Clinicopathological and molecular characteristics of rare ovarian sex cord stromal tumors with BAP1 mutation.

Ovarian sex cord stromal tumors (SCSTs) are rarely linked to BAP1 tumor predisposition syndrome (BAP1-TPDS), their morphological and molecular correlates remain incompletely defined. To expand the BAP1-associated tumor spectrum, this study characterizes three BAP1-mutated ovarian SCSTs (two with a family history of malignant tumors, suggestive of possible BAP1-TPDS, although germline genetic testing was not performed and one sporadic case). This is the first case series reporting both subtypes. Patients aged 54-63 years (median, 57 years). Microscopically, all tumors were predominantly hypercellular with a sheet growth pattern, focal cord-like, whorled, storiform, pseudopapillary and tubular growth patterns were identified. The tumor cells have spindle to oval nuclei with irregular nuclear membranes and nuclear grooves, mitotic figures are rare (2-6/10 HPF), and no necrosis is observed. Immunohistochemically, tumors expressed α-inhibin, calretinin, and SF1, with reticulin-rich stroma surrounding cell clusters and universal BAP1 loss. Next-generation sequencing identified three pathogenic BAP1 mutations: c.1153C > T (p. Arg385*), c.447_450dup (p. His151Thrfs) with BAP1 copy number loss/19q deletion, and c.205dup (p. Thr69Asnfs). Follow-up (32-37 months) showed two late recurrences, with all patients alive. These findings define a distinct BAP1-mutated ovarian SCST subset, linking specific mutations to characteristic phenotypes and expanding the BAP1-TPDS clinical-pathological spectrum.