Microscopic Invasion of Nerve Is Associated With Aggressive Behaviors in Pancreatic Neuroendocrine Tumors

OBJECTIVES: The role of neural invasion has been reported in cancers. Few studies also showed that neural invasion was related to survival rate in patients with pancreatic neuroendocrine tumor (PNET). The aim of this study is to explore the association between neural invasion and aggressive behaviors in PNET. METHODS: After excluding those patients with biopsy and with missing histological data, a total 197 patients with PNET who underwent surgery were retrospectively analyzed. The demographic data and histological data were obtained. Aggressive behavior was defined based on extra-pancreatic extension including vascular invasion, organ invasion and lymph node metastases. Logistic regression analyses were used to identify risk factor for aggressive behavior. Receiver operating characteristic (ROC) curves were performed to show the performance of nomograms in evaluating aggressive behavior of PNET. RESULTS: The prevalence of neural invasion in the cohort was 10.1% (n = 20). The prevalence of lymph node metastasis, organ invasion, and vascular invasion in PNET patients with neural invasion was higher than those in patients without neural invasion (p < 0.05). Neural invasion was more common in grade 3 (G3) tumors than G1/G2 (p < 0.01). Tumor size, tumor grade, and neural invasion were independent associated factors of aggressive behavior (p < 0.05) after adjusting for possible cofounders in total tumors and G1/G2 tumors. Two nomograms were developed to predict the aggressive behavior. The area under the ROC curve was 0.84 (95% confidence interval (CI): 0.77–0.90) for total population and was 0.84 (95% CI: 0.78–0.89) for patients with G1/G2 PNET respectively. CONCLUSIONS: Neural invasion is associated with aggressive behavior in PNET. Nomograms based on tumor size, grade and neural invasion show acceptable performances in predicting aggressive behavior in PNET.