Diagnosis and treatment of KIT-mutant metastatic melanoma

A 52-year-old man has unresectable locally recurrent melanoma of the left foot (Fig 1) and pulmonary metastases. Nine months before this presentation, he underwent a wide local excision and sentinel node biopsy for an acral melanoma on his left heel. Pathology disclosed Breslow thickness of 4.8 mm, Clark level IV, and tumor ulceration with a mitotic rate of 37 mitoses/mm(2). Both sentinel nodes in the left groin were positive for melanoma cells, which expressed S100, HMB45, and melan A. At subsequent left inguinal dissection, seven more nodes showed no additional nodal metastases. Within 3 months of his original surgery, the patient developed a local recurrence in the foot, and over the subsequent 6 months, he underwent serial local excisions and topical diphencyprone treatment. A recent staging scan showed at least 20 foci of in-transit disease in the left lower leg and foot, as well as a solitary lung metastasis (12 mm). His Eastern Cooperative Oncology Group performance status is 1, with no significant comorbidities. High-resolution melt followed by sequencing of an in-transit metastasis showed there is no BRAF exon 15 mutation. However, Sanger sequencing of KIT exons 9, 11, 13, and 17, performed as screening for a clinical trial enrolling patients with metastatic acral and mucosal melanomas, showed an exon 13 K642E mutation.