MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.

BACKGROUND Secretory carcinoma (SC; synonym: mammary analogue SC= MASC) is a low-grade salivary gland tumor which occurs both in major and in minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, that overlaps with several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intraductal carcinoma (IDC) of intercalated type in major, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumors share with SC some morphological features, SOX10 immunoreactivity, and, with the exception of AciCC, they all coexpress S100 and mammaglobin. METHODS We compare MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate its potential in differentiating these entities. RESULTS Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%) compared to none of IDCs and PACs. On the contrary, mammaglobin is frequently expressed in SC (30 of 36 cases; 83.3%), IDC (24/28; 85.7%) and PAC (7/19; 36.8%). Two of 3 high grade SCs lost MUC4 expression in the high-grade tumor component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK vs. non-ETV6-NTRK). CONCLUSION The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.