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'''Endometrial carcinoma''' 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. | [[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. | |||
An introduction to the endometrium is in the article ''[[endometrium]]''. | An introduction to the endometrium is in the article ''[[endometrium]]''. | ||
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=Clinical= | =Clinical= | ||
===Risk factors=== | ===Risk factors=== | ||
Risk factors for endometrial carcinoma - mnemonic ''COLD NUT'':<ref> | Risk factors for endometrial carcinoma - mnemonic ''COLD NUT'':<ref name=Ref_TN2007_GY40>{{Ref TN2007|GY40}}</ref> | ||
*Cancer Hx (ovarian, breast, colon). | *Cancer Hx (ovarian, breast, colon). | ||
*Obesity. | *[[Obesity]]. | ||
*Late menopause. | *Late menopause. | ||
*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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**Associated with ''endometrioid endometrial carcinoma''. | **Associated with ''endometrioid endometrial carcinoma''. | ||
*[[Lynch syndrome]] (mutation of a mismatch repair gene - there are several<ref>{{OMIM|120435}}</ref>). | *[[Lynch syndrome]] (mutation of a mismatch repair gene - there are several<ref>{{OMIM|120435}}</ref>). | ||
**Associated with ''non-endometrioid endometrial carcinoma''. | **Associated with ''non-endometrioid endometrial carcinoma''.<ref name=pmid20396392>{{cite journal |author=Okuda T, Sekizawa A, Purwosunu Y, ''et al.'' |title=Genetics of endometrial cancers |journal=Obstet Gynecol Int |volume=2010 |issue= |pages=984013 |year=2010 |pmid=20396392 |pmc=2852605 |doi=10.1155/2010/984013 |url=}}</ref> | ||
**Autosomal dominant. | **Autosomal dominant. | ||
===Management=== | ===Management=== | ||
*Hysterectomy is the standard treatment for endometrial carcinoma. | |||
**In low-grade carcinomas (i.e. low grade endometrioid type), if the woman isn't done with their childbearing, the treatment may be hormones and surveillance biopsies.<ref name=pmid19758691>{{cite journal |author=Zivanovic O, Carter J, Kauff ND, Barakat RR |title=A review of the challenges faced in the conservative treatment of young women with endometrial carcinoma and risk of ovarian cancer |journal=Gynecol. Oncol. |volume=115 |issue=3 |pages=504–9 |year=2009 |month=December |pmid=19758691 |doi=10.1016/j.ygyno.2009.08.011 |url=}}</ref> | **In low-grade carcinomas (i.e. low grade endometrioid type), if the woman isn't done with their childbearing, the treatment may be hormones and surveillance biopsies.<ref name=pmid19758691>{{cite journal |author=Zivanovic O, Carter J, Kauff ND, Barakat RR |title=A review of the challenges faced in the conservative treatment of young women with endometrial carcinoma and risk of ovarian cancer |journal=Gynecol. Oncol. |volume=115 |issue=3 |pages=504–9 |year=2009 |month=December |pmid=19758691 |doi=10.1016/j.ygyno.2009.08.011 |url=}}</ref> | ||
**Endometrial carcinomas with involvement of the endocervical canal are treated with a ''radical hysterectomy''.<ref name=pmid20871657>{{Cite journal | last1 = Ware | first1 = RA. | last2 = van Nagell | first2 = JR. | title = Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications. | journal = Obstet Gynecol Int | volume = 2010 | issue = | pages = | month = | year = 2010 | doi = 10.1155/2010/587610 | PMID = 20871657 }}</ref> | |||
Details: | Details: | ||
