Low-grade spitz melanocytoma with novel PTMA: ALK fusion

Summary: Abstract Body: Background: Spitz melanocytomas are considered intermediate low-grade melanocytic neoplasms with low malignant potential, but with histomorphologic and/or genetic signatures that place them on the pathway between nevus and melanoma. Recent advances in molecular diagnostics have identified recurrent gene fusions, including ALK (Anaplastic Lymphoma Kinase), as distinguishing features in spitzoid neoplasms. Prothymosin Alpha (PTMA), a nuclear protein involved in transcription regulation and apoptosis, may enhance ALK signaling when fused, contributing to the pathogenesis of melanocytic tumors. We present the first reported case of a Spitz melanocytoma with a PTMA-ALK fusion, offering insights into its clinical presentation, molecular profile, and recommended management strategies. Case Report: An 18-year-old male presented with a pigmented lesion on the right superior flank. Physical examination revealed a well-circumscribed, 1.8 cm dark nodule. Biopsy showed a compound melanocytic proliferation of heavily pigmented, spindled, and epithelioid melanocytes. Cytologic features included pigmented cytoplasm, enlarged nuclei with prominent nucleoli, and occasional nuclear pseudoinclusions. There was focal Ki-67 expression. Immunohistochemistry demonstrated strong Melan-A positivity, retained P16, and negative PRAME staining. Molecular testing identified a novel PTMA-ALK fusion. The lesion was classified as a low-grade Spitz melanocytoma. Conclusion: This case presents the first reported Spitz melanocytoma with a PTMA-ALK fusion. The novel rearrangement emphasizes the potential oncogenic role of ALK signaling in melanocytic tumors, with implications for both prognosis and therapeutic strategies. While ALK fusions in spitzoid tumors are typically associated with low-grade behavior, the intermediate-grade features and incomplete initial excision in this case warranted full-thickness resection with clear margins to reduce recurrence risk. Rebecca Fliorent², Michael Lee¹, Adam Rubin¹, Alexandra Flamm¹, George Jour¹, Ata S. Moshiri¹ 1. Dermatopathology, NYU Langone Health, New York, NY, United States. 2. Rowan-Virtua School of Osteopathic Medicine, Stratford, NJ, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance