Clinicopathologic Outcomes After Resection of Suspected High-Grade Pancreatic Intraepithelial Neoplasia Without Invasive Carcinoma: A Multicenter Retrospective Study

Background: High-grade pancreatic intraepithelial neoplasia (HG-PanIN) is a non-invasive precursor of pancreatic ductal adenocarcinoma and an ideal target for curative resection. However, preoperative diagnosis is difficult because HG-PanIN lacks direct imaging features. This multicenter retrospective study aimed to clarify the real-world data of the clinical outcomes for patients who underwent resection for suspected HG-PanIN without invasive carcinoma. Methods: The study retrospectively analyzed 94 patients who underwent pancreatectomy between 2008 and 2024 at four tertiary centers in Japan for lesions clinically suspected as HG-PanIN. Imaging findings, cytologic results, and final pathologic diagnoses were reviewed. A simulated diagnostic decision tree was constructed to summarize the clinical decision-making process. Results: Among 94 resected cases, 26 (27.7 %) were benign, 44 (46.8 %) were carcinoma in situ (CIS; 34 HG-PanIN, 10 high-grade intraductal mucinous papillary neoplasms), and 24 (25.5 %) were invasive carcinoma (IC). Main pancreatic duct stenosis and upstream duct dilation were common across all the groups, whereas other indirect findings showed no significant differences between the groups. Even among radiologically typical HG-PanIN cases, 22.2 % were benign and 25.4 % were IC. Pancreatic juice cytology showed a high positive predictive value (96.7 %), but 61.5 % of the cytology-negative cases presented a malignant lesion (CIS+IC). The IC group showed significantly worse survival than the CIS group. Conclusions: In cases of radiologically suspected HG-PanIN, differentiation from both benign lesions and small invasive carcinomas remains challenging. Surgical indications and limited resections should be determined cautiously.