Difference between revisions of "Endometrial carcinoma"

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Endometrial carcinoma (view source)

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[[Image:Endometrial_adenocarcinoma_gross.jpg|thumb|300px|right|Gross image of endometrial adenocarcinoma.]]
'''Endometrial carcinoma''', also '''endometrial adenocarcinoma''', is a common gynecologic malingnancy<ref name=pmid19072487>{{cite journal |author=Fowler W, Mutch D |title=Management of endometrial cancer |journal=Womens Health (Lond Engl) |volume=4 |issue=5 |pages=479–89 |year=2008 |month=September |pmid=19072487 |doi=10.2217/17455057.4.5.479 |url=}}</ref> that often arises from [[endometrial hyperplasia]].  The incidence of endometrial carcinoma is increasing, as the proportion of [[obese]] individuals is increasing.
'''Endometrial carcinoma''', also '''endometrial adenocarcinoma''', is a common gynecologic malingnancy<ref name=pmid19072487>{{cite journal |author=Fowler W, Mutch D |title=Management of endometrial cancer |journal=Womens Health (Lond Engl) |volume=4 |issue=5 |pages=479–89 |year=2008 |month=September |pmid=19072487 |doi=10.2217/17455057.4.5.479 |url=}}</ref> that often arises from [[endometrial hyperplasia]].  The incidence of endometrial carcinoma is increasing, as the proportion of [[obese]] individuals is increasing.


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*Diabetes.
*Diabetes.
*Nulliparity.
*Nulliparity.
*Unopposed estrogen (polycystic ovarian syndrome (PCOS), anovulation, hormone replacement therapy (HRT)).
*Unopposed estrogen ([[polycystic ovarian syndrome]] (PCOS), anovulation, hormone replacement therapy (HRT)).
*Tamoxifen use.
*[[Tamoxifen]] use.
**Used for breast cancer; the risk is quite small<ref name=pmid19505894>{{Cite journal  | last1 = Brown | first1 = K. | title = Is tamoxifen a genotoxic carcinogen in women? | journal = Mutagenesis | volume = 24 | issue = 5 | pages = 391-404 | month = Sep | year = 2009 | doi = 10.1093/mutage/gep022 | PMID = 19505894 }}</ref> or possibly negligent.<ref name=pmid19827879>{{Cite journal  | last1 = Ashraf | first1 = M. | last2 = Biswas | first2 = J. | last3 = Majumdar | first3 = S. | last4 = Nayak | first4 = S. | last5 = Alam | first5 = N. | last6 = Mukherjee | first6 = KK. | last7 = Gupta | first7 = S. | title = Tamoxifen use in Indian women--adverse effects revisited. | journal = Asian Pac J Cancer Prev | volume = 10 | issue = 4 | pages = 609-12 | month =  | year =  | doi =  | PMID = 19827879 }}</ref>   
**Used for breast cancer; the risk is quite small<ref name=pmid19505894>{{Cite journal  | last1 = Brown | first1 = K. | title = Is tamoxifen a genotoxic carcinogen in women? | journal = Mutagenesis | volume = 24 | issue = 5 | pages = 391-404 | month = Sep | year = 2009 | doi = 10.1093/mutage/gep022 | PMID = 19505894 }}</ref> or possibly negligent.<ref name=pmid19827879>{{Cite journal  | last1 = Ashraf | first1 = M. | last2 = Biswas | first2 = J. | last3 = Majumdar | first3 = S. | last4 = Nayak | first4 = S. | last5 = Alam | first5 = N. | last6 = Mukherjee | first6 = KK. | last7 = Gupta | first7 = S. | title = Tamoxifen use in Indian women--adverse effects revisited. | journal = Asian Pac J Cancer Prev | volume = 10 | issue = 4 | pages = 609-12 | month =  | year =  | doi =  | PMID = 19827879 }}</ref>   


