Track: Case Reports

Topic: Melanocytic Neoplasms

Abstract:

Spitz tumors are spindled and epithelioid melanocytic childhood neoplasms commonly driven by kinase fusions. The list of involved kinase genes continues to expand and many have been shown to correlate with distinctive histologic features. Herein we report a case of an atypical Spitz tumor (AST) with a rare gene fusion involving EHBP1 and RASGRF1 identified by transcriptome sequencing. A 26-year-old female with no significant past medical history presented with a left mid-upper back lesion. Histological examination revealed a predominately intradermal, roughly symmetric proliferation of epithelioid melanocytes distributed in small nests, cords, and single units in a fibrotic stroma. The melanocytes displayed enlarged pleomorphic nuclei and occasional hyperchromasia. Rare dermal mitoses (1/mm2) were identified. Additional immunohistochemical stains showed retained BAP1 and P16 expression and negative BRAF VE and PRAME stains. FISH testing was negative for copy number alterations targeting 6p25, 8q24, 11q13, and 9p21 loci. Whole transcriptome next generation sequencing identified fusion involving RASGRF1, a guanine nucleotide exchange factor for RAS protein and EHBP1, an adaptor protein involved in vesicular trafficking and autophagy. Rare fusions involving RASGRF1 result in activation by anchoring it to the cell membrane, ultimately leading to MAPK pathway activation. RASGRF1 fusions have been reported in three other spitzoid melanocytic lesions, one of which was also fused to EHBP1 and classified as a low-grade melanocytoma. Thus, combined with previous reports, our AST case represents a unique, biologically relevant kinase fusion with corresponding phenotypic characterization and advances our understanding of the histologically challenging and variegated AST

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Bethany Batson, MD PhD