Evaluation of the details and importance of lymphatic, microvascular, and perineural invasion in patients with non-functioning pancreatic neuroendocrine neoplasms based on tumor size and the 2022 World Health Organization classification: a 23-year retrospective analysis.

Background: Although, recently observation methods has been proposed as one of the treatment options for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs), determining treatment strategies may be difficult for small and low-malignant NF-PanNENs; thus, clarifying the significance of lymphatic, microvascular, and perineural invasion in these patients is of great clinical importance. This study aimed to assess the incidence and role of lymphatic, microvascular, and perineural invasion in patients with NF-PanNENs based on tumor size and the 2022 World Health Organization classification.

Methods: From 2000 to 2023, we retrospectively investigated the incidence of lymphatic, microvascular, and perineural invasion and their impact on recurrence in 80 patients who underwent curative resection and were diagnosed with NF-PanNENs.

Results: Of the 80 patients, 14 (18%), 20 (25%), and six (9%) patients had lymphatic, microvascular, and perineural invasion. Patients with neuroendocrine tumor (NET) G1 had significantly fewer occurrences of lymphatic, microvascular, and perineural invasion than those with NET G2 (10%, 15%, and 7% vs. 40%, 55%, and 35%; all P < 0.05.). Patients with a tumor size < 20 mm had significantly lower rates of lymphatic and microvascular invasions than those with a tumor size ≥ 20 mm (12% and 17% vs 33% and 48%; P = 0.034 and 0.0073, respectively). In all patients, NET G2, tumor size ≥ 20 mm, local invasion T2-3, presence of lymph node metastasis, and presence of microvascular invasion were significant risk factors for shorter recurrence-free survival (RFS) (all P < 0.05). In patients with NET G1 and tumor size < 20 mm, five (10%), eight (16%), and four (8%) patients had lymphatic, microvascular, and perineural invasion. The presence of microvascular invasion was also an independent risk factor for RFS (P < 0.05).

Conclusions: Information on the frequency and role of lymphatic, microvascular, and perineural invasion based on tumor size and malignancy on recurrence may be useful when considering treatment strategies for small- and low-grade NF-PanNENs.