] [[color]] to [[light]] [[brown]] to [[black]]
* Cosmetic concerns
|_
|-
| style="background:#DCDCDC;" align="center" + |'''[[Cutaneous]] [[myxoma]] ([[Superficial]] angiomyxoma)'''<ref>https://www.sciencedirect.com/topics/medicine-and-dentistry/cutaneous-myxoma</ref><ref name="AlaitiNelson2000">{{cite journal|last1=Alaiti|first1=Samer|last2=Nelson|first2=Fern P.|last3=Ryoo|first3=Jei W.|title=Solitary cutaneous myxoma|journal=Journal of the American Academy of Dermatology|volume=43|issue=2|year=2000|pages=377–379|issn=01909622|doi=10.1067/mjd.2000.101878}}</ref><ref name="Carney1986">{{cite journal|last1=Carney|first1=J. Aidan|title=Cutaneous Myxomas|journal=Archives of Dermatology|volume=122|issue=7|year=1986|pages=790|issn=0003-987X|doi=10.1001/archderm.1986.01660190068018}}</ref><ref name="IidaEgi2019">{{cite journal|last1=Iida|first1=Ken|last2=Egi|first2=Takeshi|last3=Shigi|first3=Masato|last4=Sogabe|first4=Yusuke|last5=Ohashi|first5=Hirotsugu|title=Cutaneous Myxoma of Multiple Lesions|journal=Plastic and Reconstructive Surgery - Global Open|volume=7|issue=2|year=2019|pages=e2040|issn=2169-7574|doi=10.1097/GOX.0000000000002040}}</ref>
|
* [[Sporadic Epithelial ovarian tumors|Sporadic]]
* Associated with:
**[[Carney's syndrome]] ([[autosomal dominant]] [[condition]] associated with [[abnormalities]] in [[chromosomes]] 2p and 17q, especially [[mutation]] in the ''[[PRKAR1A|PRKAR1α]]'' [[gene]] on the [[chromosome]] 17q22–q24 [[locus]])
**NAME [[syndrome]]
**LAMB [[syndrome]]
|
* Predominantly involves [[dermis]] and [[subcutis]]
* Multilobulated, poorly circumscribed
* [[Alcian blue]] positive, and [[hyaluronidase]] sensitive myxoid [[stroma]]/[[acellular]] [[mucin]] pools forming [[cleft]]-like spaces
* Scattered bland [[Stellate cell|stellate]] to [[Spindle cells|spindled cells]] with multiple [[oval]] [[nuclei]]
* [[Rare|Rarely]], [[pleomorphism]], and [[mitotic]] figures seen
* Occasional intranuclear pseudoinclusions
* Many thin-walled small [[blood vessels]]
* Frequent [[neutrophils]]
* Entrapped [[epithelial]] component in 20-30% of cases:
**[[Keratinous]] [[cyst]]
**Thin strands of [[squamous epithelium]]
**Basaloid buds
|Positive for:
* [[CD34]]
* [[Smooth muscle]] [[actin]] (90%)
* [[Muscle]] specific [[actin]] (67%)
* Factor XIIIa (60%)
* [[Vimentin]]
* [[S100|S-100]] (rarely, 40%)
* Factor VIIIa ([[variable]])
Negative for:
* [[Cytokeratin]]
* [[Desmin]]
* [[Glial fibrillary acidic protein|GFAP]]
* [[ER]]
* [[PR]]
|Associated with '''[[Carney complex|Carney's complex/syndrome]]''' which includes following:
*'''[[Myxomas]]:'''
**[[Cutaneous]]
**[[External ear]]
**[[Heart]]
**[[Breast]] myxoid [[fibroadenoma]]
*'''[[Cutaneous]] [[Melanocytic nevus|melanocytic]] [[lesions]]:'''
**Lentigines
**[[Blue nevus]]
*'''[[Endocrine]] [[hyperplasia]] and [[neoplasia]]''':
**[[Pituitary]]
**[[Thyroid]]
**[[Adrenal cortex]]
**[[Testis]] [[large cell]] calcifying [[Sertoli cell]] [[tumor]]
*'''Psammomatous [[Melanotic cancer|melanotic]] [[schwannoma]]'''
May be associated with '''NAME''' or '''LAMB [[syndrome]]'''
|
* [[Trunk]]
* [[Limbs]]
* [[Head]]/[[face]] ([[eyelids]] and [[external ear]] [[Canal (anatomy)|canal]] in [[Carney's syndrome]])
* [[Neck]]
* [[Perineal]]
* [[Nipples]]
* [[Buttocks]]
|
* [[Solitary]] or multiple flesh-[[Color|colored]] [[nodules]]
* 1-5cm in [[diameter]]
|
* Sometimes, may be the earliest manifestation of [[Carney complex]]
* [[Affect|Affects]] [[men]] more frequently than women
* Involves mostly middle-[[Age|aged]] [[population]]
|-
| style="background:#DCDCDC;" align="center" + |'''[[Nerve sheath]] [[myxoma]]'''<ref name="pmid16327434">{{cite journal| author=Fetsch JF, Laskin WB, Miettinen M| title=Nerve sheath myxoma: a clinicopathologic and immunohistochemical analysis of 57 morphologically distinctive, S-100 protein- and GFAP-positive, myxoid peripheral nerve sheath tumors with a predilection for the extremities and a high local recurrence rate. | journal=Am J Surg Pathol | year= 2005 | volume= 29 | issue= 12 | pages= 1615-24 | pmid=16327434 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16327434  }} </ref><ref name="pmid30820132">{{cite journal| author=Yadav SK, Singh S, Sarin N, Naeem R, Pruthi SK| title=Nerve Sheath Myxoma of Scalp: A Rare Site of Presentation. | journal=Int J Trichology | year= 2019 | volume= 11 | issue= 1 | pages= 34-37 | pmid=30820132 | doi=10.4103/ijt.ijt_45_18 | pmc=6385516 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30820132  }} </ref><ref name="pmid26023558">{{cite journal| author=Bhat A, Narasimha A, C V, Vk S| title=Nerve sheath myxoma: report of a rare case. | journal=J Clin Diagn Res | year= 2015 | volume= 9 | issue= 4 | pages= ED07-9 | pmid=26023558 | doi=10.7860/JCDR/2015/10911.5810 | pmc=4437072 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26023558  }} </ref><ref name="pmid17498433">{{cite journal| author=Avninder S, Ramesh V, Vermani S| title=Benign nerve sheath myxoma (myxoid neurothekeoma) in the leg. | journal=Dermatol Online J | year= 2007 | volume= 13 | issue= 2 | pages= 14 | pmid=17498433 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17498433  }} </ref><ref name="pmid24470676">{{cite journal| author=Kim BW, Won CH, Chang SE, Lee MW| title=A case of nerve sheath myxoma on finger. | journal=Indian J Dermatol | year= 2014 | volume= 59 | issue= 1 | pages= 99-101 | pmid=24470676 | doi=10.4103/0019-5154.123526 | pmc=3884944 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24470676  }} </ref><ref name="pmid4091218">{{cite journal| author=Pulitzer DR, Reed RJ| title=Nerve-sheath myxoma (perineurial myxoma). | journal=Am J Dermatopathol | year= 1985 | volume= 7 | issue= 5 | pages= 409-21 | pmid=4091218 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4091218  }} </ref>
|
* Unknown [[etiology]]
|
* [[Tumors]] involve the [[dermis]] and/or [[subcutis]]
* [[Distinctive feature|Distinct]] multinodular/multilobular [[Mass|masses]]
* Markedly hypocellular with abundant myxoid [[stroma]]
* Peripheral [[fibrous]] [[Borderline|border]] made up of [[Collagen, type IV, alpha 1|collagen IV]]
* [[Schwann cells]] may show the following different [[Features (pattern recognition)|features]]:
** [[Cytoplasmic]]-[[nuclear]] [[Invagination|invaginations]]
** Small [[epithelioid]] [[Schwann cells]] in corded, nested, and/or syncytial-like aggregates
** [[Schwann cells]] with a ring-like [[appearance]]
** [[Scattering|Scattered]] [[Spindle cells|spindled]] and [[Stellate cell|stellate]]-shaped [[Schwann cells]]
|Positive for:
* [[S100A1|S-100]]
* [[Glial fibrillary acidic protein]]
* [[Neuron-Specific Enolase (NSE)|Neuron specific enolase]]
* [[CD57]]
* [[Epithelial]] [[membrane]] [[antigen]]
* [[CD34]]
|_
|Can occur anywhere in [[body]]:
*Most commonly involves [[extremities]] especially:
**[[Fingers]]
**[[Knees]]
*[[Rare|Rarely]] involves:
**[[Scalp]]/[[head]]
**[[Trunk]]
|
* Painless [[skin]] [[mass]] or [[Nodule (medicine)|nodule]]
* Occasionally [[painful]] to [[touch]]
* [[Skin]] over the [[nodule]] is pink, [[Soft tissue|soft]], and usually intact (no [[ulceration]])
* 0.5-2 cm in size
* Cosmetic issue (when present in [[head]] and [[neck]] region)
|
* First described by Harkin and Reed in 1969
* Peak [[incidence]] in the fourth decade of [[life]]
* [[Strong]] predilection for the [[extremities]]
* Also known as:
** Classical [[Nerve]] Sheath [[Myxoma]]
** [[Cutaneous]] [[Lobular]] Neuro [[Myxoma]]
** [[Myxomatous]] Perineuroma
|-
| style="background:#DCDCDC;" align="center" + |'''[[Malignant peripheral nerve sheath tumor]] ([[MPNST]])/[[malignant]] [[schwannoma]]'''<ref name="Valeyrie-AllanoreIsmaili2005">{{cite journal|last1=Valeyrie-Allanore|first1=L.|last2=Ismaili|first2=N.|last3=Bastuji-Garin|first3=S.|last4=Zeller|first4=J.|last5=Wechsler|first5=J.|last6=Revuz|first6=J.|last7=Wolkenstein|first7=P.|title=Symptoms associated with malignancy of peripheral nerve sheath tumours: a retrospective study of 69 patients with neurofibromatosis 1|journal=British Journal of Dermatology|volume=153|issue=1|year=2005|pages=79–82|issn=0007-0963|doi=10.1111/j.1365-2133.2005.06558.x}}</ref><ref name="pmid12011145">{{cite journal| author=Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A| title=Malignant peripheral nerve sheath tumours in neurofibromatosis 1. | journal=J Med Genet | year= 2002 | volume= 39 | issue= 5 | pages= 311-4 | pmid=12011145 | doi= | pmc=1735122 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12011145  }} </ref><ref name="pmid24174807">{{cite journal| author=Panigrahi S, Mishra SS, Das S, Dhir MK| title=Primary malignant peripheral nerve sheath tumor at unusual location. | journal=J Neurosci Rural Pract | year= 2013 | volume= 4 | issue= Suppl 1 | pages= S83-6 | pmid=24174807 | doi=10.4103/0976-3147.116480 | pmc=3808069 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24174807  }} </ref><ref name="pmid17705563">{{cite journal| author=Ferrari A, Bisogno G, Carli M| title=Management of childhood malignant peripheral nerve sheath tumor. | journal=Paediatr Drugs | year= 2007 | volume= 9 | issue= 4 | pages= 239-48 | pmid=17705563 | doi=10.2165/00148581-200709040-00005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17705563  }} </ref><ref name="pmid12632346">{{cite journal| author=Neville H, Corpron C, Blakely ML, Andrassy R| title=Pediatric neurofibrosarcoma. | journal=J Pediatr Surg | year= 2003 | volume= 38 | issue= 3 | pages= 343-6; discussion 343-6 | pmid=12632346 | doi=10.1053/jpsu.2003.50105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12632346  }} </ref><ref name="ZehouFabre2013">{{cite journal|last1=Zehou|first1=Ouidad|last2=Fabre|first2=Elizabeth|last3=Zelek|first3=Laurent|last4=Sbidian|first4=Emilie|last5=Ortonne|first5=Nicolas|last6=Banu|first6=Eugeniu|last7=Wolkenstein|first7=Pierre|last8=Valeyrie-Allanore|first8=Laurence|title=Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review|journal=Orphanet Journal of Rare Diseases|volume=8|issue=1|year=2013|pages=127|issn=1750-1172|doi=10.1186/1750-1172-8-127}}</ref>
|
* 50% arise denovo
* 50% associated with [[neurofibromatosis]] ([[loss of heterozygosity]] of [[p53]] on 17p [[chromosome]])
|
* Generalized [[atypia]]
* Increased [[mitotic]] [[Activity (chemistry)|activity]]
* [[Diffuse]] hypercellularity
* [[Infiltration (medical)|Infiltrative]] [[growth]]
* [[Pleomorphic]] [[nuclei]]
* [[Area|Areas]] of geographic [[necrosis]] may show [[Divergent synthesis|divergent]] [[differentiation]], with [[tumor]] palisading at edges, resembling [[glioblastoma multiforme]]
* Monomorphic [[Serpentine receptor|serpentine]] [[Cells (biology)|cells]], large [[Gap phenomenon|gaping]] [[vascular]] spaces, [[Perivascular cell|perivascular]] plump [[Tumor cell|tumor cells]]
* May have bizarre [[Cells (biology)|cells]]
* 15% have [[Metaplasticity|metaplastic]] [[cartilage]], [[bone]], and [[muscle]]
* May have [[glandular]] [[differentiation]], if so, presume [[malignant]]
* May have [[melanin]] in [[Tumor cell|tumor cells]], particularly if arise from [[Roots of spinal nerves|spinal nerve roots]] (overlaps with primary [[melanoma]] of [[Nerves|nerves)]]
* Some have no discernable [[Schwann cell|Schwannian]] features at any level
[[Electron microscopy]] shows:
* [[Cell membrane]] infoldings with [[Lamellar bodies|lamellar]] [[Configuration interaction|configuration]], discontinuous [[basal lamina]], conspicuous intercellular junctions, and occasional [[dense]]-[[Core (anatomy)|core]] [[granules]]


