Atypical Spitz Tumor With RET::MXT1 Gene Rearrangement in a 14-Year-Old Girl: An Integrated Histopathologic,...

Spitz tumors represent a heterogeneous group of melanocytic neoplasms ranging from benign Spitz nevi to malignant spitzoid melanoma. Atypical Spitz tumors (ASTs) occupy an intermediate category with uncertain biological potential and pose significant diagnostic challenges, particularly in pediatric patients. We report the case of a 14-year-old girl presenting with a recently changing pigmented lesion on the upper back. Histopathologic examination revealed an asymmetric melanocytic proliferation composed predominantly of epithelioid cells with limited mitotic activity and evidence of dermal maturation. Immunohistochemistry showed diffuse Melan-A and SOX10 positivity, retained p16 expression, a gradient HMB45 staining pattern, and negative PRAME expression. For diagnostic purpose, as a part of diagnosis, next-generation sequencing was performed and identified a RET::MXT1 gene fusion in the absence of additional pathogenic mutations or copy number alterations. To our knowledge, this is the first reported case showing this type of RET fusion. This case highlights the importance of an integrated morphologic, immunophenotypic, and molecular diagnostic approach in atypical spitzoid lesions. Identification of an isolated RET fusion supports classification within the Spitz tumor spectrum and provides valuable information for risk stratification and clinical management in pediatric patients.