Correlation between basal cell adenoma and basal cell adenocarcinoma of the salivary gland: a histomorphological and molecular review of 129 cases

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are salivary gland tumors with biphasic differentiation, composed of luminal ductal cells and abluminal basal cells with a high nuclear-to-cytoplasmic ratio. While BCA is a relatively common benign tumor, BCAC is a rare malignancy, and its genetic context and relationship with BCA remain unclear. We investigated 93 BCA and 36 BCAC cases to further characterize these two tumor entities from histological and molecular perspectives. BCA/BCAC proliferated in a mixture of tubular, trabecular, solid, cribriform, and membranous patterns. A jigsaw puzzle pattern, peripheral palisading, S100-positive stroma, cystic change, and sclerosis were observed in approximately 50% of the cases. BCAC demonstrated the following malignant features: infiltration to surrounding tissue, tumor necrosis, and increased mitotic activity (81%, 22%, and 22%, respectively). The nuclear expression of β-catenin was frequently observed in both BCA and BCAC (89% and 60%), and CTNNB1 hotspot mutations were detected in 46% and 48% of BCA and BCAC cases, respectively. Tubular patterns of growth, jigsaw puzzle patterns, peripheral palisading, S100-positive stroma, and cystic changes were more common in β-catenin-positive BCA/BCAC than in β-catenin-negative BCA/BCAC. Among the β-catenin-negative BCA/BCAC cases, one case each harbored PLAG1 and MYB rearrangements. We concluded that β-catenin-positive BCA and BCAC share common histologic and molecular features, and BCAC is considered a malignant counterpart of BCA. β-Catenin-negative BCA/BCAC might include morphological mimickers, which can be genetically classified into other tumor types, including pleomorphic adenoma and adenoid cystic carcinoma.