Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous tumors with a wide range of malignant potential. Therefore, identification of prognostic factors is essential.


To systematically assess the significance of tumor border, a well-known prognostic indicator in other cancers, in the PanNETs.


We evaluated the macroscopic growth pattern (expansile [Exp] versus infiltrative [Inf]) and the microscopic tumor border (pushing [Pus] versus Inf) of 203 surgically resected PanNETs and compared them with other clinicopathologic factors.


Based on macroscopic growth pattern, 83 cases had Exp patterns whereas 84 had Inf patterns. According to microscopic tumor border, 122 PanNETs had Pus borders whereas 81 had Inf borders. Combining macroscopic growth pattern and microscopic tumor border, 65 PanNETs had Exp/Pus, 34 had Inf/Pus, 18 had Exp/Inf, and 50 had Inf/Inf status. PanNETs with Inf/Inf status were associated with higher tumor grade, pT classification, and American Joint Committee on Cancer stage grouping; lymph node metastasis; and lymphovascular and perineural invasions (all P < .001). Patients with PanNET having Inf/Inf status had significantly shorter overall survival (OS) and recurrence-free survival (RFS; all P < .001). Further, using multivariate analysis, Inf/Inf status was identified as an independent poor prognostic factor of OS (P = .02) and RFS (P = .03).


In summary, the combined Inf/Inf status was observed in approximately 25% of PanNETs and was associated with aggressive biological behavior and short OS and RFS. Therefore, assessing combined macroscopic growth pattern and microscopic tumor border can provide additional information regarding survival and recurrence in PanNET patients.

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The authors have no relevant financial interest in the products or companies described in this article.

Presented in part at the 73rd Annual Fall Meeting of the Korean Society of Pathologists; October 27–29, 2021; Seoul, Republic of Korea.

This work was supported by a grant (2015-554; to S.M.H.) from the Asan Institute for Life Sciences (Seoul, Republic of Korea), and by the National Research Foundation of Republic of Korea (NRF-2016R1A2B4009381; to S.M.H.).

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