Specific alterations involving MAPK genes (MAP3K8 fusions, MAP3K3 fusions) have been recently detected in a subgroup of spitzoid neoplasms that seem to constitute a distinctive clinicopathologic group, occur mostly in younger patients (median age 18 years) and present with atypical histologic features associated with frequent homozygous deletion of CDKN2A, qualifying a high proportion of them as Spitz melanoma (malignant Spitz tumor). Apart from lesions with spitzoid morphology harboring MAP3K8 or MAP3K3 fusion, a single case with MAP2K1 deletion has been identified. The authors report herein 4 melanocytic lesions with a MAP2K1 mutation, all showing similar microscopic appearances, including spitzoid cytology and dysplastic architectural features, resembling so-called SPARK nevus, suggesting that these lesions may represent another distinctive group.
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