Abstract
The recent introduction of immunotherapy and targeted therapy has substantially enriched the therapeutic landscape of metastatic melanoma. However, cerebral metastases remain unrelenting entities with atypical metabolic and genetic profiles compared to extracranial metastases, requiring combined approaches with local ablative treatment to alleviate symptoms, prevent recurrence and restore patients' biological and psychological resources for fighting malignancy. This paper aims to provide the latest scientific evidence about the rationale and timing of treatment, emphasizing the complementary roles of surgery, radiotherapy, and systemic therapy in eradicating brain metastases, with a special focus on the distinct response of intracranial and extracranial disease, which are regarded as separate molecular entities. To illustrate the complexity of designing individualized therapeutic schemes, we report a case of delayed BRAF-mutant diagnosis, an aggressive forearm melanoma, in a presumed psychiatric patient whose symptoms were caused by cerebral melanoma metastases. The decision to administer molecularly targeted therapy was dictated by the urgency of diminishing the tumor burden for symptom control, due to potentially life-threatening complications caused by the flourishing of extracranial disease in locations rarely reported in living patients, further proving the necessity of multidisciplinary management.