Background and Clinical Significance: Pancreatic neuroendocrine tumors (pNETs) rarely exhibit intraductal growth, a pattern that may mimic intraductal papillary mucinous neoplasms (IPMNs) or pancreatic ductal adenocarcinoma (PDAC). Preoperative recognition is challenging, particularly when associated with anatomic variants such as pancreas divisum. Case Presentation: A 63-year-old man with a history of pancreatic duct dilation presented with pruritus, weight loss, and lymphadenopathy. Cross-sectional imaging revealed a cephalopancreatic mass with upstream ductal dilatation. EUS demonstrated a hypervascular lesion with intraductal extension into the dorsal duct in the setting of pancreas divisum. EUS-FNB confirmed a well-differentiated pNET (G1) with loss of DAXX expression and preserved ATRX. Ga-68 PET/CT showed intense uptake in the primary lesion and lower-grade uptake in two additional nodules, later proven non-neoplastic. A multidisciplinary tumor board recommended preoperative optimization with somatostatin analog therapy and supervised weight reduction, followed by pylorus-preserving duodenocephalopancreatectomy. Final pathology confirmed NET G1 with intraductal growth and full concordance with preoperative EUS-FNB findings. Conclusions: in this case, a pNET showed intraductal growth within the dorsal duct in the context of pancreas divisus, further expanding the range of its reported presentations. It underscores the diagnostic value of EUS-FNB for morphologic, proliferative, and molecular characterization, and highlights the importance of multidisciplinary evaluation in guiding preoperative optimization and tailored surgical management.

Background and Aims: Pancreatic hyperenzymemia in inflammatory bowel disease (IBD) is an under-recognized and challenging condition, as elevated pancreatic enzymes may arise from heterogeneous mechanisms and do not necessarily reflect true pancreatic disorder. This multicenter study aimed to characterize the clinical spectrum, diagnostic work-up, and outcomes of hyperenzymemia in IBD. Methods: This retrospective multicenter study was conducted within the PANDORA network, including 34 international IBD centers. For the present analysis, only centers providing patient-level data on pancreatic hyperenzymemia were considered. Collected variables included demographic, clinical, biochemical, imaging, and therapeutic data. Cases were categorized into three predefined phenotypes: chronic asymptomatic pancreatic hyperenzymemia (CAPH), reclassified acute pancreatitis not meeting Atlanta criteria (recAP), and autoimmune pancreatitis (AIP). Results: A total of 148 IBD patients with elevated pancreatic enzymes were included (CAPH 54.7%, RecAP 35.1%, AIP 10.1%). Ulcerative colitis (UC) accounted for 56.8% of cases and Crohn’s disease (CD) for 43.2%. Overall, 73.6% of patients were asymptomatic at the time of enzyme elevation. Marked hyperenzymemia (≥3× ULN) occurred in 22.3% of patients and was more frequent in RecAP than in CAPH or AIP (50.0%, 6.2%, and 13.3%, respectively). IBD was clinically active in 48.6% of patients, with higher rates in CD. Notably, the clinical meaning of hyperenzymemia differed across IBD phenotypes: in CD it was more often associated with active inflammation, whereas in UC it more frequently prompted advanced imaging and led to the identification of AIP. Imaging strategies differed significantly across phenotypes, and drug withdrawal was common in CAPH and RecAP but unnecessary in AIP. Only two rechallenges confirmed a drug-related mechanism. Conclusions: Pancreatic hyperenzymemia in IBD encompasses a spectrum of conditions with different implications. A phenotype-oriented diagnostic approach is essential to avoid misclassification and unnecessary treatment changes.