Therapeutic challenges in oral mucosal melanoma: two clinical cases

Background: Mucosal melanoma (MM) is a rare and aggressive malignancy (<2% of all melanomas), most frequently arising in the head and neck mucosa and often requiring systemic therapy. Results: CASE 1 A 67-year-old woman presented with oral MM featuring a nodular area of granulomatous inflammation confirmed by biopsy.She was considered not suitable for curative surgical resection.Treatment with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) was initiated, together with topical imiquimod administered three times weekly using an intraoral splint (IS).After four cycles, a major clinical response was achieved; however, treatment was interrupted due to grade 4 immune-related hepatitis.Following complete resolution of hepatitis, nivolumab was resumed.Three months later, local progression was histologically confirmed.Axitinib (5 mg/12h) was subsequently added, achieving an excellent clinical response and a partial pathological response (viable tumoral cells [VTC]: 30%) at three months, which has been sustained for an additional six months to date, without evidence of distant metastasis.CASE 2 A 60-year-old man presented with an oral mass of 36 20 mm, histologically confirmed as MM.Baseline whole-body CT revealed bone involvement and multiple locoregional lymph nodes, without evidence of distant metastases.Curative surgery was ruled out, and treatment with ipilimumab and nivolumab plus topical imiquimod delivered via an intraoral splint was initiated.Early local tumor progression led to surgical debulking for symptomatic control.After the third cycle, dual immunotherapy was discontinued due to grade 2 immune-related nephritis, which resolved with immunosuppressive therapy.As the debulking specimen showed VTC >80%, axitinib (5mg/12h) was added to nivolumab, together with local and locoregional radiotherapy to the primary tumor bed and involved lymph nodes.An initial partial response was observed two months after initiation of this last-line treatment.Conclusions: MM exhibits aggressive behavior and represents a significant therapeutic challenge; ipilimumab plus nivolumab should be considered as first-line option in non-surgical cases.However, immunotherapy alone may be insufficient and is frequently associated with immune-related toxicity.Topical imiquimod administered to the oral mucosa using an intraoral splint represents a simple but rarely reported adjunctive strategy.The intraoral splint enables effective topical drug delivery in this anatomically challenging site and facilitates sustained local drug exposure.