Melanoma risk loci as determinants of melanoma recurrence and survival.

BACKGROUND: Steadily high melanoma mortality rates urge for the availability of novel biomarkers with a more personalized ability to predict melanoma clinical outcomes. Germline risk variants are promising candidates for this purpose; however, their prognostic potential in melanoma has never been systematically tested. METHODS: We examined the effect of 108 melanoma susceptibility single nucleotide polymorphisms (SNPs), associated in recent GWAS with melanoma and melanoma-related phenotypes, on recurrence-free survival (RFS) and overall survival (OS), in 891 prospectively accrued melanoma patients. Cox proportional hazards models (Cox PH) were used to test the associations between 108 melanoma risk SNPs and RFS and OS adjusted by age at diagnosis, gender, tumor stage, histological subtype and other primary tumor characteristics. RESULTS: We identified significant associations for rs7538876 (RCC2) with RFS (HR=1.48, 95% CI=1.20-1.83, p=0.0005) and rs9960018 (DLGAP1) with both RFS and OS (HR=1.43, 95% CI=1.07-1.91, p=0.01, HR=1.52, 95% CI=1.09-2.12, p=0.01, respectively) using multivariable Cox PH models. In addition, we developed a logistic regression model that incorporates rs7538876, rs9960018, primary tumor histological type and stage at diagnosis that has an improved discriminatory ability to classify 3-year recurrence (AUC=82%) compared to histological type and stage alone (AUC=78%). CONCLUSIONS: We identified associations between melanoma risk variants and melanoma outcomes. The significant associations observed for rs7538876 and rs9960018 suggest a biological implication of these loci in melanoma progression. The observed predictive patterns of associated variants with clinical end-points suggest for the first time the potential for utilization of genetic risk markers in melanoma prognostication.

Pigmented free-floating vitreous cyst in a child.

An 8-year-old asymptomatic boy was referred for a pigmented fundus lesion in his left eye that was suspected to be a possible choroidal melanoma. Visual acuity was 20/20 in each eye. Ocular examination in the upright position revealed a pigmented lesion measuring 4 mm in diameter and 3 mm in thickness located inferior to the fovea. Following supine positioning, the mass floated to the superior macular region. UI-trasonography confirmed a cystic vitreous mass. Observation of the benign vitreous cyst was advised. A free-floating pigmented cyst can resemble a pigmented intraocular tumor, particularly if it is immediately preretinal.