View source for Endometrial carcinoma

[[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]]''.

=Clinical=
===Risk factors===
Risk factors for endometrial carcinoma - mnemonic ''COLD NUT'':<ref name=Ref_TN2007_GY40>{{Ref TN2007|GY40}}</ref>
*Cancer Hx (ovarian, breast, colon).
*[[Obesity]].
*Late menopause.
*Diabetes.
*Nulliparity.
*Unopposed estrogen (polycystic ovarian syndrome (PCOS), anovulation, hormone replacement therapy (HRT)).
*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>  

====Family history====
Several syndromes are seen in association with endometrial cancer:<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>
*[[Cowden syndrome]] (PTEN mutation) - most common.
**Associated with ''endometrioid endometrial carcinoma''.
*[[Lynch syndrome]] (mutation of a mismatch repair gene - there are several<ref>{{OMIM|120435}}</ref>).
**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.

===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>
**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: 
*Low grade and low stage endometrioid carcinoma: ''total hysterectomy'' (includes cervix).
*Non-endometrioid ''or'' high stage endometrioid ''or'' high-grade endometrioid: ''radical hysterectomy'' (includes cervix, vaginal cuff, parametrial tissue).

==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><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)==
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:
*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 ''or'' grade 3 by definition.

==Staging==
*Stage I: confined to uterine body.
**Ia = less than half of myometrium.
**Ib = greater than half of myometrium.
*Stage II: uterus + cervix.
**II = cervical stroma involved.
***Cervical epithelium involvement does not change stage.
*Stage III: outside uterus - but inside pelvis.
**IIIa - involves serosa and/or adnexa (direct extension or metastasis)
**IIIb - vaginal involvement (direct extension or metastasis) or parametrial involvement
*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=
==Endometrioid endometrial carcinoma==
*[[AKA]] ''endometrioid endometrial adenocarcinoma''.
{{Main|Endometrioid endometrial carcinoma}}

==Mucinous carcinoma of the endometrium==
*[[AKA]] ''endometrial mucinous carcinoma''.
===General===
*Type I endometrial carcinoma.{{fact}}
*Good prognosis.

===Microscopic===
Features:<ref name=Ref_GP241>{{Ref GP|241}}</ref>
*Cells with intracytoplasmic mucin (>50% of tumour).
*Usu. mild-to-moderate nuclear atypia.

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==
*[[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===
*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===
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:
*[[Serous endometrial carcinoma]] - usually has more nuclear pleomorphism, esp. cell size variation.
*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===
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.

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=
*[[Endometrium]].
*[[Uterine tumours]] - other uterine tumours, e.g. carcinosarcoma, endometrial stromal sarcoma.
*[[Uterine cervix]].
*[[Gynecologic pathology]] - overview.

=References=
{{reflist|2}}

[[Category:Gynecologic pathology]]