Vascular Lakes in Uveal Melanoma and Their Association With Outcome

Prognostic predictors in uveal melanoma (UM) consist of clinical, histomorphologic, and genetic features. Vascular lakes (VLs) are immature blood vessels within UM with unknown significance for metastatic risk.

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.

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.

Our pilot data suggest that VL-TA is an additional poor prognostic parameter in UM.

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.