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Uterus

Carcinoma

Endometrioid carcinoma


Reviewer: Jamie Shutter, M.D., University of South Florida (see Reviewers page)
Revised: 12 December 2013, last major update August 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition
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● Relatively indolent tumors that arise in background of endometrial hyperplasia

Terminology
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● Also called type 1 endometrial carcinoma
Adenoacanthoma: endometrioid adenocarcinoma with well differentiated (benign appearing) squamous differentiation; similar prognosis as other well differentiated adenocarcinomas; prognosis is dependent on glandular, not squamous component

Epidemiology
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● Associated with estrogen replacement therapy (usually well differentiated and endometrioid with good prognosis)
● Rare if ovarian dysgenesis or castration
● Rates much higher in white vs. black women

Etiology
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● Both carcinoma and hyperplasia are linked to prolonged estrogenic stimulation without progestational agents; both are also associated with estrogen secreting tumors

Clinical
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● 80% of endometrial carcinomas
● Local or diffuse, invades through myometrium
● Most women have Stage I disease, moderate or well differentiated tumors
● 5 year survival - Stage 1 (90%), Stage 2 (30-50%), Stage 3/4 (20%)

Prognostic factors
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● Mitotic index/MIB-1 index for stage 1A/1B, low grade tumors (Mod Pathol 2002;15:365)

Case reports
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● Case report with coexisting leiomyosarcoma (Arch Pathol Lab Med 2000;124:1539)
● 43 year old woman with uterine bleeding (Case of the Week #294)

Treatment
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● Well differentiated tumors: hysterectomy plus radiation therapy if greater than 50% myometrial invasion
● Moderately differentiated tumors: hysterectomy plus radiation therapy if myoinvasive

Gross description (Macroscopy)
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● Usually large uterus if myometrial invasion, but uterus may be normal sized even with myometrial invasion if tumor begins in cornu

Gross images
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With leiomyosarcoma

Yellow-white tumor originating from the endometrium with sharply delineated leiomyoma

Micro description (Histopathology)
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● Back to back endometrial-type glands of varying differentiation/atypia with no intervening stroma
● May occasionally show a villoglandular pattern
● Stroma present is usually desmoplastic, may have foamy cells due to tumor necrosis (not specific for carcinoma, derived from stroma not histiocytes; fat positive, mucin negative)
● Adjacent endometrium often exhibits EIN or atypical hyperplasia
● Vascular invasion is associated with chronic inflammation around lymphatics
● May have trophoblastic differentiation with hCG+ cells
● Commonly has squamous metaplasia

Well differentiated (FIGO grade 1)
● Extensive, complex epithelial growth pattern with little intervening stroma
● Usually budding and branching of large glands causing papillary structures
● May be villoglandular on low power
● May have true papillae (DD: clear cell carcinoma, serous carcinoma), but without atypia
● Mild to moderate atypia is allowed or only focal; if atypia is more severe, FIGO grade is increased to moderate (FIGO grade 2)
● Some are myoinvasive
● Often has benign squamous differentiation (adenoacanthoma), focal mucinous, secretory or ciliated features
● Usually stage 1, with 95% relapse-free survival rate

Moderately differentiated (FIGO grade 2)
● 6%-50% of nonsquamous tumor is composed of sheet-like tumor cells without glandular features
● Tumor cells have moderate pleomorphism, prominent nucleoli

Poorly differentiated (FIGO grade 3)
● >50% of nonsquamous tumor is composed of sheet-like tumor cells without glandular features
● Tumor cells have high grade features
● Glands poorly formed when present
● May contain malignant squamous cells
● Angiolymphatic invasion common

Micro images
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Numerous stromal foam cells


Well differentiated tumors

               

Various well differentiated tumors

   
Compare tumor within adenomyosis (left) with true myometrial invasion (right)


The glands lack cytologic atypia but are confluent, with no intervening stroma


Several large masses of glands show a confluent or cribriform pattern, but others are separated by a desmoplastic stroma


A confluent glandular pattern is present


The glands in this field show architectural and cytologic atypia, but are still separated by thin wisps of mostly acellular stroma. Obvious carcinoma was seen in an adjacent microscopic field.


This microscopic field shows the desmoplastic or scirrhous stromal response of invasive carcinoma. Focal stromal necrosis is also present. The glands lack cytologic atypia but are confluent, with no intervening stroma.


Foam cells are seen centrally. The remainder of the stroma is replaced by neutrophils (stromal necrosis).

       
These illustrations shows small, round, regular glands growing in a confluent pattern


Visible in this illustration are confluent glands lined predominantly by a single row of cells with large, round, normochromatic nuclei that are somewhat variable in size and irregularly distributed


Endometrioid adenocarcinoma with squamous epithelium, adenoacanthoma type


Moderately differentiated tumors


Visible in this illustration are confluent glands lined predominantly by a single row of cells with large, round, normochromatic nuclei that are somewhat variable in size and irregularly distributed


Some solid sheets of tumor cells are seen in addition to glands, the nuclei are more variable in size and shape and show more irregularity of nuclear chromatin than those seen in well differentiated tumors. Because a few solid foci might be the result of tangential sectioning of glands, the nuclear atypia helps to characterize this tumor as moderately differentiated.


Another field of the above tumor shows anisonucleosis, prominent nucleoli in some nuclei and nuclear clearing with clumping of chromatin along the nuclear membrane


Poorly differentiated tumors


Only a few small round glands remain in this field to identify this tumor as adenocarcinoma of endometrioid type. Most of the tumor grows in solid sheets of anaplastic cells.


This field shows a few malignant glands at the center from which solid sheets of anaplastic tumor cells stream into a reactive spindled stroma. At the top of the large lumen in the center of the field, some of the lining cells resemble syncytiotrophoblastic cells.

   
Solid tumor masses infiltrating the myometrium


Partly solid and partly gland forming tumor masses infiltrating the myometrium


Solid tumor mass with several mitotic figures

Corded and hyalinizing pattern -

Endometrial biopsy


Total abdominal hysterectomy

Other

   

With leiomyosarcoma #1, #2

Cytology images
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This endometrial aspirate of a well differentiated tumor shows clustered and single small tumor cells in a necrotic background. The small and relatively uniform cells show some anisonucleosis, irregular chromatin clumping, and prominent nucleoli in some of the nuclei.


This endometrial aspirate of a poorly differentiated tumor shows large tumor cells with marked anisonucleosis, hyperchromatism, chromatin clumping and huge prominent nucleoli.

Electron microscopy images
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This was a well-differentiated tumor at the light-microscopic level, but in this electron micrograph, the nuclei are fairly pleomorphic. Note the numerous short microvilli at the luminal surface (right), as well as well-formed junctional complexes, numerous mitochondria, and lysosomes.


In this electron micrograph, the tumor has somewhat more irregular nuclei than the above case, but microvilli and junctional complexes are somewhat better formed. Lysosomes are also numerous in this case, free ribosomes are prominent and some lipid vacuoles are present.

Differential diagnosis
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● Ciliary metaplasia
● Papillary change
● Progesterone treatment related changes
● Shedding endometrium with papillary syncytial metaplasia
● Villoglandular endometrioid carcinoma
● Well differentiated tumors: atypical hyperplasia / EIN (Mod Pathol 2000;13:309)
● Poorly differentiated tumors: serous carcinoma

Additional references
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Am J Surg Pathol 2000;24:1201 (alternative grading scheme)

End of Uterus > Carcinoma > Endometrioid carcinoma


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