<gallery>
|Positive for:
Image:leiomyoma.jpg|Leiomyoma enucleated from a uterus. External surface on left; cut surface on right
* [[CD99]]/O13 (86%)
Image:leiomyoma2.jpg|A large, solitary leiomyoma in the uterus, distoring the endometrial cavity into a Y shape by splaying and pressing it downwards. <br> (Image courtesy of Ed Uthman, MD)
* [[S100A1|S-100]] (patchy in 62% cases)
</gallery>
* [[CD57]] (55%)
* [[Collagen, type IV, alpha 1|Collagen IV]]
* [[p53]]
* Leu7/[[CD57]] (in [[neurofibroma]]-like [[Area|areas]])
* [[Protein]] [[gene product]] 9.5 (more sensitive than [[S100A1|S100]] but not specific)
In case of [[glandular]] [[differentiation]] ([[malignant]]), positive for:
* [[Keratin]]
* EMA
* [[CEA]]
* [[Chromogranin]]
Negative for:
* [[CD19]]
|Associated with:
* [[NF1]]
May be associated with:
* [[Radiation|Radiations]]
* [[Ganglioneuroma]] ([[Rare|rarely]])
|Bulky deep-seated [[tumor]] usually arising from major [[nerves]] in:
* [[Neck]]
* [[Forearm]]
* [[Lower leg]]
* [[Buttock]]
|
* Painless [[swelling]] in [[extremities]] (arms or [[legs]], aka [[peripheral edema]])
* Difficulty [[moving]] the extremity with [[tumor]] ([[Limp|limping]])
* Localized [[Sore|soreness]] in [[tumor]] [[area]]
* [[Neurological]] [[symptoms]]
* [[Pain]] or [[discomfort]]: [[numbness]], burning, or [[Tingling|tingling (pins and needles)]]
* [[Dizziness]]
* [[Loss of balance]]
|
* Most common frequent [[soft tissue sarcoma]] in the [[pediatrics]] [[population]]
|-
| style="background:#DCDCDC;" align="center" + |'''[[Dermatofibrosarcoma protuberans]] ([[DFSP]])'''
|
* t(17,22)(q21;q13) ([[Collagen, type I, alpha 1|collagen type 1 alpha 1(COL1A1)]] [[gene]] and [[Platelet-derived growth factor|platelet derived growth factor  (PDGF)]] [[Beta-1|beta]] [[Chain (sequence)|chain]] [[gene]]), resulting [[fusion protein]] is [[Process (anatomy)|processed]] into mature [[platelet-derived growth factor]] which is a [[Potential|potent]] [[growth factor]]
* Supernumerary ring [[chromosomes]] derived from t(17;22)
|
* Usually forms a [[mass]]
* Non circumscribed, highly [[cellular]], tight storiform [[pattern]] ([[Cells (biology)|cells]] [[Radiating fibers|radiating]] in spokes at right angles around a central point that often contains a [[vessel]]) deeply [[Infiltration (medical)|infiltrating]] into [[subcutaneous tissue]] and entraping [[fat cells]] leading to  characteristic honeycomb [[pattern]]
* [[Area|Areas]] of [[Fascicle|fascicular]] [[growth]] (some [[tumors]])
* [[Distinctive feature|Distinct]] storiform [[pattern]] may be absent in early [[plaque]] stage
* Monomorphic, thin and [[Spindle cells|spindly cells]] with scant [[eosinophilic]] [[cytoplasm]] and hyperchromatic [[nuclei]] (resembling [[neurofibroma]])
* Numerous [[mitotic]] figures (not atypical ones)
* Non-polarizable and thin [[collagen]]
* Only mild [[pleomorphism]] and focal [[atypia]]
* May coexist with [[giant cell]] fibroblastoma
* Usually no [[Significant figure|significant]] [[pleomorphism]], no / [[rare]] [[histiocytes]], no [[histiocyte]]-like [[Cells (biology)|cells]], no [[foam cells]], no [[giant cells]] or other [[inflammatory cells]]
* '''Variants:''' [[Atrophic]] (depressed [[lesion]]), [[collagenous]] (with [[central]] thick [[collagen]] bundles), [[granular cell]],  myxoid, palisading, [[Pigmented Lesions|pigmented]], and sclerosing
|Positive for:
* [[CD34]] ([[strong]] in 95%)
* [[Vimentin]]
* [[Actin]] (focal)
* ApoD
* [[Bcl-2|Bcl2]]
* NKI-C3
* [[CD99]]
Negative for:
* [[S-100]]
* Factor XIIIa (usually)
* [[Keratin]]
* EMA
* [[S100A1|S100]]
* HMB45
* [[Desmin]]
* [[CD117]]
|_
|
* [[Head]]
* Deep [[soft tissue]] of ([[posterior]]) [[neck]]
* [[Trunk]]
* [[Arm|Arms]]
* [[Legs]]
* Doesn't involve [[hands]] and [[feet]]
|
* Begins as a minor firm [[area]] of [[skin]]
* 1 to 5 cm in [[diameter]]
* Resembles a [[bruise]], [[birthmark]], or [[pimple]]
* Can become a raised [[Nodule (medicine)|nodule]] after [[growth]]
* May cause [[redness]], open up or [[bleed]]
|
* Also called intermediate ([[borderline]]) [[fibrous]] [[histiocytoma]]
* More common in blacks in [[United States|US]]
* Involves [[Adult|adults]] of 20 - 40 years of [[age]]
|-
| style="background:#DCDCDC;" align="center" + |'''[[Spindle cell]] [[lipoma]]'''
|
* 16q [[abnormalities]] (usually)
|
* Delicate [[Encapsulation (pharmacology)|encapsulation]]
* Floret [[cell]] [[Formation matrix|formation]]
* No [[degenerative]] [[atypia]]
* [[Mixture]] of mature [[adipocytes]] and mildly [[pleomorphic]] bland [[spindle cells]] ([[Paleness|pale]] [[eosinophilic]] [[cytoplasm]] with uniform wavy [[nuclei]] similar to [[neurofibroma]]) in [[mucinous]] / myxoid or [[fibrous]] [[background]] with thick [[collagen]] bundles
* [[Spindle cells]] arranged in short [[fascicles]] with occasional [[nuclear]] palisading
* Hemangiopericytic or angiomatous [[vascular]] [[pattern]] may be seen
* Minimal or no [[fat]]
* Variable [[mast cells]] and [[lymphocytes]]
* No storiform [[pattern]], no lipoblasts, no/[[rare]] [[mitotic]] [[Activity (chemistry)|activity]]


|Positive for:
* [[CD34]] ([[Strong|strongly]], [[spindle cells]])
* [[Androgen receptors]] in [[men]] and usually women ([[spindle cells]])
* [[S-100]]([[Stain|stains]] only [[adipocytes]])
[[Spindle cells]] are negative for:
* [[S100A1|S100]]
* [[Desmin]]
|_
|
* [[Neck]]
* [[Posterior]] upper [[back]]
* [[Shoulder]]
|
* Multiple well-circumscribed painless [[nodules]] involving several [[body]] parts
|_
|-
| style="background:#DCDCDC;" align="center" + |'''[[Ganglioneuroma]]'''<ref name="VasiliadisPapavasiliou2012">{{cite journal|last1=Vasiliadis|first1=K.|last2=Papavasiliou|first2=C.|last3=Fachiridis|first3=D.|last4=Pervana|first4=S.|last5=Michaelides|first5=M.|last6=Kiranou|first6=M.|last7=Makridis|first7=C.|title=Retroperitoneal extra-adrenal ganglioneuroma involving the infrahepatic inferior vena cava, celiac axis and superior mesenteric artery: A case report|journal=International Journal of Surgery Case Reports|volume=3|issue=11|year=2012|pages=541–543|issn=22102612|doi=10.1016/j.ijscr.2012.07.008}}</ref><ref>https://radiopaedia.org/articles/ganglioneuroma</ref>
|[[Genes]] involved in the [[pathogenesis]] of [[ganglioneuroma]] include:
* ''MYCN'' [[oncogene]]
* [[Chromosome]] 1p36
*[[Activating group|Activating]] [[RET proto-oncogene|RET protooncogene]] [[mutation]] ([[adrenal]] [[Ganglioneuroma|ganglioneuromas]])
|
* Derived from the [[Primordial elements|primordial]] [[neural crest cells]] ([[undifferentiated]] [[Cells (biology)|cells]] of the [[sympathetic nervous system]])
* Admixture of [[ganglion cells]], [[schwann cells]], and [[fibrous tissue]]
* Doesn't contain [[neuroblasts]], intermediate [[Cells (biology)|cells]], or [[Mitotic|mitotic figures]]
* Characterized by [[spindle]]-shaped [[Cells (biology)|cells]] with [[cell]] borders in a [[Fibrillarin|fibrillar]] [[matrix]] containing [[ganglion cells]] with large round [[nuclei]], prominent [[nucleoli]], and abundant [[eosinophilic]] [[cytoplasm]]
* No [[Significant figure|significant]] [[atypia]], [[necrosis]] or [[mitotic]] [[Activity (chemistry)|activity]] is present
* Well [[Differentiate|differentiated]] [[neuronal]] [[tumors]] that do not contain immature [[Element|elements]]
*[[Ganglion cells]] are mature to mildly [[dysmorphic]]:
**Mature: [[Compact tissue|compact]], [[eosinophilic]] [[cytoplasm]] with [[Distinctive feature|distinct]] [[Cell (biology)|cell]] borders, single [[Eccentricity (mathematics)|eccentric]] [[nucleus]], prominent [[nucleolus]]
**[[Dysmorphic]]: single or multiple [[Pyknosis|pyknotic]] [[nuclei]]
**Vary in [[Distribution (pharmacology)|distribution]] and [[number]], may be quite [[Sparse coding|sparse]]
**May contain finely [[Granular cell|granular]], [[gold]] to [[brown]] [[pigment]] ([[lipofuscin]] or [[neuromelanin]])
*[[Schwann cells]]:
**Ensheath neuritic [[Process (anatomy)|processes]]
**Arranged in small intersecting [[fascicles]], separated by loose myxoid [[stroma]]
Two [[histologic]] subtypes:
*Mature = every [[ganglion cell]] is mature
*Maturing = minor component of scattered collections of [[Differentiating (disease name) from other diseases page|differentiating]] [[neuroblasts]] or maturing [[ganglion cells]] (unlike intermixed subtype of ganglioneuroblastoma, these immature foci do not form [[Distinctive feature|distinct]] [[microscopic]] nests)


