Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant Transformation? Assessment With a Validated Genomic Biomarker

Abstract

Purpose: To test the hypothesis that widely used clinical risk factors for growth of choroidal nevi are associated with malignant transformation. Methods: Fine needle biopsy for assignment of gene expression profile (class 1 or class 2) was performed in 207 choroidal melanocytic tumors < 3.5 mm in thickness. The class 2 profile was employed as a validated biomarker for malignant transformation. The following data were collected: patient age and sex, tumor diameter and thickness, distance of posterior tumor margin from the optic disc, and the presence or absence of serous retinal detachment, orange lipofuscin pigment, drusen, retinal pigment epithelial fibrosis, retinal pigment epithelial atrophy, visual symptoms, and documented tumor growth. Results: Clinical features associated with the class 2 profile included patient age > 60 years and tumor thickness > 2.25 mm (Fisher exact test, P =.002 for both). Documented growth was not associated with the class 2 profile (P =.5). The odds ratio of a tumor having the class 2 profile was 2.8 (95% confidence interval 1.3–5.9) for patient age > 60 years and 3.5 (95% confidence interval 1.4–8.8) for tumor thickness > 2.25 mm. For patients with both risk factors, the “number needed to treat” to identify 1 patient with a class 2 tumor was 4.3 (P =.0002). No other clinical feature or combination of features was associated with the class 2 profile. Conclusions: None of the widely used choroidal nevus risk factors for tumor growth, nor documented growth itself, is pathognomonic of malignant transformation as defined by class 2 gene expression profile. Patient age and tumor thickness may be helpful for identifying small choroidal melanocytic tumors that are more likely to have the class 2 profile. Observation for growth prior to treatment continues to be reasonable for most patients with suspicious choroidal nevi. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.