Dermatology Online Journal

Important risk factors in melanoma from the Dermato-Oncologic Unit of Brescia, Italy
Ausilia Maria Manganoni MD, Federica Zanotti, Camillo Farisoglio, Piero Feroldi, Fabio Facchetti, Piergiacomo Calzavara-Pinton
Dermatology Online Journal 16 (1): 17

1. Department of Dermatology, University Hospital Spedali Civili, Brescia, Italy. manganoni@spedalicivili.brescia.it
2. Department of Medical Physics, University Hospital Spedali Civili, Brescia, Italy
3. Department of Pathology I, University Hospital Spedali Civili, Brescia, Italy.

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Abstract

One of the most significant risk factors for melanoma is a positive family history of the disease. It is estimated that approximately 10 percent of melanoma cases report a first-or second-degree relative with melanoma. We reported the experience of the Dermato-Oncologic Unit of Brescia, Italy.

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One of the most significant risk factor for melanoma is the family history of the disease. It is estimated that approximately 10 percent of melanoma cases report a first-or second-degree relative with melanoma [1]. Features associated with increased genetic susceptibility to cutaneous melanoma include the presence of multiple affected first-degree relatives on one side of the family, multiple primary melanomas in the same individual, earlier age of onset, and the presence of multiple atypical nevi. However, none of these factors reliably predicts for the presence of genetic mutations [2]. Only a subset of these patients has melanoma that is attributable to the inheritance of mutations in melanoma susceptibility genes. The proportion of all cutaneous melanomas that is due to these genes is unknown, but is estimated to be less than 1 to 2 percent [3].

We reported the experience of the Dermato-Oncologic Unit of Brescia, Italy between January 1, 1984 and June 30, 2009. A retrospective review identified, in a total of 1625 patients; 22 patients (12 males and 10 females) had histologically confirmed family members with melanoma (Table 1). Only the patients that had a family member also in our unit were included. The age of diagnosis ranged from 24 to 73 (average 41.5), compared with an average of 53.5 for melanoma in the general population [4]. In addition to a positive family history, a number of individuals had other markers of genetic susceptibility to melanoma: 2 patients had a second primary melanoma, developing from 1-28 years after the initial cancer; 3 patients had 3 primary melanomas, and 1 patient developed 11 melanomas. The total number of melanomas was 40, all in sun-exposed areas. In addition, 11 patients had dysplastic nevi biopsied at a different time than melanoma.

According to Breslow thickness there were 12 cases in situ (30%), 20 cases with Breslow thickness less than 1 mm (50%), 4 cases ranged from 1 to 2 mm (10%), 3 cases ranged from 2 to 3 mm (7.5%), and 1 case with Breslow higher than 4 mm (2.5%). Anatomically, the lesions appeared most frequently on the trunk (40.5%) followed by upper extremities (31%), lower extremities (23.7%), and head and neck (4.8%). Genetic analysis showed that the female with 11 melanomas had a CDKN2A mutation in chromosome 9p21, identified as the common p16 missense mutation (Gly101Trp). This patient had a Fitzpatrick skin type II, many melanocytic nevi, widespread solar lentigines, and a history of sunburns in childhood. There was an interval of 19 years between the removal of her first and eleventh melanoma; the age at first diagnosis was 38 years. All 11 melanomas occurred in sun-exposed areas: 4 on the upper trunk, 2 on left leg, one on the right leg, one on the face, one on the right forearm, one on the left arm, and one on the right arm. Out of the 11 tumors, 5 melanomas were in situ and 6 melanomas had a thickness of ≤ 0.86 mm.

Moreover recent literature data point to the genetic predisposition for melanoma but suggest that new genetic loci could be linked to melanoma susceptibility [5, 6, 7]. From a clinical point of view, melanoma requires a multidisciplinary approach and a constant clinical follow-up by dermatologists with a goal of the early detection of the disease.

References

1. Hayward NK. Genetics Of melanoma predisposition. Oncogene 2003;22(20) :3053-62. [PubMed]

2. Santillan AA, Cherpelis BS, Glass LF, Sondak VK. Management of familial melanoma and nonmelanoma skin cancer syndromes. Surg Oncol Clin N Am 2009;18(1):73-98 [PubMed]

3. Kefford RF, Mann GJ. Is there a role for genetic testing in patients with melanoma? Curr Opinin Oncol 2003;15(2):157-161 [PubMed]

4. Buettner PG, Leiter U, Eigentler TK, Garbe C. Development of prognostic factors and survival in cutaneous melanoma over 25 years. Cancer 2005;103(3):616-24. [PubMed]

5. Kerstann KF.,Bradford PT, Steighner R et al. No Evidence for Linkage with Melanoma in Italian Melanoma-Prone Families. Cancer Epidemiol Biomarkers Prev 2008;17(7):1838-40. [PubMed]

6. Vignoli M, Scaini MC, Ghiorzo P. et al. Genomic rearrangements of the CDKN2A locus are infrequent in Italian malignant melanoma families without evidence of CDKN2A/CDK4 point mutations. Melanoma Res 2008;18 (6):431-7. [PubMed]

7. Pastorino L., Bonelli L., Ghiorzo P. et al CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. Pigment Cell Melanoma Res. 2008 21(6):700-9. [PubMed]

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