==epidemiology and demographics==
*[[Background]] may include [[lobules]] of mature [[adipose tissue]] (especially at [[periphery]] of [[lesion]]), [[mast cells]], [[Chronic (medicine)|chronic]] [[inflammation]], [[dense]] [[Collagen|collagenized]] [[stroma]]
The disease is 5 times more common in Afro-American females.
*Mild variation in [[Cellular|cellularity]] may be present
*[[Masculinization|Masculinizing]] [[ganglioneuroma]] is an admixture of [[ganglioneuroma]] and [[Leydig cells]] with crystalloids of [[Reinke's edema|Reinke]] or strands/[[Cluster (epidemiology)|clusters]] of [[Cells (biology)|cells]] resembling [[Adrenal cortex|adrenal cortical]] [[Cells (biology)|cells]]
*[[Electron microscopy]]:
**[[Mixture]] of [[neural]] bundles and normal [[Appearance|appearing]] [[ganglion cells]] with [[Eccentricity (mathematics)|eccentric]] [[nuclei]] and large [[Number|numbers]] of [[cytoplasmic]] [[organelles]]
|Positive for:
*[[Schwann cells]]/[[stroma]]:
**[[S100A1|S100]]
**[[Synaptophysin]]
**[[Neurofilament protein|Neurofilament (NF) protein]]
*[[Ganglion cells]]:
**[[S100A1|S100]]
**[[Synaptophysin]]
**[[Chromogranin A]]
**[[Neurofilament protein|NF protein]]
**[[Glial fibrillary acidic protein]] ([[GFAP]])
**PGP 9.5
**[[Type IV collagen]]
**[[Vasoactive intestinal peptide]] ([[VIP]])
Negative for:
*EMA
*[[Cytokeratin]]
*HMB45
*[[WT1]]
*[[CD99]]
*[[CD45]]
*[[Desmin]]
*[[Myogenic]] [[Marker|markers]] ([[myogenin]], MyoD1)
|
[[Ganglioneuroma|Ganglioneuromas]] may be associated with:
* [[Multiple endocrine neoplasia]] type IIb ([[mucosal]] [[Ganglioneuroma|ganglioneuromas]])
* [[Turner syndrome]]
* [[Neurofibromatosis type 1]]
|
Located along [[Distribution (pharmacology)|distribution]] of [[sympathetic nervous system]]:
* [[Posterior]] paraspinal [[mediastinum]] (most common)
* [[Adrenal gland]] (~20-30% of cases)
* Paraspinal [[retroperitoneum]] (especially [[presacral space]])
*[[Cervical]] and [[Parapharyngeal space infection|parapharyngeal area]] in [[neck]]
*[[Urinary bladder]]
*[[Prostate]]
*[[Bone]]
*[[Pancreas]]
*[[Skin]]
*[[Orbit (anatomy)|Orbit]]
*Paratesticular [[area]]
*[[Appendix]]
*[[Gastrointestinal tract]]
|[[Symptoms]] of [[ganglioneuroma]] vary depending on the [[Location parameter|location]] of [[tumor]], and include the following:
* [[Mediastinum]]:
** [[Dyspnea]]
** [[Chest pain]]
**[[Trachea]] compression
* [[Retroperitoneum]]:
** [[Abdominal pain]]
** [[Bloating]]
* [[Spinal cord]]:
** [[Paresis]]
** [[Pain]] and [[numbness]]/[[loss of sensation]] in [[limbs]]
[[Patients]] with [[ganglioneuroma]] may also have [[paraneoplastic syndrome]], which may manifest with:
* [[Diarrhea]]
* [[Diaphoresis]]
* [[Hirsuitism|Hirsutism]]
*[[Clitoris enlargement|Enlarged clitoris]] (in [[females]])
*[[High blood pressure]]
*[[Sweating]]
|
[[Ganglioneuroma|Ganglioneuromas]] are included in the ''neuroblastic [[tumors]]'' [[Group (sociology)|group]], which includes:
* [[Ganglioneuroma]] ([[benign]])
* Ganglioneuroblastoma (intermediate)
* [[Neuroblastoma]] (aggressive)
|-
| style="background:#DCDCDC;" align="center" + |'''Myxoid [[liposarcoma]]'''<ref>{{Cite journal
| author = [[Khin Thway]], [[Rashpal Flora]], [[Chirag Shah]], [[David Olmos]] & [[Cyril Fisher]]
| title = Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors
| journal = [[The American journal of surgical pathology]]
| volume = 36
| issue = 3
| pages = 462–469
| year = 2012
| month = March
| doi = 10.1097/PAS.0b013e3182417330
| pmid = 22301498
}}</ref><ref>{{Cite journal
| author = [[J. Rosai]], [[M. Akerman]], [[P. Dal Cin]], [[I. DeWever]], [[C. D. Fletcher]], [[N. Mandahl]], [[F. Mertens]], [[F. Mitelman]], [[A. Rydholm]], [[R. Sciot]], [[G. Tallini]], [[H. Van den Berghe]], [[W. Van de Ven]], [[R. Vanni]] & [[H. Willen]]
| title = Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group)
| journal = [[The American journal of surgical pathology]]
| volume = 20
| issue = 10
| pages = 1182–1189
| year = 1996
| month = October
| pmid = 8827023
}}</ref><ref name="Dal CinKools1993">{{cite journal|last1=Dal Cin|first1=Paola|last2=Kools|first2=Patrick|last3=Sciot|first3=Raf|last4=De Wever|first4=Ivo|last5=Van Damme|first5=Boudewijn|last6=Van de Ven|first6=Wim|last7=Van Den Berghe|first7=Herman|title=Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors|journal=Cancer Genetics and Cytogenetics|volume=68|issue=2|year=1993|pages=85–90|issn=01654608|doi=10.1016/0165-4608(93)90001-3}}</ref><ref name="Dei TosDoglioni2000">{{cite journal|last1=Dei Tos|first1=Angelo P.|last2=Doglioni|first2=Claudio|last3=Piccinin|first3=Sara|last4=Sciot|first4=Raf|last5=Furlanetto|first5=Alberto|last6=Boiocchi|first6=Mauro|last7=Dal Cin|first7=Paola|last8=Maestro|first8=Roberta|last9=Fletcher|first9=Christopher D. M.|last10=Tallini|first10=Giovanni|title=Coordinated expression and amplification of theMDM2,CDK4, andHMGI-C genes in atypical lipomatous tumours|journal=The Journal of Pathology|volume=190|issue=5|year=2000|pages=531–536|issn=0022-3417|doi=10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W}}</ref><ref name="Dei Tos2000">{{cite journal|last1=Dei Tos|first1=A|title=Liposarcoma: New entities and evolving concepts|journal=Annals of Diagnostic Pathology|volume=4|issue=4|year=2000|pages=252–266|issn=10929134|doi=10.1053/adpa.2000.8133}}</ref><ref>{{Cite journal
| author = [[M. D. Kraus]], [[L. Guillou]] & [[C. D. Fletcher]]
| title = Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked variant of a common sarcoma
| journal = [[The American journal of surgical pathology]]
| volume = 21
| issue = 5
| pages = 518–527
| year = 1997
| month = May
| pmid = 9158675
}}</ref><ref>{{Cite journal
| author = [[P. Argani]], [[F. Facchetti]], [[G. Inghirami]] & [[J. Rosai]]
| title = Lymphocyte-rich well-differentiated liposarcoma: report of nine cases
| journal = [[The American journal of surgical pathology]]
| volume = 21
| issue = 8
| pages = 884–895
| year = 1997
| month = August
| pmid = 9255251
}}</ref><ref>{{Cite journal
| author = [[H. L. Evans]]
| title = Liposarcoma: a study of 55 cases with a reassessment of its classification
| journal = [[The American journal of surgical pathology]]
| volume = 3
| issue = 6
| pages = 507–523
| year = 1979
| month = December
| pmid = 534388
}}</ref><ref>{{Cite journal
| author = [[A. P. Dei Tos]], [[T. Mentzel]], [[P. L. Newman]] & [[C. D. Fletcher]]
| title = Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases
| journal = [[The American journal of surgical pathology]]
| volume = 18
| issue = 9
| pages = 913–921
| year = 1994
| month = September
| pmid = 8067512
}}</ref><ref>{{Cite journal
| author = [[D. C. Dahlin]], [[K. K. Unni]] & [[T. Matsuno]]
| title = Malignant (fibrous) histiocytoma of bone--fact or fancy?
| journal = [[Cancer]]
| volume = 39
| issue = 4
| pages = 1508–1516
| year = 1977
| month = April
| pmid = 192432
}}</ref>
|
Atypical [[Lipomatous neoplasm|lipomatous tumor]]/well differentiated [[liposarcoma]] and dedifferentiated [[liposarcoma]] are associated with:
* Presence of a large/giant [[marker]][[chromosome]] and/or [[Ring chromosome|ring chromosomes]] at 12q13-15 region
* [[Amplification]] of this [[chromosome]] region rich in [[Protooncogene|protooncogenes]], including ''[[CHOP]]'', ''[[Cyclin-dependent kinase 4|CDK4]]'', ''[[MDM2]]'', ''HMGI-C'', ''[[GLI1|GLI]]'', ''[[SASS6|SAS]]'', ''OS1'', [[HMGA2]] and''[[OS9 (gene)|OS9]]''
Myxoid [[liposarcoma]] is associated with:
* t(12:16)(q13;p11) - [[CHOP]]([[DDIT3 gene|DDIT3]]) / [[FUS]]<nowiki/>or t(12;22)(q13;q22) - [[CHOP]]([[DDIT3 gene|DDIT3]]) / [[EWSR1 gene|EWS]]
[[Pleomorphic]][[liposarcoma]] is associated with:
* [[Complex (chemistry)|Complex]] [[Karyotype|karyotypic]]<nowiki/>aberrations
|
'''Well-differentiated liposarcoma''':
* '''Sclerosing [[liposarcoma]] ('''distinctive [[stromal]] [[Cells (biology)|cells]] distributed across the [[Tissue (biology)|tissue]], associated with lipoblasts filled with multiple [[vacuoles]], and [[collagenous|collageno]]<nowiki/>[[collagenous|us]] background of fibrillary appearance)
* '''[[Adipocyte|Adipocytic]][[liposarcoma]]''' ([[adipocytes]] with different [[Cell (biology)|cell]] sizes, hyperchromasia, and [[nuclear]] atypia. [[Fibrous]] [[septa|sept]]<nowiki/>[[septa|a]]<nowiki/>containing hyperchromatic [[stromal cells|stromal cel]]<nowiki/>[[stromal cells|ls]] surrounding [[adipocytes]])
* '''[[Inflammatory]][[liposarcoma]]''' (heavy [[Chronic (medical)|chronic]] [[inflammatory]]<nowiki/>infiltrate composed of different lympho-plasmacytic aggregates)
* '''[[Spindle cells|Spindle cell]][[liposarcoma]]'''([[proliferation]] of [[neural]]-like [[spindle cells]] organized in a [[fibrous]] [[Structure factor|structure]]<nowiki/>containing lipoblasts)
'''De-differentiated [[liposarcoma]]''':
* '''Myxoid [[liposarcoma]]''' ( non-homogenous [[appearance]] with [[cystic]] and [[solid|soli]]<nowiki/>[[solid|d]] components)
* '''Round [[cell]][[liposarcoma]]''' (small, round, or [[spindle cells]] with sparse [[Eosinophilia|eosinophilic]] and [[Granular cell|granular]] [[cytoplasm]]<nowiki/>a<nowiki/>nd large [[nuclei]],scattered lipoblasts and [[Area|areas]] <nowiki/>of [[necrosis]])
* '''[[Pleiomorphic|Pleomorphic]][[liposarcoma]]''' ([[pleiomorphic|pleomorphic]] [[Cells (biology)|cells]] <nowiki/>with enlarged round to bizarre [[nuclei]])
|
Atypical [[Lipomatous neoplasm|lipomatous tumor]]/well differentiated [[liposarcoma]] is positive for:
* [[MDM2]]
* [[Cyclin-dependent kinase 4|CDK4]]
* [[p16]]
* [[S100A1|S100]] ([[Stain|stains]][[adipocytes]] and lipoblasts)
|
* [[Chemical]] [[carcinogens]]
** Phenoxyacetic [[herbicides]]
** Chlorophenols
** [[Dioxin]][[Contamination|contaminations]]
** [[Arsenic]]
** [[Thorium dioxide]] ([[Thorotrast]])
* [[Radiation]] ([[dose]] of 50 GY)
* [[Immunodeficiency]](regional [[acquired]][[immunodeficiency]])
* [[Genetic]] susceptibility
*** [[Li-Fraumeni syndrome]]
*** [[Neurofibromatosis]]([[NF1]]; [[von Recklinghausen disease]])
*** [[Gardner syndrome]] ([[Familial adenomatous polyposis]])
*** [[Retinoblastoma]]
*** [[Werner syndrome]]
*** [[Basal cell carcinoma|Nevoid basal cell carcinoma]] ([[Gorlin syndrome]])
** [[Viral infection|Viral infections]]
|
* [[Retroperitoneum]]
* [[Esophagus]]
* [[Bowel]]
* [[Mediastinum]]
|
* '''[[Retroperitoneal]][[liposarcoma]]''' maybe [[asymptomatic]] or [[causes]]:
** [[Weight loss]]
** [[Abdominal pain]]
** [[Oliguria]]
** [[renal failure]] (due to [[ureters]] or [[kidneys]]' compression)
** [[Palpable]] [[abdominal]][[mass]]
** [[Abdominal tenderness]]
** [[Abdominal distention]]
* '''[[Esophageal]] [[liposarcoma]]''' may [[Causes|cause]]:
** [[Dysphagia]]
** [[Vomiting]]
** [[Cough]]
** [[Gastrointestinal bleeding]]
** [[Hoarseness]]
* '''[[Bowel]] [[liposarcoma]]''' may cause:
** [[Gastrointestinal tract|Gastrointestinal]][[bleeding]]
* '''[[Mediastinal]] [[liposarcoma]]''' may [[Causes|cause]]:
** [[Dyspnea]]
** [[Cough]]
** [[Chest pain]]
** [[Weight loss]]
|_
|-
| style="background:#DCDCDC;" align="center" + |'''[[Leiomyoma]]'''<ref name="pmid7611533">{{cite journal| author=Coffin CM, Watterson J, Priest JR, Dehner LP| title=Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. | journal=Am J Surg Pathol | year= 1995 | volume= 19 | issue= 8 | pages= 859-72 | pmid=7611533 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7611533  }} </ref><ref name="pmid8635024">{{cite journal| author=Wenig BM, Devaney K, Bisceglia M| title=Inflammatory myofibroblastic tumor of the larynx. A clinicopathologic study of eight cases simulating a malignant spindle cell neoplasm. | journal=Cancer | year= 1995 | volume= 76 | issue= 11 | pages= 2217-29 | pmid=8635024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8635024  }} </ref><ref name="pmid8847061">{{cite journal| author=Ramachandra S, Hollowood K, Bisceglia M, Fletcher CD| title=Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases. | journal=Histopathology | year= 1995 | volume= 27 | issue= 4 | pages= 313-23 | pmid=8847061 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8847061  }} </ref><ref name="pmid12673560">{{cite journal| author=Häusler M, Schaade L, Ramaekers VT, Doenges M, Heimann G, Sellhaus B| title=Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review. | journal=Hum Pathol | year= 2003 | volume= 34 | issue= 3 | pages= 253-62 | pmid=12673560 | doi=10.1053/hupa.2003.35 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12673560  }} </ref><ref name="pmid16160478">{{cite journal| author=Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA| title=Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. | journal=Am J Surg Pathol | year= 2005 | volume= 29 | issue= 10 | pages= 1348-55 | pmid=16160478 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16160478  }} </ref><ref name="pmid16967468">{{cite journal| author=Kovach SJ, Fischer AC, Katzman PJ, Salloum RM, Ettinghausen SE, Madeb R et al.| title=Inflammatory myofibroblastic tumors. | journal=J Surg Oncol | year= 2006 | volume= 94 | issue= 5 | pages= 385-91 | pmid=16967468 | doi=10.1002/jso.20516 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16967468  }} </ref><ref name="pmid9606802">{{cite journal| author=Coffin CM, Dehner LP, Meis-Kindblom JM| title=Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations. | journal=Semin Diagn Pathol | year= 1998 | volume= 15 | issue= 2 | pages= 102-10 | pmid=9606802 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9606802  }} </ref><ref name="pmid6336632">{{cite journal| author=Berardi RS, Lee SS, Chen HP, Stines GJ| title=Inflammatory pseudotumors of the lung. | journal=Surg Gynecol Obstet | year= 1983 | volume= 156 | issue= 1 | pages= 89-96 | pmid=6336632 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6336632  }} </ref><ref name="pmid8635024">{{cite journal| author=Wenig BM, Devaney K, Bisceglia M| title=Inflammatory myofibroblastic tumor of the larynx. A clinicopathologic study of eight cases simulating a malignant spindle cell neoplasm. | journal=Cancer | year= 1995 | volume= 76 | issue= 11 | pages= 2217-29 | pmid=8635024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8635024  }} </ref><ref name="pmid16160478">{{cite journal| author=Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA| title=Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. | journal=Am J Surg Pathol | year= 2005 | volume= 29 | issue= 10 | pages= 1348-55 | pmid=16160478 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16160478  }} </ref><ref name="pmid17414097">{{cite journal| author=Coffin CM, Hornick JL, Fletcher CD| title=Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. | journal=Am J Surg Pathol | year= 2007 | volume= 31 | issue= 4 | pages= 509-20 | pmid=17414097 | doi=10.1097/01.pas.0000213393.57322.c7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17414097  }} </ref>
|
* Loss of normal [[chromosome]] 1q ([[hereditary]][[leiomyomatosis]])
* [[Renal cell cancer]](HLRCC) [[gene mutation]]
|
* Prominent [[cellular]] [[atypia]]
* [[Nuclear]] [[atypia]], including [[nuclear]]  [[pleomorphism]], hyperchromatism, irregularity in [[nuclear|nucle]]<nowiki/>[[nuclear|ar]]  [[Membrane|membranes]], high [[nuclear]] size, and prominent [[nucleoli]]
* [[Cigar]]-shaped [[nuclei]]
* Abundant [[mitoses]], [[mitotic index]] higher than 10 or more per 10 <nowiki/>high-power fields
* [[Area]]<nowiki/>s of [[coagulative necrosis]] ([[tumor cell]][[necrosis]])
* Pali<nowiki/>sading and extensive [[degenerative]] [[Change|changes]] in the form of hyalinization, [[calcification]], and myxoid changes
* Elon<nowiki/>gated [[Cells (biology)|cells]] with [[eosinophilic]] or occasional [[Fibrillarin|fibrillar]] [[cytoplasm]] with [[Distinctive feature|distinct]] [[cell membranes]]
|
Positive for:
* HHF35 (90%)
* Alpha-[[smooth muscle]] [[actin]] (90%)
* [[Vimentin]]
* [[Desmin]] (75%)
* H-[[caldesmon]]
* [[Phosphotungstic acid hematoxylin|PTAH]] ([[Stain|stains]][[myofibrils]])
* [[Keratin]] (30%)
* [[ER]] (usually in [[uterine]] and [[female]][[retroperitoneal]][[tumors]])
* [[S100A1|S100]] (occasionally weak [[staining]])
* EMA (may be focal)
* [[CD34]]
Negative for:
* [[CD117]]
|
* Immundeficiency ([[HIV]])
* [[Dioxin|Digoxin]] [[Exposure assessment|exposure]]
* [[HHV-8|Human herpes virus type-8 (HHV-8)]]
* [[Epstein barr virus mononucleosis|Epstein barr virus]]
* Long term [[tamoxifen]] use
* [[History and Physical examination|History]] of [[pelvic]][[Radiation|radiations]]
* [[Hereditary]] [[breast carcinoma]] with [[BRCA1]][[mutation]]
* [[Hereditary nonpolyposis colorectal cancer|Hereditary nonpolyposis colorectal carcinoma]] with [[MSH2]] [[mutation]]
* [[Li-Fraumeni syndrome]]
* [[Malignant]] [[melanoma]]
* [[Retinoblastoma]]
|
* [[Uterus]]
* [[Abdomen]]
* [[Esophagus]]
* [[Rectum]]
* [[Skin]] / [[subcutis]]
* [[Retroperitoneum]]
* [[Extremities]]
* Large [[vessels]] ([[inferior vena cava]], [[saphenous vein]], [[femoral vein]], [[pulmonary artery]], [[femoral artery]])
* [[Superficial]] or deep [[Soft tissue|soft tissues]]
* [[Bone]]
* [[Breast]]
* [[Colon]]
* [[Epididymis]]
* [[Mediastinum]]
* [[Lungs]]
|
* [[Asymptomatic]]
* [[Uterine|(uterine]] [[leiomyosarcoma]]<nowiki/>may be associated with:
** Irregular [[vaginal bleeding]](intermenstrual or [[postmenopausal]])
** New [[lump]] or a [[mass]]<nowiki/>protruding into [[vagina]]<nowiki/>or growing [[mass]] in [[abdomen]] or [[pelvis]]
** [[Abdominal pain]]
** [[Abdominal distension]]
** [[Pelvic pain]]
** [[Urinary system|Urinary]] [[symptoms]]
* [[Esophageal]][[leiomyosarcoma]] may cause:
