Pancreatic neuroendocrine tumors (PNETs), traditionally termed islet cell tumors, are rare cancers occurring in approximately 1000 patients per year in the United States, representing 3% of all pancreatic tumors.1 The incidence of neuroendocrine tumors has increased over the last three decades, likely from increased use of and improvement in imaging modalities.2-4 The incidence overall of PNETs is increasing from .17 per 100,000 people in 1973 to .47 per 100,000 people in 2007.5 The peak incidence for PNET is between the ages of 40 and 69 years. While survival is significantly longer than patients with pancreatic adenocarcinoma, once patients have metastatic disease cure is not likely. However, surgical treatment plays a very important role in palliation of symptoms from hormone-producing tumors. Overall survival rate of resected tumors is 55%, but is only 15% with metastatic disease. Surgical resection for localized disease is the only curative treatment. The majority of PNETs are nonfunctional; however, some may secrete active gastrointestinal hormones that produce clinical syndromes. Most tumors are sporadic; however, some are associated with syndromes such as multiple endocrine neoplasia (MEN), von Hippel–Lindau syndrome, neurofibromatosis, tuberous sclerosis, and von Recklinghausen syndrome. Tumors associated with MEN syndromes are more likely to be aggressive and multifocal.
PNETs have a wide spectrum of biologic behavior. Some are low grade and indolent, while others behave aggressively and have a propensity to metastasize. Some functional tumors are more likely to be benign, such as insulinomas, while others such as glucagonomas are almost always malignant. Tumors may produce multiple hormones complicating the diagnosis. The functional tumors typically produce symptoms related to the dominant hormone that is produced. This chapter reviews the clinical syndromes, workup, and treatment for pancreatic endocrine tumors.
Endocrine tumors of the pancreas originate from islet cells, hence the traditional name of islet cell tumors. The islets arise from either neural crest cells or embryonic foregut endoderm. They appear histologically similar to carcinoid tumors of the gastrointestinal tract. The tumors are broadly classified into functional and nonfunctional tumors. Nonfunctional tumors compose 40% to 90% of all PNETs and are more common than functional tumors. Functional tumors cause symptoms that are indicative of the hormone the tumor produces. Most commonly these include gastrinomas, vasoactive intestinal polypeptide-secreting tumors (VIPomas), glucagonomas, somatostatinomas, and other rare functional tumors (Table 74-1; Fig. 74-1).
TABLE 74-1FUNCTIONAL TUMOR TYPES ||Download (.pdf) TABLE 74-1 FUNCTIONAL TUMOR TYPES
|Cell Type ||Hormone ||Tumor Type ||Presentation ||Location ||Malignant |
|Alpha ||Insulin ||Insulinoma ||Whipple triad ||Entire pancreas ||10% |
|Beta ||Glucagon ||Glucagonoma ||Necrolytic migratory erythema ||Tail ||>70% |
|Delta ||Somatostatin ||Somatostatinoma ||Diabetes, diarrhea, cholelithiasis ||Pancreas, duodenum, small bowel ||70% |
|G ||Gastrin ||Gastrinoma ||Ulcer disease ||Passaro triangle || |
|D2 ||VIP ||VIPoma/WDHA ||Watery diarrhea, hypokalemia, achlorhydria ||Tail ||50% |
Incidence of pancreatic endocrine tumors.