Difference between revisions of "Endometrial carcinoma"

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Endometrial carcinoma (view source)

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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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Risk factors for endometrial carcinoma - mnemonic ''COLD NUT'':<ref name=Ref_TN2007_GY40>{{Ref TN2007|GY40}}</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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*Hysterectomy is the standard treatment for endometrial carcinoma.
*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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|-
|-
|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==
*Stage I: confined to uterine body.
*Stage I: confined to uterine body.
**Ia = endometrium only.
**Ia = less than half of myometrium.
**Ib = less than half of myometrium.
**Ib = greater than half of myometrium.
**Ic = greater than half of myometrium.
*Stage II: uterus + cervix.
*Stage II: uterus + cervix.
**IIa = endocervical glands only.
**II = cervical stroma involved.
**IIb = cervix stroma.
***Cervical epithelium involvement does not change stage.
*Stage III: outside uterus - but inside pelvis.
*Stage III: outside uterus - but inside pelvis.
**IIIa = serosal or adnexal involvement or peritoneal cytology positive.
**IIIa - involves serosa and/or adnexa (direct extension or metastasis)
**IIIb = vaginal metstases.
**IIIb - vaginal involvement (direct extension or metastasis) or parametrial involvement
**IIIc = pelvic or paraaortic nodes.
*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.
**IVa = bladder or bowel mucosa.
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>.
**IVb = distant mets (intraabdominal, inguinal nodes).
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>.


=Specific types=
=Specific types=
==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.
 
===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.
 
Note:
* † 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 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]].
 
Image:
*[http://www.diagnosticpathology.org/content/2/1/40/figure/F1?highres=y Squamous morule with dyskeratotic cell (diagnosticpathology.org)].


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


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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>
 
===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.
 
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>
*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> > 50% ''or'' 75%% of the tumour - depending on the paper one reads.
*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/>
 
Others:
*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>
 
Note:
*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>


==Clear cell carcinoma of the endometrium==
==Clear cell carcinoma of the endometrium==
*[[AKA]] ''clear cell endometrial carcinoma''.
*[[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>
*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:
*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.
**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:
*[[Serous endometrial carcinoma]] - usually has more nuclear atypia.
*[[Serous endometrial carcinoma]] - usually has more nuclear pleomorphism, esp. cell size variation.
*High grade [[endometrioid endometrial carcinoma]].
*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===
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*ER -ve.
*ER -ve.
*PR -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:
Note:
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*[[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.


=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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