Histological and genetic features of 51 Melanocytic Neoplasms with Protein Kinase C fusion genes

Fusion genes involving homologues of protein kinase C (PKC) have been identified in a variety of tumors. We report the clinical and histological presentation of 51 cutaneous melanocytic neoplasms with a PKC-fusion gene (involving PRKCA in 35 cases, PRKCB in 15 cases, and PRKCG in a single case). Most tumors were in young adults (median age 29.5; range 1-73), but some presented in newborns. Histologically, 42 tumors were classified as benign, presenting predominantly as biphasic dermal proliferation (88%) with nests of small melanocytes surrounded by fibrosis with haphazardly arranged spindled and dendritic melanocytes, resembling those reported as "combined blue nevi." Most tumors (60%) were heavily pigmented, and in 15%, hyperpigmented epithelioid melanocytes were present at the dermo-epidermal junction. Two lesions were paucicellular and showed marked sclerosis. Three tumors, including two proliferating nodules, were considered intermediate grade. Six tumors had sheets of atypical melanocytes infiltrating the dermis and were classified as melanomas. Two of the melanomas displayed loss of BAP1 nuclear expression. The median follow-up time was 12 months, with 1 patient alive with metastatic disease and 1 dying of their melanoma. These results suggest that melanocytic tumors with PKC fusion genes have characteristic histopathological features, which are more similar to blue nevi than to pigmented epithelioid melanocytomas. As is the case with GNA-mutated blue nevi, they can progress to melanomas via BAP1 inactivation and metastasize.