** [[Dysphagia]]
** [[Hematemesis]]
* [[rectal]] [[leiomyosarcoma]]<nowiki/>may cause:
** [[Black]], [[tarry stools]]
** [[Rectal bleeding]]
|_
|-
| style="background:#DCDCDC;" align="center" + |'''[[Inflammatory]] myofibroblastic [[tumor]](IMT)'''<ref name="pmid7611533">{{cite journal| author=Coffin CM, Watterson J, Priest JR, Dehner LP| title=Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. | journal=Am J Surg Pathol | year= 1995 | volume= 19 | issue= 8 | pages= 859-72 | pmid=7611533 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7611533  }} </ref><ref name="pmid8635024">{{cite journal| author=Wenig BM, Devaney K, Bisceglia M| title=Inflammatory myofibroblastic tumor of the larynx. A clinicopathologic study of eight cases simulating a malignant spindle cell neoplasm. | journal=Cancer | year= 1995 | volume= 76 | issue= 11 | pages= 2217-29 | pmid=8635024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8635024  }} </ref><ref name="pmid8847061">{{cite journal| author=Ramachandra S, Hollowood K, Bisceglia M, Fletcher CD| title=Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases. | journal=Histopathology | year= 1995 | volume= 27 | issue= 4 | pages= 313-23 | pmid=8847061 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8847061  }} </ref><ref name="pmid12673560">{{cite journal| author=Häusler M, Schaade L, Ramaekers VT, Doenges M, Heimann G, Sellhaus B| title=Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review. | journal=Hum Pathol | year= 2003 | volume= 34 | issue= 3 | pages= 253-62 | pmid=12673560 | doi=10.1053/hupa.2003.35 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12673560  }} </ref><ref name="pmid16160478">{{cite journal| author=Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA| title=Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. | journal=Am J Surg Pathol | year= 2005 | volume= 29 | issue= 10 | pages= 1348-55 | pmid=16160478 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16160478  }} </ref><ref name="pmid16967468">{{cite journal| author=Kovach SJ, Fischer AC, Katzman PJ, Salloum RM, Ettinghausen SE, Madeb R et al.| title=Inflammatory myofibroblastic tumors. | journal=J Surg Oncol | year= 2006 | volume= 94 | issue= 5 | pages= 385-91 | pmid=16967468 | doi=10.1002/jso.20516 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16967468  }} </ref><ref name="pmid9606802">{{cite journal| author=Coffin CM, Dehner LP, Meis-Kindblom JM| title=Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations. | journal=Semin Diagn Pathol | year= 1998 | volume= 15 | issue= 2 | pages= 102-10 | pmid=9606802 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9606802  }} </ref><ref name="pmid6336632">{{cite journal| author=Berardi RS, Lee SS, Chen HP, Stines GJ| title=Inflammatory pseudotumors of the lung. | journal=Surg Gynecol Obstet | year= 1983 | volume= 156 | issue= 1 | pages= 89-96 | pmid=6336632 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6336632  }} </ref><ref name="pmid8635024">{{cite journal| author=Wenig BM, Devaney K, Bisceglia M| title=Inflammatory myofibroblastic tumor of the larynx. A clinicopathologic study of eight cases simulating a malignant spindle cell neoplasm. | journal=Cancer | year= 1995 | volume= 76 | issue= 11 | pages= 2217-29 | pmid=8635024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8635024  }} </ref><ref name="pmid16160478">{{cite journal| author=Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA| title=Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. | journal=Am J Surg Pathol | year= 2005 | volume= 29 | issue= 10 | pages= 1348-55 | pmid=16160478 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16160478  }} </ref><ref name="pmid17414097">{{cite journal| author=Coffin CM, Hornick JL, Fletcher CD| title=Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. | journal=Am J Surg Pathol | year= 2007 | volume= 31 | issue= 4 | pages= 509-20 | pmid=17414097 | doi=10.1097/01.pas.0000213393.57322.c7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17414097  }} </ref>
|
Unknown underlying [[etiology]], may be due to [[inflammatory]] reaction to:
* [[Infection]]
* Underlying low grade [[malignancy]]
[[Mutations]] such as:
* [[Anaplastic large cell lymphoma, ALK positive|ALK (anaplastic lymphoma kinase)]][[gene]] [[mutations]] in the [[tyrosine kinase]][[locus]] at band 2p23
|
* [[Spindle]] to [[Stellate cell|stellate]]-shaped [[Cell (biology)|cells]]
* [[Spindle cells]]<nowiki/>arranged in short [[fascicles]] with a focal storiform (whorled or cartwheel-like) architecture
* [[Spindle cells]] show features of [[fibroblasts]]<nowiki/>and [[myofibroblasts]]
* Variably dense, chronic, mixed [[polymorphic]] infiltrateof [[Mononuclear cells|mononuclear]][[inflammatory]] [[Cells (biology)|cells]] ([[plasma cells]] and [[lymphocytes]], [[histiocytes]], [[neutrophils]], and occasional [[eosinophils]])
* [[Histiocytes]] have [[multinucleated]] forms with finely vacuolated [[cytoplasmic]] [[lipid]]<nowiki/>droplets
* [[Plasma cells]] with [[cytoplasmic]] [[Russell bodies]] ([[Globular protein|globular]][[cytoplasmic]][[inclusions]] of [[immunoglobulin]]) and [[polyclonal]] pattern of [[light chain]] [[expression]]
* Absent hyperchromasia and atypical [[mitoses]]
|
Positive for:
* IG+ ([[plasma cells]])
* [[IL-1]]
* [[Interleukin 6|IL-6]]
* [[Smooth muscle]] [[actin]]
* [[Desmin]]
* [[Calponin]]
* [[Activin]]-like [[kinase]] 1
Negative for:
* [[Beta-catenin]]
|
* [[Multiple organ dysfunction syndrome|Multiorgan disease]] in association with [[Chronic (medical)|chronic]]<nowiki/>persistent [[Eikenella corrodens]] [[infection]]
* [[Epstein-Barr Virus|Epstein Barr virus]][[infection]]
* [[HHV-8|Human herpes virus-8(HHV-8)]] [[infection]]([[Kaposi's sarcoma]], multicentric [[Castleman's disease]])
|
* [[Lungs]]
* [[Gastrointestinal system]]
* [[Pelvic]] region
** [[Urinary bladder|Bladder]]
** [[Uterus]]
* [[Retroperitoneum]]
* [[Skin]]
* [[Bone]] ([[femur]], [[temporal bone]], [[jaw]][[bone]])
* [[CNS]]
* [[Soft tissue|Soft tissues]]
* [[Larynx]]
* [[Heart]] ([[right ventricle]]<nowiki/>is most commonly involved)
* [[Pancreas]] (rarely)
|
* [[Asymptomatic]] (70%)
* Painless [[asymptomatic]][[mass]]/[[lump]]/[[swelling]]
* [[Pulmonary]] IMT presents as:
** [[Chest pain]]
** [[Cough]]
** [[Dyspnea]]
** [[Hemoptysis]] (recurrent)
** [[Fever]]
** [[Fatigue]]
** [[Weight loss]]
** [[Appetite loss]]
* [[Bone]] [[IMT]] presents with:
** Mild [[bone pain]]
** Easy [[fractures]]
** [[Headache]]
** [[Dizziness]]
** [[Numbness]] at [[tumor]]<nowiki/>site
** [[Bone marrow]]<nowiki/>involvement in some cases
* [[Heart]] [[IMT]] presents with:
** [[Chest pain]]
** [[Difficulty breathing]]
** [[Palpitations]]
** [[Fainting]]
** [[Obstruction]] of [[blood flow]] in the [[heart]] (large [[tumors]])
* [[Urinary bladder|Bladder]] [[IMT]] presents with:
** Painless [[hematuria]]
** [[Chronic (medical)|Chronic]] [[pelvic pain]]
** [[Difficulty passing urine|Difficulty in urinating]]
** Presence of [[Burning sensation throughout the urethra|burning sensation]]
* [[CNS]] [[IMT]] presents with:
** Presence of [[solitary]] or multiple [[tumors]] at various [[Location parameter|location]]<nowiki/>s in the [[brain]]
** Recurrent [[headaches]]
** [[Headache]]
** [[Nausea and vomiting]]
** [[Blurred vision]]
** [[Double vision]]
** [[Ptosis|Drooping of the eyelid]]
** [[Dizziness]]
** [[Back pain]] (if [[spine]]<nowiki/>involved)
** [[Seizures]]
|
Also known as:
* Pseudo-[[inflammatory]][[tumors]]
* [[Inflammatory]] pseudotumor
* [[Plasma cell]] [[granuloma]]
* [[Inflammatory]] pseudotumor
* [[Fibrous histiocytoma]]
* [[Fibroxanthoma]]
* [[Xanthogranuloma]]
* [[Inflammatory]]<nowiki/>pseudosarcoma
* Atypical fibromyxoid [[tumor]]
* Atypical myfibroblastic [[tumor]]
|-
| style="background:#DCDCDC;" align="center" + |'''[[Fibroepithelial polyp]]/[[Acrochordon]]'''<ref name="pmid30997841">{{cite journal| author=Cukic O, Jovanovic MB| title=Large Fibroepithelial Polyp of the Palatine Tonsil. | journal=Ear Nose Throat J | year= 2019 | volume=  | issue=  | pages= 145561319841203 | pmid=30997841 | doi=10.1177/0145561319841203 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30997841  }} </ref><ref name="pmid30916216">{{cite journal| author=Vatansever M, Dinç E, Dursun Ö, Oktay ÖÖ, Arpaci R| title=Atypical presentation of fibroepithelial polyp: a report of two cases. | journal=Arq Bras Oftalmol | year= 2019 | volume=  | issue=  | pages=  | pmid=30916216 | doi=10.5935/0004-2749.20190050 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30916216  }} </ref><ref name="pmid30864355">{{cite journal| author=Rexhepi M, Trajkovska E, Besimi F, Rufati N| title=Giant Fibroepithelial Polyp of Vulva: A Case Report and Review of Literature. | journal=Pril (Makedon Akad Nauk Umet Odd Med Nauki) | year= 2018 | volume= 39 | issue= 2-3 | pages= 127-130 | pmid=30864355 | doi=10.2478/prilozi-2018-0051 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30864355  }} </ref><ref name="pmid30778021">{{cite journal| author=Jabbour J, Chappell JR, Busby M, McCubbery NW, Brown DF, Park SJK et al.| title=Glottic Obstruction from Fibroepithelial Polyp. | journal=Am J Case Rep | year= 2019 | volume= 20 | issue=  | pages= 219-223 | pmid=30778021 | doi=10.12659/AJCR.914907 | pmc=6388646 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30778021  }} </ref><ref name="pmid30448831">{{cite journal| author=Hong P, Cai Y, Li Z, Fan S, Yang K, Hao H et al.| title=Modified Laparoscopic Partial Ureterectomy for Adult Ureteral Fibroepithelial Polyp: Technique and Initial Experience. | journal=Urol Int | year= 2019 | volume= 102 | issue= 1 | pages= 13-19 | pmid=30448831 | doi=10.1159/000494804 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30448831  }} </ref><ref name="pmid30426076">{{cite journal| author=Uçar M, Baş E, Akkoç A, Topçuoğlu M| title=Fibroepithelial Polyp of the Ureter: A Rare Cause of Hydronephrosis. | journal=J Endourol Case Rep | year= 2018 | volume= 4 | issue= 1 | pages= 166-168 | pmid=30426076 | doi=10.1089/cren.2018.0031 | pmc=6225073 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30426076  }} </ref><ref name="pmid30425926">{{cite journal| author=Chaker K, Rhouma SB, Daly KM, Zehani A, Bibi M, Chehida MAB et al.| title=Benign fibroepithelial polyp of the ureter: A case report. | journal=Urol Case Rep | year= 2019 | volume= 22 | issue=  | pages= 52-53 | pmid=30425926 | doi=10.1016/j.eucr.2018.10.019 | pmc=6226574 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30425926  }} </ref><ref name="pmid30421620">{{cite journal| author=Hajji F, Moufid K, Ghoundale O, Touiti D| title=A rare case of successful endoscopic management of a fibroepithelial polyp with intussusception of the ureter and periodic prolapse into bladder. | journal=Ann R Coll Surg Engl | year= 2019 | volume= 101 | issue= 2 | pages= e66-e70 | pmid=30421620 | doi=10.1308/rcsann.2018.0198 | pmc=6351868 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30421620  }} </ref><ref name="pmid30401014">{{cite journal| author=Lee H, Sade I, Gilani S, Zhong M, Lombardo G| title=A Giant Fibroepithelial Polyp of the Small Bowel Associated with High-Grade Obstruction. | journal=Am Surg | year= 2018 | volume= 84 | issue= 7 | pages= e210-e211 | pmid=30401014 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30401014  }} </ref><ref name="pmid30319938">{{cite journal| author=Chaker K| title=Benign fibroepithelial polyp of the ureter: A case report. | journal=Urol Case Rep | year= 2019 | volume= 22 | issue=  | pages= 15-16 | pmid=30319938 | doi=10.1016/j.eucr.2018.09.021 | pmc=6180234 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30319938  }} </ref><ref name="pmid30009441">{{cite journal| author=Lozano-Peña AK, Lamadrid-Zertuche AC, Ocampo-Candiani J| title=Giant fibroepithelial polyp of the vulva. | journal=Australas J Dermatol | year= 2019 | volume= 60 | issue= 1 | pages= 70-71 | pmid=30009441 | doi=10.1111/ajd.12886 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30009441  }} </ref><ref name="pmid29883781">{{cite journal| author=Eckstein M, Agaimy A, Woenckhaus J, Winter A, Bittmann I, Janzen J et al.| title=DICER1 mutation-positive giant botryoid fibroepithelial polyp of the urinary bladder mimicking embryonal rhabdomyosarcoma. | journal=Hum Pathol | year= 2019 | volume= 84 | issue=  | pages= 1-7 | pmid=29883781 | doi=10.1016/j.humpath.2018.05.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29883781  }} </ref><ref name="pmid29843497">{{cite journal| author=Akdere H, Çevik G| title=Rare Fibroepithelial Polyp Extending Along the Ureter: A Case Report | journal=Balkan Med J | year= 2018 | volume= 35 | issue= 3 | pages= 275-277 | pmid=29843497 | doi=10.4274/balkanmedj.2017.1537 | pmc=5981127 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29843497  }} </ref><ref name="pmid29800931">{{cite journal| author=Ballard DH, Rove KO, Coplen DE, Chen TY, Hulett Bowling RL| title=Fibroepithelial polyp causing urethral obstruction: Diagnosis by cystourethrogram. | journal=Clin Imaging | year= 2018 | volume= 51 | issue=  | pages= 164-167 | pmid=29800931 | doi=10.1016/j.clinimag.2018.05.009 | pmc=6404776 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29800931  }} </ref><ref name="pmid29574427">{{cite journal| author=Amin A, Amin Z, Al Farsi AR| title=Septic presentation of a giant fibroepithelial polyp of the vulva. | journal=BMJ Case Rep | year= 2018 | volume= 2018 | issue=  | pages=  | pmid=29574427 | doi=10.1136/bcr-2017-222789 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29574427  }} </ref><ref name="pmid29487969">{{cite journal| author=Gupta R, Smita S, Sinha R, Sinha N, Sinha L| title=Giant fibroepithelial polyp of the thigh and retroperitoneal fibromatosis in a young woman: a rare case. | journal=Skeletal Radiol | year= 2018 | volume= 47 | issue= 9 | pages= 1299-1304 | pmid=29487969 | doi=10.1007/s00256-018-2904-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29487969  }} </ref><ref name="pmid29200704">{{cite journal| author=Rajeesh Mohammed PK, Choudhury BK, Dalai RP, Rana V| title=Fibroepithelial Polyp with Sebaceous Hyperplasia: A Case Report. | journal=Indian J Med Paediatr Oncol | year= 2017 | volume= 38 | issue= 3 | pages= 404-406 | pmid=29200704 | doi=10.4103/ijmpo.ijmpo_124_17 | pmc=5686997 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29200704  }} </ref><ref name="pmid28791276">{{cite journal| author=Lee MH, Hwang JY, Lee JH, Kim DH, Song SH| title=Fibroepithelial polyp of the vulva accompanied by lymphangioma circumscriptum. | journal=Obstet Gynecol Sci | year= 2017 | volume= 60 | issue= 4 | pages= 401-404 | pmid=28791276 | doi=10.5468/ogs.2017.60.4.401 | pmc=5547092 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28791276  }} </ref><ref name="pmid28693464">{{cite journal| author=Ten Donkelaar CS, Houwert AC, Ten Kate FJW, Lock MTWT| title=Polypoid arteriovenous malformation of the ureter mimicking a fibroepithelial polyp, a case report. | journal=BMC Urol | year= 2017 | volume= 17 | issue= 1 | pages= 55 | pmid=28693464 | doi=10.1186/s12894-017-0237-z | pmc=5504856 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28693464  }} </ref><ref name="pmid28603622">{{cite journal| author=Saito N, Yamasaki M, Daido W, Ishiyama S, Deguchi N, Taniwaki M| title=A bronchial fibroepithelial polyp with abnormal findings on auto-fluorescence imaging. | journal=Respirol Case Rep | year= 2017 | volume= 5 | issue= 5 | pages= e00244 | pmid=28603622 | doi=10.1002/rcr2.244 | pmc=5465754 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28603622  }} </ref>
|Associated with:
* [[Human papillomavirus|HPV 6]] (low risk)
* [[Human papillomavirus|HPV 11]]
|
* Fibrovascular [[Core (anatomy)|cores]] covered by [[squamous epithelium]]
* Larger [[lesions]] may have a [[Flat affect|flattened]] [[Epidermis (skin)|epidermis]]
* Smaller [[lesions]] can have [[epidermal]] [[hyperplasia]] or [[seborrheic keratosis]]-like changes
* [[Central]] [[Core (anatomy)|core]] composed of [[Loose connective tissue|loose]] [[collagen]] with increased [[blood vessels]]
* In larger [[lesion]], may have a [[central]] [[Core (anatomy)|core]] of [[adipose tissue]]
* [[Pagetoid]] [[Dyskeratosis congenita|dyskeratosis]] is sometimes present as an [[incidental finding]]
* May have [[ischemic necrosis]] due to [[torsion]]
|Positive for:
* [[Desmin]]
* [[Vimentin]]
* [[ER]]
* [[PR]]
Negative for:
* [[Actin]]
|Associated with:
* [[Diabetes]] (elevated [[blood sugar]] and [[insulin]])
* [[Abnormal]] [[lipid profile]]
* Other components of [[metabolic syndrome]]
* [[Birt-Hogg-Dubé syndrome|Birt-Hogg-Dube syndrome]]
* [[Acromegaly]]
* [[Polycystic ovary syndrome]]
* May increase in [[number]] during [[pregnancy]]
|
* Occurs usually in intertriginous [[Area|areas]] (i.e. [[axilla]], [[groin]])
* [[Face]]
* [[Neck]]
* [[Eyelids]]
* [[Vulva]]
* [[Tonsils]]
* [[Ureter]]
* [[Bowel]]
* [[Urinary bladder]]
* [[Bronchi]]
|
* [[Soft tissue|Soft]] [[papilloma]], [[flesh]] [[Color|colored]] to dark [[brown]], [[sessile]] to [[pedunculated]]
* A few [[millimeters]] to multiple [[Centimeter|centimeters]] in size
* Larger [[lesions]] often [[Attachment theory|attach]] to [[skin]] by slender stalks
|
* [[Benign]] [[skin]] [[lesions]] in [[Adult|adults]], excised for cosmetic [[Reasoning|reasons]]
Also known as:
* [[Skin tags|Skin tag]]
* [[Soft tissue|Soft]] [[fibroma]]
* [[Cutaneous]] [[papilloma]]
* [[Cutaneous]] tag
* [[Fibroma]] pendulum
* [[Fibroma]] [[molluscum]]
|}