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==Subtypes - overview== | ==Subtypes - overview== | ||
They are commonly grouped based on clinicopathologic features:<ref name=pmid21309259>{{Cite journal | last1 = Lim | first1 = D. | last2 = Oliva | first2 = E. | title = Nonendometrioid endometrial carcinomas. | journal = Semin Diagn Pathol | volume = 27 | issue = 4 | pages = 241-60 | month = Nov | year = 2010 | doi = | PMID = 21309259 }}</ref> | They are commonly grouped based on clinicopathologic features:<ref name=pmid21309259>{{Cite journal | last1 = Lim | first1 = D. | last2 = Oliva | first2 = E. | title = Nonendometrioid endometrial carcinomas. | journal = Semin Diagn Pathol | volume = 27 | issue = 4 | pages = 241-60 | month = Nov | year = 2010 | doi = | PMID = 21309259 }}</ref><ref name=Ref_GP241>{{Ref GP|241}}</ref> | ||
{| class="wikitable sortable" | |||
!Feature | |||
!Type I | |||
!Type II | |||
|- | |||
|Histologic types | |||
|[[endometrioid endometrial carcinoma]], [[mucinous endometrial carcinoma]] | |||
|[[serous carcinoma of the endometrium]], [[clear cell carcinoma of the endometrium]], undifferentiated carcinoma | |||
|- | |||
|Clinical <br>characteristics | |||
| premenopausal, estrogen excess, obesity | |||
| postmenopausal, no estrogen excess, atrophic endometrium | |||
|- | |||
|Prognosis | |||
| good | |||
| poor | |||
|- | |||
|Genetic <br>abnormalities | |||
| microsatellite instability, PTEN & [[KRAS mutation]]s | |||
| p53 mutations | |||
|- | |||
|Precursor lesion(s) | |||
| [[endometrial hyperplasia]] | |||
| possibly ''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> † | |||
|} | |||
Notes: | |||
* † ''Endometrial intraepithelial carcinoma'' should '''not''' be confused with ''[[endometrial intraepithelial neoplasia]]'' (EIN). | |||
==Grading (FIGO)== | ==Grading (FIGO)== | ||
Based on gland formation & adjusted by nuclear pleomorphism:<ref>{{Ref PBoD|1087-8}}</ref><ref>URL: [http://www.pathologyoutlines.com/uterus.html#endometrialcarc http://www.pathologyoutlines.com/uterus.html#endometrialcarc].</ref><ref>URL: [http://www.emedicine.com/med/topic2832.htm http://www.emedicine.com/med/topic2832.htm].</ref><ref name=pmid12496701>{{cite journal |author=Ayhan A, Taskiran C, Yuce K, Kucukali T |title=The prognostic value of nuclear grading and the revised FIGO grading of endometrial adenocarcinoma |journal=Int. J. Gynecol. Pathol. |volume=22 |issue=1 |pages=71–4 |year=2003 |month=January |pmid=12496701 |doi= |url=}}</ref> | |||
*Grade 1: <5% solid component. | |||
*Grade 2: 5-50% solid component. | |||
*Grade 3: >50% solid component. | |||
Modifiers/adjustment: | Modifiers/adjustment: | ||
*High grade nuclei upgrades cancer by one; high grade nuclei = increased size, irregular large nucleoli, irregular chromatin pattern (clumped, coarse).<ref>{{Ref DCHH|240}}</ref> | *High grade nuclei upgrades cancer by one; high grade nuclei = increased size, irregular large nucleoli, irregular chromatin pattern (clumped, coarse).<ref>{{Ref DCHH|240}}</ref> | ||
* | |||
Notes: | |||
*Officially only sanctioned for ''[[endometrioid endometrial carcinoma]]''. | |||
**May be used for [[mucinous endometrial carcinoma]]. | |||
**Papillary serous carcinoma and clear cell carcinomas are ''not'' assigned a grade; however, can be thought of as grade 3 by definition. | |||
==Staging== | ==Staging== | ||
*Stage I: confined to uterine body. | *Stage I: confined to uterine body. | ||
