Clinical and Driver Mutation Analysis of Melanoma of Unknown Primary and a Review of Japanese Literature

The clinical features and genotype of melanoma of unknown primary (MUP) in Japan are unknown. We performed a clinical investigation and genetic analysis of 6 patients with MUP who had visited our department during the past 15 years. The average age of the patients was 56.6 years and the ratio of males to females was 1 : 1. The disease was diagnosed with subcutaneous tumors in 4 cases and images in 2 cases. The metastatic sites at the first visit were all lymph nodes, followed by metastases into the subcutaneous, lung, brain, bone, and liver tissues. The survival time of the fatal 4 cases was 10.5 months. Driver mutations were detected in 4 out of 6 patients. The BRAFV600E mutation was found in 2 patients. Two other patients had gene mutations of BRAFV600E + CDK4 R24C and EPHB6 G404S + PDGFRA E996K + ERBB4 E452K, respectively. MUP resembles the genotype of 29 cases of primary cutaneous melanoma.