Atypical Deep Penetrating Melanocytic Tumors and Melanomas With Beta Catenin Mutations. A Case Series

Deep penetrating nevus (DPN) is an uncommon type of benign melanocytic nevus with distinct clinicopathologic features. More recently, DPN-like borderline tumor (DPBT) and DPN-like melanoma have been described that show greater cytologic atypia and have metastatic potential. Although B-catenin is considered an important diagnostic confirmatory marker for DPN, the role of B-catenin mutations and other molecular features in the treatment of DPBT and DPN-like melanoma remains unclear. We report 3 cases of DPBTs, 1 DPN-like melanoma, and 1 B-catenin mutated acral melanoma, highlighting their clinical, pathologic, immunologic, and molecular features, including immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The DPBT showed B-catenin mutations and aberrant nuclear B-catenin expression and was negative for PRAME and PD-L1, and showed variable CD8 + T-cell infiltrates. Two of the 3 patients with DPBT showed lymph node involvement, received targeted immunotherapy, and all 3 are alive and free of disease. We also report clinical and molecular features and treatment response for the melanoma arising in a DPN and in the B-catenin mutated acral melanoma. DPBT is a distinct clinicopathologic–molecular entity. Specific mutations such as B-catenin in melanocytic neoplasms may have not only diagnostic implications but also implications for treatment including immunotherapies and other targeted therapies.