==CT==
==Epidemiology and Demographics==
'''CT images demonstrate a right broad ligament leiomyoma'''
===Age===
<gallery>
*Leiomyoma commonly affects individuals between [[menarche]] and [[menopause]].
Image:
*The incidence increases with age during [[reproductive]] years.<ref name="pmid12548202">{{cite journal| author=Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM| title=High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. | journal=Am J Obstet Gynecol | year= 2003 | volume= 188 | issue= 1 | pages= 100-7 | pmid=12548202 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12548202  }} </ref>
===Race===
*Leiomyoma usually affects African-American women.<ref name="pmid12548202">{{cite journal| author=Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM| title=High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. | journal=Am J Obstet Gynecol | year= 2003 | volume= 188 | issue= 1 | pages= 100-7 | pmid=12548202 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12548202  }} </ref>
**[[Incidence]] rates are approximately threefold greater in African-American women than in white women.


Broad ligament fibroid 001.jpg
==Risk Factors==
*Common [[risk factors]] in the [[development]] of uterine leiomyoma include:<ref name="pmid12548202" /><ref name="pmid20693498">{{cite journal| author=Dragomir AD, Schroeder JC, Connolly A, Kupper LL, Hill MC, Olshan AF et al.| title=Potential risk factors associated with subtypes of uterine leiomyomata. | journal=Reprod Sci | year= 2010 | volume= 17 | issue= 11 | pages= 1029-35 | pmid=20693498 | doi=10.1177/1933719110376979 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20693498  }}</ref><ref name="pmid15808789">{{cite journal| author=Baird DD, Newbold R| title=Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development. | journal=Reprod Toxicol | year= 2005 | volume= 20 | issue= 1 | pages= 81-4 | pmid=15808789 | doi=10.1016/j.reprotox.2005.01.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15808789  }}</ref><ref name="pmid9757871">{{cite journal| author=Marshall LM, Spiegelman D, Goldman MB, Manson JE, Colditz GA, Barbieri RL et al.| title=A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. | journal=Fertil Steril | year= 1998 | volume= 70 | issue= 3 | pages= 432-9 | pmid=9757871 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9757871  }}</ref><ref name="pmid9782674">{{cite journal| author=Sato F, Nishi M, Kudo R, Miyake H| title=Body fat distribution and uterine leiomyomas. | journal=J Epidemiol | year= 1998 | volume= 8 | issue= 3 | pages= 176-80 | pmid=9782674 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9782674  }}</ref><ref name="pmid10472866">{{cite journal| author=Chiaffarino F, Parazzini F, La Vecchia C, Chatenoud L, Di Cintio E, Marsico S| title=Diet and uterine myomas. | journal=Obstet Gynecol | year= 1999 | volume= 94 | issue= 3 | pages= 395-8 | pmid=10472866 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10472866  }}</ref><ref name="pmid15218005">{{cite journal| author=Wise LA, Palmer JR, Harlow BL, Spiegelman D, Stewart EA, Adams-Campbell LL et al.| title=Risk of uterine leiomyomata in relation to tobacco, alcohol and caffeine consumption in the Black Women's Health Study. | journal=Hum Reprod | year= 2004 | volume= 19 | issue= 8 | pages= 1746-54 | pmid=15218005 | doi=10.1093/humrep/deh309 | pmc=1876785 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15218005  }}</ref>
**African-American [[race]]
**Early [[menarche]]
**[[Prenatal]] exposure to [[diethylstilbestrol]]
**[[Parity]]
***Having one or more [[pregnancies]] extending beyond 20 weeks
**[[Obesity]]
**[[Diet]]
***Significant consumption of [[beef]] and other reds meats
***[[Vitamin D deficiency]]
**[[Alcohol]] consumption
**[[Smoking]]
**[[Hormonal contraception]]


