Reis H, et al. - Researchers sought to determine the potential utility of immune checkpoint blockade in patients with urothelial carcinoma (UC) with predominant or pure variant histology (UCV) via analyzing UCV for PD-L1 expression and comparing 3 commonly used and commercially available PD-L1 antibodies. From 84 UCV cases, they stained full sections with clones SP263, 22C3, and SP142, all of which are considered predictive assays to identify UC patients who are more likely to respond to anti-PD-1/PD-L1 inhibitors durvalumab, pembrolizumab, and atezolizumab, respectively. A significant percentage of UCV cases showed PD-L1 expression at different cutoff points (cutoff 1% tumor cells (TC): 37% to 54%, cutoff 5% TC: 23% to 37%); the highest expression was noted in UC with squamous differentiation. Results suggest that anti-PD-1/PD-L1 therapy may benefit patients with UCV and do not support the exclusion of UC with predominant or pure variant histology. In both TC and tumor-infiltrating immune cells (IC), they noted the highest expression with clone SP263, followed by 22C3 and SP142; all clones showed strong agreement in a pairwise comparison, both in TC and IC, indicating the potential utility of all 3 clones in the evaluation of PD-L1 expression in UCV.