High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations
Open accessAbstract
This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors’ review of the literature followed by discussions at the Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed “dedifferentiated carcinoma”) is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.
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Immunohistochemistry may demonstrate positive stains for HNF-1B, Napsin-A, AMACR, CK-7, and p53 in clear cell carcinoma.
“Moreover, immunohistochemistry may demonstrate positive stains for HNF-1B, Napsin-A, AMACR, CK-7, and p53 [21].”
From Clear cell carcinoma arising from abdominal wall endometriosis—A report on two cases and literature review (2022) · cites this paper as [21]
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- Authors
- Murali, R., Davidson, B., Fadare, O., Carlson, J. A., Crum, C. P., Gilks, C. B., Irving, J. A., Malpica, A., Matias-Guiu, X., McCluggage, W. G., Mittal, K., Oliva, E., Parkash, V., Rutgers, J. K. L., Staats, P. N., Stewart, C. J. R., Tornos, C., & Soslow, R. A.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Soslow, Robert A.
- ORCID
- Venue
- International Journal of Gynecological Pathology
- Published
- 2019-01
- Volume
- 38
- Issue
- Supplement 1
- Pages
- S40-S63
- ISSN
- 0277-1691 (ISSN-L)
- PMC
- PMC6296248
- OpenAlex
- W2904313334
- Cited by
- 278
- References
- 152
- Citations by year
- 2026: 20 · 2025: 38 · 2024: 33 · 2023: 53 · 2022: 42 · 2021: 42 · 2020: 33 · 2019: 17
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Gynecological Pathology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repositori ObertUDL (University of Lleida) (publishedVersion, other-oa)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- National Institutes of Health (CA008748)
- National Cancer Institute (CA008748, P30CA008748)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- high-grade endometrial cancer, endometrioid carcinoma, serous carcinoma, clear cell carcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, carcinosarcoma, immunohistochemistry, p53, p16, DNA mismatch repair, PTEN, ARID1A, Napsin A, AMACR, diagnostic criteria, overdiagnosis, SWI/SNF chromatin remodeling, E-cadherin
- MeSH terms
- Female, Humans, Immunohistochemistry, Societies, Medical, Biomarkers, Tumor, Endometrial Neoplasms, Practice Guidelines as Topic, Carcinoma, Endometrioid, Neoplasm Grading
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