Image:
== Natural History, Complications and Prognosis==
*The majority of patients with uterine leiomyoma remain [[asymptomatic]] for a long time; they are usually found incidentally on [[imaging]] or examined after [[Patient|patients]] start having [[Symptom|symptoms]].
*Studies have shown that  7 to 40% of [[premenopausal]] patients with leiomyoma may witness regression of fibroids over 6 months to 3 years.<ref name="pmid12100797">{{cite journal| author=DeWaay DJ, Syrop CH, Nygaard IE, Davis WA, Van Voorhis BJ| title=Natural history of uterine polyps and leiomyomata. | journal=Obstet Gynecol | year= 2002 | volume= 100 | issue= 1 | pages= 3-7 | pmid=12100797 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12100797  }}</ref>
*At [[menopause]] most fibroids will start to shrink as [[Menstrual cycle|menstrual cycles]] stop and [[hormone]] levels wane.<ref name="pmid12100797" />
*Common [[complications]] of uterine leiomyoma include:<ref name="GuptaManyonda2009">{{cite journal|last1=Gupta|first1=Sahana|last2=Manyonda|first2=Isaac T.|title=Acute complications of fibroids|journal=Best Practice & Research Clinical Obstetrics & Gynaecology|volume=23|issue=5|year=2009|pages=609–617|issn=15216934|doi=10.1016/j.bpobgyn.2009.01.012}}</ref><ref name="pmid15599545">{{cite journal |vauthors=Cordiano V |title=Complete remission of hyperprolactinemia and erythrocytosis after hysterectomy for a uterine fibroid in a woman with a previous diagnosis of prolactin-secreting pituitary microadenoma |journal=Ann. Hematol. |volume=84 |issue=3 |pages=200–2 |date=March 2005 |pmid=15599545 |doi=10.1007/s00277-004-0973-5 |url=}}</ref><ref name="pmid18339376">{{cite journal |vauthors=Pritts EA, Parker WH, Olive DL |title=Fibroids and infertility: an updated systematic review of the evidence |journal=Fertil. Steril. |volume=91 |issue=4 |pages=1215–23 |date=April 2009 |pmid=18339376 |doi=10.1016/j.fertnstert.2008.01.051 |url=}}</ref>
**[[Dysmenorrhea]]
**[[Dyspareunia]]
**Leiomyoma degeneration or [[torsion]]
**Transcervical prolapse
**[[Miscarriage]]
*Less common complications of uterine leiomyoma include:<ref name="pmid17070199">{{cite journal |vauthors=Ferrero S, Abbamonte LH, Giordano M, Parisi M, Ragni N, Remorgida V |title=Uterine myomas, dyspareunia, and sexual function |journal=Fertil. Steril. |volume=86 |issue=5 |pages=1504–10 |date=November 2006 |pmid=17070199 |doi=10.1016/j.fertnstert.2006.04.025 |url=}}</ref><ref name="pmid14667888">{{cite journal |vauthors=Lippman SA, Warner M, Samuels S, Olive D, Vercellini P, Eskenazi B |title=Uterine fibroids and gynecologic pain symptoms in a population-based study |journal=Fertil. Steril. |volume=80 |issue=6 |pages=1488–94 |date=December 2003 |pmid=14667888 |doi= |url=}}</ref><ref name="pmid19821668">{{cite journal |vauthors=Fletcher H, Wharfe G, Williams NP, Gordon-Strachan G, Pedican M, Brooks A |title=Venous thromboembolism as a complication of uterine fibroids: a retrospective descriptive study |journal=J Obstet Gynaecol |volume=29 |issue=8 |pages=732–6 |date=November 2009 |pmid=19821668 |doi=10.3109/01443610903165545 |url=}}</ref>
**Venous compression
**[[Polycythemia]] from autonomous production of [[erythropoietin]]
**[[Hypercalcemia]] from autonomous production of [[parathyroid hormone-related protein]]
**[[Hyperprolactinemia]]


