Early detection of melanoma: the best strategy for a favorable prognosis

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Of all the skin tumors, cutaneous melanoma represents the greatest challenge for secondary prevention and early detection aimed at finding early curable disease. Melanoma is a highly malignant tumor with an alarming increase in incidence over the last few decades, among the highest in cancer, that is directly related to a rise in the mortality rate. The current lifetime risk is 1 in 71 Americans.1 These statistics compel physicians to make the utmost effort to detect melanomas at an early, treatable stage when simple excision can provide a cure. Most melanomas develop in the skin and are clinically classified into four major subtypes, with recent identification of additional variants (Table 1). Melanoma can arise in any melanocyte-containing tissue, including the uveal tract, central nervous system, and mucosal surfaces, including the oral cavity, vulva, vagina, nasopharynx, paranasal sinuses, tracheobronchial tree, anal canal, and urinary tract. Frequently neglected are subungual melanomas, which are often mistaken for benign or traumatic conditions of the nailbed; they occur at a higher frequency in African Americans, who have 12% of all subungual melanomas in contrast to 1% of cutaneous melanomas.2 Malignant melanoma is very rare before the age of 20, accounting for 2% of cases,1 of which 0.3%–0.4% are prepubertal melanomas.1 Childhood melanoma is divided into five categories based on the mode of occurrence3: development from healthy skin, accounting for most cases; transformation from a giant congenital nevus, accounting for a third of the cases4,5; transplacental transmission from mother to fetus; transformation of a pre-existing nevus; and associated conditions like xeroderma pigmentosum, albinism, or dysplastic nevus syndrome. Melanoma is the second most common cancer in men aged 30–49 years and the fourth most common cancer in men aged 50–59.6 It is the most common cancer in women aged 25–29 and second only to breast cancer in women aged 30–35 years.7 The overall incidence is highest in New Zealand and Australia, exceeding 55 per 100,000.8 These rates have risen sharply with a more modest increase in the mortality rate, mainly due to a substantial increase in melanoma surveillance that has led to identification of early, curable melanomas and reduction in the emergence of advanced disease and melanoma-related mortality.9 Melanoma incidence and mortality rates are influenced by gender and geography. In Europe, melanoma occurs at a higher frequency among women than men, whereas in Australia and America the incidence is slightly higher in men.10 Mortality rate is higher in southern than in northern European countries and rose 3% per year for men and 1% for women for each year from 1976 to 19876 (Table 2). Large studies have shown a female survival advantage over men of 22% and a disease-free survival advantage at 5 years of 17% for woman over men.11 This survival advantage was most commonly seen in early stages of the disease and was often lost in advanced disease. The most pronounced discrepancy occurred in the progression of the disease to stage III, while there was no evident survival advantage at further progression to stage IV. This indicates that female sex steroids could slow the tumor progression at early stages of the disease.12 With regard to hormone status, the female advantage was equally strong in preand post-menopausal periods in some studies13 but restricted to premenopausal women in other studies.14 Despite widespread research, the basis for the female survival advantage is still not established. It has been suggested that estrogenic compounds reduce the invasion of human melanoma cells through fibronectin, as opposed to androgenic compounds, which seem to have no anti-invasive capacities.12,15 How estrogenic compounds affect melanoma cell invasion through fibronectin remains to be determined. Another known effect of estradiol, progesterone, and dihydrotestosterone is their ability to inhibit interleuFrom the Department of Dermatology, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Address correspondence to Sarah Brenner, MD, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6 Weizman St., Tel Aviv 64239, Israel. E-mail address: derma@tasmc.health.gov.il