Fatal Spitz Melanoma With MAD1L1::BRAF Fusion: A Case Report and Literature Review

Spitz melanoma is extremely rare, and only a few cases of distant metastases have been reported. Herein, we describe a case of Spitz melanoma with multiple distant metastases. A 37-year-old woman presented with a 5.5-mm-diameter nodule on the right lower leg. She experienced multiple distant metastases, involving the lungs, liver, thyroid, stomach, ovary, bones, and skin, along with multiple lymph node metastases within 1 year. The patient succumbed to the disease 1 year and 6 months following the first excision. Histopathological examination revealed a dense distribution of large solid nests comprising large, atypical epithelioid melanocytes with abundant eosinophilic cytoplasm in the upper dermis. Diffuse PRAME and loss of p16 immunoexpression profiles were observed. Targeted DNA and Sanger sequencing revealed an in-frame MAD1L1(e16)::BRAF(e9) fusion in both primary tumor and metastatic subcutaneous lesion. A review of previously reported cases confirmed as Spitz melanoma with distant metastases (n = 7) revealed a broad age range (11-71 years, median 46 years), high mortality (5/7), frequent BRAF fusions (6/7), and recurrent TERT promotor mutations and CDKN2A/B deletions. This report adds valuable insights into our understanding of the clinical and genetic characteristics of Spitz melanoma with distant metastases.