Abstract

Recent advances in molecular biology have led to significant discoveries about the pathogenesis of Spitz neoplasms. In this study, we attempt to further expand upon the clinicopathologic features of ROS1-associated Spitz nevi. A database search at our institution identified 13 cases of Spitz neoplasms with ROS1 expression by immunohistochemistry. Ten cases were benign while three were found to be atypical (no cases of melanoma were identified). There was a female predilection (>2:1 female:male), and the predominant anatomic site was the lower extremity (38%). Sixty percent of the lesions had a plaque-like configuration (less commonly were nodular, wedge-shaped or macular). Most of the lesions were compound (9/13) while few were intradermal (3/13) with one junctional case (1/13). The predominant pattern was plexiform (8/13) (3/13 were angiomatoid and 2/13 were desmoplastic). Pagetoid growth was appreciated in 5/13 cases. Cytologically, most cases demonstrated mixed epithelioid-spindled forms and other commonly seen features included epidermal hyperplasia, Kamino bodies, and vertically oriented junctional nests with artifactual clefts. For the first time, to our knowledge, we identified two cases with Reed-like features (abundant melanin pigmentation in junctional nests with a spindled cytomorphology). A complete excision was performed for five cases and none showed recurrence or metastasis at follow-up. Herein we aim to expand the clinical and histomorphologic spectrum of Spitz nevi with ROS1 overexpression. Although we were unable to correlate a distinct histomorphologic feature with this driver mutation, we identified for the first time two cases with Reed-like features.