The Role of the Mesopancreas in Pancreatic Neuroendocrine Neoplasms

Background: Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous tumor entity with a steadily rising incidence, mainly due to advances in imaging and growing diagnostic awareness. In pancreatic ductal adenocarcinoma (PDAC), the mesopancreas (MP) has been identified as a frequent site of microscopic tumor spread and a key determinant of circumferential resection margin (CRM) status, leading to the concept of standardized mesopancreatic excision (MPE). While its oncological relevance in PDAC is increasingly recognized, the role of the mesopancreas in PanNENs remains unclear. This study aimed to systematically evaluate mesopancreatic infiltration in PanNENs and to identify associated clinicopathological predictors. Methods: Consecutive patients undergoing oncological pancreatoduodenectomy, spleen-preserving distal pancreatectomy, or distal splenopancreatectomy for PanNENs and PanNECs were included. The mesopancreas was histopathologically examined for tumor infiltration within CRM assessment. Results: MP infiltration was detected in 60% of patients. It was associated with higher Ki-67 index, larger tumor size, lymph node involvement, venous invasion, and positive CRM status. A Ki-67 index ≥ 5% and tumor size ≥ 21.5 mm were identified as predictors of MP infiltration. Higher T stage predicted reduced overall survival (OS), whereas MP infiltration, lymphatic (L1) and venous (V1) invasion, and Ki-67 ≥ 5% were associated with impaired disease-free survival (DFS). Conclusion: Mesopancreatic infiltration is frequently present in PanNENs and correlates with aggressive tumor characteristics. Given its association with CRM positivity and reduced DFS, consideration of the mesopancreas in staging and surgical strategies appears oncologically justified. Larger studies are required to validate these findings.