Thomas C. Wilson, Deqin Ma, Anup Tilak, Brennan Tesdahl, Robert A. Robinson

Basal cell adenoma and basal cell adenocarcinoma represent basaloid salivary gland neoplasms that show cyto-morphologic similarity but differ at the histologic level by their invasive qualities, as adenocarcinomas show invasion beyond their capsule, a finding not seen in the adenomas. Due to the low incidence of these tumors, the molecular mechanism underlying their pathogenesis is poorly understood. We sought to further delineate these neoplasms through mutation profiling by targeted next-generation sequencing (NGS). Twenty cases (basal cell adenocarcinoma = 10; basal cell adenoma = 10) were retrospectively selected from a previous analysis. NGS was performed using the Ion AmpliSeq™ Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA). The data was analyzed using the Ion Torrent Suite Software (Life Technologies) followed by a laboratory-developed pipeline. One of eight cases of basal cell adenocarcinoma had a mutation, which was an activating mutation in PIK3CA (c.3140A>G, p.H1047R). No mutations were detected in the remaining basal cell adenocarcinomas. In the basal cell adenomas, the CTNNB1 p.I35T mutation was identified in three of nine (3/9) cases. A missense mutation in the ATM gene (c.2572T>C, p.F858L) was seen in a basal cell adenoma with an allele frequency of 53 %, raising the possibility of a germline mutation. The overall findings suggest that although there is cytomorphologic similarity, differences exist between these two tumors at the histologic and genetic level. Although the numbers of cases are limited, the aberrations in genes affecting different signaling pathways in the basal cell adenocarcinoma versus the basal cell adenomas suggest that basal cell adenocarcinoma likely arises de novo and not from basal cell adenoma.