BAP1 Tumor Predisposition Syndrome Presenting as a Recurrent Ovarian Sex Cord-Stromal Tumor

Abstract

The BRCA1-associated protein 1 ( BAP1 ) gene encodes a tumor suppressor that functions as a ubiquitin hydrolase involved in DNA damage repair. BAP1 germline mutations are associated with increased risk of multiple solid malignancies, including mesothelioma, uveal melanoma, renal cell carcinoma, and high-grade rhabdoid meningiomas. Here, we describe the case of a 52-yr-old woman who experienced multiple abdominal recurrences of an ovarian sex cord-stromal tumor that was originally diagnosed at age 25 and who was found to have a germline mutation in BAP1 and a family history consistent with BAP1 tumor predisposition syndrome. Recurrence of the sex cord-stromal tumor demonstrated loss of BAP1 expression by immunohistochemistry. Although ovarian sex cord-stromal tumors have been described in mouse models of BAP1 tumor predisposition syndrome, this relationship has not been previously described in humans and warrants further investigation. The case presentation, tumor morphology, and immunohistochemical findings have overlapping characteristics with peritoneal mesotheliomas, and this case represents a potential pitfall for surgical pathologists.

Figure 1.

Pedigree of patient with BAP1 germline mutation, including family history of cancer diagnoses. The arrow indicates the index patient. Shading reflects individuals with a cancer diagnosis, with age at diagnosis reported in parentheses. Pedigree generated using CeGaT Pedigree Chart Designer.

Figure 2.

Histologic appearance of ovarian SCST and recurrence with loss of BAP1 nuclear expression. (A) H&E-stained section of the patient’s ovarian primary tumor at low power (4X magnification) demonstrates a hypercellular neoplasm adjacent to normal ovarian surface and parenchyma. (B) H&E-staining at high power (40X magnification) demonstrates sheets of monomorphic cells with round nuclei and indistinct cell borders. (C) H&E-stained section of the patient’s splenic recurrence at high power (40X magnification) shows monomorphic cells with plump nuclei with powdery chromatin and prominent nucleoli. (D) IHC for BAP1 shows loss of nuclear staining in tumor cells and retained nuclear staining in lymphocytes at high power (40X magnification).