Track: Case Reports

Topic: Melanocytic Neoplasms

Abstract:

Spitz melanocytic neoplasms are one of the most challenging areas in dermatopathology that are defined genomically by HRAS activating mutations or kinase fusions involving BRAF, ALK-1, ROS-1, RET, MET, MAPK or NTRK. Herein, we present a case of atypical Spitz tumor (Spitz melanocytoma) with a novel VIM::NTRK3 fusion. A 51-year-old male presented with a nodule on the left foot with a clinical suspicion of melanoma. Excisional biopsy revealed an atypical compound melanocytic proliferation with Spitzoid features. The junctional component showed few non-confluent nests and single units of severely atypical spindled and epithelioid melanocytes along the dermal-epidermal junction, with minimal pagetoid scatter. The dermal component showed variably sized fascicles, nests, and single units of severely atypical spindled and epithelioid melanocytes in a fibrotic stroma. The neoplasm extended into the deep reticular dermis. Lesional melanocytes had abundant amphophilic-glassy cytoplasm and ovoid, hyperchromatic nuclei, with variably prominent nucleoli. Immunohistochemistry revealed the cells were diffusely positive for SOX10, pan-TRK, and patchy Melan-A. P16 and BAP-1 expression were retained. Rare scattered junctional melanocytes (<25% of tumor cells) were PRAME positive. The tumor cells were negative for ALK-1, ROS-1, BRAF V600E, and RAS Q61R. Next-generation sequencing revealed a VIM::NTRK3 fusion, in keeping with Spitz lineage. VIM::NTRK3 fusion has been described in papillary thyroid cancer, but not melanocytic tumors. Previously reported NTRK3 fusion partners in Spitz tumor include ETV6, MYH9, and MYO5A. This finding furthers our understanding of the pathogenesis and molecular landscape of Spitz melanocytic tumors.

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Cuihong Wei, Bach Med