Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used for the diagnosis of pancreaticobiliary diseases. Although its clinical safety profile is generally favorable, procedure-related adverse events such as bleeding, pancreatitis, and infection have been reported. Most existing evidence is based on clinical observations, whereas studies evaluating tissue-level effects are scarce. This study aimed to assess the histopathological impact of EUS-FNA on the pancreas using resected surgical specimens and to clarify the procedure’s safety from a pathological perspective.

We retrospectively reviewed patients who underwent EUS-FNA followed by pancreatic resection between 2021 and 2024 (EUS-FNA group, n=29). A control group consisted of patients who underwent pancreatic resection during the same period without preceding EUS-FNA or ERCP (n=35). Clinical characteristics and procedural details were collected, and histopathological findings in resected specimens were compared between the two groups. Fat necrosis, neutrophil infiltration, fibrosis, protein plugs, fat replacement, and squamous metaplasia were graded on a four-point scale (0: none, 1: mild, 2: moderate, 3: severe). Group differences were analyzed using t-tests. For neoplastic lesions, needle tract seeding was specifically evaluated.

Baseline characteristics for the EUS-FNA and control groups were as follows: median age 70 and 72 years; male sex 31.0% and 51.4%. Underlying diseases included conventional pancreatic ductal adenocarcinoma (21 vs. 8), IPMN (1 vs. 5), other pancreatic tumors (6 vs. 11), extrapancreatic malignancies (1 vs. 10), and benign disease (0 vs. 1). Surgical procedures included pancreatoduodenectomy (19 vs. 16) and distal pancreatectomy (10 vs. 19). All EUS-FNA procedures were performed using a 22-gauge needle, with a mean of two passes. The only clinical abnormality was asymptomatic hyperamylasemia in five patients; no procedure-related pancreatitis, bleeding, or infection occurred. Mean histological scores in the EUS-FNA and control groups, respectively, were: fat necrosis 0.167 vs. 0.059 (p=0.289), neutrophil infiltration 0.033 vs. 0.059 (p=0.637), fibrosis 0.967 vs. 0.706 (p=0.177), protein plugs 0.300 vs. 0.235 (p=0.618), fat replacement 0.900 vs. 0.909 (p=0.968), and squamous metaplasia 0.100 vs. 0.031 (p=0.278). None of the differences were statistically significant. No needle tract seeding was identified in any specimen.

Pancreatic resection specimens obtained after EUS-FNA showed no significant histopathological alterations compared with specimens from patients without prior puncture, suggesting that EUS-FNA does not induce measurable tissue injury. Notably, even patients who developed transient hyperamylasemia demonstrated no corresponding histopathological changes, indicating that asymptomatic enzyme elevation may not reflect true pancreatic damage. The absence of clinically apparent adverse events in this cohort represents a limitation; larger studies including cases with documented complications are warranted to further clarify the tissue-level safety profile of EUS-FNA.