Spitz melanocytoma with AKAP9::BRAF fusion: clinicopathologic and molecular insights

Spitz melanocytoma is a melanocytic neoplasm of intermediate malignant potential. BRAF fusions are rare in Spitz tumors, and AKAP9::BRAF rearrangements are exceptionally uncommon. We describe the clinicopathological and molecular features of a Spitz melanocytoma in a 41-year-old woman, analyzed by next-generation sequencing (NGS). The lesion was a well-circumscribed dermal proliferation of spindle melanocytes within a collagen-rich stroma, lacking cytological atypia, mitoses, or necrosis. Immunohistochemistry demonstrated positivity for S100, SOX10, and MART1, weak HMB45 staining, and a very low proliferative index (<1%) on MART1/Ki-67; preferentially expressed antigen in melanoma protein (PRAME) expression was weak and focal. NGS identified an AKAP9 (exon 32)::BRAF (exon 9) fusion, without TERT promoter mutations or other high-risk alterations. This case highlights a rare molecular subset of Spitz melanocytoma and underscores the importance of integrated molecular and histopathological assessment for accurate diagnosis, prognostic evaluation, and potential targeted therapy.