Basal cell salivary
neoplasms display similar cyto-morphologic features and are classified into
adenoma and
adenocarcinoma based on the presence or absence of
tumor invasion at diagnosis. These
neoplasms also share considerable phenotypic resemblance and co-exist with certain dermal adnexal
tumors harboring the CYLD gene mutations inferring common genetic association. We sequenced the CYLD gene in both
basal cell adenomas and
adenocarcinomas and correlated the findings with CYLD, NF-κB, and β-
catenin expression levels and clinicopathologic factors. Twenty mutations were identified and comprised of 3 synonymous and 17 non-synonymous (missense) types involving the coding exons of the CYLD gene. Mutations in exons 9-11 were identified in both
adenomas and
adenocarcinomas, while mutations in exons 12-20, encoding the USP domain, were exclusively found in
carcinomas. Although no significant correlation between CYLD mutations and expression levels of CYLD, NF-κB, and β-
catenin or clinicopathologic parameters was found,
basal cell adenocarcinomas with multiple mutations showed reduction in
CYLD protein expression and pursued aggressive clinical behavior. Our study revealed high incidence and sequential CYLD mutations in both
basal cell adenoma and
adenocarcinoma supporting a single neoplastic continuum for their evolution and provides evidence for potential diagnostic and therapeutic utility.