Mucosal melanoma

Mucosal melanoma arises from melanocytes in the sinonasal tract, oral cavity, anorectum, vulva, vagina and, rarely, the urinary tract, biliary tree and oesophagus. It is not caused by ultraviolet light and its genome differs from cutaneous melanoma: a low mutation burden, frequent structural rearrangements and amplifications, KIT mutations or amplifications in a substantial minority, SF3B1 mutations, and BRAF V600 mutations in only about one in twenty. Presentation is late because the sites are hidden, and most patients have thick, often ulcerated or multifocal primaries; five-year survival is well below that of cutaneous melanoma at any stage.

Surgery is the mainstay for localised disease, but local recurrence is frequent and radical operations at head and neck or anorectal sites carry heavy morbidity, so postoperative radiotherapy is often added to improve local control even though it has not lengthened survival. In China, where the disease is common, a randomised trial found adjuvant temozolomide-cisplatin chemotherapy improved relapse-free and overall survival over high-dose interferon and observation, and it remains an option there. Sentinel node biopsy is less standardised than in cutaneous disease.

Immunotherapy works less well than in cutaneous melanoma: in the pooled analysis of the nivolumab trials the response rate was 23 percent with nivolumab alone and 37 percent with nivolumab plus ipilimumab, and pembrolizumab produced responses in 19 percent in the pooled KEYNOTE analysis. Chinese investigators combined toripalimab with the VEGF receptor inhibitor axitinib and reported responses in nearly half of chemotherapy-naive patients in phase 1b, and the pairing is being tested in randomised trials. Imatinib produces responses in roughly one in four tumours with KIT exon 11 or 13 mutations, and the MEK inhibitor tunlametinib is approved in China for NRAS-mutant melanoma, a group that includes many mucosal tumours.