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

Abstract

Abstract: 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.