Cited by 295Endometrial and Cervical Cancer TreatmentsNeuroendocrine Tumor Research AdvancesCervical Cancer and HPV Research

High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations

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Murali, Rajmohan, Davidson, Ben, Fadare, Oluwole, Carlson, Joseph A., Crum, Christopher P., Gilks, C. Blake, Irving, Julie A., Malpica, Anais +10 more·2019·International Journal of Gynecological Pathology

Abstract

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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  1. [103]Zaino R Carinelli SG Ellenson LH Kurman RJ Epithelial tumors and precursors. WHO Classification of Tumours of the Female Reproductive Organs. Lyon, France: IARC; 2014: 125– 135.
  2. [113]Silverberg SG Nogales F Tavassoli FA Devilee P Tumours of the uterine corpus. Pathology and Genetics: Tumours of the Breast and Female Genital Organs. Lyon, France: IARC Press. World Health Organization Classification of Tumours; 2003: 217– 57.
  3. [114]Zaino R Carinelli SG Eng C Kurman RJ Carcangiu ML Herrington CS Young RH Tumours of the uterine corpus. WHO Classification of Tumours of Female Reproductive Organs. Lyon, France: IARC Press. World Health Organization Classification of Tumours; 2014: 121– 54.

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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.
Venue
International Journal of Gynecological Pathology
Published
2019-01
Volume
38
Issue
Supplement 1
Pages
S40-S63
ISSN
0277-1691 (ISSN-L)
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
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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