Vascular lakes in uveal melanoma and their association with outcome

Purpose: Prognostic predictors in uveal melanoma (UM) consist of clinical, histomor-phologic, and genetic features. Vascular lakes (VLs) are immature blood vessels within UM with unknown significance for metastatic risk. Methods: A clinically well-phenotyped cohort of 136 hematoxylin and eosin–stained slides of UM enucleation specimens were retrospectively analyzed on scanned whole-slide images. These were annotated for VL in QuPath, assessing VL number and area. Using SPSS (V27.0), the Mann–Whitney U test and Cox regression were applied to evaluate whether there was any correlation between VL number and area within the tumor (VL-TA) compared with other prognostic parameters and patient survival times. Results: UMs with monosomy 3 (M3) have significant differences in their VL numbers (P = 0.008) and VL-TA ratios (P = 0.002) compared with disomy 3-UM. Nuclear BAP1-negative (nBAP1^– ) UMs have significant differences in their VL-TA ratio (P = 0.002) compared to nBAP1⁺ UMs. Survival times of patients with UM with epithelioid-celled tumors varied depending on their VL-TA ratio (P = 0.057). Similarly, in M3-UM, significant differences in survival (P = 0.009) were seen in patients, depending on VL number. Finally, patients with UM with shorter overall survival showed significant differences in their tumor VL-TA ratios (P = 0.043) and the number of VLs present (P = 0.002) than patients with UM who had longer survival. Conclusions: Our pilot data suggest that VL-TA is an additional poor prognostic param-eter in UM. Translational Relevance: Digital analysis of UM can be easily performed to assess various prognostic parameters. Our pilot study demonstrates that UM-VL could be combined with other parameters to determine metastatic risk of patients with UM.