Cytomorphologic Correlates of PD-L1 Expression in Advanced Gallbladder Carcinoma: A Prospective Cross-Sectional Study Using Fine Needle Aspiration Cell-Blocks.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been evaluated in gallbladder carcinoma (GBC), predominantly in histopathologic specimens, while the cytomorphologic correlates in advanced GBC remain poorly characterized. We evaluated PD-L1 expression and its cytomorphologic associations in a prospective cohort of advanced GBC diagnosed by fine-needle aspiration cytology (FNAC). METHODS: This prospective study included 70 treatment-naïve patients with advanced GBC diagnosed by ultrasound-guided FNAC. PD-L1 immunocytochemistry was performed on FNAC-derived cell blocks using the SP263 clone, and the tumour proportion score (TPS) was calculated. Associations between PD-L1 expression and clinicoradiologic and cytomorphologic parameters were evaluated. RESULTS: PD-L1 expression (TPS ≥ 1%) was identified in 14/70 (20%) tumours; 10 had TPS 1%-49% and four had TPS ≥ 50%. PD-L1 expression differed significantly by cytologic subtype (p = 0.046) and was more frequent in squamous cell carcinoma (4/6; 66.7%) than in conventional adenocarcinoma (9/55; 16.4%) (OR: 10.22; 95% CI: 1.62-64.47). A strong association was observed with nuclear pleomorphism (p = 0.0001): 8/11 (72.7%) tumours with marked pleomorphism were PD-L1-positive compared with 6/56 (10.7%) with moderate pleomorphism (OR: 22.22; 95% CI: 4.60-107.25; Fisher's exact p = 0.0001). PD-L1 expression was not significantly associated with cytologic grade or clinicoradiologic parameters. CONCLUSIONS: PD-L1 expression was identified in 20% of advanced GBCs diagnosed by FNAC. Marked nuclear pleomorphism and squamous differentiation were strongly associated with PD-L1 positivity. These findings, although they require further large-scale validation, expand the cytomorphologic characterization of PD-L1-expressing advanced GBC where surgical tissue is unavailable.