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|-
|-
|Genetic <br>abnormalities
|Genetic <br>abnormalities
| microsatellite instability, PTEN & KRAS mutations
| microsatellite instability, PTEN & [[KRAS mutation]]s
| p53 mutations
| p53 mutations
|-
|-
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*Officially only sanctioned for ''[[endometrioid endometrial carcinoma]]''.
*Officially only sanctioned for ''[[endometrioid endometrial carcinoma]]''.
**May be used for [[mucinous endometrial carcinoma]].
**May be used for [[mucinous endometrial carcinoma]].
**Papillary serous carcinoma and clear cell carcinomas are ''not'' assigned a grade ''or'' grade 3 by definition.
**Papillary serous carcinoma and clear cell carcinomas are ''not'' assigned a grade; however, can be thought of as grade 3 by definition.


==Staging==
==Staging==
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==Endometrioid endometrial carcinoma==
==Endometrioid endometrial carcinoma==
*[[AKA]] ''endometrioid endometrial adenocarcinoma''.
*[[AKA]] ''endometrioid endometrial adenocarcinoma''.
 
{{Main|Endometrioid endometrial carcinoma}}
===General===
*Good prognosis - usually.
*Women in 40s & 50s.
*Associated with estrogen excess.
**Typical patient is [[obese]].
 
===Gross===
*Thickened endometrium.
 
===Microscopic===
Features:
*Atypical (ovoid) glands with - one of the following four:<ref name=Ref_GP239>{{Ref GP|239}}</ref><ref name=pmid7074572>{{Cite journal  | last1 = Kurman | first1 = RJ. | last2 = Norris | first2 = HJ. | title = Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. | journal = Cancer | volume = 49 | issue = 12 | pages = 2547-59 | month = Jun | year = 1982 | doi =  | PMID = 7074572 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf]. Accessed on: 12 January 2012.</ref>
*#[[Desmoplastic stromal response]].
*#Confluent cribriform growth. †
*#Extensive papillary growth. †
*#Severe cytologic atypia. †
*Squamous metaplasia - very common.
**Look for ''squamous morules'':
***Ball of cells with an intensely eosinophilic cytoplasm - '''key feature'''.
***Central nucleus.
***Intercellular bridges - may be hard to find.
***+/-Dyskeratotic cells.
 
Notes:
* † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.<ref name=pmid7074572/>
*Dyskeratosis = abnormal keratinization;<ref>URL: [http://dictionary.reference.com/browse/dyskeratosis http://dictionary.reference.com/browse/dyskeratosis]. Accessed on: 5 September 2011.</ref> classically have intensely eosinophilic cytoplasm +/- nuclear fragmentation ([http://dictionary.reference.com/browse/karyolysis?db=medical&q=karyolysis karyorrhexis]) - see: [http://www.drmihm.com/pictures/Figure%203.jpg several dyskeratotic cells].
*[[Squamous metaplasia]] != neoplastic -- it may occur due to hormones.<ref name=pmid7748076>{{Cite journal  | last1 = Miranda | first1 = MC. | last2 = Mazur | first2 = MT. | title = Endometrial squamous metaplasia. An unusual response to progestin therapy of hyperplasia. | journal = Arch Pathol Lab Med | volume = 119 | issue = 5 | pages = 458-60 | month = May | year = 1995 | doi =  | PMID = 7748076 }}</ref>
*Squamous morules in endometrioid endometrial carcinoma - not associated with [[HPV]] infection.<ref name=pmid15333650>{{Cite journal  | last1 = Chinen | first1 = K. | last2 = Kamiyama | first2 = K. | last3 = Kinjo | first3 = T. | last4 = Arasaki | first4 = A. | last5 = Ihama | first5 = Y. | last6 = Hamada | first6 = T. | last7 = Iwamasa | first7 = T. | title = Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus. | journal = J Clin Pathol | volume = 57 | issue = 9 | pages = 918-26 | month = Sep | year = 2004 | doi = 10.1136/jcp.2004.017996 | PMID = 15333650 }}</ref>
 
 
DDx:
*[[Complex endometrial hyperplasia with atypia]].
*[[Complex endometrial hyperplasia]].
*[[Microglandular hyperplasia]] of the cervix.
*[[Endocervical adenocarcinoma]].
*[[Serous carcinoma of the endometrium]] - esp. if high-grade nuclear features are present diffusely.
*[[Clear cell carcinoma of the endometrium]] - esp. when clear cells present.
 
