Number and Distribution of Childhood Nevi Predict Melanoma in Subjects From Families With Familial Melanoma
In a study reported in JAMA Dermatology, Astrid Vredenborg, MD, of Leiden University Medical Center in the Netherlands, and colleagues evaluated whether acquired melanocytic nevi in childhood are an indicator of melanoma risk in children from families with familial melanoma. They found that number and distribution of nevi are predictive of melanoma later in life.
Study Details
In the study, data on melanocytic nevi were collected over 20 years from 133 members of families with familial melanoma 2 to 18 years of age with variable risk of being a mutation carrier. Childhood nevus number was compared with adult nevus number in a subgroup of 40 subjects.
The mean age of subjects was 13 years at childhood and 34 years at adulthood. The mean nevus count in childhood was 36. Among the 40 subjects with nevi counted in adulthood, the mean was 39 in childhood and 121 in adulthood. Fifteen subjects (11.3%) developed one or more melanoma or melanoma in situ, at a mean age of 26 years. A total of 247 lesions were removed, including 22 melanomas and 5 melanomas in situ.
In total, 66.2% of subjects were from families with proven p16-Leiden mutation and 6.0% were from families with proven CDKN2A mutation. Among all subjects, 9.0% were proven to have a gene mutation. On the basis of their position in familial pedigree, 39.1% of subjects had a gene mutation risk of 50%, 30.8% a risk of ≤ 25%, and 21.1% were had no gene mutation in themselves or in their parents or grandparents.
For purposes of analysis, subjects were divided into groups with ≥ 50% risk of mutation (48.1% of subjects) and with ≤ 25% risk (51.9%). Of the 15 subjects with one or more melanoma, 10 were carriers of the p16-Leiden mutation, 4 were not formally tested, and 1 had no mutation but was from a family with the mutation.
Childhood Predictors
The total number of nevi in childhood was a significant predictor of melanoma in later life among all subjects (hazard ratio [HR] = 1.02, P = .04) and in the ≥ 50% risk group (HR = 1.02, P = .03) but not in the ≤ 25% risk group (HR = 0.98, P = .75). Total nevus count on the legs in childhood was a significant predictor among all subjects (HR = 1.04, P < .001) and in the ≥ 50% risk group (HR = 1.04, P < .001) but not in the ≤ 25% risk group.
The total count of childhood nevi with a diameter ≥ 5 mm was not a significant predictor. The presence of childhood nevi ≥ 5 mm on the buttocks was a significant predictor (HR = 1.47, P = .005) and was associated with particularly high risk in the ≥ 50% risk group (HR = 6.47, P = .02).
The total count of atypical nevi in childhood was associated with increased risk in all subjects (HR = 1.21, P = .03) and in the ≥ 50% risk group (HR = 1.19, P = .047) but not in the ≤ 25% risk group (HR = 0.08, P = .57). In all subjects, atypical nevi count on the ventral body site (HR = 1.48, P = .04) and on the buttocks in childhood (HR = 14.00, P = .001) were associated with increased risk.
Adulthood Predictors
Total nevus count in adulthood was not predictive of melanoma among all subjects (HR = 1.00, P = .23) or among the ≤ 25% risk group (HR = 0.99, P = .61) but was predictive in the ≥ 50% risk group (HR = 1.01, P = .03). Total nevus count on the lower half of the body was associated with significantly increased risk (HR = 1.05, P = .01), whereas total count on the upper half of the body was associated with reduced risk (HR = 0.97, P = .04). There was no association between risk of melanoma and nevus size ≥ 5 mm or atypical nevus count.
The number of removed melanocytic lesions was associated with increased risk of melanoma in all subjects (HR = 1.27, P < .001) and particularly in the ≥ 50% risk group. There was a significant association between number of nevi on a particular body site in childhood and the site of melanoma in adulthood (correlation = 0.89, P < .001) and between nevus distribution in adulthood and melanoma distribution in adulthood (correlation = 0.99, P < .001).
No association was found between gene mutation status and count or distribution of nevi, number of nevi ≥ 5 mm, number of atypical nevi, or number of removed lesions.
The investigators concluded, “Numbers and distribution of melanocytic nevi in childhood are major indicators of the risk of melanoma in patients from families with familial melanoma.”
Wilma Bergman, MD, PhD, of Leiden University Medical Center, is the corresponding author for the JAMA Dermatology article.
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