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'''Endometrial stromal tumours''' is like water in the sea - very very common.  Many hysterectomies are done for 'em... the most common are leiomyomata (AKA fibroids).
This article deals with '''[[uterus|uterine]] tumours''', with the exception of the tumours that arise from the [[endometrium]].  


==Leiomyomas==
Uterine tumours are like water in the sea - very very common. Many hysterectomies are done for them. The most common are leiomyomata ([[AKA]] fibroids).
===General===
*Often called "fibroids".
*Extremely common... 40% of women by age 40.
*Benign.
**Can be a cause of [[AUB]] (abnormal uterine bleeding).
**Large & multiple associated with infertility.


====Variants====
Pre-malignant [[endometrium]] and endometrial tumours are dealt with in the articles, ''[[endometrial hyperplasia]]'' and ''[[endometrial carcinoma]]''.
*Lipoleiomyoma - with adipose tissue.
*Hypercellular leiomyoma - hypercellularity assoc. with more mutations.<ref>[http://www3.interscience.wiley.com/journal/119360394/abstract http://www3.interscience.wiley.com/journal/119360394/abstract]</ref>
*Atypical leiomyoma (AKA ''symplastic leiomyoma'') - leiomyoma with nuclear atypia.
**Image: [http://commons.wikimedia.org/wiki/File:Atypical_leiomyoma_intermed_mag.jpg Atypical leiomyoma (wikimedia.org)].


===Gross===
=Common benign=
* Sharply circumscribed.
==Uterine leiomyoma==
* Gray-white.
*Often called ''fibroids''.
* Whorled appearance.
{{Main|Uterine leiomyoma}}


Look for...
=Uncommon benign=
* Haemorrhage.
==Uterine adenofibroma==
* Cystic degeneration.
*[[AKA]] ''[[adenofibroma]] of the uterus''.
* Necrosis.
===General===
*Uncommmon.
*Benign looking lesions can reoccur.<ref name=pmid2351327>{{Cite journal  | last1 = Seltzer | first1 = VL. | last2 = Levine | first2 = A. | last3 = Spiegel | first3 = G. | last4 = Rosenfeld | first4 = D. | last5 = Coffey | first5 = EL. | title = Adenofibroma of the uterus: multiple recurrences following wide local excision. | journal = Gynecol Oncol | volume = 37 | issue = 3 | pages = 427-31 | month = Jun | year = 1990 | doi =  | PMID = 2351327 }}</ref>
**It has been proposed that these lesions are in fact well-differentiated ''adenosarcomas''.<ref name=pmid18941402>{{Cite journal  | last1 = Gallardo | first1 = A. | last2 = Prat | first2 = J. | title = Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases challenging the existence of adenofibroma. | journal = Am J Surg Pathol | volume = 33 | issue = 2 | pages = 278-88 | month = Feb | year = 2009 | doi = 10.1097/PAS.0b013e318181a80d | PMID = 18941402 }}</ref>


===Microscopy===
===Microscopic===
Look for ...
Features:
* Necrosis (low power) -- suggestive of leiomyosarcoma.
*Moderately demarcated lesion with:
* Hypercellularity.
**Pale stroma and epithelioid/spindle cells.
**Simple cuboidal (or columnar) epithelium with eosinophilic cytoplasm.
*Low mitotic rate.
*Nuclear atypia minimal.


===IHC===
Note:
Work-up of suspicious leiomyomas:<ref>STC. 25 February 2009.</ref>
*Appearance similar to ''[[fibroadenoma]]''.
*CD10 (+ve).
*Ki-67 (-ve).
*SMA (+ve).
*Desmin (+ve).


==Adenomatoid tumour==
DDx:
General:
*Adenosarcoma.
*Grossly mimics leiomyoma.<ref name=pmid8543111>{{Cite journal  | last1 = Huang | first1 = CC. | last2 = Chang | first2 = DY. | last3 = Chen | first3 = CK. | last4 = Chou | first4 = YY. | last5 = Huang | first5 = SC. | title = Adenomatoid tumor of the female genital tract. | journal = Int J Gynaecol Obstet | volume = 50 | issue = 3 | pages = 275-80 | month = Sep | year = 1995 | doi =  | PMID = 8543111 }}
</ref>
*Benign tumour.


===Microscopy===
Images:
Features:
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496288/figure/F2/ Adenofibroma (nlm.nih.gov)].<ref>{{cite journal |authors=Chawla L, Vatsa R, Roy KK, Kumar S |title=Uterine Adenofibroma: An Unsual Cause of Nonpuerperal Uterine Inversion in Postmenopausal Female |journal=J Midlife Health |volume=8 |issue=2 |pages=95–97 |date=2017 |pmid=28706412 |pmc=5496288 |doi=10.4103/jmh.JMH_27_17 |url=}}</ref>
*Contains small tubulocystic spaces lined by cytologically normal mesothelium.


===IHC===
==Adenomatoid tumour==
*CK7 +ve. (???)<ref>LAE. 9 December 2009.</ref>
:Should '''not''' be confused with the [[bone tumour]] ''[[adamantinoma]]''.
*Calretin +ve.
{{Main|Adenomatoid tumour}}


==Carcinosarcoma==
=Uncertain malignant potential=
* AKA "malignant mixed muellerian tumour" (MMMT)
==Smooth muscle tumour of uncertain malignant potential==
* May have differentiation to:
*Abbreviated ''STUMP''.
** Muscle,
{{Main|Smooth muscle tumour of uncertain malignant potential}}
** Cartilage or
** Bone.
* Assoc. with previous radiation exposure.
* Metstasize as adenocarcinoma.


==Adenosarcoma==
=Malignant=
Features:<ref>PBoD P.1089</ref>
==Uterine carcinosarcoma==
*Benign glands with an abnormal shape.
* [[AKA]] ''malignant mixed muellerian tumour'', abbreviated ''MMMT''.
{{Main|Uterine carcinosarcoma}}


DDx:
==Adenosarcoma of the uterus==
*Benign polyp.
*[[AKA]] ''uterine adenosarcoma''.  
{{Main|Adenosarcoma of the uterus}}


Tx:
==Uterine leiomyosarcoma==
*TAH + BSO.
{{Main|Leiomyosarcoma}}
 
==Leiomyocarcoma==
===General===
===General===
*Poor prognosis.
*Poor prognosis.
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===Gross===
===Gross===
Features:
*"Fleshy" appearance.
*"Fleshy" appearance.
*Necrosis.
*Necrosis.
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===Microscopic===
===Microscopic===
#Cellular atypia - common.
Features:
#Necrosis.
*Smooth muscle differentiation - '''essential'''.
#*Should be patchy/multifocal.
**Fascicular architecture.
#*Zonal necrosis is suggestive of vascular cause.
***Whorled look at low power.
#Mitoses - '''key feature'''.
***Groups of spindle cells cut peripendicular to their long axis adjacent to groups of spindle cells cut in the plane of their long axis.
#*10/HPF.
**May rely on [[IHC]] - if poorly differentiated.
#*5/HPF - if epithelioid.
*Malignant histomorphologic features - two of three required - '''key features''':<ref name=pmid21865091>{{Cite journal  | last1 = Ip | first1 = PP. | last2 = Cheung | first2 = AN. | title = Pathology of uterine leiomyosarcomas and smooth muscle tumours of uncertain malignant potential. | journal = Best Pract Res Clin Obstet Gynaecol | volume = 25 | issue = 6 | pages = 691-704 | month = Dec | year = 2011 | doi = 10.1016/j.bpobgyn.2011.07.003 | PMID = 21865091 }}</ref>
#*2/HPF - if myxoid.
*#[[Nuclear pleomorphism]].
*#Coagulative tumour cell [[necrosis]]
*#*Should be patchy/multifocal.
*#*Zonal necrosis is suggestive of vascular cause and may be a degenerative change.
*#**Zonal necrosis may be seen in (benign) leiomyomas.
*#Mitoses.
*#*10 mitoses/10 HPF.
*#*5 mitoses/10 HPF - if epithelioid.
*#*2 mitoses/10 HPF - if [[myxoid]].
 
Note:
*The mitotic rate seems to be a relatively weak predictor; a modest rate may be malignant and a high rate benign.<ref name=pmid9388868>{{Cite journal  | last1 = Guo | first1 = L. | last2 = Liu | first2 = T. | last3 = Huang | first3 = H. | title = [Reappraisal of the pathological criteria for uterine leiomyosarcoma]. | journal = Zhonghua Bing Li Xue Za Zhi | volume = 25 | issue = 5 | pages = 266-9 | month = Oct | year = 1996 | doi =  | PMID = 9388868 }}</ref>
 
DDx:
*[[Endometrial stromal sarcoma]].
*[[Uterine carcinosarcoma]].
*[[Undifferentiated endometrial sarcoma]].
*[[Smooth muscle tumour of uncertain malignant potential]].
*[[Uterine leiomyoma]].


