When the disease is localized (without lymph node involvement, arterial infiltration or distant metastases), the mainstay of therapy is surgical resection. 

There is no consensus about the best surgical strategy for small lesions, that are increasingly being detected on cross-sectiona imaging. There seems to be a linear correlation between tumor size and aggressive behavior, such that parenchyma sparing resections with limited or no lymphadenectomy have been proposed for neoplasms < 2 cm. In particular, middle segment pancreatectomy is indicated to remove primary tumors located in the pancreatic body, while enucleation is technically feasible when the primary neoplasm is not too deep in the parenchyma, and distant enough from the main pancreatic duct (in order to minimize the risk of inadvertent intraoperative duct damage). If an enucleation is performed, intraoperative ultrasonography has been shown to help confirm a safety distance between the tumor and the duct. Parenchyma-sparing resections are associated with an increased rate of postoperative complications such as pancreatic fistula, but long-term functional outcome is excellent, the rate of exocrine insufficiency and endocrine insufficiency being almost nil.

In some studies, however, tumor size did not predict the biologic behavior of non-functional neoplasms and of functional neoplasms other than insulinoma. A fraction of patients with small primary neoplasms (7%) was found with nodal disease and eventually developed metastases. Therefore, the decision on whether to perform a parenchyma-sparing operation on the basis of tumor size has been questioned, and regional lymph node sampling with intraoperative pathologic examination has been proposed to guide the surgical approach.

On the opposite end of the spectrum, many authors proposed an initial non-operative approach for small (< 2cm) incidentally diagnosed non-functional pancreatic neuroendocrine neoplasms. The theoretical advantage of non-operative management would be to avoid the morbidity (40-50%) and mortality (2%) associated with pancreatic resections in patients with a very low perceived risk of malignancy. Patients managed non-operativey should be enrolled in a very strict clinical-and radiologic surveillance protocol, and should be informed about the risk of tumor progression during the follow-up. Such risk seems to be in the range of 6-8%.

Long-term observational studies are lacking, and the management of small incidentally diagnosed neoplasms should be carefully decided by an expert multidisciplinary team and discussed with the patient and his/her family. The patient must be aware of the risk and benefits of each therapeutic decision.

In resectable primary meoplasms > 2cm, or in neoplasms with superior mesenteric vein/portal vein infiltration, formal resections (pancreaticoduodenectomy and left pancreatectomy) are the procedures of choice.