Pancreatic endocrine tumors are rare and occur with an annual incidence of approximately 5 cases per 1,000,000 population.1 They are classified as “functioning” if they produce symptoms related to hormone overproduction, or as “nonfunctioning.” The morbidity from pancreatic endocrine tumors arises from the secretion of active gastrointestinal hormones leading to the characteristic syndromes and physiologic derangements associated with pancreatic endocrine tumors. These tumors can occur sporadically or can be associated with inherited disorders. The diagnosis of pancreatic endocrine tumors is usually established by biochemical assay of abnormally high blood hormone levels consistent with the observed clinical syndrome. Even with the diagnosis, management can be difficult because localization is the key to the treatment. Benign and malignant neuroendocrine tumors appear histologically similar, as clustered nests of normal islet cells. Malignancy is defined by the presence of local invasion or metastasis to distant sites, and the functional status is determined by tissue staining for the specific hormone product.
Surgical resection is the mainstay of treatment and only curative option for pancreatic endocrine tumors. Unlike patients with tumors arising from the exocrine pancreas, surgical resection offers a high chance for cure in patients with localized disease. Surgical resection even has a role in metastatic disease, serving to debulk the disease and limit the associated debilitating symptoms arising from hormone overproduction. This chapter reviews the clinical syndromes, diagnostic tools, and therapeutic approach to pancreatic endocrine tumors.
Pancreatic islets are of part of the family of amine precursor uptake and decarboxylation (APUD) cells and constitute less than 2% of the pancreatic mass. Each pancreatic islet contains an average of over 3000 cells and is composed of four cell types (Table 60-1): Alpha (A) cells that secrete glucagon, beta (B) cells that secrete insulin and amylin, delta (D) cells that secrete somatostatin, D2 cells that secrete vasoactive intestinal peptide (VIP), and F cells that secrete pancreatic polypeptide (PP). B cells are located centrally within the islets and constitute approximately 70% of the islet cell mass. F cells and A cells are located along the islet periphery and constitute 15 and 10% of the islet mass, respectively. D cells are evenly distributed throughout the islets and constitute the remaining 5% of the islet cell mass (Fig. 60-1).2 Cells secreting gastrin (G cells) are not present in the pancreas in the nondisease state.
This diagram depicts the cells that compose a pancreatic islet and their typical location within the islet (ie, alpha cells on the periphery and beta cells localized to the central region). The dots within the beta cell cytoplasm depict the strong staining often seen from insulin-containing granules. Delta and PP cells constitute only a minority of the pancreatic islets endocrine cells. The rich blood supply is demonstrated by the abundance of venous sinusoids within the islet.