Difference between revisions of "Endometrial carcinoma"

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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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**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.
*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>
#Type I:
{| class="wikitable sortable"
#*Histologic types:
!Feature
#**Endometrioid (most common).
!Type I
#**Mucinous.
!Type II
#*Clinical characteristics: premenopausal, estrogen excess.
|-
#Group II:
|Histologic types
#*Histologic types:
|[[endometrioid endometrial carcinoma]], [[mucinous endometrial carcinoma]]
#**Serous carcinoma.
|[[serous carcinoma of the endometrium]], [[clear cell carcinoma of the endometrium]], undifferentiated carcinoma
#**Clear cell carcinoma.
|-
#*Clinical characteristics: postmenopausal, no estrogen excess, poor prognosis.
|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> †
|}


The most common as a list:
Notes:
#Endometrioid - '''most common''', patient typically is 55-65 years old and obese.
* † ''Endometrial intraepithelial carcinoma'' should '''not''' be confused with ''[[endometrial intraepithelial neoplasia]]'' (EIN).
#Serous - patients classically older than endometrioid subtype, arise in atrophic endometrium.
#Clear cell.


==Grading (FIGO)==
==Grading (FIGO)==
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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).
Ref: <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}}


==Mucinous carcinoma of the endometrium==
*[[AKA]] ''endometrial mucinous carcinoma''.
===General===
===General===
*Good prognosis - usually.
*Type I endometrial carcinoma.{{fact}}
*Women in 40s & 50s.
*Good prognosis.
*Associated with estrogen excess.
**Typical patient is obese.


===Microscopic===
===Microscopic===
Features:
Features:<ref name=Ref_GP241>{{Ref GP|241}}</ref>
*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>
*Cells with intracytoplasmic mucin (>50% of tumour).
*#Desmoplastic stromal response.
*Usu. mild-to-moderate nuclear atypia.
*#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:
DDx:
*[[Complex endometrial hyperplasia with atypia]].
*[[Endometrioid endometrial carcinoma]].
*[[Complex endometrial hyperplasia]].
*Metastatic [[mucinous carcinoma]].


Image:
===IHC===
*[http://www.diagnosticpathology.org/content/2/1/40/figure/F1?highres=y Squamous morule with dyskeratotic cell (diagnosticpathology.org)].
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==
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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}}
==Clear cell carcinoma of the endometrium==
*[[AKA]] ''clear cell endometrial carcinoma''.
*[[AKA]] ''endometrial clear cell carcinoma''.


===General===
===General===
*Arising in the setting of atrophy.
*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>
*Usu. post-menopausal.
*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 - serous:
Features:<ref name=pmid22885379/>
*Architecture:
*Clear cells - with moderate nuclear pleomorphism - '''key feature'''.
*#Papillary - common.
**Classically clear cells... but not always.
*#*May be glomeruloid.
*[[Hobnail pattern]] -- apical cytoplasm > cytoplasm on basement membrane.
*#Tubulocystic.
*Usually tubular/cystic, may be solid or papillary.
*#Solid - uncommon.
**Papillae may be pseudopapillae -- with edema instead of vessels.
*Cytology:
 
**Columnar cells.  
Notes:
**Cilia.
*May have [[psammoma bodies]] - esp. in papillary area; may lead to confusion with serous carcinoma.
*[[Psammoma bodies]].


DDx:
DDx:
*High-grade [[endometrioid endometrial carcinoma]].
*[[Serous endometrial carcinoma]] - usually has more nuclear pleomorphism, esp. cell size variation.
*[[Clear cell carcinoma of the endometrium]] - usu. have less nuclear pleomorphism and less mitoses.
*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===
*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>
Features:<ref name=Ref_GP250>{{Ref GP|250}}</ref>
*p53 +ve > 50% ''or'' 75%% of the tumour.
*p53 -ve usu. - unlike [[uterine serous carcinoma]].
*ER -ve.
*PR -ve.


==Clear cell carcinoma of the endometrium==
Others:<ref name=pmid22885379/>
*[[AKA]] ''clear cell endometrial carcinoma''.
*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>


===General===
Note:
*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>
*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]].
 
===Microscopic===
Features:
*Clear cells:
**Classically clear cells... but not always.
*Hobnail pattern -- apical cytoplasm > cytoplasm on basement membrane.


