Tumors of the endocrine pancreas are a collection of tumor cell types collectively referred to as pancreatic neuroendocrine tumors (NETs). These tumors originate in islet cells. Although they may be similar or identical in histologic appearance to carcinoid tumors of the gastrointestinal tract, differences in their underlying biology and likely differences in response to therapeutic agents suggest that they should be treated and investigated as a distinct entity. They are uncommon cancers with about 1,000 new cases per year in the United States. They account for 3% to 5% of pancreatic malignancies and overall have a better prognosis than the more common pancreatic exocrine tumors.[2,3] Five-year survival is about 55% when the tumors are localized and resected but only about 15% when the tumors are not resectable. Overall 5-year survival rate is about 42%.
Figure 1. Cancer of the Pancreas: Relative Survival Rates (%) by Histologic Subtype, Ages 20+, 12 SEER Areas, 1988-2001. Key, C. Ch 7: Cancer of the pancreas. In: Ries LAG, Young JL, Keel GE, et al. (eds). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.
Most pancreatic NETs are sporadic, but some occur as part of the autosomal dominant multiple endocrine neoplasia type-1 (MEN-1) inherited syndrome consisting of tumors of the anterior pituitary, parathyroid, and endocrine pancreas glands, which results from the inactivation of the tumor suppressor gene Menin located on chromosome 11q13. When part of the MEN-1 syndrome, there may be multiple pancreatic tumors.
Islet tumors may either be functional (produce one or more active hormones) or nonfunctional. The functional tumors, which usually present with symptoms of hormone hypersecretion, include:
Most islet cell cancers are functional, but about 15% are nonfunctional, with presentations similar to the far more common exocrine adenocarcinomas of the pancreas.[5,6,7] Because of the presence of several cell types in the pancreatic islets (alpha, beta, delta, A, B, C, D, E, F), the term, islet cell tumors, refers to at least five distinct cancers that, when functional, produce unique metabolic and clinical characteristics. 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. Functional tumors may even be too small to be detected by conventional imaging techniques.
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 the following:
- Alpha-subunit of human chorionic gonadotropin (alpha-hCG).
- Neuron-specific enolase.
- Pancreatic polypeptide.
- Chromogranin A.