S100-positive stroma in salivary gland basal cell adenomas: a neoplastic component with CTNNB1 mutations

Basal cell adenomas (BCAs) are benign epithelial tumors of the salivary gland, characterized by the proliferation of basaloid and luminal cells. In addition, a distinctive spindle cell stroma, that is immunohistochemically-positive for S100, is often observed in BCAs. Based on the ultrastructural findings, the S100-positive stroma was presumed to originate from neoplastic myoepithelial cells. However, immunohistochemical studies do not provide strong evidence supporting a myoepithelial origin, and the true nature of this stroma remains elusive. The aim of this study was to determine whether the S100-positive stroma was neoplastic through a molecular analysis. We selected 2 cases involving BCAs with at least one S100-positive stromal area within the tumor, measuring ≥ 0.2 × 0.2 mm. CTNNB1 I35T mutations were detected in both tumors by Sanger sequencing. Two areas of S100-positive stroma from these two tumors were successfully dissected by manual microdissection using a stereomicroscope without contamination from the surrounding neoplastic bilayered epithelial cells. Because of the small number of dissected stromal cells, the mutation status of these two areas was analyzed using digital PCR, and CTNNB1 I35T mutations were detected in both. In conclusion, this study demonstrated that the S100-positive stroma of BCAs exhibits a neoplastic nature from a molecular perspective. While future studies are needed to confirm whether the S100-positive stroma originates from myoepithelial cells, BCAs morphologically display tricellular differentiation, with neoplastic spindle-shaped stromal cells along with a bilayered neoplastic epithelium.