**Ia | **Ia = less than half of myometrium. | ||
**Ib = greater than half of myometrium. | |||
** | |||
*Stage II: uterus + cervix. | *Stage II: uterus + cervix. | ||
** | **II = cervical stroma involved. | ||
** | ***Cervical epithelium involvement does not change stage. | ||
*Stage III: outside uterus - but inside pelvis. | *Stage III: outside uterus - but inside pelvis. | ||
**IIIa | **IIIa - involves serosa and/or adnexa (direct extension or metastasis) | ||
**IIIb | **IIIb - vaginal involvement (direct extension or metastasis) or parametrial involvement | ||
*Stage IV: outside true pelvis or in mucosa of bladder or GI tract. | *Stage IV: outside true pelvis or in mucosa of bladder or GI tract. | ||
References: <ref>{{Ref PBoD|1088}}</ref><ref>[http://www.emedicine.com/med/topic2832.htm http://www.emedicine.com/med/topic2832.htm]</ref><ref>[http://www.cancerfacts.com/GeneralContent/Uterine/Gen_Diagnosis.asp?CB=11 Staging with groovy graphics (cancerfacts.com)]</ref><ref>URL: [http://en.wikibooks.org/wiki/Radiation_Oncology/Endometrium/Staging http://en.wikibooks.org/wiki/Radiation_Oncology/Endometrium/Staging]. Accessed on: 2 May 2012.</ref>. | |||
=Specific types= | =Specific types= | ||
==Endometrioid endometrial carcinoma== | ==Endometrioid endometrial carcinoma== | ||
*[[AKA]] ''endometrioid endometrial adenocarcinoma''. | *[[AKA]] ''endometrioid endometrial adenocarcinoma''. | ||
{{Main|Endometrioid endometrial carcinoma}} | |||
==Mucinous carcinoma of the endometrium== | |||
*[[AKA]] ''endometrial mucinous carcinoma''. | |||
===General=== | ===General=== | ||
* | *Type I endometrial carcinoma.{{fact}} | ||
* | *Good prognosis. | ||
===Microscopic=== | ===Microscopic=== | ||
Features | Features:<ref name=Ref_GP241>{{Ref GP|241}}</ref> | ||
*Cells with intracytoplasmic mucin (>50% of tumour). | |||
* | *Usu. mild-to-moderate nuclear atypia. | ||
* | |||
DDx: | DDx: | ||
*[[ | *[[Endometrioid endometrial carcinoma]]. | ||
*[[ | *Metastatic [[mucinous carcinoma]]. | ||
===IHC=== | |||
Features:<ref name=pmid17649817>{{Cite journal | last1 = Shabani | first1 = N. | last2 = Mylonas | first2 = I. | last3 = Jeschke | first3 = U. | last4 = Thaqi | first4 = A. | last5 = Kuhn | first5 = C. | last6 = Puchner | first6 = T. | last7 = Friese | first7 = K. | title = Expression of estrogen receptors alpha and beta, and progesterone receptors A and B in human mucinous carcinoma of the endometrium. | journal = Anticancer Res | volume = 27 | issue = 4A | pages = 2027-33 | month = | year = | doi = | PMID = 17649817 }}</ref> | |||
*ER-alpha +ve. | |||
*PR-alpha +ve. | |||
*PR-beta +ve. | |||
==Serous carcinoma of the endometrium== | ==Serous carcinoma of the endometrium== | ||
*AKA ''serous endometrial carcinoma''. | *[[AKA]] ''serous endometrial carcinoma''. | ||
*AKA ''serous carcinoma of the uterus''. | |||
*AKA ''uterine serous carcinoma''. | |||
*AKA ''uterine papillary serous carcinoma''. | |||
{{Main|Serous carcinoma of the endometrium}} | |||
==Clear cell carcinoma of the endometrium== | |||
*[[AKA]] ''clear cell endometrial carcinoma''. | |||
*[[AKA]] ''endometrial clear cell carcinoma''. | |||
===General=== | ===General=== | ||
* | *Ten-year survival ~ 40%.<ref name=pmid8859187>{{Cite journal | last1 = Abeler | first1 = VM. | last2 = Vergote | first2 = IB. | last3 = Kjørstad | first3 = KE. | last4 = Tropé | first4 = CG. | title = Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern. | journal = Cancer | volume = 78 | issue = 8 | pages = 1740-7 | month = Oct | year = 1996 | doi = | PMID = 8859187 }}</ref> | ||
