Diagn Cytopathol. 2026 Apr 9. doi: 10.1002/dc.70122. Online ahead of print.
ABSTRACT
The National Comprehensive Cancer Network (NCCN) guidelines recommend routine, broad-panel based next-generation sequencing (NGS) testing for non-small cell lung carcinomas (NSCLCs) to guide targeted therapies. While cell blocks are the most commonly used cytology specimens, the NCCN advises using non-formalin-fixed, paraffin-embedded (FFPE) specimens when possible. Fine needle aspiration (FNA) cytology smears offer high-quality DNA from intact nuclei without formalin fixation, allow faster processing than cell blocks, and may reduce NGS turnaround time. In this study, we evaluated the utility of smears for molecular analysis in lung adenocarcinomas. We tested 28 smears using the Oncomine Focus Hotspot (OFA) NGS assay and compared NGS quality metrics with paired FFPE specimens (including cell blocks and/or other paired surgical pathology specimens). NGS was successful in 22 of 28 cases with 100% concordance in variant detection between smears and FFPE specimens. The average DNA yield from smears was lower than FFPE, but the difference was not statistically significant. All quality metrics from smears exceeded NGS assay thresholds, with significantly higher percent mapped reads, uniformity and percent on-target compared to FFPE. Thus, despite lower DNA yield, direct smears are excellent alternatives to FFPE specimens for NGS testing in NSCLC.
PMID:41954035 | DOI:10.1002/dc.70122
