Detection of Circulating Tumor Cells in Patients with Small Choroidal Melanocytic Lesions

Abstract

Purpose: To determine the presence of circulating tumor cells (CTCs) in patients with indeterminate small choroidal melanocytic lesions (SCMLs).

Design: Retrospective case series.

Participants: Forty-seven patients with choroidal melanocytic lesions 2.5 mm or less in tumor thickness and ≤ 10 mm in largest basal diameter (LBD).

Methods: Blood samples were analyzed for CTCs and the presence of monosomy-3 (M3) in CTCs. Tissue biopsy was performed in the patients who were CTC-positive (pCTC).

Main outcome measures: Presence and M3 status of the CTCs with regard to the clinical characteristics and results from tissue biopsy.

Results: Median thickness of all (n = 47) lesions was 1.1 mm (range: 0.2-2.5 mm), and LBD was 5.6 mm (range: 2.0-10.0 mm). Circulating tumor cells were found in 25 patients (n = 25). This group was classified as pCTC and compared with the CTC-negative (nCTC) group consisting of 22 patients (n = 22). Median tumor dimensions in the pCTC versus the nCTC group were 1.6 mm (range: 0.6-2.5 mm) versus 0.5 mm (range: 0.2-2.5 mm) for thickness and 6.6 mm (range: 4.1-10.0 mm) versus 4.0 mm (range: 2.0-8.0 mm) for LBD, respectively. Both LBD and thickness were positively associated (P < 0.001) with the presence of CTC. Compared with the nCTC group, a higher percentage of the pCTC group exhibited LBD > 5 mm (36% vs. 88%), subretinal fluid (9.1% vs. 56%), orange pigment (4.5% vs. 60%), sonographic hollowness (9.1% vs. 60%), and the presence of multiple risk factors (0% vs. 68% for ≥3 factors) with P < 0.001 for all parameters. No significant difference was detected in the clinical parameters of the patients who had disomy-3 (D3) (n = 7) versus M3 (n = 17) in their CTC. The tissue biopsy confirmed the uveal melanoma (UM) in 22 of the 25 pCTC patients (88%), whereas no conclusive diagnosis could be determined in the remaining 3 cases because of insufficient or invalid material.

Conclusions: We report compelling evidence for the potential of liquid biopsy as an additional tool to screen SCMLs for malignancy. These findings pave the way toward the implementation of liquid biopsy to detect small UM and monitor melanocytic lesions.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Choroidal nevi; Circulating tumor cells; Liquid biopsy; Tumor biopsy; Uveal melanoma.