The pancreas is a retroperitoneal organ that is composed of multiple lineages of neuroendocrine cells interspersed within the larger structure of its exocrine ductal system. The neuroendocrine cells are histologically grouped into islands known as islets of Langerhaans. These islet cells are differentiated such that they each synthesize and secrete only one of six pancreatic endocrine hormones. These hormones play an integral role in the fine balance of normal physiology. Both benign and malignant neoplastic processes can affect the pancreatic neuroendocrine cells. This tumor formation may be the result of a sporadic, somatic mutation or an inherited genetic predisposition to tumorigenesis. Although some of the tumors that develop retain sufficient differentiation to elicit the specific hormone made by the cell of origin, defects are often present in the normal feedback control of hormone release. This may result in a clinically detectable syndrome of hormone excess that may be diagnostically useful before detection of symptoms related to the primary tumor mass or metastatic burden. Pancreatic neuroendocrine tumors (PNETs) are relatively rare, with approximately five cases occurring per 1 million people annually.
PNETs are named relative to the chief hormone produced by the tumor cells. For example, there are insulinomas, gastrinomas, glucagonomas, somatostatinomas, and vasoactive intestinal peptide (VIP)-omas. Insulinomas and gastrinomas are discussed elsewhere in this manual. Occasional functional PNETs elicit hormones not normally produced by the pancreatic islet cells, including neurotensin, adrenocorticotropic hormone, parathyroid hormone–related protein, and growth hormone–releasing factor. Tumors that do not produce a specific hormone product and yet are derived from a neuroendocrine progenitor cell are known as nonfunctional neuroendocrine tumors.1 Roughly 75% of the nonfunctional neuroendocrine tumors produce pancreatic polypeptide but have no associated endocrine syndrome. Hence, these tumors could be referred to as pancreatic polypeptide or PP-omas. These nonfunctional tumors can be identified based on their histologic appearance, cell surface markers, and the presence of immunohistochemical staining for markers such as chromogranin A and neuron-specific enolase.2 Each PNET can be characterized by a unique endocrine syndrome that includes hormone overproduction (with the exception of nonfunctional neuroendocrine tumors), the location of the tumor, the frequency of the tumor being malignant, and the relative efficacy of medical management to control the associated endocrinopathy (Table 20-1).
Table 20-1. Other Functional and Nonfunctional Neuroendocrine Tumors ||Download (.pdf)
Table 20-1. Other Functional and Nonfunctional Neuroendocrine Tumors
|Tumor Type||Location (Prevalence)||Medical Therapy||% Malignant||% Associated with MEN1|
|Nonfunctional||Pancreas (100%)||None||> 60||Frequent|
|Glucagonoma||Pancreas (100%)||Octreotide, TPN||60–70||3|
|Somatostatinoma||Pancreas (85%) Duodenum, (15%)||IFN-α||90||1|
|VIPoma||Pancreas (85%) Duodenum, (15%)||Octreotide, glucocorticoids||60–80||1|
|GRFoma||Pancreas (90%) Duodenum, (10%)||Octreotide||30||30|
Nonfunctional PNETs represent approximately 30% of ...