Image:
*[http://www.diagnosticpathology.org/content/2/1/40/figure/F1?highres=y Squamous morule with dyskeratotic cell (diagnosticpathology.org)].
 
===IHC===
*Vimentin +ve.
*ER +ve.
*PR +ve.
 
Others:
*p16 -ve -- positive in [[serous endometrial carcinoma]]<ref name=pmid17581420/> and [[endocervical adenocarcinoma]].
*CEA -ve.
 
===Sign out===
<pre>
ENDOMETRIUM, BIOPSY:
- ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA, FIGO GRADE I/III.
</pre>
 
====Micro====
The sections show endometrium with complex, fused glands with scant intervening stroma over a region measuring greater than 2.1 millimetres. Focally, a desmoplastic stroma is also identified. No nuclear atypia is appreciated.
 
====Endocervical versus endometrial - biopsy====
The foamy histiocytes in the stroma and lack of desmoplasia slightly favour an endometrial origin; however, the lesion would be best classified with an excisional specimen and in conjunction with the clinical impression.


==Mucinous carcinoma of the endometrium==
==Mucinous carcinoma of the endometrium==
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DDx:
DDx:
*[[Endometrioid endometrial carcinoma]].
*[[Endometrioid endometrial carcinoma]].
*Metastatic mucinous tumour.
*Metastatic [[mucinous carcinoma]].


===IHC===
===IHC===
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*AKA ''uterine serous carcinoma''.
*AKA ''uterine serous carcinoma''.
*AKA ''uterine papillary serous carcinoma''.
*AKA ''uterine papillary serous carcinoma''.
 
{{Main|Serous carcinoma of the endometrium}}
===General===
*Arising in the setting of atrophy.
*Usually post-menopausal.
*Precursor lesion: ''endometrial intraepithelial carcinoma''.<ref name=pmid22249577>{{Cite journal  | last1 = Roelofsen | first1 = T. | last2 = van Kempen | first2 = LC. | last3 = van der Laak | first3 = JA. | last4 = van Ham | first4 = MA. | last5 = Bulten | first5 = J. | last6 = Massuger | first6 = LF. | title = Concurrent endometrial intraepithelial carcinoma (EIC) and serous ovarian cancer: can EIC be seen as the precursor lesion? | journal = Int J Gynecol Cancer | volume = 22 | issue = 3 | pages = 457-64 | month = Mar | year = 2012 | doi = 10.1097/IGC.0b013e3182434a81 | PMID = 22249577 }}</ref>
*Aggressive behaviour - high probability of disseminated disease.
 
===Gross===
*Thin endometrium.
*+/-Polypoid mass.
 
===Microscopic===
Features - serous:
*Architecture - classically papillary.
**May be glomeruloid, tubulocystic, solid (uncommon).
*Cytology:
**Columnar or cuboidal cells.
**#Moderate to marked nuclear pleomorphism - variation of size, shape and staining.
**#*Large nuclear size variation between cells often esp. prominent.
**#Singular prominent, classically red, [[red nucleolus|nucleolus]].
*+/-[[Psammoma bodies]].
 
DDx:
*High-grade [[endometrioid endometrial carcinoma]] - uncommon, typically younger age.
*[[Clear cell carcinoma of the endometrium]] - usually have less nuclear pleomorphism and less mitoses.
*[[Arias-Stella reaction]].
 
Images:
*[http://commons.wikimedia.org/wiki/File:Uterine_papillary_serous_carcinoma_low_mag.jpg Uterine serous carcinoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Uterine_serous_carcinoma_high_mag.jpg Uterine serous carcinoma - high mag. (WC)].
 