===IHC===
===IHC===
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**Caldesmon.
**Caldesmon.
**Smooth muscle myosin.
**Smooth muscle myosin.
*p16 +ve.<ref name=pmid18156978>{{Cite journal  | last1 = Gannon | first1 = BR. | last2 = Manduch | first2 = M. | last3 = Childs | first3 = TJ. | title = Differential Immunoreactivity of p16 in leiomyosarcomas and leiomyoma variants. | journal = Int J Gynecol Pathol | volume = 27 | issue = 1 | pages = 68-73 | month = Jan | year = 2008 | doi = 10.1097/pgp.0b013e3180ca954f | PMID = 18156978 }}</ref>
**Useful for differentiation from leiomyoma.


==Smooth muscle tumour of uncertain malignant potential (STUMP)==
=Endometrial stromal tumours=
*Like ''[[PUNLMP]]'' and ''[[ASCUS]]'' - a waffle category... when one isn't sure it is a ''leiomyoma'' vs. ''leiomyosarcoma''.
This grouping includes the gamut from benign to malignant.
*Clinical behaviour: usually benign.<ref name=pmid19417585>PMID 19417585.</ref>
*Can be subclassified into four groups - as per Stanford.
 
Features associated with recurance:<ref name=pmid19417585/>
*p16+, p53+, nuclear atypia.


===Management===
==Overview==
*Long-term follow-up.<ref name=pmid19417585/>
WHO classification:<ref name=Ref_WMSP426>{{Ref WMSP|426}}</ref>
 
==Endometrial stromal tumours==
===Overview===
WHO classification:<ref>WMSP P.426.</ref>
*Endometrial stromal nodule - not a tumour.
*Endometrial stromal nodule - not a tumour.
*Endometrial stromal sarcoma (ESS), low grade.
*Endometrial stromal sarcoma (ESS), low grade.
*Undifferentiated endometrial sarcoma
*Undifferentiated endometrial sarcoma (UES).


Notes:
Notes:
*Some believe in a "high grade ESS"... some don't.<ref name=pmid15491769>{{cite journal |author=Amant F, Vergote I, Moerman P |title=The classification of a uterine sarcoma as 'high-grade endometrial stromal sarcoma' should be abandoned |journal=Gynecol. Oncol. |volume=95 |issue=2 |pages=412–3; author reply 413 |year=2004 |month=November |pmid=15491769 |doi=10.1016/j.ygyno.2004.07.021 |url=http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WG6-4DF46J8-3&_user=1166899&_coverDate=11%2F01%2F2004&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1204975755&_rerunOrigin=google&_acct=C000051839&_version=1&_urlVersion=0&_userid=1166899&md5=d6ec1eee2941460a085d1dac6615b5a5}}</ref>
*Some believe in a "high grade ESS"... some don't.<ref name=pmid15491769>{{cite journal |author=Amant F, Vergote I, Moerman P |title=The classification of a uterine sarcoma as 'high-grade endometrial stromal sarcoma' should be abandoned |journal=Gynecol. Oncol. |volume=95 |issue=2 |pages=412–3; author reply 413 |year=2004 |month=November |pmid=15491769 |doi=10.1016/j.ygyno.2004.07.021 |url=http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WG6-4DF46J8-3&_user=1166899&_coverDate=11%2F01%2F2004&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1204975755&_rerunOrigin=google&_acct=C000051839&_version=1&_urlVersion=0&_userid=1166899&md5=d6ec1eee2941460a085d1dac6615b5a5}}</ref>


==Low grade endometrial stromal sarcoma==
==Endometrial stromal nodule==
*Abbreviated ''ESN''.
 
===General===
*Benign.
 
