Melanocytic Neoplasm With KIT and APC Mutations: A New Subtype of Melanocytoma?

Abstract

We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. β-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm2). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes (CDKN2A, MYB, MYC, CCND1 and RREB1). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).