Difference between revisions of "Endometrial carcinoma"

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'''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.
[[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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|-
|-
|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.
 
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]].
*[[Microglandular hyperplasia]] of the cervix.
*[[Endocervical adenocarcinoma]].
*[[Serous carcinoma of the endometrium]] - esp. if high-grade nuclear features are present diffusely.
 
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>
 
====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==
*[[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>
*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/>
 
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==
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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.
Line 250: Line 153:
*[[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]]

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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