12019/4/ Endometrial carcinoma - Libre Pathology

Endometrial carcinoma
From Libre Pathology

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.

Contents
Gross image of endometrial adenocarcinoma.
1 Clinical
1.1 Risk factors
1.1.1 Family history
1.2 Management
1.3 Subtypes - overview
1.4 Grading (FIGO)
1.5 Staging
2 Specific types
2.1 Endometrioid endometrial carcinoma
2.2 Mucinous carcinoma of the endometrium
2.2.1 General
2.2.2 Microscopic
2.2.3 IHC
2.3 Serous carcinoma of the endometrium
2.4 Clear cell carcinoma of the endometrium
2.4.1 General
2.4.2 Microscopic
2.4.2.1 Images
2.4.3 Stains
2.4.4 IHC
3 See also
4 References
5 External links

Clinical
Risk factors

Risk factors for endometrial carcinoma - mnemonic COLD NUT:[2]

Cancer Hx (ovarian, breast, colon).

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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

serous carcinoma of the endometrium, clear cell
Histologic endometrioid endometrial carcinoma,
carcinoma of the endometrium, undifferentiated
types mucinous endometrial carcinoma
carcinoma
Clinical premenopausal, estrogen excess, postmenopausal, no estrogen excess, atrophic
characteristics obesity endometrium
Prognosis good poor
Genetic microsatellite instability, PTEN &
p53 mutations
abnormalities KRAS mutations
Precursor
endometrial hyperplasia possibly endometrial intraepithelial carcinoma[11] †
lesion(s)

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Notes:

† Endometrial intraepithelial carcinoma should not be confused with endometrial intraepithelial neoplasia
(EIN).

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:

Officially only sanctioned for endometrioid endometrial carcinoma.

May be used for mucinous endometrial carcinoma.
Papillary serous carcinoma and clear cell carcinomas are not assigned a grade; however, can be
thought of as grade 3 by definition.

Staging
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

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AKA endometrial mucinous carcinoma.

General

Type I endometrial carcinoma.[citation needed]

Good prognosis.

Microscopic

Features:[10]

Cells with intracytoplasmic mucin (>50% of tumour).

Usu. mild-to-moderate nuclear atypia.

DDx:

Endometrioid endometrial carcinoma.

Metastatic mucinous carcinoma.

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]

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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.[23]
Arias-Stella reaction - esp. in the context of pregnancy.
Papillary cystadenoma - benign; bland nuclei.[23]

DDx weird stuff:[23]

PEComa.
Epithelioid leiomyosarcoma.

Images

www:

Clear cell carcinoma of the endometrium - classical - high mag. (webpathology.com) (http://www.webpathol
ogy.com/image.asp?n=29&Case=569).
Clear cell carcinoma of the endometrium - high mag. (webpathology.com) (http://www.webpathology.com/i
mage.asp?case=569&n=27).
Clear cell carcinoma of the endometrium - low mag. (webpathology.com) (http://www.webpathology.com/im
age.asp?n=28&Case=569).

Stains

PAS-D stain +ve ~ glycogen.[23]

IHC

Features:[24]

p53 -ve usu. - unlike uterine serous carcinoma.

ER -ve.
PR -ve.

Others:[23]

CAM5.2 +ve.
CK34betaE12 +ve.
WT1 -ve.[25]
Often +ve/-ve in serous carcinoma of the endometrium.
CK7 +ve.[26]

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12019/4/
CK20 -ve.[26]
Vimentin +ve.[26]
Napsin A +ve.[27]
Note:
HNF1beta - not useful[28] - 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
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5. Okuda T, Sekizawa A, Purwosunu Y, et al. (2010).
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External links
Endometrial cancer staging (cancer.org) (http://www.cancer.org/cancer/endometrialcancer/detailedguide/end
ometrial-uterine-cancer-staging).

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