Background: Small pancreatic neuroendocrine tumors (PNETs) are a unique subset of pancreatic neoplasms. Chromogranin A (CgA) levels, mitotic rate, and histologic differentiation are often used to characterize PNET behavior. This study evaluates the impact of these factors on survival in patients with PNETs.

Methods: The US National Cancer Data Base (1998-2012) was reviewed for patients with stages I-III, nonfunctional PNETs ≤2 cm. Clinicopathologic characteristics were collected, and univariate and multivariate survival analyses were performed.

Results: Of 1159 patients, 872 had tumor differentiation recorded, 403 had mitotic rate, and 217 patients had CgA. Mitotic rate >20 mitoses per 10 high-power microscopic fields was significantly associated with survival (hazard ratio [HR] = 10.6, P = 0.002) in multivariate analysis. Of those who underwent resection, there was no significant difference in positive lymph nodes between high (>100 ng/mL) and low (≤100 ng/mL) CgA levels (0.27 versus 0.37, P = 0.4440). Multivariate analyses of patients with both grade and CgA recorded found poorly differentiated tumors and very high CgA (>400 ng/mL) negatively impacted survival (HR = 2.99, P < 0.0001, HR = 3.47, P < 0.0001, respectively). Propensity score matching demonstrated improved 5-y survival in patients who underwent surgical resection, P < 0.0001.

Conclusions: Poorly differentiated disease should be considered an indicator of worse prognosis in nonfunctional PNETs ≤2 cm. Surgical resection appears to improve survival in these patients.