Impact of chromogranin A, differentiation, and mitoses in nonfunctional pancreatic neuroendocrine tumors ≤ 2 cm

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.