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Pancreatic Neuroendocrine Cancer Information

Pancreatic Neuroendocrine Tumor Information

The majority of neuroendocrine tumors can be divided into two classes: carcinoid and pancreatic neuroendocrine tumors. Neuroendocrine tumors that arise in the pancreas are called “pancreatic neuroendocrine tumors” or “islet cell tumors.” Pancreatic neuroendocrine tumors can include: nonfunctional tumors, insulinomas, glucagonomas, gastrinomas, VIPomas, somatostatinomas, GHRHomas, and other less frequent tumors.

Pancreatic neuroendocrine tumors are usually indolent (slow-growing) by nature and develop over the course of many years.  Pancreatic neuroendocrine tumors are usually more indolent, with better prognosis than adenocarcinoma of the pancreas (Carriaga & Henson, 1995). However, aggressive, fast growing pancreatic neuroendocrine tumors exist and different types of pancreatic neuroendocrine tumors exhibit different clinical courses and growth rates (Metz & Jensen, 2008). 

Since neuroendocrine tumor cells are derived from neuroendocrine cells, many of these tumor cells can behave like cells they originated from and can secrete a variety of functional hormones and chemicals (Metz & Jensen, 2008).  Pancreatic neuroendocrine tumors secrete Chromogranin A which can be used as a diagnostic and prognostic tool (Norton, Kivlen, Li, Schneider, Chuter, & Jensen, 2003).  A functioning pancreatic neuroendocrine tumor secretes biologically active hormones causing a characteristic clinical syndrome. Non-functioning pancreatic neuroendocrine tumors do not cause a characteristic clinical syndrome. 

Functioning pancreatic neuroendocrine tumors can hyper-secrete (over produce) substances such as gastrin, insulin, glucagon, vasoactive intestinal peptide (VIP), and somatostatin, resulting in a characteristic clinical syndrome (Tomasseti, Migliori, Lalli, Campana, Tomassetti, Corinaldesi, 2001).

Pancreatic neuroendocrine tumors can occur outside of the pancreas such as duodenal gastrinomas and small intestinal somatostatinomas.  Pancreatic neuroendocrine tumors are at times associated with low blood sugar (due to secretion of insulin), diabetes (due to secretion of glucagon), or ulcer disease (due to secretion of gastrin). In other cases, neuroendocrine tumors may not secrete any hormones (Oberg, Reubi, Kwekkenboom, & Krenning, 2010).

Pancreatic neuroendocrine tumors are classified as rare cancers.  Recent studies have determined that 4 to 5 out of every 100,000 people are diagnosed yearly with a neuroendocrine tumor and that there are over 100,000 people currently living with neuroendocrine tumors within the United States (Yao, Hassan, Phan, Dagohoy, Leary, Mares, Abdalla, Fleming, Vauthey, Rashid, & Evans, 2008; Vinik, Woltering, Go, Warner, & Caplin, 2009). Within this pancreatic neuroendocrine tumors are diagnosed in 0.3 - 0.4 out of every 100,000 people each year (Yao et al., 2008; Tomasseti et al. 2001). For unknown reasons, the incidence of neuroendocrine tumors is currently rising.

Pancreatic neuroendocrine can be difficult to diagnosis with the average time between tumor development and diagnosis being between 5 and 10 years (Vinik, Feliberti, Perry & Nakave, 2008; Vinik et al., 2009). Survival rates for individuals with pancreatic neuroendocrine tumors vary and depend upon tumor type, the location of the tumors, the size of the tumors, the extent and growth rate of liver and bone metastases, proliferative indices, presence of clinical syndromes and many other factors (Metz & Jensen, 2008). Currently, surgery is the only option that offers hope for a cure (Ramage, Ahmed, Ardill, Bax, Breen, Caplin, Corrie, Davar, Davies, Lewington, Meyer, Newell-Price, Poston, Reed, Rockall, Steward, Thakker, Toubanakis, Valle, Verbeke, Grossman, and UK and Ireland Neuroendocrine Tumor Society, 2012; Metz & Jensen, 2008).

Pancreatic neuroendocrine tumors can be associated with genetic syndromes such as Multiple Endocrine Neoplasia Type 1 (MEN1), Von Hippel-Lindau Disease (VHL), Tuberous Sclerosis Complex and Neurofibromatosis Type 1 (NF1) (Metz & Jensen, 2008). MEN1 is the most significant genetic syndrome - over 80% of patients with MEN1 develop pancreatic neuroendocrine tumors, over 40% of patients develop gastrinomas and smaller percentages develop other types of pancreatic neuroendocrine tumors (Metz & Jensen, 2008; Gibril & Jensen, 2004; Brandi et al., 2002).

