CORRESPONDENCE

Re: Melanocytic Nevi, Solar Keratoses, and Divergent Pathways to Cutaneous Melanoma

Paolo Carli, Domenico Palli

Affiliations of authors: Department of Dermatology, University of Florence, Florence, Italy (PC); Molecular and Nutritional Epidemiology Unit, Centro per lo Studio e la Prevenzione Oncologica, Scientific Institute of Tuscany, Florence (DP).

Correspondence to: Paolo Carli, MD, Department of Dermatology, University of Florence, Via degli Alfani 31, 50121 Florence, Italy (e-mail: carli{at}unifi.it)

Whiteman et al. (1), studying a predominantly fair-skinned population, sug-gested that cutaneous melanomas may arise through two pathways: one associated with melanocyte proliferation and the other with chronic exposure to sunlight. Elwood and Gallagher (2) reported that, in individuals younger than 50 years, intermittent sun exposure had a greater potential for producing melanoma than continuous exposure, although in those who are older, melanoma was more common on body sites with continuous sun exposure. Only lentigo maligna melanoma occurs almost exclusively on the face, even at younger ages (2).

To test this hypothesis in a population of different ethnicity and complexion, we analyzed a set of data collected in a multicenter survey of the Italian Multidisciplinary Group on Melanoma, recently reported elsewhere (3). We excluded all lesions classified as lentigo maligna and lentigo maligna melanoma and all cases of melanoma occurring on anatomic sites other than the head and neck or the trunk. The final series included 207 patients (121 [58.5%] of whom were male), 178 (86.0%) with superficial spreading melanoma and 29 (14.0%) with nodular melanoma.

In univariate analyses, the 42 patients with head and neck melanoma, compared with the 165 patients with trunk melanoma, were statistically significantly older (mean age ± standard deviation = 62.8 ± 15.9 years and 48.7 ± 15.3 years, respectively; P<.001) and less frequently had more than 30 melanocytic nevi (four [9.5%] of 42 patients versus 46 [27.9%] of 165 patients; two-sided Fisher's exact test, P = .01). The cutoff point of 30 nevi was chosen because it was used in a previous case–control study in the same population (4). To reduce misclassification between melanocytic nevi and other pigmented skin lesions, such as freckles, solar lentigines, dermatofibromas, and pigmented seborrheic keratosis, the total-body nevi counts were performed by dermatologists experienced in the diagnosis of pigmented skin lesions (3).

A multivariable logistic analysis (including terms for age, sex, and number of nevi) in our series also confirmed a positive association between head and neck melanoma and an older age and an inverse association between such melanomas and a higher number of nevi. Italian patients older than 50 years, compared with those 50 years old or younger, more frequently had a diagnosis of a melanoma located on the head and neck (odds ratio = 3.50, 95% confidence interval = 1.48 to 8.26). Patients with more than 30 nevi, compared with those with 30 nevi or fewer, were less likely—although with borderline statistical significance—to be diagnosed with melanoma at these sites (odds ratio = 0.34, 95% confidence interval = 0.11 to 1.04; P = .058). Other models showed that, in this Mediterranean series, there was no evidence of a nonlinear relationship between age and the risk of melanoma on the head and neck, justifying a quadratic term for age (in years) as in the analyses described by Whiteman et al. (1) in a fair-skinned population.

Our findings in a different population thus lend support to the hypothesis (1,2) that divergent pathways can lead to cutaneous melanoma. In view of the possible implications in understanding melanoma pathogenesis and improving preventive strategies, we are convinced that the hypothesis of divergent pathways to melanoma (trunk melanoma associated with a high number of nevi and head and neck melanoma associated with chronic sun exposure) deserves additional investigations.

NOTES

The following is a list of investigators and participating centers involved in the Italian Multidisciplinary Group on Melanoma study (all are located in Italy): Paolo Carli, Vincenzo De Giorgi, Benvenuto Giannotti, Department of Dermatology, University of Florence, Florence; Domenico Palli, Molecular and Nutritional Epidemiology Unit, Centro per lo Studio e la Prevenzione Oncologica, Florence; Andrea Maurichi, National Cancer Institute, Milan; Patrizio Mulas, Dermatology Unit, Businco Hospital, Cagliari; Catiuscia Orlandi, Dermatology Unit, Bufalini Hospital, Cesena; Gian Lorenzo Imberti, Dermatology Clinic, Ospedali Riuniti, Bergamo; Ignazio Stanganelli, Center for Cancer Prevention, Center for Oncologic Research, Ravenna; Pierfranco Soma, Unit of Plastic Surgery, Cannizaro Hospital, Catania; Domenico Dioguardi, Unit of Plastic Surgery, University of Bari, Bari; Caterina Catricalá, Dermatology Unit, Ospedale S. Gallicano, Rome; Roberto Betti, Dermatology Unit, Ospedale S. Paolo, Milan; Roberto Cecchi, Dermatology Unit, Ospedale del Ceppo, Pistoia; Ugo Bottoni, Dermatology Clinic, University La Sapienza, Rome; Giovanni Lo Scocco, Dermatology Unit, Reggio Emilia; Massimiliano Scalvenzi, Department of Dermatology, Universitá Federico II, Naples.

REFERENCES

1 Whiteman DC, Watt P, Purdie DM, Hughes MC, Hayward NK, Green AC. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J Natl Cancer Inst 2003;95:806–12.[Abstract/Free Full Text]

2 Elwood JM, Gallagher RP. Body site distribution of cutaneous malignant melanoma in relationship to patterns of sun exposure. Int J Cancer 1998;78:276–80.[CrossRef][ISI][Medline]

3 Carli P, De Giorgi V, Palli D, Maurichi A, Mulas P, Orlandi C, et al. Dermatologist detection and skin self-examination are associated with thinner melanomas: results from a survey of the Italian Multidisciplinary Group on Melanoma. Arch Dermatol 2003;139:607–12.[Abstract/Free Full Text]

4 Carli P, Biggeri A, Giannotti B. Malignant melanoma in Italy: risks associated with common and clinically atypical melanocytic nevi. J Am Acad Dermatol 1995;32(5 Pt 1):734–9.[ISI][Medline]



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