Fundamentals of Cancer Prevention by David Alberts & Lisa M. Hess

Author:David Alberts & Lisa M. Hess
Language: eng
Format: epub
Publisher: Springer Berlin Heidelberg, Berlin, Heidelberg

Based on histological features, melanoma development has been described by Li and Herlyn as follows: (1) common acquired and congenital nevi with normal melanocytes that have a finite lifespan and no cytogenetic abnormalities, (2) DN that displays both cellular and architectural atypia, (3) radial growth of a melanoma, (4) vertical growth phase of the primary melanoma, and (5) metastatic melanoma (Li and Herlyn 2000).

While there remains controversy over whether DNs progress to melanoma, it is very evident that DNs confer a major risk for melanoma (Farber et al. 2012; Elder 2010). DNs are found at a much higher frequency in patients with a history of melanoma. Prevalence rates range from 34 to 59 % (Farber et al. 2012). One study demonstrated that on average, 34 % of patients with melanoma had DN, in comparison with 11 % of control subjects. Relative risk ranged from 1.0 to 16.7 for melanoma in the presence of DN. Several studies also reported an increased risk for melanoma with an increase in the number of DN. Cohort studies of patients with familial DN have also provided evidence for presence of DN as a risk factor for the development of new melanomas (Greene 1997). In a retrospective study drawn from 820 patients diagnosed with a first primary cutaneous melanoma, 82 % of 50 examined patients with multiple melanomas were clinically diagnosed with DN (Stam-Posthuma et al. 2001). Histological confirmation was demonstrated in 78.0 % of these patients, and 16 of 37 patients had more than 30 clinically diagnosed DNs, 8 patients had 11–20 DNs, 4 patients had 21–30 DNs, and 9 patients had 1 DN. Finally, prospective studies have concluded that patients with DN and no family history also have an increased risk of melanoma (Greene 1997).

Other studies have investigated the idea that melanoma actually arises from DN (Marras et al. 1999). One such report performed cytogenetic analyses of DN in a young patient with a family history of melanoma (Marras et al. 1999). A t(6;15)(q13;q21) translocation found in one of the DN was similar to a translocation, with a breakpoint at 6q13 reported in a benign, nondysplastic nevi (Richmond et al. 1986) and in a cutaneous metastatic melanoma (Thompson et al. 1995). The repeated occurrence of this rearrangement provides initial support for the hypothesis that melanoma progresses from normal melanocytes to benign nevus, to DN, to early melanoma, to late melanoma, and then to metastatic melanoma.

In a study by investigators at the National Cancer Institute (NCI) and the University of Pennsylvania, almost all members of a family cohort with melanoma also had DN. New melanomas were only diagnosed in family members with DN (Greene et al. 1985a, b). These data suggest that not only are DNs risk factors for melanoma, but they may also be the precursor lesions from which new melanomas evolve.

The use of dysplastic nevi, as a precancerous lesion and an indication of chemoprevention efficacy, has been used in previous research and is proposed in upcoming trials. To date, four chemoprevention trials with topical tretinoin have been performed on individuals with DN (Stam-Posthuma 1998).

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