===IHC===
*p16 +ve<ref name=pmid17581420>{{Cite journal  | last1 = Chiesa-Vottero | first1 = AG. | last2 = Malpica | first2 = A. | last3 = Deavers | first3 = MT. | last4 = Broaddus | first4 = R. | last5 = Nuovo | first5 = GJ. | last6 = Silva | first6 = EG. | title = Immunohistochemical overexpression of p16 and p53 in uterine serous carcinoma and ovarian high-grade serous carcinoma. | journal = Int J Gynecol Pathol | volume = 26 | issue = 3 | pages = 328-33 | month = Jul | year = 2007 | doi = 10.1097/01.pgp.0000235065.31301.3e | PMID = 17581420 }}</ref> - should be strong.
*p53 +ve<ref name=pmid19623034>{{Cite journal  | last1 = Yemelyanova | first1 = A. | last2 = Ji | first2 = H. | last3 = Shih | first3 = IeM. | last4 = Wang | first4 = TL. | last5 = Wu | first5 = LS. | last6 = Ronnett | first6 = BM. | title = Utility of p16 expression for distinction of uterine serous carcinomas from endometrial endometrioid and endocervical adenocarcinomas: immunohistochemical analysis of 201 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 10 | pages = 1504-14 | month = Oct | year = 2009 | doi = 10.1097/PAS.0b013e3181ac35f5 | PMID = 19623034 }}</ref> diffuse & strong > 50% ''or'' 75% of the tumour - depending on the paper one reads.
**Subset is p53 -ve.
*Ki-67 "high" - no cut-point defined.
*ER often -ve.<ref name=pmid10786803>{{Cite journal  | last1 = Kounelis | first1 = S. | last2 = Kapranos | first2 = N. | last3 = Kouri | first3 = E. | last4 = Coppola | first4 = D. | last5 = Papadaki | first5 = H. | last6 = Jones | first6 = MW. | title = Immunohistochemical profile of endometrial adenocarcinoma: a study of 61 cases and review of the literature. | journal = Mod Pathol | volume = 13 | issue = 4 | pages = 379-88 | month = Apr | year = 2000 | doi = 10.1038/modpathol.3880062 | PMID = 10786803 }}</ref>
*PR often -ve.<ref name=pmid10786803/>
 
High-grade endometrioid carcinoma versus serous carcinoma:<ref name=pmid15577675>{{Cite journal  | last1 = Darvishian | first1 = F. | last2 = Hummer | first2 = AJ. | last3 = Thaler | first3 = HT. | last4 = Bhargava | first4 = R. | last5 = Linkov | first5 = I. | last6 = Asher | first6 = M. | last7 = Soslow | first7 = RA. | title = Serous endometrial cancers that mimic endometrioid adenocarcinomas: a clinicopathologic and immunohistochemical study of a group of problematic cases. | journal = Am J Surg Pathol | volume = 28 | issue = 12 | pages = 1568-78 | month = Dec | year = 2004 | doi =  | PMID = 15577675 }}</ref>
*p53 -ve, PR +ve, PTEN loss -- suggest endometrioid.
*p16 and PTEN superior to ER, PR, and p53.<ref name=pmid20567148>{{Cite journal  | last1 = Alkushi | first1 = A. | last2 = Köbel | first2 = M. | last3 = Kalloger | first3 = SE. | last4 = Gilks | first4 = CB. | title = High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes. | journal = Int J Gynecol Pathol | volume = 29 | issue = 4 | pages = 343-50 | month = Jul | year = 2010 | doi = 10.1097/PGP.0b013e3181cd6552 | PMID = 20567148 }}</ref>
 
