Vulvovaginal Epithelioid Mesenchymal Neoplasm With "Deciduoid" Morphology: Report of a Novel Entity Frequently Associated With Inactivating Germline BAP1 Variants.

A wide variety of mesenchymal lesions arise in the vulvovaginal region, some relatively site-specific. We report 4 cases of a novel vulvovaginal mesenchymal lesion, which we term vulvovaginal epithelioid mesenchymal neoplasm with "deciduoid" morphology, reflecting the predominant morphologic feature of epithelioid cells with a granular glassy "deciduoid" appearance. The tumors arose in women aged 34 to 48 years and involved the vagina (2 cases) or the vulval Bartholin's gland region (2 cases). The size ranged from 25 to 55 mm and they were solid and well-circumscribed. The tumors were composed of epithelioid and lesser numbers of spindle-shaped cells with abundant granular glassy eosinophilic cytoplasm, imparting a "deciduoid" morphology; there was prominent vascularity and a mild lymphoid infiltrate. Immunohistochemistry showed consistent diffuse estrogen receptor, progesterone receptor, CD63, and vimentin positivity with no other consistent immunophenotype. Two of the tumors showed immunohistochemical BAP1 loss and exhibited inactivating germline BAP1 variants (BAP1 tumor predisposition syndrome). On molecular testing, all tumors showed copy number loss of genes in 14q and/or 17q regions. Alterations of genes involved in the MAPK pathway were also present in all cases (including NF1 loss, a likely pathogenic variant in FLT3, and variants of unknown significance in FLT3, BMPR1A, and RUNX1). One of the cases harbored a novel FBXL20::MSI2 fusion. On follow-up (8 mo to 15 y), none of the tumors recurred. In reporting this novel neoplasm, we describe in detail the morphologic, immunohistochemical, and molecular features, discuss the differential diagnosis and histogenesis, and establish this novel entity as part of the BAP1 tumor predisposition syndrome.