PD-L1 in Lung Cytology: The Path for Standardization

Area of Science:

• Oncology
• Pathology
• Immunohistochemistry

Background:

• Programmed death-1 (PD-1)/PD-L1 inhibitors have transformed lung cancer therapy.
• Accurate PD-L1 immunohistochemical (IHC) assessment is crucial for treatment selection.
• PD-L1 testing on cytology samples presents significant challenges compared to histological specimens.

Purpose of the Study:

• To review and address the complexities of PD-L1 IHC testing in cytological samples.
• To focus on validation guidelines, quality assessment, cyto-histological correlation, and interobserver variability.
• To synthesize current guidelines and research for reliable PD-L1 assessment in cytology.

Main Methods:

• Review of current guidelines, particularly from the College of American Pathologists (CAP).
• Analysis of 48 original articles on cyto-histological concordance for PD-L1 expression.
• Discussion of challenges in quality assessment and interobserver variability in cytological samples.

Main Results:

• Recent CAP guidelines emphasize rigorous validation for non-formalin-fixed specimens.
• Cyto-histological concordance for PD-L1 expression shows significant variability (54-100% at 1% cutoff, 82-100% at 50% cutoff).
• Interobserver variability is particularly notable in the 1-49% PD-L1 expression range.

Conclusions:

• PD-L1 testing in cytology faces hurdles in validation, quality control, and interobserver agreement.
• Standardized guidelines and thorough validation are essential for accurate PD-L1 assessment in cytological specimens.
• Addressing these challenges is critical for optimizing immunotherapy in lung cancer patients.