SOX2 Can Support a Diagnosis of PiMHEC With Rare to Absent Ghost Cells and Can Distinguish PiMHEC From Its Most Problematic Mimickers.

Authors

Jin Xu, Paul S Weisman

Published in

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is an aggressive variant of endometrioid adenocarcinoma characterized by divergent pilomatrical differentiation. While classic cases are usually recognizable, the diagnosis can be challenging when ghost cells are rare or absent, or when encountering mimickers that share overlapping features. We investigated the utility of SOX2 immunohistochemistry as a diagnostic marker for PiMHEC. SOX2 expression was evaluated in 26 cases of PiMHEC (24 endometrial, 2 ovarian). We also analyzed problematic mimickers, including non-PiMHEC FIGO grade 3 endometrioid carcinomas (EMCA) with aberrant beta-catenin expression (n=4) and undifferentiated/dedifferentiated EMCA (UD-EMCA) with aberrant beta-catenin expression (n=7). In addition, a tissue microarray (TMA) of 84 EMCA cases (FIGO grade 1-3 and UD-EMCA) was screened. All 26 PiMHEC cases (100%) showed robust SOX2 positivity. In contrast, all non-PiMHEC FIGO grade 3 EMCAs with aberrant beta-catenin expression were negative for SOX2. While 2 of 7 UD-EMCAs with aberrant beta-catenin expression showed very focal SOX2 expression, these were easily distinguished from PiMHEC by their lack of cytokeratin expression. In the TMA cohort, only 5 of 84 cases (all FIGO grade 3) showed SOX2 positivity; these cases all had membranous beta-catenin expression, had no histologic features of PiMHEC and followed an indolent clinical course. SOX2 is a useful marker for confirming a diagnosis of PiMHEC, especially when ghost cells are inconspicuous. It effectively differentiates PiMHEC from its FIGO grade 3 mimickers with aberrant beta-catenin expression.

PMID:
42498260
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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