Tumor-Associated Retinal Pigmentation in Choroidal Melanoma

Purpose: To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology.Design: Imaging and histologic analysis of a retrospective cohort of patients.Participants: Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023.Methods: Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA).Main Outcome Measures: Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated.Results: Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51-88 years). The median largest basal diameter was 16.10 mm (range, 9.17-21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40-13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68 thorn melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative.Conclusions: Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies.

Automated summary

This study reports a previously unrecognized clinical feature of choroidal melanoma, termed tumor-associated retinal pigmentation (TARP), which represents tumor-associated macrophages. This feature is associated with choroidal melanomas of high metastatic-risk clinical and genetic characteristics.