Abstract

Fusion-driven serine/threonine kinase activation plays an important role in the pathogenesis of melanocytic tumors.  While RAF1 fusions have been identified in a small subset of melanomas, they have very rarely been reported in premalignant melanocytic tumors.  We present a case of a 7-year-old boy with a nodule on the ankle, morphologically and immunohistochemically consistent with a Spitz melanocytoma that exhibited loss of p16 expression, partial loss of Melan-A and a mildly increased Ki-67 proliferation index without PRAME expression. Next-generation sequencing revealed a GOLGA4-RAF1 kinase fusion with a low mutational burden. Single nucleotide polymorphism microarray identified a heterozygous chromosome 9 loss without additional abnormalities. Transcriptome analysis indicated under-expression of CDKN2A. Overall, the findings failed to meet the diagnostic criteria for melanoma, and therefore this lesion was best classified as a melanocytoma.  The patient underwent successful wide local surgical excision with no residuum. To the authors’ knowledge, this is the first reported Spitz melanocytoma with a GOLGA4-RAF1 fusion. Our case corroborates a possible propensity of RAF1 fusion melanocytic tumors to arise in pediatric patients. In comparison to melanomas, the rarity of this particular fusion in melanocytomas may suggest the possibility of rapid malignant transformation, and patients diagnosed with this entity should be monitored closely.