LC-WGS-based Chromosomal Instability Analysis of EUS-FNA Specimens for Diagnosing Solid Pancreatic Lesions

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Abstract

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to obtain tissue for the diagnosis of solid pancreatic lesions, but indeterminate or inconclusive pathology remains challenging. This study evaluated low-coverage whole-genome sequencing (LC-WGS)-based chromosomal instability (CIN) analysis as a salvage diagnostic strategy for EUS-FNA specimens. METHODS: Patients with solid pancreatic lesions undergoing EUS-FNA were prospectively enrolled. Genomic DNA from FNA specimens was analyzed by LC-WGS, and CIN results were classified as positive or negative using a prespecified threshold. Diagnostic performance was assessed against a composite reference standard. RESULTS: The analysis included 51 patients. Conventional pathology showed a sensitivity of 55.3% and an accuracy of 66.7%. The patients were classified into three groups: Salvage, defined as indeterminate, suspicious, or nondiagnostic initial pathology (n = 12); Malignant Control, defined as final malignant diagnosis with conclusive initial pathology (n = 26); and Benign Control, defined as final benign diagnosis with benign initial pathology (n = 13). The CIN analysis achieved a sensitivity of 81.6%, a specificity of 92.3%, an accuracy of 84.3%, a positive predictive value of 96.9%, and a negative predictive value of 63.2%. In the Salvage group, CIN correctly identified malignancy in 9 of 12 unresolved cases. Combining CIN with pathology increased sensitivity to 86.8% and accuracy to 88.2%. CONCLUSION: An LC-WGS-based CIN analysis may provide complementary molecular information for solid pancreatic lesions with nondefinitive EUS-FNA pathology.

Abstract as published, via PubMed.