A small tumor size may impact the diagnostic performance of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing solid pancreatic lesions (SPLs). We aimed to compare the diagnostic yield of EUS-guided fine-needle aspiration (FNA) and biopsy (FNB) in SPLs with a diameter ≤ 15 mm. Consecutive patients who underwent EUS-TA for SPLs ≤ 15 mm between January 2015 and December 2022 in a tertiary referral center were retrospectively evaluated. The primary endpoint was diagnostic accuracy. The final diagnosis was based on surgical pathology or disease evolution after a minimum follow-up of 6 months. Inadequate samples were all considered false negatives for the study. Secondary outcomes included sample adequacy, factors impacting accuracy, and safety. We included 368 patients (52.4% male; mean age: 60.2 years) who underwent FNA in 72 cases and FNB in 296. The mean size of SPLs was 11.9 ± 2.6 mm. More than three passes were performed in 5.7% and 61.5% of patients in the FNB and FNA groups, respectively (p < 0.0001). FNB outperformed FNA in terms of diagnostic accuracy (89.8% vs. 79.1%, p = 0.013) and sample adequacy (95.9% vs. 86.1%, p < 0.001). On multivariate analysis, using FNA (OR: 2.10, 95% CI: 1.07-4.48) and a final diagnosis (OR: 3.56, 95% CI: 1.82-6.94) of benign conditions negatively impacted accuracy. Overall, the adverse event rate was 0.8%, including one pancreatitis in the FNA group and one pancreatitis and one bleeding in the FNB group, all mild and conservatively managed. EUS-TA for SPLs ≤ 15 mm has a high diagnostic yield and safety. This study suggests the superiority of FNB over FNA, with better performance even with fewer passes performed.
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