Interim analysis of small choroidal melanocytic tumors with and without identifiable driver mutations

Abstract

Purpose : To evaluate differences in baseline clinical features of small choroidal melanocytic tumors with and without detectable uveal melanoma associated mutations (UMAM).

Methods : Patients enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) with choroidal melanocytic tumors <3mm in thickness were evaluated for UMAMs using a customized targeted next generation sequencing panel. Clinical characteristics and gene expression profile (GEP) prognostic classification were recorded. Logistic regression was used for assessment of statistical significance.

Results : Eighty-nine consecutive cases meeting entry criteria were included. The mean age was 58 years (SD 13.2), 54% were female, mean largest basal dimension was 8.52 mm (SD 3.1), mean tumor thickness was 2.3 mm (SD 0.5). Biopsy approach was trans-vitreal in 78% and trans-scleral in 22%. GEP was class 1A in 65%, class 1B in 25%, and class 2 in 10%. Mutations were identified in GNA11 in 26% , GNAQ in 28%, PLCB4 in 22%, CYSLTR2 in 11%, EIF1AX in 26%, SF3B1 in 8%, and BAP1 in 13%. At least one UMAM was identified in 58% of biopsy samples, including 52% of class 1A, 45% of class 1B, and 100% of class 2 tumors. The absence of a UMAM was associated with closer tumor proximity to the optic nerve (p=0.007) and trans-vitreal biopsy technique (p=0.03). Due to the strong association between biopsy technique and tumor location, only distance to the optic nerve was significant in multivariate analysis (p=0.021).

Conclusions : Since choroidal melanocytic tumors are thought to harbor UMAM, an intraocular biopsy sample with no UMAM may not contain neoplastic melanocytes. Samples lacking UMAM were associated with posteriorly located tumors and a more surgically challenging trans-vitreal approach. Samples lacking UMAM were all class 1 GEP, which is also seen in normal choroidal melanocytes, as one potential explanation for this finding. Mutations in PLCB4 and CYSLTR2 were more common than previously reported, highlighting their importance in mutation profiling. Ongoing analysis of this cohort will allow the development of best practices in the management of small choroidal melanocytic tumors.

This is a 2020 ARVO Annual Meeting abstract.