The Critical Role of Preanalytical Factors in Validating Cytology Specimens for Hybrid-Capture Next-Generation Sequencing

Cytologic specimens, often the only available sample, are increasingly relied upon for comprehensive genomic profiling in patients with advanced malignancies, necessitating detailed characterization of next-generation sequencing (NGS) assay performance. Whether quality thresholds based predominantly on formalin-fixed, paraffin-embedded (FFPE) tissue can be directly applied to cytologic preparations remains uncertain. This study retrospectively analyzed 10,900 unique specimens sequenced on a custom NGS panel, including a focused subset of 455 consecutive cytologic specimens and 2759 FFPE surgical pathology controls.