Melanoma is a form of cancer that originates in melanocytes, the cells responsible for producing the pigment melanin. Although widely recognized as a skin cancer, its presence in the brain represents a serious medical complication. Recent scientific advances have introduced new treatment options that have improved outcomes for many patients facing this diagnosis. The management of this condition requires a multi-disciplinary approach, combining local control methods with sophisticated systemic therapies.
Primary vs. Metastatic Brain Melanoma
The vast majority of melanoma cases found in the central nervous system are metastatic, resulting from the spread of a primary tumor elsewhere in the body. This occurs when original cancer cells travel through the bloodstream or lymphatic system to form secondary tumors in the brain. For patients with late-stage, or Stage IV, melanoma, the likelihood of developing brain metastases is high, with over 60% of patients experiencing this complication.
In rare instances, melanoma can arise directly within the brain or spinal cord, termed primary central nervous system (CNS) melanoma. This form develops from melanocytes that reside in the meninges, the protective layers of tissue covering the brain and spinal cord. When the disease spreads diffusely throughout these layers, it is described as leptomeningeal disease. Understanding whether the tumor is primary or metastatic is fundamental, as metastatic spread from the skin or eye is the dominant concern and guides the treatment strategy.
Recognizing Neurological Signs and Symptoms
The signs of melanoma in the brain often stem from tumors occupying space, leading to increased pressure within the skull or disrupting normal brain function. Headaches are one of the most common symptoms reported, occurring in 40% to 50% of patients. These headaches may be persistent, worsening over time, and sometimes accompanied by nausea or vomiting.
Seizures are a frequent presentation, resulting from the irritation of brain tissue by the tumor mass. Depending on the tumor’s location, patients may experience focal neurological deficits. This can manifest as weakness or paralysis on one side of the body, changes in vision, or difficulty with balance and coordination. Cognitive changes, such as confusion, memory issues, or shifts in personality, may also become apparent as the disease progresses.
Diagnostic Imaging and Confirmation
When neurological symptoms arise in a patient with a history of melanoma, doctors rely on advanced imaging to confirm the presence and extent of brain lesions. Magnetic Resonance Imaging (MRI) is considered the most sensitive diagnostic technique and the gold standard for detecting brain metastases. The MRI is typically performed with a contrast agent to make the tumors stand out clearly against the surrounding healthy brain tissue.
Computed Tomography (CT) scans may be used for initial screening or in emergency situations, but they lack the fine detail and sensitivity of MRI for small lesions. Melanoma lesions sometimes have distinctive features on imaging, such as T1-weighted hyperintensity, due to the presence of melanin pigment or blood products within the tumor. While imaging can strongly suggest the diagnosis, tissue sampling through a biopsy or surgical resection is sometimes required to definitively confirm malignancy and analyze the tumor’s molecular characteristics. CSF analysis may also be performed if leptomeningeal disease is suspected to look for cancer cells.
Targeted Therapeutic Strategies
The treatment for brain melanoma involves a combination of local and systemic therapies, often requiring a team of specialists. Local control options include surgical resection and radiation therapy, which are used to manage the tumor. Surgery is primarily considered for a single, large, or symptomatic tumor that is easily accessible and causing severe symptoms.
Radiation therapy is frequently used, particularly the technique known as Stereotactic Radiosurgery (SRS), which delivers a focused, intense dose of radiation to small, limited lesions. This approach minimizes damage to the surrounding healthy brain tissue and is preferred over Whole-Brain Radiation Therapy (WBRT) due to its potential for cognitive side effects. WBRT is generally reserved for cases with numerous lesions or diffuse disease.
Systemic therapies represent recent advances in treating melanoma that has spread to the brain, as these treatments are designed to cross the blood-brain barrier to attack cancer cells throughout the CNS. Immunotherapy, particularly the use of immune checkpoint inhibitors like nivolumab and pembrolizumab, works by unleashing the patient’s own immune system to recognize and destroy cancer cells. Combining two types of inhibitors, such as nivolumab and ipilimumab, has demonstrated improved overall survival rates for patients with asymptomatic brain metastases.
Targeted therapy is another systemic option, especially for patients whose tumors harbor specific genetic mutations. The BRAF V600 mutation is found in approximately half of all melanoma cases and makes the cancer susceptible to a drug combination of a BRAF inhibitor and a MEK inhibitor. Examples of these combinations include dabrafenib plus trametinib, which have shown high response rates and tumor shrinkage in the brain. The choice between immunotherapy and targeted therapy often depends on the tumor’s molecular profile and the patient’s overall health, but both have revolutionized the prognosis associated with melanoma of the brain.