Diagnostic and therapeutic challenges in cutaneous and mucosal melanoma: a literature review.

Current scientific research demonstrates that cutaneous melanoma and mucosal melanoma are two distinct disease entities, considering the complexities of their diagnosis and treatment. Mucosal melanoma is characterized by a significantly poorer prognosis than cutaneous melanoma, with a 5-year overall survival (OS) rate of less than 20%. Surgical resection remains the gold standard of management; however, there is currently a paradigm shift away from routine, complication-prone completion lymph node dissection toward selective surveillance using serial ultrasound. This approach significantly improves patients’ quality of life without negatively impacting OS. Due to anatomical constraints (e.g., oral cavity, paranasal sinuses), narrow resection margins are supplemented with radiotherapy. Although this effectively reduces the risk of local recurrence, it does not prolong OS due to rapid distant metastasis, which occurs in approximately half of the patients within the first year. In systemic treatment, the standard of care involves dual immune checkpoint blockade (nivolumab plus ipilimumab) as well as BRAF/MEK and tyrosine kinase inhibitors (imatinib, nilotinib). The efficacy of immunotherapy in mucosal melanoma is significantly lower compared to that in cutaneous melanoma. The application of nivolumab plus ipilimumab yields slightly better outcomes than anti-PD-1 monotherapy; however, the proportion of patients achieving a durable response to treatment and the long-term survival rates remain highly unsatisfactory. The insufficient efficacy of current treatment paradigms highlights a critical need for the development of novel strategies. These include the broader application of Mohs micrographic surgery and the implementation of experimental therapies currently under investigation, such as anti-angiogenic treatments, oncolytic viruses, vaccines, adoptive T-cell therapies (e.g. CAR-T), bispecific antibodies (e.g. brenetafusp), and gut microbiome modulation.