Comprehensive Molecular Profiling of Oncocytic Salivary Gland Malignancies

Oncocytic histologic features can be seen in a variety of salivary gland carcinomas. We performed a comprehensive molecular profiling of 15 salivary gland malignancies with oncocytic features (diagnosed as oncocytic carcinoma, carcinoma NOS with oncocytic features, or salivary duct carcinoma with oncocytic features). We reveal multiple novel molecular alterations that have not been previously described in other salivary gland malignancies, including, but not limited to, KEL amplification (13.3%, 2/15), PARP1 amplification (13.3%, 2/15), and EPHB4 amplification (13.3%, 2/15). Alterations in KMT2C (13.3%, 2/15), ERBB3 (13.3%, 2/15), CTNNA1 (13.3%, 2/15), and SMAD4 (20%, 3/15) were also found in this series and have been reported in other salivary gland malignancies. Alterations that have been reported in salivary duct carcinoma were also identified, including TP53 (40%, 6/15), ERBB2 mutations (13.3%, 2/15), ERBB2 amplification (13.3%, 2/15), PIK3CA (26.7%, 4/15), PTEN (20%, 3/15), BRCA2 (20%, 3/15), BRAF (20%, 3/15), CDKN2A/B (20%, 3/15), CDH1 (13.3%, 2/15), and HRAS (13.3%, 2/15). Oncocytic salivary gland malignancies are a molecularly heterogenous group of tumors with partial overlap with salivary duct carcinoma subtypes.