Pathology
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Intratumoural heterogeneity of pulmonary adenocarcinoma challenges the accurate interpretation of programmed death ligand 1 (PD-L1) immunohistochemistry, which is the only validated predictive marker for successful anti-PD-1/PD-L1 immunotherapy. The aim of this study was to determine whether PD-L1 expression is related to adenocarcinoma histological differentiation in a retrospective analysis of tumour biopsies with intratumoural histological heterogeneity. Adenocarcinomas with high intratumoural heterogeneity were categorised as 'mixed adenocarcinomas'. ⋯ In conclusion, PD-L1 expression is associated with poorly differentiated morphology in adenocarcinomas with intratumoural histological heterogeneity. Consequently, a TPS approach may not account for the contribution of more aggressive tumour components with higher levels of PD-L1 expression in within the tumour. Performing spectral analyses of PD-L1 expression across tumours is likely to be more accurate.