Basal cell adenoma with S100 protein-positive "stroma": a distinct triphasic salivary gland neoplasm characterized by CTNNB1 mutation

Area of Science:

• Oral pathology
• Neoplastic pathology
• Molecular diagnostics

Background:

• Basal cell adenoma (BCA) is a benign salivary neoplasm with diverse growth patterns.
• A subset of BCAs features abundant S100 protein-positive stroma, suggesting a potential link to pleomorphic adenoma (PA).

Purpose of the Study:

• To investigate the immunophenotypic and molecular characteristics of BCAs with abundant S100 protein-positive stroma.
• To differentiate this BCA subset from typical BCAs and myoepithelial cell-rich PAs.

Main Methods:

• Immunohistochemistry (IHC) for S100 protein, SOX10, PLAG1, HMGA2, p63/p40, cytokeratins, EMA, LEF1, and β-catenin.
• Next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and methylation analysis.

Main Results:

• BCAs with S100-positive stroma showed SOX10 positivity in stroma and frequent LEF1/β-catenin expression.
• These tumors harbored CTNNB1 mutations, unlike PAs which showed PLAG1 rearrangements.
• This subset demonstrated a triphasic differentiation pattern.

Conclusions:

• BCAs with abundant S100 protein-positive stroma represent a distinct triphasic variant of BCA.
• This subset is immunophenotypically and molecularly different from pleomorphic adenoma.
• The findings clarify the classification of salivary gland neoplasms.