Pancreatic endocrine tumors (PETs) are rare cancers which account for 1% to 2% of all pancreatic malignancies with approximately 1,000 new cases per year in the United States (1
). Epidemiological data show a worldwide increase in the prevalence and incidence of pancreatic neuroendocrine tumors in the past few decades, which is probably due to improved methods of detection of these tumors. PETs originate in islet cells of the endocrine pancreas. There is no gender or age predilection for PETs. The peak incidence for PETs is from age 30 to 60 years, while patients with multiple endocrine neoplasia 1 (MEN1) syndrome have tumors that occur at a younger age.
PETs tend to have an indolent behavior, and long-term survival is common. Five-year survival of PETs is about 55% when the tumors are localized and resected but only about 15% when the tumors are not resectable (2
). Overall, PETs still have a much better prognosis than the common exocrine adenocarcinomas of the pancreas (1
Pancreatic endocrine tumors (PETs) have been a focus of fascination for both pathologists and clinicians for almost a century. Nicholls documented an example of a pancreatic neoplasm in 1902 that was termed an “islet cell adenoma,” and Fabozzi described a biologically malignant counterpart of that lesion the following year (3
). Patients can present with symptoms due to hormonal excess or a local mass effect or be asymptomatic (4
Most PETs are functional, but about 15% are nonfunctional. Because of the presence of several cell types in the pancreatic islets (alpha, beta, delta, PP and Epsilon cells), the term, islet cell tumors, refers to at least five distinct cancers that, when functional, produce unique metabolic and clinical characteristics (4
). Functional tumors may even be too small to be detected by conventional imaging techniques. The clinical manifestations in functional tumors may result from the distinctive metabolic effects of the polypeptide(s) secreted by the cancer cells rather than from tumor bulk or metastatic disease. The functional tumors, which usually present with symptoms due to hypersecretion of hormone or bioamines, are often classified by the hormone most strongly secreted, for example: Insulinoma (45%), Gastrinoma (20%), Glucagonoma (13%), VIP (vasoactive intestinal peptide)oma (10%), and Somatostatinoma (5%). (I) Insulinoma: hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide (4
). (II) Gastrinoma: the excessive gastrin causes Zollinger-Ellison Syndrome (ZES) with peptic ulcers and diarrhea (5
). (III) Glucagonoma: the symptoms are not all due to glucagon elevations, and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels (5
). (IV) Somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea (5
). (V) VIPoma: producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome) (5
The less common types include ACTHoma, CRHoma, Serotoninoma, Calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone-related peptide tumor.
Nonfunctioning PETs are either an incidental finding or are associated with an expanding mass rather than a hormonal syndrome. Nonfunctional tumors tend to present at later clinical stages with symptoms attributable to mass effect or metastases. Although nonfunctional tumors do not produce specific clinical syndromes, they may secrete inactive amine and peptide products such as neurotensin, alpha-subunit of human chorionic gonadotropin (alpha-hCG), neuron-specific enolase, pancreatic polypeptide (PP) and chromogranin A.