BAP1 is a tumor suppressor gene located on chromosome 3p21.3 that functions as a deubiquitinating enzyme that interacts with the BRCA1 RING finger domain, among other proteins, and has roles in cell growth as well as genomic maintenance and stability [5–11]. BAP1 alterations are represented among many human neoplasms, including mesothelioma, cholangiocarcinoma, renal cell carcinoma, and melanoma [12]. A recent query of The Foundation Medicine database performed by Laitman and colleagues found BAP1 alterations in adenoid cystic carcinoma as well as 6.18% of salivary gland adenocarcinoma; however, the specific diagnostic type of salivary gland malignancy remained unspecified in the report [12]. One study found BAP1 alterations in 20.8% of mucoepidermoid carcinomas studied (n = 48) [13]; however, a second study of mucoepidermoid carcinomas found no such alterations (n = 40) [14].
The findings in the current case are unique because of the well-delineated loss of BAP1 protein expression by immunohistochemistry in the SDC component of the neoplasm with retention in histologic areas of residual PA and at least partial retention in the EMC component, a finding that suggests that BAP1 alterations may be relevant to SDCs.
The identification of BAP1 alterations has both prognostic and treatment implications. For example, somatic BAP1 inactivation has been implicated in metastatic potential in uveal melanoma [15] and is associated with an aggressive clinical course in high-grade meningiomas [16]. Germline BAP1 alterations cause BAP1 tumor predisposition syndrome, which predisposes patients to uveal and cutaneous melanomas, renal cell carcinoma, and mesothelioma [17–18]; however, such a syndromic association with salivary gland neoplasms has not been reported. Finally, emerging studies suggest therapeutic strategies in BAP1-altered tumors, including platinum-based chemotherapies, such as cisplatin [19], and poly(ADP-ribose) polymerase (PARPI) inhibitors, such as niraparib and Olaparib [11, 20–21].
Other alterations in this intraductal CXPA are discussed as follows. PIK3CA alterations are reported in SDC [22–23]. BRCA2 alterations are identified in a substantial number of PAs and CXPAs [24]. NF1 alterations are identified in SDC and adenocarcinoma, not otherwise specified, but not in CXPA in one study [25]. A FANCA mutation is reported in a SDC in a patient with a germline BRCA1 mutation [26]. AR expression is reported in many CXPA cases as well as approximately one third of PAs in one limited study [27]. FBXO32::PLAG1 rearrangements are reported in both PA and CXPA [28].
In conclusion, we report the first documented case of a BAP1 alteration in the SDC component of an intracapsular CXPA, both by immunohistochemistry and next generation sequencing. This finding may carry prognostic and treatment implications, and additional studies are needed to further investigate BAP1 alterations in salivary gland malignancies.