Notes:
*p16 +ve in tubal metaplasia.<ref name=pmid17429140>{{Cite journal  | last1 = Horree | first1 = N. | last2 = Heintz | first2 = AP. | last3 = Sie-Go | first3 = DM. | last4 = van Diest | first4 = PJ. | title = p16 is consistently expressed in endometrial tubal metaplasia. | journal = Cell Oncol | volume = 29 | issue = 1 | pages = 37-45 | month =  | year = 2007 | doi =  | PMID = 17429140 }}</ref>
*WT1 usu. -ve -- useful to differentiate from [[ovarian serous carcinoma]].<ref name=pmid21993272>{{Cite journal  | last1 = Bárcena | first1 = C. | last2 = Oliva | first2 = E. | title = WT1 expression in the female genital tract. | journal = Adv Anat Pathol | volume = 18 | issue = 6 | pages = 454-65 | month = Nov | year = 2011 | doi = 10.1097/PAP.0b013e318234aaed | PMID = 21993272 }}</ref>


==Clear cell carcinoma of the endometrium==
==Clear cell carcinoma of the endometrium==
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*Clear cells - with moderate nuclear pleomorphism - '''key feature'''.
*Clear cells - with moderate nuclear pleomorphism - '''key feature'''.
**Classically clear cells... but not always.
**Classically clear cells... but not always.
*Hobnail pattern -- apical cytoplasm > cytoplasm on basement membrane.
*[[Hobnail pattern]] -- apical cytoplasm > cytoplasm on basement membrane.
*Usually tubular/cystic, may be solid or papillary.
*Usually tubular/cystic, may be solid or papillary.
**Papillae may be pseudopapillae -- with edema instead of vessels.
**Papillae may be pseudopapillae -- with edema instead of vessels.
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*[[PEComa]].
*[[PEComa]].
*Epithelioid [[uterine leiomyosarcoma|leiomyosarcoma]].
*Epithelioid [[uterine leiomyosarcoma|leiomyosarcoma]].
====Images====
www:
*[http://www.webpathology.com/image.asp?n=29&Case=569 Clear cell carcinoma of the endometrium - classical - high mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=569&n=27 Clear cell carcinoma of the endometrium - high mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=28&Case=569 Clear cell carcinoma of the endometrium - low mag. (webpathology.com)].


===Stains===
===Stains===
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*CAM5.2 +ve.
*CAM5.2 +ve.
*CK34betaE12 +ve.
*CK34betaE12 +ve.
*WT1 -ve.<ref name=pmid15084838>{{Cite journal  | last1 = Acs | first1 = G. | last2 = Pasha | first2 = T. | last3 = Zhang | first3 = PJ. | title = WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium. | journal = Int J Gynecol Pathol | volume = 23 | issue = 2 | pages = 110-8 | month = Apr | year = 2004 | doi =  | PMID = 15084838 }}</ref>
**Often +ve/-ve in serous carcinoma of the endometrium.
*CK7 +ve.<ref name=pmid11444201>{{Cite journal  | last1 = Vang | first1 = R. | last2 = Whitaker | first2 = BP. | last3 = Farhood | first3 = AI. | last4 = Silva | first4 = EG. | last5 = Ro | first5 = JY. | last6 = Deavers | first6 = MT. | title = Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract. | journal = Int J Gynecol Pathol | volume = 20 | issue = 3 | pages = 252-9 | month = Jul | year = 2001 | doi =  | PMID = 11444201 }}</ref>
*CK20 -ve.<ref name=pmid11444201/>
*Vimentin +ve.<ref name=pmid11444201/>
*Napsin A +ve.<ref name=pmid25971546>{{Cite journal  | last1 = Iwamoto | first1 = M. | last2 = Nakatani | first2 = Y. | last3 = Fugo | first3 = K. | last4 = Kishimoto | first4 = T. | last5 = Kiyokawa | first5 = T. | title = Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium. | journal = Hum Pathol | volume = 46 | issue = 7 | pages = 957-62 | month = Jul | year = 2015 | doi = 10.1016/j.humpath.2015.03.008 | PMID = 25971546 }}</ref>


Note:
Note:
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=References=
=References=
{{reflist|2}}
{{reflist|2}}
=External links=
*[http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancer-staging Endometrial cancer staging (cancer.org)].


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