Basaloid adenosquamous carcinoma mimicking adenoid cystic carcinoma (BAC MAC): A novel subtype of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (SCC) has many subtypes, including basaloid (BSCC) and adenosquamous carcinoma (ASC). We describe a surface-derived carcinoma with features of both BSCC and ASC, along with frequent myoepithelial differentiation. Five cases were retrieved, slides were reviewed and results tabulated. DNA- and RNA-sequencing were performed in 4 and 5 cases, respectively. Patients were 4 men and 1 woman, from 55 to 78 years (mean, 68.6). Sites of origin were 2 hypopharynx, 2 oral cavity and 1 oropharynx. All cases demonstrated basaloid morphology and duct formation. Squamous dysplasia was in the overlying epithelium in 4 of 5. The tumors showed marked pleomorphism, mitotic activity, and necrosis. By immunohistochemistry, the tumors demonstrated non-diffuse p40/p63 expression sparing ducts. SOX10 and S100 were positive to varying extents in all, while SMA/SMMS was positive in 4 of 5. MYB IHC/RNA ISH were positive in all cases. Neuroendocrine markers were negative. Sequencing demonstrated SCC-like genetics with TP53 mutations (4 of 4), 11q13 amplification (3 of 4), and structural variants of unknown significance in 2 of 5 (Case 4 GLI3::ZNF804B, Case 5 ZNF521::AC090403.1 and CYLD::FSTL1). We demonstrate SCCs with basaloid features, non-diffuse p40/p63, as well as ductal and often myoepithelial differentiation. Despite features which traditionally point to a salivary-type carcinoma, especially high-grade AdCC, they exhibited squamous dysplasia/conventional SCC, SCC-like mutational profiles, and absence of MYB/MYBL1/NFIB fusions, strongly supporting squamous derivation. We propose the term basaloid ASC mimicking AdCC (BAC MAC). Recognition of this new SCC variant is important to avoid misdiagnosis and mismanagement.