What is a Tumor?

Cells are the building blocks of all life. All cells have highly specific functions, but not all cells have the same function. When cells that have similar functions are grouped together they form a tissue. Tissues when grouped together to perform a specific function are called organs. All cells of the human body have the same DNA (genetic language). Cell growth and replication is highly controlled and is encoded in each cell’s DNA. However if there are enough mutations (changes) within a cell’s DNA, a cell can grow and replicate uncontrollably. 

A tumor is a mass formed by an abnormal growth of cells within the body. A tumor can be non-cancerous (benign) or cancerous (malignant). A tumor is considered cancerous when it has uncontrolled proliferation (abnormal growth) and can invade and destroy surrounding tissue.  Malignant tumors can also have the ability to metastasize (spread to other organs of the body). 

What is a Neuroendocrine Tumor?

The neuroendocrine system consists of highly specialized neuroendocrine cells which act as an interface or junction between the nervous system and the endocrine system. The endocrine system is made up of cells whose function is to produce and secrete hormones into the bloodstream. Hormones are biochemical messengers that help to regulate many different processes within the body. The nervous system is composed of specialized cells (neurons) that control the activities of all body parts.  A neuroendocrine cell is a cell which receives neuronal input (a signal from a nerve cell) and releases hormones in response to this signal.

A neuroendocrine tumor can develop anywhere there are neuroendocrine cells. The most common sites from which neuroendocrine tumors arise are the lungs, appendix, small intestine, rectum and pancreas (Yao, Hassan, Phan, Dagohoy, Leary, Mares, Abdalla, Fleming, Vauthey, Rashid, & Evans, 2008). Neuroendocrine tumors that arise in the pancreas are called pancreatic neuroendocrine tumors or islet cell tumors. When neuroendocrine tumors originate in other areas, they are often classified as carcinoid tumors.

Since neuroendocrine tumor cells are derived from neuroendocrine cells, many of these tumor cells can behave like cells they originated from and can secrete a variety of hormones. A functioning neuroendocrine tumor is one that secretes biologically active hormones causing a clinical syndrome. Non-functioning neuroendocrine tumors do not cause clinical syndromes. 

Carcinoid tumors and pancreatic neuroendocrine tumors share similarities including often indolent behavior, ability to secrete biologically active hormones, and well-differentiated histology (Reidy, Tang & Saltz, 2009).

References

Carriaga, M. and Henson, D. (1995). Liver, gallbladder, extrahepatic bile ducts, and pancreas. Cancer, 75, 171-190.

Jensen, R., Berna, M., Bingham, D. and Norton, J. (2008). Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer, 113(7), 1807-1843. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/18798544.

Metz, D. and Jensen, R. (2008). Gastrointestinal neuroendocrine tumors, pancreatic endocrine tumors. Gastroenterology, 135(5), 1469-1492. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/18703061.

Norton, J., Kivlen, M., Li, M., Schneider, D., Chuter, T., and Jensen, R. (2003). Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Archives of Surgery, 138(8), 859-866. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/12912744.

Oberg, K. E., Reubi, J. C., Kwekkeboom, D. J., Krenning, E. P. (2010) Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology, 139(3), 742-753. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/20637207.

Ramage, J., Ahmed, A., Ardill, J., Bax, N., Breen, D.J, Caplin, M.E., Corrie, P., Davar, J., Davies, A.H., Lewington, V., Meyer, T., Newell-Price, J., Poston, G., Reed, N., Rockall, A., Steward, W., Thakker, R.V., Toubanakis, C., Valle, J., Verbeke, C., and Grossman, A.B., and UK and Ireland Neuroendocrine Tumor Society (2012) . Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut, 61(1):6-32. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/22052063

 

Tomasseti, P., Migliori, M., Lalli, S., Campana, D., Tomassetti, V., Corinaldesi, R. (2001). Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. Annals of Oncology, 12(2), S95-S99. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/11762360.

Vinik, A. I., Feliberti, E., Perry, R., Nakave, A. (2008). Diffuse Hormonal Systems and Endocrine Tumor Syndromes. Retrieved from: http://www.endotext.org/guthormones/index.htm/.

Vinik, A. I., Silva, M. P., Woltering, E. A., Go, V., Warner, R., Caplin, M. (2009). Biochemical Testing for Neuroendocrine Tumors. Pancreas, 38(8), 876-899. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/19855234.

Yao J. C., Hassan, M., Phan, A., Dagohoy, C., Leary, C., Mares, J. E., Abdalla, E. K., Fleming, J. B., Vauthey, J. N., Rashid, A., Evans, D. B. (2008). One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Journal of Clinical Oncology, 20(26), 3063-3072. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/18565894.

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