Multiple primary melanoma revisited

Abstract

BACKGROUND Incidence of cutaneous melanoma continues to increase in the Caucasian population worldwide. Approximately 5% of melanoma patients develop additional primary melanoma. This rate is significantly higher than the estimated lifetime risk of an individual for developing the disease (1.4%). These features suggest that a genetic predisposition may underlie multiple primary melanomas (MPMs). Prior studies had identified CDKN2A mutations in a few MPM individuals. The objectives of this study were to determine the frequency of family history of melanoma in MPM cases, to characterize other clinical features including history of other cancer, and to determine the association with functional CDKN2A mutations. METHODS This study used a case series design. All living patients who had been seen in the Pigmented Lesion Clinic at the University of Pennsylvania and who had more than one primary invasive malignant melanoma or an invasive primary followed by an in situ melanoma were eligible for participation. RESULTS Individuals with MPM frequently had a family history of melanoma, dysplastic nevi (DN), and/or another cancer including basal cell carcinoma (BCC), and squamous cell carcinoma breast cancer, and a personal history of DN, and basal cell carcinoma. Germline mutations in CDKN2A gene were identified in 8 of 96 MPM cases (8.3%, 95% confidence interval, 6.7–9.9%). CONCLUSIONS These data indicate that the presence of MPM is associated with a modest incidence of a family history of melanoma, DN, or BCC and a small association with CDKN2A mutations. Therefore, in addition to the MPM index case, other family members can benefit from screening and regular surveillance for melanoma, DN, and BCC. Cancer 2002;94:2248–55. © 2002 American Cancer Society. DOI 10.1002/cncr.10454

Single versus multiple primary melanomas

“…34 It has been estimated that germline mutations in CDKN2A occur in 8.3% to 15% of patients with MPM. 10,34,35 In a population-based, case-control study, Berwick et al reported a relative risk of 4.3 for a functionally relevant mutation in CDKN2A in patients with MPM versus patients with SPM. 36 Furthermore, allelic variants of melanocortin-1-receptor (MC1R) may modify the penetrance of CDKN2A mutations and have been observed at an increased frequency in patients with MPM.…”

“…1,2 Various single-center and population-based studies have reported that between 1.2% and 8.6% of patients who have a history of melanoma will develop subsequent melanomas. [3][4][5][6][7][8][9][10][11][12] Several risk factors for the development of more than 1 primary melanoma have been established, the most important of which include a family history of melanoma and a personal history of dysplastic nevi. 10,[12][13][14] The initial melanoma in patients who have multiple primary melanomas (MPM) usually is the thickest of the melanomas that eventually develop.…”

“…[3][4][5][6][7][8][9][10][11][12] Several risk factors for the development of more than 1 primary melanoma have been established, the most important of which include a family history of melanoma and a personal history of dysplastic nevi. 10,[12][13][14] The initial melanoma in patients who have multiple primary melanomas (MPM) usually is the thickest of the melanomas that eventually develop. 3,6,7,9,12,[15][16][17][18][19][20][21] The 2 competing explanations for this trend include early detection of subsequent melanomas and less aggressive tumor biology in patients with MPM.…”

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

“…The incidence of these malignancies in the world was 54.41% for BCC,grow slowly and does not metastasize to the bloodstream (Schatton et al, 2008), while SCC tumors are metastatic, aggressive and fatal. Malignant melanoma (MM) is an aggressive tumor that its occurrence has increased rapidly during the past two decades (Blackwood et al, 2002;Gyrylova et al, 2014). The incidence rate of melanoma has been reported to be correlated with age, socioeconomic status, tumor localization (Jemal et al, 2011), and gender (Gyrylova et al, 2014).…”

Ambient UV, personal sun exposure and risk of multiple primary melanomas

“…Studies of risk of multiple primary melanomas have been concerned mainly with influences of the previous history of melanoma, presence of dysplastic nevi, or possible genetic susceptibility [2][3][4]. While sun exposure is recognized as the major cause of melanoma in populations of European origin [5], studies of sun exposure and melanoma so far published have compared sun exposure in people with a first melanoma, or any melanoma, with that in people who have not had a melanoma.…”