Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors.
Pancreatic neuroendocrine tumors (PNETs) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for PNETs ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small PNETs. The National Cancer Database was queried for patients with PNETs ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LN were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 versus 95 months, log-rank p<0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p<0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these four factors, 25% were node-positive. Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional lymph node dissection to fully stage patients with small PNETs. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.