* | *Uncommon <=5 % of endometrial carcinomas.<ref name=pmid22885379>{{Cite journal | last1 = Offman | first1 = SL. | last2 = Longacre | first2 = TA. | title = Clear cell carcinoma of the female genital tract (not everything is as clear as it seems). | journal = Adv Anat Pathol | volume = 19 | issue = 5 | pages = 296-312 | month = Sep | year = 2012 | doi = 10.1097/PAP.0b013e31826663b1 | PMID = 22885379 }}</ref> | ||
*Type II endometrial cancer - estrogen-independent, usually post-menopausal women. | |||
===Microscopic=== | ===Microscopic=== | ||
Features | Features:<ref name=pmid22885379/> | ||
* | *Clear cells - with moderate nuclear pleomorphism - '''key feature'''. | ||
**Classically clear cells... but not always. | |||
* | *[[Hobnail pattern]] -- apical cytoplasm > cytoplasm on basement membrane. | ||
*Usually tubular/cystic, may be solid or papillary. | |||
* | **Papillae may be pseudopapillae -- with edema instead of vessels. | ||
* | |||
** | Notes: | ||
*May have [[psammoma bodies]] - esp. in papillary area; may lead to confusion with serous carcinoma. | |||
*[[ | |||
DDx: | DDx: | ||
*High | *[[Serous endometrial carcinoma]] - usually has more nuclear pleomorphism, esp. cell size variation. | ||
*[[Clear cell carcinoma of the endometrium]] - | *High grade [[endometrioid endometrial carcinoma]] - have non-clear areas.<ref name=pmid22885379/> | ||
*[[Arias-Stella reaction]] - esp. in the context of [[pregnancy]]. | |||
*Papillary cystadenoma - benign; bland nuclei.<ref name=pmid22885379/> | |||
DDx weird stuff:<ref name=pmid22885379/> | |||
*[[PEComa]]. | |||
*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=== | |||
*[[PAS-D stain]] +ve ~ glycogen.<ref name=pmid22885379/> | |||
===IHC=== | ===IHC=== | ||
*p53 | Features:<ref name=Ref_GP250>{{Ref GP|250}}</ref> | ||
* | *p53 -ve usu. - unlike [[uterine serous carcinoma]]. | ||
*ER -ve. | |||
*PR -ve. | |||
== | Others:<ref name=pmid22885379/> | ||
* | *CAM5.2 +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: | |||
* | *HNF1beta - not useful<ref name=pmid22495362>{{Cite journal | last1 = Fadare | first1 = O. | last2 = Liang | first2 = SX. | title = Diagnostic Utility of Hepatocyte Nuclear Factor 1-Beta Immunoreactivity in Endometrial Carcinomas: Lack of Specificity For Endometrial Clear Cell Carcinoma. | journal = Appl Immunohistochem Mol Morphol | volume = | issue = | pages = | month = Apr | year = 2012 | doi = 10.1097/PAI.0b013e31824973d1 | PMID = 22495362 }}</ref> - unlike for [[ovarian clear cell carcinoma]]. | ||
=See also= | =See also= | ||
*[[Endometrium]]. | *[[Endometrium]]. | ||
*[[Uterine tumours]] - other uterine tumours, e.g. carcinosarcoma, endometrial stromal sarcoma. | *[[Uterine tumours]] - other uterine tumours, e.g. carcinosarcoma, endometrial stromal sarcoma. | ||
*[[Uterine cervix]]. | |||
*[[Gynecologic pathology]] - overview. | *[[Gynecologic pathology]] - overview. | ||
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{{reflist|2}} | {{reflist|2}} | ||
=External links= | |||
*[http://www. | *[http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancer-staging Endometrial cancer staging (cancer.org)]. | ||
[[Category:Gynecologic pathology]] | [[Category:Gynecologic pathology]] |
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