A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families.
BACKGROUND
Few long-term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes.


METHODS
Thirty-three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups.


RESULTS
All the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early.


CONCLUSIONS
The melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families.
Tucker
Margaret A
MA
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892-7236, USA. tuckerp@exchange.nih.gov
Fraser
Mary C
MC
Goldstein
Alisa M
AM
Struewing
Jeffery P
JP
King
Mary A
MA
Crawford
John T
JT
Chiazze
Ellen A
EA
Zametkin
Deborah P
DP
Fontaine
Laura S
LS
Clark
Wallace H
WH
D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004416:Dysplastic Nevus Syndrome / Q000235:genetics* / Q000473:pathology; D019942:Genes, p16; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins; D016353:Self-Examination; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases