Abstract
We have recently shown that the breast cancer (BRCA)1-associated protein-1 tumor suppressor gene (BAP1) is inactivated in a subset of clinically aggressive meningiomas that display rhabdoid histomorphology. Immunohistochemistry for BAP1 protein provides a rapid and inexpensive method for screening suspected cases. Notably, some patients with BAP1-mutant meningiomas have germline BAP1 mutations and BAP1 tumor predisposition syndrome (TPDS). It appears that nearly all patients with germline BAP1 mutations develop malignancies by age 55, most frequently uveal melanoma, cutaneous melanoma, pleural or peritoneal malignant mesothelioma, or renal cell carcinoma, although other cancers have also been associated with BAP1 TPDS. Therefore, when confronted with a patient with a potentially high-grade rhabdoid meningioma, it is important that neuropathologists assess the BAP1 status of the tumor and that the patient's family history of cancer is carefully ascertained. In the appropriate clinical setting, genetic counseling and germline BAP1 DNA sequencing should be performed. A cancer surveillance program for individuals who carry germline BAP1 mutations may help identify tumors such as uveal melanoma, cutaneous melanoma, and renal cell carcinoma at early and treatable stages. Because BAP1-mutant meningiomas are rare tumors, multi-institutional efforts will be needed to evaluate therapeutic strategies and to further define the clinicopathologic features of these tumors.