Scoring of Programmed Death-Ligand 1 Immunohistochemistry on Cytology Cell Block Specimens in Non–Small Cell Lung Carcinoma

Abstract

Objectives Recent investigations have shown strong correlations between cytology and surgical non–small cell lung carcinoma (NSCLC) specimens in programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) evaluations. Our study aims to evaluate the reproducibility of PD-L1 IHC scoring in NSCLC cytology cell blocks (CBs) and to assess the impact of CB cellularity, method of sample collection, and observer subspecialty on scoring agreement. Methods PD-L1 IHC was performed on 54 NSCLC cytology CBs and was scored independently by seven cytopathologists (three of seven with expertise in pulmonary pathology). Three-tier scoring of negative (<1%), low positive (1%-49%), and high positive (≥50%) and interrater agreement were assessed. Results Total and majority agreement among cytopathologists was achieved in 48% and 98% of cases, respectively, with κ = 0.608 (substantial agreement; 95% confidence interval, 0.50-0.72). Cytopathologists with pulmonary pathology expertise agreed in 67% of cases (κ = 0.633, substantial agreement), whereas the remaining cytopathologists agreed in 56% of cases (κ = 0.62, substantial agreement). CB cellularity (P = .36) and sample collection type (P = .59) had no statistically significant difference between raters. Conclusions There is substantial agreement in PD-L1 IHC scoring in cytology CB specimens among cytopathologists. Additional expertise in pulmonary pathology, sample collection type, and CB cellularity have no statistically significant impact on interobserver agreement.

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

“…Studies analyzing PD‐L1 testing on lung carcinoma cytology specimens originated mostly from the USA, followed by publications arising from Italy, Canada, United Kingdom, China, Germany, Japan, India, Turkey and other countries. The Dako clone 22C3 was the most common clone analyzed on cytology specimens, followed by the Ventana SP263 clone 17–67 . The data collected included the clone type used in each study.…”

Technical aspects of the use of cytopathological specimens for diagnosis and predictive testing in malignant epithelial neoplasms of the lung

“…Gosney et al's systematic review 105 analysed studies that compared PD-L1 scores on cytological CBs with histology; they showed good concordance using tumour cell expression cutoffs of ≥1% and ≥50%, provided 100 tumour cells are present. 106 Nevertheless, false negatives may occur with cytology samples due to low numbers of tumour cells and PD-L1 heterogeneity within tumours. Cytological samples are not suitable for PD-L1 assays using the SP142 antibody clone which includes a count of positive tumour infiltrating immune cells, due to the lack of tissue context and inability to determine if immune cells are tumour-related.…”

“…Degenerate tumour cells may show loss of cell membrane integrity and display spurious cytoplasmic staining. Hernandez et al 106 found that correlation with histology was better when pathologists with pulmonary expertise assessed the samples.…”

Molecular cytology of the respiratory tract and pleura

“…To maintain high accuracy, it is important to adhere to the minimum adequacy requirement of 100 viable tumour cells, 54 to rigorously validate new PD-L1 protocols on cytology specimens, and to train the cytopathologists. 34,55 Most studies on PD-L1 expression in cytology material have used cell blocks 48,[56][57][58][59] or direct smears. 60,61 Though few clinical trials thus far use cytology samples, several studies show that PD-L1 can be assessed on cell blocks and smears with high interobserver agreement and agreement with surgical samples (Figure 3).…”