Program death ligand‐1 immunocytochemistry in lung cancer cytological samples: A systematic review

In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death‐1 (PD‐1)/program death ligand‐1 (PD‐L1) axis have become an integral part of treating advanced stage non‐small cell lung carcinoma (NSCLC) and many other cancer types. Multiple monoclonal antibodies are available commercially to detect PD‐L1 expression in tumor cells by immunohistochemistry (IHC). As most clinical trials initially required tumor biopsy for PD‐L1 detection by IHC, many of the currently available PD‐1/PD‐L1 assays have been developed and validated on formalin fixed tissue specimens. The majority (>50%) of lung cancer cases do not have a surgical biopsy or resection specimen available for ancillary testing and instead must rely primarily on fine needle aspiration biopsy specimens for diagnosis, staging and ancillary tests. Review of the literature shows multiple studies exploring the feasibility of PD‐L1 IHC on cytological samples. In addition, there are studies addressing various aspects of IHC validation on cytology preparations including pre‐analytical (e.g., different fixatives), analytical (e.g., antibody clone, staining platforms, inter and intra‐observer agreement, cytology‐histology concordance) and post‐analytical (e.g., clinical outcome) issues. Although promising results in this field have emerged utilizing cytology samples, many important questions still need to be addressed. This review summarizes the literature of PD‐L1 IHC in lung cytology specimens and provides practical tips for optimizing analysis.