The MITF gene is an oncogenic transcription factor acting as a master gene of melanocyte homeostasis. The p.E318K MITF mutation has been associated with an increased melanoma risk and development of multiple primary melanomas (MPM). In all previous studies concerning melanoma, the p.E318K variant has been always reported in a heterozygous status. Herein, we report a MPM patient who carried the p.E318K MITF mutation in homozygosis, describing the dermoscopic and confocal features of his melanomas and melanocytic nevi. Dermoscopic and confocal images of MPM and of several melanocytic nevi were obtained by DermLite Photo®(3Gen, California) and Vivastack® (Vivascope ®1500, Germany), respectively. Mutational screening of all exons of CDKN2A, exon 2 of CDK4, exon 10 of MITF, the entire open reading frame of MC1R and genotyping of the p.S270N POT1 substitution were carried out by sequencing on germline DNA extracted from whole blood. The first melanoma was dermoscopically characterized by a peripheral atypical network, areas of negative pigment network and different degrees of pinkish and grey pigmentation. At the confocal examination, a severe cyto-architectural atypia was observed, with polymorphous cells and atypical melanocytic nests at the junctional layer. The second melanoma was characterized by an irregular brown network with a widespread negative pigment network. Confocal examination showed intraepidermal and junctional atypical melanocytic proliferation and architectural disarray. Overall, two main dermoscopic nevus patterns were observed: a hypopigmented type with a predominant dermal-congenital pattern and a pigmented type with a predominant reticular/homogenous pattern. Sequencing data revealed the presence of the *500C>G polymorphism in CDKN2A, a homozygous p.E318K mutation in MITF and the p.R160W variant in MC1R. No were found in CDK4 and POT1 genes. Of note, this is the first case of the MITF p.E318K mutation occurring in homozygosis in melanoma.

Clinical, dermoscopic and confocal features of nevi and melanomas in a multiple primary melanoma patient with the MITF p.E318K homozygous mutation