Clinical, Morphologic, and Molecular Findings in MET Fusion Spitz Neoplasms

Characterizing the typical clinical, morphologic, and molecular findings of distinct subtypes of Spitz neoplasms may help facilitate diagnosis and management of these cases. Approximately 1%–2% of Spitz neoplasms have a MET fusion driver. However, there is minimal data in the current literature regarding this specific subtype of Spitz neoplasm. Most cases in our series (9/10) were diagnosed as atypical Spitz tumors, whereas 1 case was diagnosed as a Spitz nevus. We found 3 characteristic morphologic patterns, the first consisted of either expansile nests of spindle shaped spitzoid melanocytes with plexiform arrangement in the dermis forming a large nodular lesion or thin chords and fascicles of spindle shaped spitzoid melanocytes with a tightly interwoven plexiform pattern in the dermis forming a plaque-like architecture. The second pattern consisted of sheets of epithelioid melanocytes with spitzoid cytology, and the third pattern consisted of a both epithelioid and spindle shaped cytology with plexiform arrangement in the dermis as seen in various subtypes of Spitz neoplasms. Compared to a cohort of 81 control Spitz neoplasms, MET fusions were more likely to have spindle cytology and a plexiform growth pattern in the dermis. The most common fusion pattern was ZKSCAN1 (4/10). Copy number gains of the fusion gene were frequent, seen in 61% of cases. None of our cases had a TERT promoter mutation or homozygous deletions of CDKN2A . All of our patients had an uneventful clinical course with no evidence of recurrence after reexcision with average follow-up time of 35 months.