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

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2019Author
Murali, Rajmohan
Davidson, Ben
Fadare, Oluwole
Carlson, Joseph A.
Crum, Christopher
Gilks, C. Blake
Irving, Julie A.
Malpica, Anais
McCluggage, W. Glenn
Mittal, Khush
Oliva, Esther
Parkash, Vinita
Rutgers, Joanne
Staats, Paul
Stewart, Colin
Tornos, Carmen
Soslow, Robert A.
Suggested citation
Murali, Rajmohan;
Davidson, Ben;
Fadare, Oluwole;
Carlson, Joseph A.;
Crum, Christopher;
Gilks, C. Blake;
...
Soslow, Robert A..
(2019)
.
High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations.
International Journal of Gynecological Pathology, 2019, vol. 38, p. S40–S63.
https://doi.org/10.1097/PGP.0000000000000491.
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This review of challenging diagnostic issues concerning high-grade endometrial carcinomasisderivedfromtheauthors’ reviewoftheliteraturefollowedbydiscussionsatthe Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible,giventhatthelevelsofevidenceareweakormoderateduetosmallsamplesizesand 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 squamousareas), orwhenan architecturallyFIGOgrade2endometrioid carcinomaexhibits 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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International Journal of Gynecological Pathology, 2019, vol. 38, p. S40–S63European research projects
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