Broad ligament fibroid 002.jpg
== Diagnosis ==


Image:
=== Diagnostic Study of Choice ===
* The [[diagnosis]] of uterine leiomyoma is based on a clinical diagnosis, which includes a [[Pelvic examination|pelvic exam]] and [[pelvic ultrasound]] finding of leiomyomas.
* A [[pelvic ultrasound]] is indicated when [[patients]] suffer from [[Symptom|symptoms]] of leiomyoma.
* A [[biopsy]] is usually not needed to make the [[diagnosis]], but should be performed if clinician is suspicious that the mass is not a [[fibroid]].<ref name="pmid70262952">{{cite journal| author=Buttram VC, Reiter RC| title=Uterine leiomyomata: etiology, symptomatology, and management. | journal=Fertil Steril | year= 1981 | volume= 36 | issue= 4 | pages= 433-45 | pmid=7026295 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7026295  }}</ref>


Broad ligament fibroid 003.jpg
=== Symptoms ===
*The majority of patients with leiomyoma are usually [[asymptomatic]].
* [[Symptom|Symptoms]] of uterine leiomyoma may include the following:<ref name="pmid7026295">{{cite journal| author=Buttram VC, Reiter RC| title=Uterine leiomyomata: etiology, symptomatology, and management. | journal=Fertil Steril | year= 1981 | volume= 36 | issue= 4 | pages= 433-45 | pmid=7026295 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7026295  }}</ref>
:* [[Abnormal uterine bleeding]]
:* Heavy or prolonged [[menstrual bleeding]]
:* Painful [[Intercourse|sexual intercourse]]
:* [[Abdominal discomfort]] or [[bloating]]
:* [[Back pain]]
:* [[Urinary frequency]]
:* [[Urinary retention]]
:* [[Constipation]]
:* [[Infertility]]


Image:
=== Physical Examination ===
*Common [[physical examination]] findings of [[uterine]] leiomyoma include enlarged, mobile [[uterus]] with an irregular contour on bimanual [[pelvic examination]].<ref name="pmid7026295" />
===Imaging Findings===
*[[Pelvic ultrasound]] is helpful in the [[diagnosis]] of uterine leiomyoma.
*Findings on an [[ultrasound]] diagnostic of [[uterine]] leiomyoma include fibroids as focal masses with a heterogeneous texture, which usually cause shadowing of the [[ultrasound]] beam.<ref name="pmid19881092">{{cite journal| author=Wilde S, Scott-Barrett S| title=Radiological appearances of uterine fibroids. | journal=Indian J Radiol Imaging | year= 2009 | volume= 19 | issue= 3 | pages= 222-31 | pmid=19881092 | doi=10.4103/0971-3026.54887 | pmc=2766886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19881092  }}</ref>
=== Other Diagnostic Studies ===
*[[Uterine]] leiomyoma may also be diagnosed using diagnostic [[hysteroscopy]], [[magnetic resonance imaging]], and [[hysterosalpingography]].


Broad ligament fibroid 004.jpg
== Treatment ==
=== Medical Therapy ===
*[[Uterine]] leiomyomas usually shrink and regress during [[menopause]] and the [[postpartum]] period.
*Literature is lacking concerning the medical therapy for leiomyoma, and due to their self-limited nature, expectant management is considered in some cases.<ref name="pmid18288885">{{cite journal| author=Viswanathan M, Hartmann K, McKoy N, Stuart G, Rankins N, Thieda P et al.| title=Management of uterine fibroids: an update of the evidence. | journal=Evid Rep Technol Assess (Full Rep) | year= 2007 | volume=  | issue= 154 | pages= 1-122 | pmid=18288885 | doi= | pmc=4781116 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18288885  }} </ref><ref name="pmid21492823">{{cite journal| author=Laughlin SK, Hartmann KE, Baird DD| title=Postpartum factors and natural fibroid regression. | journal=Am J Obstet Gynecol | year= 2011 | volume= 204 | issue= 6 | pages= 496.e1-6 | pmid=21492823 | doi=10.1016/j.ajog.2011.02.018 | pmc=3136622 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21492823  }} </ref>
*[[Pharmacological|Pharmacologic]] medical therapy in the form of [[oral contraceptives]] is recommended among [[premenopausal]] patients with mild [[symptoms]] and mildly enlarged [[Uterus|uteri]].<ref name="pmid8134067">{{cite journal| author=Carlson KJ, Miller BA, Fowler FJ| title=The Maine Women's Health Study: II. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain. | journal=Obstet Gynecol | year= 1994 | volume= 83 | issue= 4 | pages= 566-72 | pmid=8134067 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8134067  }} </ref>
*[[Pharmacologic]] medical therapies for leiomyoma include:<ref name="pmid22296076">{{cite journal |vauthors=Donnez J, Tomaszewski J, Vázquez F, Bouchard P, Lemieszczuk B, Baró F, Nouri K, Selvaggi L, Sodowski K, Bestel E, Terrill P, Osterloh I, Loumaye E |title=Ulipristal acetate versus leuprolide acetate for uterine fibroids |journal=N. Engl. J. Med. |volume=366 |issue=5 |pages=421–32 |date=February 2012 |pmid=22296076 |doi=10.1056/NEJMoa1103180 |url=}}</ref><ref name="pmid28444736">{{cite journal |vauthors=Murji A, Whitaker L, Chow TL, Sobel ML |title=Selective progesterone receptor modulators (SPRMs) for uterine fibroids |journal=Cochrane Database Syst Rev |volume=4 |issue= |pages=CD010770 |date=April 2017 |pmid=28444736 |doi=10.1002/14651858.CD010770.pub2 |url=}}</ref><ref name="pmid8496313">{{cite journal |vauthors=Carr BR, Marshburn PB, Weatherall PT, Bradshaw KD, Breslau NA, Byrd W, Roark M, Steinkampf MP |title=An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial |journal=J. Clin. Endocrinol. Metab. |volume=76 |issue=5 |pages=1217–23 |date=May 1993 |pmid=8496313 |doi=10.1210/jcem.76.5.8496313 |url=}}</ref><ref name="pmid11083008">{{cite journal |vauthors=Starczewski A, Iwanicki M |title=[Intrauterine therapy with levonorgestrel releasing IUD of women with hypermenorrhea secondary to uterine fibroids] |language=Polish |journal=Ginekol. Pol. |volume=71 |issue=9 |pages=1221–5 |date=September 2000 |pmid=11083008 |doi= |url=}}</ref>
**[[Oral contraceptives|Estrogen-progestin contraceptives]]
**Levonorgestrel-releasing [[Intrauterine device|intrauterine]] system
**Progestin implants, [[injections]], and pills
**[[Progesterone]] receptor modulators
**[[Ulipristal acetate]]
**[[Mifepristone]]
**[[Gonadotropin-releasing hormone agonist|Gonadotropin-releasing hormone agonists]]
**[[Nonsteroidal anti-inflammatory drugs]]
**[[Danazol]] and [[gestrinone]]


</gallery>
=== Surgery ===
*[[Surgery operation|Surgery]] is the mainstay of therapy for [[uterine]] leiomyoma.
*[[Uterine artery embolization]] in conjunction with [[laparotomy|laparotomic]] [[myomectomy]] is the most common approach to the treatment of leiomyoma.
*[[Hysteroscopy|Hysteroscopic]] [[myomectomy]] can also be performed for patients with uterine leiomyoma.<ref name="pmid26646122">{{cite journal| author=Borah BJ, Laughlin-Tommaso SK, Myers ER, Yao X, Stewart EA| title=Association Between Patient Characteristics and Treatment Procedure Among Patients With Uterine Leiomyomas. | journal=Obstet Gynecol | year= 2016 | volume= 127 | issue= 1 | pages= 67-77 | pmid=26646122 | doi=10.1097/AOG.0000000000001160 | pmc=4689646 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26646122  }} </ref>
*Surgical indications of leiomyoma include followings:
**[[Abnormal uterine bleeding]] or bulk-related symptoms
**[[Infertility]] or recurrent [[pregnancy loss]]
*There is different types of surgery for leiomyoma include followings:<ref name="pmid21644937">{{cite journal |vauthors=Lönnerfors C, Persson J |title=Pregnancy following robot-assisted laparoscopic myomectomy in women with deep intramural myomas |journal=Acta Obstet Gynecol Scand |volume=90 |issue=9 |pages=972–7 |date=September 2011 |pmid=21644937 |doi=10.1111/j.1600-0412.2011.01207.x |url=}}</ref><ref name="pmid19104365">{{cite journal |vauthors=El-Nashar SA, Hopkins MR, Creedon DJ, St Sauver JL, Weaver AL, McGree ME, Cliby WA, Famuyide AO |title=Prediction of treatment outcomes after global endometrial ablation |journal=Obstet Gynecol |volume=113 |issue=1 |pages=97–106 |date=January 2009 |pmid=19104365 |pmc=2977517 |doi=10.1097/AOG.0b013e31818f5a8d |url=}}</ref><ref name="pmid11960047">{{cite journal |vauthors=Lichtinger M, Hallson L, Calvo P, Adeboyejo G |title=Laparoscopic uterine artery occlusion for symptomatic leiomyomas |journal=J Am Assoc Gynecol Laparosc |volume=9 |issue=2 |pages=191–8 |date=May 2002 |pmid=11960047 |doi= |url=}}</ref><ref name="pmid17197583">{{cite journal |vauthors=Hald K, Kløw NE, Qvigstad E, Istre O |title=Laparoscopic occlusion compared with embolization of uterine vessels: a randomized controlled trial |journal=Obstet Gynecol |volume=109 |issue=1 |pages=20–7 |date=January 2007 |pmid=17197583 |doi=10.1097/01.AOG.0000249602.39339.31 |url=}}</ref>
**[[Hysterectomy]]
**[[Myomectomy]]
**[[Endometrial ablation]]
**Myolysis
**[[Uterine artery]] occlusion


{{Soft tissue tumors and sarcomas}}
==References==
 
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2]; Cafer Zorkun, M.D., Ph.D. [3]; Shanshan Cen, M.D. [4]; Ammu Susheela, M.D. [5]

Synonyms and keywords: Uterine myoma; Fibroid; Fibroids; Uterine; Fibroid Tumor; Fibroid Uterus; Uterine fibromyoma; Leiomyomata

Overview

Uterine leiomyoma was first discovered by Hippocrates in 460-375 B.C and called it “uterine stone”. Uterine leiomyoma may be classified according to their location into 3 subtypes: submucosal, subserous, and intramural. The pathogenesis of leiomyoma is characterized by benign smooth muscle neoplasm. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus. Chromosome aberrations such as t(12; 14)(q14-q15;q23–24), del(7)(q22q32), rearrangements involving 6p21, 10q, trisomy 12, and deletions of 1p3q has been associated with the development of leiomyoma. Uterine leiomyoma must be differentiated from other diseases that cause uterine mass, such as: uterine adenomyoma, pregnancy, hematometra, uterine sarcoma, uterine carcinosarcoma, and metastasis. Leiomyoma is more commonly observed among patients aged 40 years and older. Common risk factors in the development of uterine leiomyoma include African-American race, early menarche, prenatal exposure to diethylstilbestrol, having one or more pregnancies extending beyond 20 weeks, obesity, significant consumption of beef and other red meats, hypertension, family history, and alcohol consumption. Physical examination may be remarkable for enlarged, mobile uterus with an irregular contour on bimanual pelvic examination. The mainstay of therapy for uterine leiomyoma is oral contraceptive pills, either combination pills or progestin-only, Gonadotropin-releasing hormone analogs. Surgery is also part of mainstay therapy for uterine leiomyoma.

