Julie R. Lange, Leslie A. Fecher, William H. Sharfman, Rhoda M. Alani, Radha Mikkilineni, Suzanne L. Topalian, and Charles M. Balch
S U M M ARY
P OI NT S
tumor ≥4 mm), either with interferonalfa or as part of a clinical trial. Although interferon has been approved by the U.S. Food and Drug Administration (FDA) for high-risk patients, subsequent clinical trialsof interferon have shown a consistent disease-free survival (DFS) beneﬁt, but failed to show a clear overall survival beneﬁt; thus its routine use remains controversial. For advanced melanoma, dacarbazine (DTIC) and high-dose interleukin-2 (IL-2) are the only FDA-approved agents. Durable complete responses with highdose IL-2 are possible, and this therapy should be considered for all eligiblepatients. A number of promising new molecular and immunologic agents are under active investigation.
• The incidence of melanoma has risen dramatically over the past few decades. • Approximately 59,940 new cases of invasive melanoma are diagnosed each year in the United States, and it is estimated that 1 in 49 men and 1 in 73 women in the United States will be diagnosed with melanoma intheir lifetime.
Etiology and Epidemiology
• Risk of melanoma is strongly related to exposure to ultraviolet irradiation, and to a susceptible host phenotype: fair hair and skin, a tendency to burn, and numerous benign or atypical nevi. • Family and personal history of skin cancers also are important risk factors.
• Staging categorization of the primary lesion relies on accuratedetermination of the thickness of the lesion and determination of whether histologic ulceration is present. • The current American Joint Committee on Cancer (AJCC) 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.
•Primary Therapy and Salvage Therapy: Surgical
• All primary melanomas need wide local excision for local control. • Margins of excision are determined by the thickness of the primary lesion. • For patients presenting with a new primary melanoma ≥1 mm and a clinically negative regional node basin, sentinel node biopsy is used to determine the node status. • For patients with known metastaticnodes, regional node dissection is performed.
• The most important pathologic features of the primary lesion are thickness (in mm), presence or absence of histologic ulceration, and mitotic rate
• Many primary melanomas display typical features of border irregularity and variegated pigmentation. • Some melanomas may be recognized by a patient’s report of achange in the size or color of a pigmented lesion or by a report of itching or bleeding from a skin lesion. • Other primary melanomas may lack these features and, therefore, may be more difﬁcult to recognize.
• Prognosis is strongly related to the thickness and ulceration status of the tumor at its original presentation and the nodal status. • Today, most patients are diagnosedearly and usually have an excellent prognosis. • Once disseminated metastatic disease is recognized, median survival is approximately 6 to 9 months. • With current therapies, the outcome for patients with advanced disease is poor. Further research is needed to identify therapeutic targets and to improve systemic therapies for melanoma patients.
• Primary surgical therapy usually canbe accomplished with preservation of full function and reasonable cosmesis. Node dissection carries a risk of lymphedema.
Differential Diagnosis and Staging
• Any suspicious lesion or questionable new or changing lesion should have a full-thickness biopsy.
Primary Therapy and Salvage Therapy: Systemic
• Adjuvant therapy should be offered to patients with high-risk, resected disease...