BSND: An emerging immunohistochemical marker that reliably distinguishes benign from malignant oncocytic salivary gland tumors.

Oncocytic cells appear in various salivary gland lesions (SGLs) like oncocytic hyperplasia, metaplasia and several neoplasms. It is particularly challenging to distinguish oncocytoma and Warthin tumor from oncocytic and Warthin-like mucoepidermoid carcinoma (MEC) in the absence of molecular testing. A spectrum of oncocytic SGLs underwent immunohistochemistry for BSND, a novel marker of striated ducts and oncocytic tumor cells. MAML2 fluorescence in situ hybridization (FISH) was performed in suspected MECs. BSND immunoexpression was assessed in 138 SGLs, including 132 in-house and 4 consult cases. In-house cases comprised 5 non-neoplastic, 43 benign and 84 malignant SGLs. All nodular oncocytic hyperplasia (100 %) were BSND positive, while intercalated duct hyperplasia was negative. Among benign tumors, oncocytic cystadenomas (3/3), Warthin tumor (15/15), and oncocytoma (1/1) were BSND-positive (100 %). One clear cell oncocytoma reclassified as clear cell MEC on resection was BSND-negative. All remaining benign tumors were negative. Among all malignant tumors, one Warthin-like MEC was reclassified as infarcted metaplastic Warthin tumor on morphology and as it lacked MAML2 rearrangement; it was BSND positive. All remaining 83 malignant neoplasms were BSND-negative (100 %). All consult cases submitted as oncocytoma and oncocytic carcinoma were reclassified on ancillary testing, with BSND reliably distinguishing benign from malignant SGLs. In 21 cases with MAML2 FISH, MAML2 rearrangement was mutually exclusive with BSND immunopositivity. BSND is thus newly validated as an immunomarker to resolve diagnostic uncertainty in oncocytic SGLs. Use of BSND in routine practice could streamline the diagnostic process and improve patient management by reducing reliance on ambiguous morphological features, particularly in settings lacking molecular testing.