Abstract

Subungual melanomas accounting for 0.7-3.5% of all melanomas. Multiple concurrent subungual melanomas are extremely rare, with only three cases previously reported in the English literature. Here, we present a unique case of three synchronous subungual melanomas. A 41-year-old woman with a history of left shin melanoma and bulky metastasis to left femoral and iliac lymph nodes (BRAFpV600E-positive), was treated with surgery and high-dose interferon therapy, 4 years prior. While under close clinical observation, she developed three new-onset longitudinal melanonychia in a 2-month period, involving left thumb, left 4^th toe and right 3^rd finger. Nail matrix biopsies revealed melanoma in-situ in left thumb and left 4^th toe, characterized by disorganized, confluent and pagetoid intraepithelial proliferation of mostly single cytologically atypical melanocytes, followed by surgical excision. The atypical melanocytic proliferation was most pronounced in the right middle finger with at least melanoma in-situ, but invasion could not be excluded due to extensive tissue fragmentation and was treated by amputation of distal phalanx. Due to patient’s history of metastatic melanoma, the possibility of metastasis was considered, but the subungual melanomas were negative for BRAFpV600E by immunohistochemistry. The patient subsequently developed recurrence of left inguinal metastatic melanoma, treated with BRAF and MEK inhibitors, during which she developed longitudinal melanonychia of left 4^th finger, biopsy of which revealed subepithelial melanophages only. She eventually progressed to leptomeningeal disease and is currently undergoing intrathecal aldesleukin, nivolumab and radiation therapy. This case highlights the diagnostic challenge and the need for multidisciplinary management of synchronous subungual melanomas.