=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.


Line 166: Line 191:
{{reflist|2}}
{{reflist|2}}


==External links==
=External links=
*[http://www.diagnosticpathology.org/content/2/1/40/figure/F1?highres=y Image of squamous morule with dyskeratotic cell (diagnosticpathology.org)].
*[http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancer-staging Endometrial cancer staging (cancer.org)].


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

Latest revision as of 18:24, 30 August 2023

Gross image of endometrial adenocarcinoma.

Endometrial carcinoma, also endometrial adenocarcinoma, is a common gynecologic malingnancy[1] 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:[2]

  • 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[3] or possibly negligent.[4]

Family history

Several syndromes are seen in association with endometrial cancer:[5]

  • Cowden syndrome (PTEN mutation) - most common.
    • Associated with endometrioid endometrial carcinoma.
  • Lynch syndrome (mutation of a mismatch repair gene - there are several[6]).
    • Associated with non-endometrioid endometrial carcinoma.[5]
    • 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.[7]
    • Endometrial carcinomas with involvement of the endocervical canal are treated with a radical hysterectomy.[8]

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:[9][10]

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
characteristics 		premenopausal, estrogen excess, obesity postmenopausal, no estrogen excess, atrophic endometrium
Prognosis good poor
Genetic
abnormalities 		microsatellite instability, PTEN & KRAS mutations p53 mutations
Precursor lesion(s) endometrial hyperplasia possibly endometrial intraepithelial carcinoma[11] †

Notes:

Grading (FIGO)

Based on gland formation & adjusted by nuclear pleomorphism:[12][13][14][15]

  • 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).[16]

Notes:

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: [17][18][19][20].

Specific types

Endometrioid endometrial carcinoma

  • AKA endometrioid endometrial adenocarcinoma.
Main article: Endometrioid endometrial carcinoma

Mucinous carcinoma of the endometrium

  • AKA endometrial mucinous carcinoma.

General

Microscopic

Features:[10]

  • Cells with intracytoplasmic mucin (>50% of tumour).
  • Usu. mild-to-moderate nuclear atypia.

DDx:

IHC

Features:[21]

  • 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 article: 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%.[22]
  • Uncommon <=5 % of endometrial carcinomas.[23]
  • Type II endometrial cancer - estrogen-independent, usually post-menopausal women.

Microscopic

Features:[23]

  • 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 weird stuff:[23]

Images

www:

Stains

IHC

Features:[24]

Others:[23]

  • CAM5.2 +ve.
  • CK34betaE12 +ve.
  • WT1 -ve.[25]
    • Often +ve/-ve in serous carcinoma of the endometrium.
  • CK7 +ve.[26]
  • CK20 -ve.[26]
  • Vimentin +ve.[26]
  • Napsin A +ve.[27]

Note:

