Pilomatrix-Like High-Grade Endometrial Carcinoma (PiMHEC) With Secondary Vaginal Involvement: A Rare Variant of CTNNB1-Mutated Endometrial Carcinoma Mimicking Mesonephric-Like Adenocarcinoma

Abstract

Pilomatrix-like high-grade endometrial carcinoma (PiMHEC) is a recently recognized, clinically aggressive variant of endometrial carcinoma that is frequently misdiagnosed due to its morphological and immunophenotypic overlap with other high-grade endometrial malignancies. We report a 52-year-old woman who presented with widely metastatic high-grade carcinoma of endometrial origin, involving the vagina and distant sites including the brain, lung, and lymph nodes. Histologically, the tumor displayed a predominantly solid basaloid architecture with extensive geographic necrosis and abrupt keratinization with conspicuous shadow cells, supporting pilomatrix-like differentiation. Immunohistochemically, the tumor demonstrated strong, diffuse, aberrant nuclear β-catenin expression; patchy, heterogeneous expression of TTF1, GATA3 and CD10; and variable expression of CK7, CDX2, and p16. The tumor was negative for PAX8, ER, PR, and p40. p53 showed a wild-type pattern, and mismatch repair was retained (pMMR). Next-generation sequencing (NGS) identified a pathogenic exon 3 CTNNB1 p.S33Ymutation. The morphologic, immunophenotypic, and molecular findings supported a diagnosis of PiMHEC. Notably, expression of TTF-1, GATA3, and CD10, together with absence of ER and PR expression, creates substantial immunophenotypic overlap with mesonephric-like adenocarcinoma (MLA) and represents a potential diagnostic pitfall. Recognition of characteristic shadow cell keratinization and aberrant nuclear β-catenin expression, integrated with molecular findings, is critical for distinguishing PiMHEC from MLA. This case expands the clinicopathologic spectrum of this underrecognized aggressive neoplasm and highlights the importance of integrating morphology, immunohistochemistry, and molecular findings to avoid diagnostic misclassification.