Neoplasms of the Endocrine Pancreas

Updated: Apr 14, 2015
  • Author: Evan S Ong, MD, MS; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Overview

Background

Neoplasms of the endocrine pancreas can be divided into functional and nonfunctional varieties. Most pancreatic endocrine neoplasms discovered clinically are functional; ie, they secrete one or more hormonal products into the blood, which leads to a recognizable clinical syndrome. In 1927, Wilder et al described the first hormone-producing pancreatic tumor syndrome in a patient with hypoglycemia and a metastatic islet cell tumor, extracts of which caused hypoglycemia.

Subsequent to this initial description of insulinoma syndrome, four other classic pancreatic endocrine tumor syndromes have been described. The first is Zollinger-Ellison syndrome (also termed gastrinoma syndrome), described by Zollinger and Ellison in 1955. [1]

The second types comprise a group of three tumor syndromes, termed Verner-Morrison syndrome, WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome, and pancreatic cholera (also termed vasoactive intestinal peptide [VIP]–releasing tumor or VIPoma); these were described by Verner and Morrison in 1958. [2]

The third is glucagonoma syndrome, described by Mallinson et al in 1974. The fourth is somatostatinoma syndrome, described by Ganda et al and Larsson et al in 1977. [3, 4]

Several other rare clinical syndromes have been proposed as possible functional endocrine syndromes associated with pancreatic neoplasms. These include the following:

  • Calcitoninoma [5, 6]
  • Parathyrinoma [7]
  • Growth hormone–releasing factor–secreting tumor (GRFoma)
  • Adrenocorticotropin hormone–secreting tumor (ACTHoma)
  • Neurotensinoma [8]

Patients with pancreatic neoplasms that have the histologic characteristics of a pancreatic endocrine tumor but no associated elevation in plasma hormone levels, excluding the pancreatic polypeptide level, and those without a recognizable clinical syndrome are considered to have nonfunctional pancreatic endocrine tumors. A subset of these patients have nonfunctional pancreatic endocrine neoplasms that secrete pancreatic polypeptide (ie, PPomas). Pancreatic polypeptide (PP) is a product that appears to be a marker for pancreatic endocrine tumors, but it is not a mediator of any specific PP-related clinical syndrome. [9] Other nonfunctional pancreatic endocrine tumors likely secrete unknown products that are of little or no clinical significance.

Each of the classic pancreatic endocrine tumor syndromes is discussed in detail in other Medscape Reference articles. See Insulinoma, Gastrinoma, Zollinger-Ellison Syndrome, VIPomas, WDHA Syndrome, Glucagonoma, and Somatostatinomas.

Further, Medscape Reference articles are available on Wermer Syndrome (MEN Type 1) and von Hippel-Lindau Disease, conditions with which pancreatic endocrine tumors are associated.

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Pathophysiology

The cells in pancreatic endocrine neoplasms are termed amine precursor uptake and decarboxylation (APUD) cells because they have a high amine content, are capable of amine precursor uptake, and contain an amino acid decarboxylase. [10] Pearse first used the term APUD in 1968 to unify a group of functionally and structurally similar neuroendocrine cells that are present throughout the body. [11] APUD cells were once believed to originate from the embryologic neural crest, but current evidence suggests that these cells—and thus endocrine tumors of the pancreas and other endocrine tumors of the upper gastrointestinal tract (eg, carcinoid tumors)—actually develop from the embryologic endoderm. [12]

Although the term islet cell tumor is often used to identify neoplasms of the endocrine pancreas, this is a misnomer because many pancreatic neuroendocrine tumors do not develop directly from islet cells. [13] Instead, the tumors arise from APUD stem cells, which are pluripotential neuroendocrine cells located within the ductular epithelium of the exocrine pancreas and elsewhere in the distal foregut. [14] The fact that many gastrinomas and somatostatinomas are found close to, but not within, the pancreatic parenchyma supports the notion of the possible extrapancreatic development of these neoplasms. [15]

Patients with functional pancreatic endocrine neoplasms have physiologic derangements related to the normal action of the hormonal product that the tumors overproduce. Thus, patients with an insulin-secreting tumor (ie, insulinoma) have the pathophysiologic manifestations of hypoglycemia; patients with a gastrin-secreting tumor (ie, gastrinoma) have hypersecretion of gastric acid, which often leads to the development of peptic ulcers (ie, Zollinger-Ellison syndrome); and so on. In contrast, patients with nonfunctional pancreatic endocrine neoplasms typically present later in the course of their disease, when their tumors begin to cause symptoms related to a mass effect.

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Epidemiology

United States

Neoplasms of the endocrine pancreas occur in two distinct epidemiologic groups. Solitary tumors that develop in patients without a significant personal or family history of endocrine disorders are characterized as the sporadic form. The second form affects kindreds with the multiple endocrine neoplasia type 1 (MEN 1) syndrome in a pattern of autosomal dominant inheritance. [16] Approximately 80% of individuals with MEN 1 syndrome have one or more pancreatic neoplasms in their lifetime; gastrinoma and insulinoma are the most commonly identified lesions. [17]

Clinically recognized neoplasms of the endocrine pancreas are rare, with an overall annual incidence in the United States of 3-10 cases per million persons. [18, 19] However, the much higher prevalence of these tumors in unselected autopsy specimens, 0.5-1.5%, reflects the indolent nature of many of these tumors. [20, 21]

Insulinomas and gastrinomas occur with roughly equal annual incidences; together they account for more than half of all clinically apparent pancreatic endocrine tumors. [21] VIPomas are one-eighth and glucagonomas are one-seventeenth as common, whereas somatostatinomas are even more rare. [18] Nonfunctional tumors account for 14-48% of all recognized neoplasms of the endocrine pancreas. [22, 23]

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Mortality/Morbidity

Because of the relative rarity of pancreatic endocrine tumors in the general population, accurate rates of morbidity and mortality for persons with these lesions are difficult to determine. However, both the survival and the quality of life of patients with neoplasms of the endocrine pancreas are generally improving secondary to improvements in the modalities used to diagnose and treat these lesions (also see Complications and Prognosis).

Race-, Sex-, and Age-related Demographics

Sporadic and inherited forms of pancreatic endocrine tumors appear to occur with equal frequency among the different racial groups in the United States.

Neoplasms of the endocrine pancreas seem to have a slightly higher incidence in women than in men. [24, 16, 25] As would be expected in patients with a genetic disorder of autosomal dominant inheritance, no significant sex predilection is observed among patients with pancreatic endocrine tumors as part of MEN 1 syndrome. [15]

Patients with sporadic pancreatic endocrine tumors present most commonly at the age of 30-50 years. [26] In contrast, patients with pancreatic endocrine tumors that develop as part of MEN 1 syndrome tend to present when younger, commonly at age 10-30 years. [16]

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