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The risk of hereditary cutaneous malignant melanoma was evaluated in 401 members of 14 families with an autosomal dominant form of melanoma. We documented 127 primary melanomas in 69 family members, including 39 new melanomas diagnosed in 22 study participants from the time of first examination through a maximum of 8 years of follow-up. The 39 newly diagnosed melanomas occurred only in family members with dysplastic nevi, a known precursor of familial melanoma. Of 77 patients with dysplastic nevus syndrome without prior melanomas, 4 developed their first melanoma during prospective follow-up, as compared with 0.03 cases expected. The prospective age-adjusted incidence for melanoma was 14.3/1000 patients with dysplastic nevus per year, with a cumulative melanoma risk (+/- SE) of 7.2% (+/- 3.6) at 8 years. The actuarial probability of melanoma developing in family members with dysplastic nevi was 56.0% (+/- 10.1) from age 20 to age 59. This study confirms that dysplastic nevi are clinical markers of high risk for, and precursors of, hereditary melanoma.
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