Salivary gland neoplasms have diverse histopathologic features and biological behaviors. Among these, adenoid cystic carcinoma (ACC), basal cell adenoma (BCA), basal cell adenocarcinoma (BCAC), and pleomorphic adenoma (PA) frequently render diagnostic challenges due to their overlapping basaloid morphologic characteristics [1], [2], [3], [4]. However, the four entities have distinct tumor biology, treatment strategies, and prognostic outcomes. The accurate pathologic diagnosis is critical for these tumors.

The advances in molecular pathology have revealed characteristic genetic alterations underlying these tumors [5], [6], [7]. The particular t (6;9) (q22–23; p23–24) translocation involving MYB and NFIB was the most significant genetic alteration in the ACCs [7]. The MYBL1 is a homolog of MYB, sharing structural and functional similarities. It also acts as a transcription factor involved in cell cycle regulation. The MYBL1 gene rearrangements serve as an alternative oncogenic driver in tumors lacking MYB alterations [8], [9]. The immunohistochemical marker MYB was frequently used in differentiating ACC from other benign and malignant salivary gland neoplasms [4], [9], [10]. The Wnt/β-catenin signaling pathway encompasses a group of proteins that are essential for regulating embryonic development and maintaining tissue homeostasis in adults [12]. WNT signaling is constitutively activated by mutations affecting exon 3 of the CTNNB1 gene, which are the driver mutations of some salivary gland tumors, including BCA and BCAC [5], [13]. The lymphoid enhancer-binding factor 1 (LEF1), a downstream indicator of WNT pathway activity, is typically activated in the nucleus [14]. LEF1 can serve as a substitute marker, which is usually simpler to evaluate and interpret than β-catenin [15], [16], [17].

In this study, we evaluated the expression of a panel of immunohistochemical markers (MYB, MYBL1, β-catenin, and LEF1) in various basaloid salivary gland tumors and validated their utility for differential diagnosis.