Historical Perspective

  • Uterine leiomyoma was first discovered by Hippocrates, an ancient Greek physician, in 460-375 B.C and called it “uterine stone”.
  • In the second century AD, Galen described the lesion as "scleromas".
  • In 1860 and 1863, Rokitansky and Klob coined the term fibroid.
  • In 1854, Virchow, a German pathologist, demonstrated that those tumors originated from the uterine smooth muscle.
  • In 1809, the first laparotomy was conducted by Ephraim McDowell to treat leiomyoma in Danville, USA.[1]

Classification

Pathophysiology

Causes

  • Chromosome aberrations in uterine leiomyoma include:[14]
    • T(12;14)(q14-q15;q23–24)
    • Deletion of (7)(q22q32)
    • Rearrangements involving 6p21, 10q
    • Trisomy 12
    • Deletion of 1p3q have been associated with the development of leiomyoma

Differentiating Leiomyoma from other Diseases

Differentiating Leiomyoma from Other Diseases
Disease entity Etiology (Genetic or others) Histopathological findings Immunohistochemical staining Risk factors Common site of involvement Clinical manifestations Other associated features
Leiomyoma[15][16][17][18][19][20][21][22][16][19][23] Positive for:

Negative for:

_
Neurofibroma[24][25][26][27][28][29][30][27][31][32][33][34]

Can be sporadic or as a part of Neurofibromatosis 1 and 2

Neurofibroma with degenerative atypia ("ancient change") has following microscopic features:

Positive for:

Negative for:

Schwannoma[35][36][37][38][39] Positive for:

Negative for:

Symptoms of schwannoma depend on the location of the tumor:

Palisaded encapsulated neuroma (PEN) /solitary circumscribed neuroma[40] Positive for:

Negative for:

90% lesions affect the face involving:

Remaining 10% can occur anywhere in body involving:

Traumatic neuroma[41][42][43][44] Positive for: Most common oral locations are:

Rarely involves:

Also known as:
Neurotized melanocytic nevus[45][46][47][48] Positive for:

Negative for:

Can occur anywhere in body, mostly involving following areas: _
Cutaneous myxoma (Superficial angiomyxoma)[49][50][51][52] Positive for:

Negative for:

Associated with Carney's complex/syndrome which includes following:

May be associated with NAME or LAMB syndrome

Nerve sheath myxoma[53][54][55][56][57][58] Positive for: _ Can occur anywhere in body:
Malignant peripheral nerve sheath tumor (MPNST)/malignant schwannoma[59][60][61][62][63][64]

Electron microscopy shows:

Positive for:

In case of glandular differentiation (malignant), positive for:

Negative for:

Associated with:

May be associated with:

Bulky deep-seated tumor usually arising from major nerves in:
Dermatofibrosarcoma protuberans (DFSP) Positive for:

Negative for:

_
Spindle cell lipoma Positive for:

Spindle cells are negative for:

_
  • Multiple well-circumscribed painless nodules involving several body parts
_
Ganglioneuroma[65][66] Genes involved in the pathogenesis of ganglioneuroma include:

Two histologic subtypes:

Positive for:

Negative for:

Ganglioneuromas may be associated with:

Located along distribution of sympathetic nervous system:

Symptoms of ganglioneuroma vary depending on the location of tumor, and include the following:

Patients with ganglioneuroma may also have paraneoplastic syndrome, which may manifest with:

Ganglioneuromas are included in the neuroblastic tumors group, which includes:

Myxoid liposarcoma[67][68][69][70][71][72][73][74][75][76]

Atypical lipomatous tumor/well differentiated liposarcoma and dedifferentiated liposarcoma are associated with:

Myxoid liposarcoma is associated with:

Pleomorphicliposarcoma is associated with:

Well-differentiated liposarcoma:

De-differentiated liposarcoma:

Atypical lipomatous tumor/well differentiated liposarcoma is positive for:

_
Leiomyoma[15][16][17][18][19][20][21][22][16][19][23]

Positive for:

Negative for:

_
Inflammatory myofibroblastic tumor(IMT)[15][16][17][18][19][20][21][22][16][19][23]

Unknown underlying etiology, may be due to inflammatory reaction to:

Mutations such as:

Positive for:

Negative for:

Also known as:

Fibroepithelial polyp/Acrochordon[77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96] Associated with: Positive for:

Negative for:

Associated with:

Also known as:

Epidemiology and Demographics

Age

Race

  • Leiomyoma usually affects African-American women.[97]
    • Incidence rates are approximately threefold greater in African-American women than in white women.

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Symptoms

  • The majority of patients with leiomyoma are usually asymptomatic.
  • Symptoms of uterine leiomyoma may include the following:[112]

Physical Examination

Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

References

  1. Bozini, Nilo; Baracat, Edmund C (2007). "The history of myomectomy at the Medical School of University of São Paulo". Clinics. 62 (3). doi:10.1590/S1807-59322007000300002. ISSN 1807-5932.
  2. Munro MG, Critchley HO, Fraser IS, FIGO Menstrual Disorders Working Group (2011). "The FIGO classification of causes of abnormal uterine bleeding in the reproductive years". Fertil Steril. 95 (7): 2204–8, 2208.e1–3. doi:10.1016/j.fertnstert.2011.03.079. PMID 21496802.
  3. Ip PP, Tse KY, Tam KF (March 2010). "Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy". Adv Anat Pathol. 17 (2): 91–112. doi:10.1097/PAP.0b013e3181cfb901. PMID 20179432.
  4. O'Connor DM, Norris HJ (February 1990). "Mitotically active leiomyomas of the uterus". Hum. Pathol. 21 (2): 223–7. PMID 2307449.
  5. Perrone T, Dehner LP (January 1988). "Prognostically favorable "mitotically active" smooth-muscle tumors of the uterus. A clinicopathologic study of ten cases". Am. J. Surg. Pathol. 12 (1): 1–8. PMID 3337336.
  6. Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW (August 2011). "Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features". J. Med. Genet. 48 (8): 505–12. doi:10.1136/jmg.2011.088807. PMID 21659347.
  7. Alam NA, Bevan S, Churchman M, Barclay E, Barker K, Jaeger EE, Nelson HM, Healy E, Pembroke AC, Friedmann PS, Dalziel K, Calonje E, Anderson J, August PJ, Davies MG, Felix R, Munro CS, Murdoch M, Rendall J, Kennedy S, Leigh IM, Kelsell DP, Tomlinson IP, Houlston RS (May 2001). "Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43". Am. J. Hum. Genet. 68 (5): 1264–9. doi:10.1086/320124. PMC 1226106. PMID 11283798.
  8. Halama N, Grauling-Halama SA, Daboul I (October 2005). "Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?". BMC Gastroenterol. 5: 33. doi:10.1186/1471-230X-5-33. PMC 1266363. PMID 16223449.
  9. Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomäki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA (April 2002). "Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer". Nat. Genet. 30 (4): 406–10. doi:10.1038/ng849. PMID 11865300.
  10. Hashimoto K, Azuma C, Kamiura S, Kimura T, Nobunaga T, Kanai T; et al. (1995). "Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene". Gynecol Obstet Invest. 40 (3): 204–8. doi:10.1159/000292336. PMID 8529956.
  11. Mashal RD, Fejzo ML, Friedman AJ, Mitchner N, Nowak RA, Rein MS; et al. (1994). "Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata". Genes Chromosomes Cancer. 11 (1): 1–6. PMID 7529041.
  12. Genetics of Uterine Leiomyomas. glowm (2016). http://www.glowm.com/section_view/heading/Genetics%20of%20Uterine%20Leiomyomas/item/363 Accessed on April 19, 2016
  13. Zhu X, Fei J, Zhang W, Zhou J (2015). "Uterine leiomyoma mimicking a gastrointestinal stromal tumor with chronic spontaneous hemorrhage: A case report". Oncol Lett. 9 (6): 2481–2484. doi:10.3892/ol.2015.3083. PMC 4473300. PMID 26137094.
  14. Medikare V, Kandukuri LR, Ananthapur V, Deenadayal M, Nallari P (July 2011). "The genetic bases of uterine fibroids; a review". J Reprod Infertil. 12 (3): 181–91. PMC 3719293. PMID 23926501.
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  20. 20.0 20.1 20.2 Kovach SJ, Fischer AC, Katzman PJ, Salloum RM, Ettinghausen SE, Madeb R; et al. (2006). "Inflammatory myofibroblastic tumors". J Surg Oncol. 94 (5): 385–91. doi:10.1002/jso.20516. PMID 16967468.
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  24. Rodriguez, Fausto J.; Folpe, Andrew L.; Giannini, Caterina; Perry, Arie (2012). "Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems". Acta Neuropathologica. 123 (3): 295–319. doi:10.1007/s00401-012-0954-z. ISSN 0001-6322.
  25. Choi, Kwangmin; Komurov, Kakajan; Fletcher, Jonathan S.; Jousma, Edwin; Cancelas, Jose A.; Wu, Jianqiang; Ratner, Nancy (2017). "An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system". Scientific Reports. 7 (1). doi:10.1038/srep43315. ISSN 2045-2322.
  26. Liao, Chung-Ping; Booker, Reid C.; Brosseau, Jean-Philippe; Chen, Zhiguo; Mo, Juan; Tchegnon, Edem; Wang, Yong; Clapp, D. Wade; Le, Lu Q. (2018). "Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis". Journal of Clinical Investigation. 128 (7): 2848–2861. doi:10.1172/JCI99424. ISSN 0021-9738.
  27. 27.0 27.1 Staser, K.; Yang, F.-C.; Clapp, D. W. (2010). "Mast cells and the neurofibroma microenvironment". Blood. 116 (2): 157–164. doi:10.1182/blood-2009-09-242875. ISSN 0006-4971.
  28. Muir, David; Neubauer, Debbie; Lim, Ingrid T.; Yachnis, Anthony T.; Wallace, Margaret R. (2001). "Tumorigenic Properties of Neurofibromin-Deficient Neurofibroma Schwann Cells". The American Journal of Pathology. 158 (2): 501–513. doi:10.1016/S0002-9440(10)63992-2. ISSN 0002-9440.
  29. Wilkinson, Lana M.; Manson, David; Smith, Charles R. (2004). "Best Cases from the AFIP". RadioGraphics. 24 (suppl_1): S237–S242. doi:10.1148/rg.24si035170. ISSN 0271-5333.
  30. Bernthal, Nicholas; Jones, Kevin; Monument, Michael; Liu, Ting; Viskochil, David; Randall, R. (2013). "Lost in Translation: Ambiguity in Nerve Sheath Tumor Nomenclature and Its Resultant Treatment Effect". Cancers. 5 (4): 519–528. doi:10.3390/cancers5020519. ISSN 2072-6694.
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