"Surface epithelial slackening" pattern in endometrioid carcinoma: A morphological feature for differentiating the POLE mutation-subtype from the no specific molecular profile subtype.

Endometrial cancers are classified into mismatch repair (MMR) deficient- (MMRd), p53 mutation- (p53mut), DNA polymerase epsilon (POLE) mutation (POLE mut), and no specific molecular profile (NSMP) subtypes according to The Cancer Genome Atlas (TCGA). The distinction between POLE mut and NSMP subtypes is made on the basis of molecular analysis because the specific histological and immunohistochemical features of these two subtypes are still unknown. In this study, we analyzed histological features by scoring the presence of a mucinous pool, giant cells, clear cells, keratinization, neutrophilic abscess, and surface proliferating pattern in 82 cases of endometrial cancers in which an integrative diagnosis was confirmed by immunohistochemistry and genomic profiles showing POLE mutations, tumor mutation burden, and microsatellite instability. In contrast to the hierarchical branching of micropapillary proliferation observed in serous carcinoma, POLE mut-subtype endometrioid carcinomas often showed a surface epithelial slackening (SES) pattern in the tumor cells facing the uterine surface. The POLE mut subtype exhibited higher scores for clear cells and SES patterns than the other three subtypes. The scores for giant cells, clear cells, and the SES pattern were significantly higher in the POLE mut subtype than in the NSMP subtype, suggesting that these morphometric parameters are useful for differentiating POLE mut- and NSMP-subtype endometrioid carcinomas, although genomic profiling is still necessary for a definite molecular diagnosis. [ABSTRACT FROM AUTHOR]