Endometrial cancer

Author: Mikael Häggström

Presentations

• Hysterectomy
• Endometrial curettage
• Endometrial polyp
• Endometrial thickening

Gross processing

Gross pathology of extensive endometrial adenocarcinoma (endometrioid type).

A regular hysterectomy grossing is performed, but with the following sampling and additions:

• 2 longitudinal sections through ecto/endocervix (1 anterior and 1 posterior).
• 2 longitudinal sections through upper endocervix/lower uterine segment (1 anterior and 1 posterior), contiguous with sections taken from cervix.
• Tumor:

• Measure greatest dimension of tumor.

• If tumor is smaller than 3 cm, submit entirely.
• If tumor is larger than 3 cm, submit 1 per cm.

• Measure tumor thickness (cavity to border of invasion) and entire thickness of the wall (cavity to serosa), at the location of greatest percentage of tumor relative to wall thickness.
• Include 2 full-thickness sections (1 anterior and 1 posterior), including location with greatest percentage. It may need multiply contiguous sections.
• Remaining sections can be superficial to include tumor and inner myometrium, such as from lower uterine segment to fundus to maintain orientation.
• If possible, include 1 section with interface between tumor and normal.

• Sections of any additional pathology, such as leiomyomas, polyps in their entirety.
• 1 section of uninvolved endometrium if present.
• Inspect serosa for implants and submit sections if grossly detected.
• For serous carcinomas, submit the entire ovary and fallopian tube:

• Ovary, serially sectioned perpendicular to long axis.
• SEE-FIM protocol for fallopian tubes:

• Remove the distal 2 cm (fimbriae) and section it parallel to the long axis.

Section the remainder of the tube transversely at 2-3 mm intervals.

• For all other cancer types, submit adnexa as follows:

• Ovaries: 2 representative sections of each.
• Fallopian tubes: Entire fimbriae (longitudinally sectioned) and 2 representative cross-sections on each side.

• Lymph nodes

• Size smaller than 2 mm: submit intact.
• Size larger than 2 mm: serially section perpendicular to the long axis in 2 mm intervals.

• If no gross tumor, submit entirely.
• If grossly positive, submit 1-2 representative sections showing the greatest tumor dimension and extranodal fat.

Microscopic evaluation

Diagnosis

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  Relative incidences of endometrial carcinomas by histopathology, being endometrioid in a majority of cases. Endometrioid carcinoma has patterns reminiscent of normal endometrium, with many new glands formed from columnar epithelium with some abnormal nuclei:

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  Endometrioid adenocarcinoma, with low-grade being distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.

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  Complex hyperplasia with atypia for comparison: Sparse intervening stroma.

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  Papillary serous carcinoma of uterus, with characteristic discohesiveness of cells (like falling apart) around fibrovascular cores.

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  Papillary serous carcinoma of uterus, in this case showing both papillary and micropapillary architecture.

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  Clear cell carcinoma of the endometrium with papillary architecture, characteristically small round papillae lacking overt stratification. Clear cell carcinoma is defined as a carcinoma demonstrating a combination of papillary, tubulocystic and/or solid architectural patterns, with cuboidal or polygonal cells containing nuclei with a variable pleomorphism (although usually lacking discernible pleomorphism).

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  Clear cell carcinoma of the endometrium with tubulocystic architecture.

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  Clear cell carcinoma of the endometrium with solid architecture.

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  Dedifferantiated carcinoma, a tumor that contains a component of undifferentiated endometrial carcinoma (UEC) and a component of conventional, usually lower-grade, endometrioid adenocarcinoma.

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  Carcinosarcoma of the endometrium, with carcinoma in addition to sarcoma (seen here as atypical fibrovascular cores).

Endometrioid adenocarcinoma

For endometrioid adenocarcinoma, perform grading:

• Grade 1: ≤5% solid non-glandular, non-squamous growth
• Grade 2: >5% and ≤50% solid non-glandular, non-squamous growth
• Grade 3: >50% solid non-glandular, non-squamous growth

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  Grade 1

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  Grade 2.

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  Grade 2 (with mucinous differentiation)

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  Grade 3, with glandular architecture.

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  Grade 3, with solid architecture. Carcinomas with identifiable endometrial component, and with over 50% solid architecture should be classified as grade 3 endometrioid carcinoma.

((Also perform nuclear grading:))

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  Nuclear grade 1: Oval, mildly enlarged nucleus with evenly distributed chromatin.

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  Nuclear grade 2: Intermediate features.

• Nuclear grade 3: Markedly enlarged and pleomorphic nuclei, with coarse chromatin and distinct nucleoli.

Staging

If possible, perform staging by the FIGO system:

For biopsies, at least look for myometrial invasion (pictured).

Generally look for lymphovascular invasion (pictured) as well.

Stage	Description
IA	Tumor is confined to the uterus with less than half myometrial invasion
IB	Tumor is confined to the uterus with more than half myometrial invasion
II	Tumor involves the uterus and the cervical stroma
IIIA	Tumor invades serosa or adnexa
IIIB	Vaginal and/or parametrial involvement
IIIC1	Pelvic lymph node involvement
IIIC2	Para-aortic lymph node involvement, with or without pelvic node involvement
IVA	Tumor invades bladder mucosa and/or bowel mucosa
IVB	Distant metastases including abdominal metastases and/or inguinal lymph nodes

Further workup

Generally perform the following molecular testing on endometrial carcinomas:

• ER/PR and p53 for all high grade carcinomas regardless of stage.
• HER2 on all high grade carcinomas, or only on serous carcinomas, or those that are stage III or IV or recurrent.
• MMR on all cancer types and grades with further testing for MLH1 promotor methylation if MLH1 is lost.

Microscopy report

Example:

(Endometrium, polypectomy:) Endometrial adenocarcinoma, endometrioid type, FIGO grade 2, with mucinous differentiation. Carcinoma focally invades myometrial smooth muscle.

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.

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