Melanoma
Tara C. Gangadhar, Leslie A. Fecher, Chris J. Miller, Giorgos Karakousis, Robert Vonderheide, George Xu and Lynn M. Schuchter
Summary of Key Points
Incidence
• The incidence of melanoma has increased dramatically during the past few decades.
• Approximately 76,250 new cases of invasive melanoma are diagnosed each year in the United States, and it is estimated that 1 in 36 men and 1 in 55 women in the United States will be diagnosed with melanoma in their lifetime.
Biologic Characteristics
• The risk of melanoma is strongly related to exposure to ultraviolet irradiation; people with fair hair and skin, a tendency to burn, and numerous benign or atypical nevi are also at increased risk.
• Approximately 50% of melanomas have a somatic activating mutation in BRAF.
• The important pathologic features of the primary lesion are thickness (in millimeters), the presence or absence of histologic ulceration, and the mitotic rate, all of which have prognostic value.
Staging Evaluation
• A full-thickness biopsy should be performed for any suspicious, new, or changing lesion; an excisional biopsied is preferred.
• The current American Joint Committee on Cancer staging system includes the thickness and presence or absence of ulceration of the primary tumor, the number of positive nodes, whether the nodes are microscopically or macroscopically positive, and whether distant disease is present.
• The extent of radiologic staging evaluation depends on the risk of recurrence. In general, computed tomography or positron emission tomography/computed tomography imaging can be considered for patients with stage III melanoma.
Primary Therapy
• Surgery is the primary treatment for melanoma. All primary melanomas require a wide local excision for local control.
• The margins of wide excision are determined by the thickness of the primary lesion.
• Sentinel lymph node mapping is a useful staging procedure for melanoma and provides prognostic information.
• A sentinel lymph node biopsy should be offered to patients with melanomas >1 mm in thickness or melanomas ≤1 mm that are associated with either ulceration or a mitotic rate >1 mitosis/mm2 and can be considered for patients with other high-risk features (e.g., size >0.75 mm, lymphovascular invasion, or Clark level IV).
• The current standard of care is to offer patients with known nodal involvement a regional completion lymph node dissection.
Treatment of Metastatic Disease
• The median survival for patients with melanoma after distant metastatic disease has been identified is approximately 9 to 12 months.
• Treatment options include molecularly targeted therapy, immune therapy, cytotoxic chemotherapy, and participation in clinical trials.
• All patients with advanced melanoma should have their tumor tissue assessed for the presence or absence of the BRAF V600 E mutation. The presence of the mutation is predictive of response to targeted therapy with BRAF inhibitors.
• Immune therapy options include CTLA-4 inhibition with ipilimumab, high-dose interleukin-2, and clinical trials.
• Cytotoxic chemotherapy options include dacarbazine-based or temozolomide-based therapy.
• Additional supportive and palliative care options should be considered for all patients; brain metastases are managed with surgery and/or radiation therapy, depending on the size and number of lesions.
