Are phenotypic characteristics, MC1R variants, and prior amelanotic melanoma associated with amelanotic melanoma?
In this analysis of population-based and cancer-based registries, absence of back nevi, presence of many freckles, a sun-sensitive phenotype, and prior amelanotic melanoma were associated with development of amelanotic melanoma. MC1R was associated with amelanotic melanoma, but this association lost significance in a model with phenotype.
Prior amelanotic melanoma and the phenotypes associated with it should raise clinician index of suspicion for amelanotic melanoma when examining a suspicious but nonpigmented skin lesion, and clinicians might also use these characteristics to prompt periodic, meticulous screening of nonpigmented as well as pigmented skin lesions.
We previously reported that survival is poorer from histopathologically amelanotic than pigmented melanoma because of more advanced stage at diagnosis. Identifying patients at risk of amelanotic melanoma might enable earlier diagnosis and improved survival; however, the phenotypic characteristics and underlying genetics associated with amelanotic melanoma are unknown.
To determine whether phenotypic characteristics, carriage of MC1R variants, and history of amelanotic melanoma are associated with histopathologically amelanotic melanoma.
Design, Setting, and Participants
The Genes, Environment, and Melanoma (GEM) study is an international cohort study that enrolled patients with incident primary cutaneous melanomas from population-based and hospital-based cancer registries (1998 to 2003). The GEM participants included here were 2387 patients with data for phenotypes, MC1R genotype, and primary melanomas scored for histopathologic pigmentation. Of these 2387 patients with incident melanomas scored for pigmentation, 527 had prior primary melanomas also scored for pigmentation.
Main Outcomes and Measures
Associations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported. Association of histopathologic pigmentation between incident and prior melanomas was analyzed using an exact logistic regression model.
This study included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3 [16.1] years) and 2917 primary melanomas. In a multivariable model including phenotypic characteristics, absence of back nevi, presence of many freckles, and a sun-sensitive phenotypic index were independently associated with amelanotic melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but lost statistical significance in a model with phenotype. Further, patients with incident primary amelanotic melanomas were more likely to have had a prior primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with incident primary pigmented melanomas.
Conclusions and Relevance
Absence of back nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior amelanotic melanoma increase odds for development of amelanotic melanoma. An increased index of suspicion for melanoma in presenting nonpigmented lesions and more careful examination for signs of amelanotic melanoma during periodic skin examination in patients at increased odds of amelanotic melanoma might lead to earlier diagnosis and improved survival.
Vernali S, Waxweiler WT, Dillon PM, Kanetsky PA, Orlow I, Luo L, Busam KJ, Kricker A, Armstrong BK, Anton-Culver H, Gruber SB, Gallagher RP, Zanetti R, Rosso S, Sacchetto L, Dwyer T, Cust AE, Ollila DW, Begg CB, Berwick M, Thomas NE, for the GEM Study Group. Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma. JAMA Dermatol. Published online July 26, 2017. doi:10.1001/jamadermatol.2017.2444