===Microscopic===
Features:
Features:
*Highly cellular Islands with a wavy irregular border.
*Well-circumscribed - '''key feature'''.
**Border has finger-like projections/tongue-like projections.
**The interface of the lesion may not have more than three finger-like irregularities/projections into the surround myometrium that are >= 3 mm.<ref name=pmid17347285>{{Cite journal  | last1 = Baker | first1 = P. | last2 = Oliva | first2 = E. | title = Endometrial stromal tumours of the uterus: a practical approach using conventional morphology and ancillary techniques. | journal = J Clin Pathol | volume = 60 | issue = 3 | pages = 235-43 | month = Mar | year = 2007 | doi = 10.1136/jcp.2005.031203 | PMID = 17347285 | url = http://jcp.bmj.com/content/60/3/235.full }}</ref>
**Benign uterine smooth muscle between islands of tumour cells.
***If it does... it is an [[ESS]].
*Epithelioid cells.
*No [[vascular invasion]].
*High NC ratio.
*Thin blood vessels within islands of cells.
**Tumour cells pallisade around the vessels.


Notes:
DDx:
*Vaguely resembles the stroma of proliferative endometrium.
*[[Endometrial stromal sarcoma]] (ESS), [[UES]] - myometrial invasion or [[vascular invasion]].
 
Images:
*[http://commons.wikimedia.org/wiki/File:EndometrialStromalNodule.JPG ESN (WC)].
 
==Endometrial stromal sarcoma==
*Abbreviated ESS.
*Previously known as ''low-grade endometrial stromal sarcoma''.
{{Main|Endometrial stromal sarcoma}}


==Undifferentiated endometrial sarcoma==
==Undifferentiated endometrial sarcoma==
*Abbreviated as ''UES''.
*Previously known as ''high-grade endometrial stromal sarcoma''.<ref name=pmid24146786>{{Cite journal  | last1 = Feng | first1 = W. | last2 = Malpica | first2 = A. | last3 = Skaland | first3 = I. | last4 = Gudlaugsson | first4 = E. | last5 = Robboy | first5 = SJ. | last6 = Dalen | first6 = I. | last7 = Hua | first7 = K. | last8 = Zhou | first8 = X. | last9 = Baak | first9 = JP. | title = Can proliferation biomarkers reliably predict recurrence in world health organization 2003 defined endometrial stromal sarcoma, low grade? | journal = PLoS One | volume = 8 | issue = 10 | pages = e75899 | month =  | year = 2013 | doi = 10.1371/journal.pone.0075899 | PMID = 24146786 }}</ref>
===General===
*Malignant.
*Rare.
*This can be thought of as ''[[pleomorphic undifferentiated sarcoma]]'' in the [[uterus]].
===Microscopic===
Features:
Features:
#Marked nuclear atypia.
#Marked nuclear atypia.
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DDx:
DDx:
*Leiomyosarcoma.
*[[Leiomyosarcoma]].
*Carcinosarcoma.
*[[Uterine carcinosarcoma|Carcinosarcoma]].
*Rhabdomyosarcoma.
*[[Rhabdomyosarcoma]].
*Melanoma.
*[[Melanoma]].
 
===IHC===
Features:<ref name=pmid21464730>{{Cite journal  | last1 = Abeler | first1 = VM. | last2 = Nenodovic | first2 = M. | title = Diagnostic immunohistochemistry in uterine sarcomas: a study of 397 cases. | journal = Int J Gynecol Pathol | volume = 30 | issue = 3 | pages = 236-43 | month = May | year = 2011 | doi = 10.1097/PGP.0b013e318200caff | PMID = 21464730 }}</ref>
*SMA ~50% +ve.
 
Typically negative:<ref name=pmid21464730/>
*Smooth muscle markers: desmin, h-caldesmon.
*Skeletal muscle markers: Myf4, actin.
*Melanoma: S100, HMB-45.
*GIST: CD117.
 
=Weird stuff=
==Trophoblastic tumours==
*[[Choriocarcinoma]].
*[[Epithelioid trophoblastic tumour]].
*[[Placental site trophoblastic tumour]].
 
==Uterine tumour resembling an ovarian sex cord stromal tumour==
*Abbreviated ''UTROSCT''.
{{Main|Uterine tumour resembling an ovarian sex cord stromal tumour}}
 
==Atypical polypoid adenomyoma of the uterus==
*Abbreviated ''APA''.
*[[AKA]] ''atypical polypoid adenomyoma''.
{{Main|Atypical polypoid adenomyoma of the uterus}}
 
=See also=
*[[Gynecologic pathology]].
*[[Endometrial carcinoma]].
*[[Endometrial hyperplasia]].
*[[Endometrial polyp]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}




[[Category:Gynecologic pathology]]
[[Category:Gynecologic pathology]]
Michael
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