PD-L1 immunohistochemical testing: A review with reference to cytology specimens

Immunotherapy based on disruption of the PD-1/PD-L1 axis is standard of care for many high stage malignancies including melanomas, non-small cell carcinomas of the lung, triple negative breast carcinomas, and squamous cell carcinomas of the head and neck. Eligibility for immunotherapy requires immunohistochemical assessment of PD-L1 expression. Currently, many high stage malignancies are diagnosed by cytology and cytologic material is the only specimen available for ancillary testing. Formal guidelines do not currently exist defining the optimal specimen type, antibody to be used or the best scoring system for cytologic material. Significant information has been published for PD-L1 testing of pulmonary specimens but much less data exists for the reproducibility, accuracy and best practices for material obtained from other body sites and types of malignancy.

We searched the PubMed data base for manuscripts relating to PD-L1 testing of cytologic specimens. The search period was between 2016 and 2022. The search terms used were PD-L1, cytology, FNA, immunotherapy, immunohistochemistry, immunocytochemistry, cytology-histology correlation. Cross referencing techniques were used to screen for the most relevant manuscripts. The abstracts of these were then reviewed for final data collection and analysis.

A total of 86 studies were identified conforming to study relevancy. These were reviewed in their entirety by two authors (LJL, TZ) for extraction of data. The majority of studies involved pulmonary specimens (79) with three relating to PD-L1 testing of head and neck cytologic specimens and one each for PD-L1 testing of cytology specimens from melanomas, pancreas, pleural fluids, and triple negative breast carcinomas. While smears could be used, most studies found cell blocks optimal for testing.

Currently, four drugs are approved for immunotherapy based on PD-L1 status. These drugs require specific antibody clones as well as scoring systems. Scoring systems and cut points vary with the type of neoplasm being treated. Cytology specimens from the lung, head and neck and melanomas can all be used for PD-L1 testing with good agreement with corresponding histology specimens.