See also

References

  1. ↑ Fowler W, Mutch D (September 2008). "Management of endometrial cancer". Womens Health (Lond Engl) 4 (5): 479–89. doi:10.2217/17455057.4.5.479. PMID 19072487.
  2. ↑ Greenwald, J.; Heng, M. (2007). Toronto Notes for Medical Students 2007 (2007 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. GY40. ISBN 978-0968592878.
  3. ↑ Brown, K. (Sep 2009). "Is tamoxifen a genotoxic carcinogen in women?". Mutagenesis 24 (5): 391-404. doi:10.1093/mutage/gep022. PMID 19505894.
  4. ↑ Ashraf, M.; Biswas, J.; Majumdar, S.; Nayak, S.; Alam, N.; Mukherjee, KK.; Gupta, S.. "Tamoxifen use in Indian women--adverse effects revisited.". Asian Pac J Cancer Prev 10 (4): 609-12. PMID 19827879.
  5. ↑ 5.0 5.1 Okuda T, Sekizawa A, Purwosunu Y, et al. (2010). "Genetics of endometrial cancers". Obstet Gynecol Int 2010: 984013. doi:10.1155/2010/984013. PMC 2852605. PMID 20396392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852605/.
  6. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 120435
  7. ↑ Zivanovic O, Carter J, Kauff ND, Barakat RR (December 2009). "A review of the challenges faced in the conservative treatment of young women with endometrial carcinoma and risk of ovarian cancer". Gynecol. Oncol. 115 (3): 504–9. doi:10.1016/j.ygyno.2009.08.011. PMID 19758691.
  8. ↑ Ware, RA.; van Nagell, JR. (2010). "Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications.". Obstet Gynecol Int 2010. doi:10.1155/2010/587610. PMID 20871657.
  9. ↑ Lim, D.; Oliva, E. (Nov 2010). "Nonendometrioid endometrial carcinomas.". Semin Diagn Pathol 27 (4): 241-60. PMID 21309259.
  10. ↑ 10.0 10.1 Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 241. ISBN 978-0443069208.
  11. ↑ Roelofsen, T.; van Kempen, LC.; van der Laak, JA.; van Ham, MA.; Bulten, J.; Massuger, LF. (Mar 2012). "Concurrent endometrial intraepithelial carcinoma (EIC) and serous ovarian cancer: can EIC be seen as the precursor lesion?". Int J Gynecol Cancer 22 (3): 457-64. doi:10.1097/IGC.0b013e3182434a81. PMID 22249577.
  12. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1087-8. ISBN 0-7216-0187-1.
  13. ↑ URL: http://www.pathologyoutlines.com/uterus.html#endometrialcarc.
  14. ↑ URL: http://www.emedicine.com/med/topic2832.htm.
  15. ↑ Ayhan A, Taskiran C, Yuce K, Kucukali T (January 2003). "The prognostic value of nuclear grading and the revised FIGO grading of endometrial adenocarcinoma". Int. J. Gynecol. Pathol. 22 (1): 71–4. PMID 12496701.
  16. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 240. ISBN 978-0470519035.
  17. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1088. ISBN 0-7216-0187-1.
  18. ↑ http://www.emedicine.com/med/topic2832.htm
  19. ↑ Staging with groovy graphics (cancerfacts.com)
  20. ↑ URL: http://en.wikibooks.org/wiki/Radiation_Oncology/Endometrium/Staging. Accessed on: 2 May 2012.
  21. ↑ Shabani, N.; Mylonas, I.; Jeschke, U.; Thaqi, A.; Kuhn, C.; Puchner, T.; Friese, K.. "Expression of estrogen receptors alpha and beta, and progesterone receptors A and B in human mucinous carcinoma of the endometrium.". Anticancer Res 27 (4A): 2027-33. PMID 17649817.
  22. ↑ Abeler, VM.; Vergote, IB.; Kjørstad, KE.; Tropé, CG. (Oct 1996). "Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern.". Cancer 78 (8): 1740-7. PMID 8859187.
  23. ↑ 23.0 23.1 23.2 23.3 23.4 23.5 23.6 Offman, SL.; Longacre, TA. (Sep 2012). "Clear cell carcinoma of the female genital tract (not everything is as clear as it seems).". Adv Anat Pathol 19 (5): 296-312. doi:10.1097/PAP.0b013e31826663b1. PMID 22885379.
  24. ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 250. ISBN 978-0443069208.
  25. ↑ Acs, G.; Pasha, T.; Zhang, PJ. (Apr 2004). "WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium.". Int J Gynecol Pathol 23 (2): 110-8. PMID 15084838.
  26. ↑ 26.0 26.1 26.2 Vang, R.; Whitaker, BP.; Farhood, AI.; Silva, EG.; Ro, JY.; Deavers, MT. (Jul 2001). "Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract.". Int J Gynecol Pathol 20 (3): 252-9. PMID 11444201.
  27. ↑ Iwamoto, M.; Nakatani, Y.; Fugo, K.; Kishimoto, T.; Kiyokawa, T. (Jul 2015). "Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium.". Hum Pathol 46 (7): 957-62. doi:10.1016/j.humpath.2015.03.008. PMID 25971546.
  28. ↑ Fadare, O.; Liang, SX. (Apr 2012). "Diagnostic Utility of Hepatocyte Nuclear Factor 1-Beta Immunoreactivity in Endometrial Carcinomas: Lack of Specificity For Endometrial Clear Cell Carcinoma.". Appl Immunohistochem Mol Morphol. doi:10.1097/PAI.0b013e31824973d1. PMID 22495362.

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