Evaluation of PD-L1 Immunohistochemistry Expression in Carcinomatous Effusion and Its Correlation with Paired Primary Histology

Tumor immune escape represents a fundamental mechanism of cancer progression, and therapeutic modulation of the tumor immune microenvironment has become an integral component of modern oncology. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis is a key immune checkpoint regulating antitumor immune responses and is an established target for immunotherapy. In patients with advanced malignancies, cytological specimens from malignant effusions may constitute the only available material for both diagnosis and predictive biomarker assessment. This study was undertaken to evaluate PD-L1 expression in carcinomatous effusions and to determine its concordance with matched histological specimens from primary or metastatic tumors. This study aimed to evaluate PD-L1 protein expression in carcinomatous effusion samples and to determine the level of concordance between PD-L1 expression in effusion cytology and corresponding histological specimens in patients with advanced malignancies, wherever paired samples were available. A combined retrospective (January 2019–March 2022) and prospective (April 2022–March 2024) observational study was performed at a tertiary care center. Seventy paired cases of carcinomatous effusions with corresponding histological samples were included. PD-L1 immunohistochemistry was performed using the 22C3 pharmDx clone in breast carcinoma cases and the SP263 clone in all other malignancies. Tumor cell membrane staining in ≥1% of cells was considered positive. The study population comprised predominantly female patients (87.1%), with ascitic fluid being the most frequent effusion type (82.9%). PD-L1 expression was negative in the majority of cytology (92.8%) and histology samples (87.1%). Concordant PD-L1 expression between cytology and histology was observed in 64 of 70 cases (91.4%), while discordance was identified in 6 cases (8.6%). The level of agreement was moderate, with a Cohen's kappa value of 0.528. The findings demonstrate a moderate level of concordance between PD-L1 expression in carcinomatous effusions and corresponding histological samples, supporting the potential utility of cytological specimens for PD-L1 assessment in advanced cancers with metastatic effusions. Larger, multi-institutional studies are warranted to further validate these observations.