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.
Highlights
Summary and recommendations: Carcinomas with a readily identifiable endometrioid component, as evidenced by endometrioid type glands with tall columnar epithelium and stratified nuclei, squamous or mucinous differentiation, and with > 50% solid architecture should be diagnosed as grade 3 endometrioid carcinoma
Immunohistochemistry can be a useful adjunct for the distinction between grade 3 endometrioid carcinoma and serous carcinoma
A feature that is usually present in clear cell carcinoma is a relatively low mitotic index compared with the degree of atypia; a high mitotic index does not preclude a diagnosis of clear cell carcinoma in an otherwise cytoarchitecurally typical tumor
Summary
Definition An endometrial carcinoma that usually shows marked and diffuse cytologic atypia and a papillary, Int J Gynecol Pathol Vol 38, No 1 Supplement 1, January 2019. Expression (diffusely and strongly positive or entirely negative) with p53, whereas grade 3 endometrioid carcinomas are more likely to be positive for ER and PR, negative for PTEN (correlating with genetic aberrations of PTEN[19]), focally positive for p16 and show wild-type staining for p53 Exceptions to this typical staining pattern occur in both tumor types and in general a panel of markers is the most reliable approach [2]. In the most comprehensive study of potential markers useful in the distinction between grade 3 endometrioid carcinoma and serous carcinoma published to date, Han et al [3] analyzed the diagnostic role of 12 proteins (ER, PR, p16, p53, Ki-67, PTEN, beta-catenin, vimentin, IMP3, TFF3, ARID1A, and HNF1B) in this differential diagnosis. ER, despite its expression in a significant number of serous carcinomas, appears to be useful in
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