Neuroendocrine tumors

Definition

Neuroendocrine tumors are tumors that develop from the cells of the diffuse neuroendocrine system, such as the enterochromaffin (EC) cells. These tumors are characterized by the presence of cells that possess secretory granules and have the ability to secrete neurohormones.

Description

The endocrine system is a network of glands consisting of endocrine cells that produce hormones in the body. The neuroendocrine system cells are specialized endocrine cells of the nervous system and produce neurohormones. Neuroendocrine cells do not form a specific gland; instead, they are found distributed in a wide variety of body organs where they help regulate body function.

Neuroendocrine tumors therefore represent a large class of cancers that can occur wherever neuroendocrine cells are found throughout the body. They are sometimes called carcinoid tumors, but it would be more accurate to consider these tumors as a sub-category of the larger family of neuroendocrine tumors. Neuroendocrine tumors are most often found in the digestive system and the lung. Statistically, 38% occur in the appendix, 23% in the ileum, 13% in the rectum and 11.5% in the bronchi. Neuroendocrine pancreatic tumors are rather rare cancers with an incidence of 1-2 cases per 100, 000 people. They occur with the same frequency in men and women and the average age at diagnosis is 53 years. Neuroendocrine tumors are also known as apudomas, or tumors that contain apud cells. These cells release excessive amounts of a variety of neurohormones in the bloodstream with chemical composition that varies with location, as does their effect on the body. Neuroendocrine tumors therefore have symptoms that vary with location. Unlike other cancers that are located in a specific organ, the hormone-releasing action of these tumors causes other symptoms to appear in many other organs of the body as well. The majority of neuroendocrine tumors can give rise to metastases with time if they are left untreated.

Types of cancers

Because they can occur wherever neuroendocrine cells are found, neuroendocrine tumors come in a wide variety of types and have been classified according to their site of origin, usually either as digestive system, pancreatic or lung neuroendocrine tumors.

Neuroendocrine tumors of the digestive system

The types of neuroendocrine tumors found in the digestive system are also indicative of their general location:

• Foregut neuroendocrine tumors. Foregut tumors arise in the stomach or duodenum (first part of small intestine) and represent approximately 15% to 25% of neuroendocrine tumors.
• Midgut neuroendocrine tumors. Midgut tumors are the most common variety and they include small and large intestine tumors.
• Hindgut neuroendocrine tumors. Hindgut tumors occur less frequently and are found in parts of the colon and in the rectum.

Pancreatic neuroendocrine tumors

Most neuroendocrine pancreatic tumors produce multiple hormones but usually there is excessive production of only one hormone. This is why neuroendocrine pancreatic tumors are often classified according to the predominant hormone secreted or resulting symptoms observed. For example, insulinomas produce excessive amounts of insulin, and gastrinomas produce excessive amounts of the peptide gastrin. Glucagonomas are associated with skin lesions and irritation around the eyes, and somatostatinomas are associated with gallstones, slight diabetes and diarrhea or constipation.

Lung neuroendocrine tumors

There are four main types of neuroendocrine lung tumors:

• Small-cell lung cancer (SCLC). SCLC represents one of the most rapidly growing types of cancer.
• Large-cell neuroendocrine carcinoma . A rare form of cancer, similar to SCLC in prognosis and treatment, except that the cancer cells are unusually large.
• Typical carcinoid tumors. These types of neuroendocrine lung tumors grow slowly and do not often spread beyond the lungs.
• Atypical carcinoid tumors. Atypical lung carcinoids tumors grow faster than the typical tumors and are more likely to metastasize to other organs.

Other classifications for neuroendocrine tumors

Additionally, neuroendocrine tumors are sub-classified into "functionally active" and "functionally inactive" tumors. Functionally active neuroendocrine tumors display specific symptoms, such as the excessive release of specific neurohormones from the tumor cell, as described above for pancreatic neuroendocrine tumors.

A recent classification groups neuroendocrine tumors into two types, depending on the kind of cells they develop from:

• Group I (epithelial). This group includes neuroendocrine carcinomas, graded 1, 2, and 3. Grade 1 neuroendocrine carcinomas are also known as carcinoid tumors. Grade 2 include tumors such as atypical carcinoid tumors, medullary thyroid carcinomas, and some pancreatic endocrine tumors. Grade 3 includes small-cell as well as large-cell neuroendocrine carcinomas.
• Group II (neural). Group II neuroendocrine tumors include paragangliomas, neuroblastomas, primitive neuroectodermal tumors, medulloblastomas, retinoblastomas, pineoblastomas and peripheral neuroepitheliomas.

See Also Adenoma; Carcinoid tumors, gastrointestinal; Carcinoid tumors, lung; Cushing's syndrome; Endocrine system tumors; Lung cancer, small cell; Merkel cell carcinoma; Pancreatic cancer, endocrine; Parathyroid cancer; Pituitary tumors; Zollinger-Ellison syndrome

Resources

BOOKS

Poliak, J. M., ed. Diagnostic and Histopathology of Neuroen docrine Tumours. Edinburgh: Churchill-Livingstone, 1993.

Wiedenmann, B. "Molecular and Cell Biological Aspects of Gastroenteropancreatic Neuroendocrine Tumor Disease." Annals of the New York Academy of Sciences, Vol. 733 New York: New York Academy of Sciences, 1994.

PERIODICALS

Chatal, J. F., M. F. Le Bodic, F. Kraeber-Bodere, C. Rousseau, and I. Resche. "Nuclear medicine applications for neu roendocrine tumors." World Journal of Surgery 24 (November 2000):1285-1289.

Eriksson, B. "Neuroendocrine pancreatic tumors: clinical pre sentation, diagnosis and medical treatments." Carcinoid Patient Association Bulletin 1 (1994).

R. T. Jensen. "Carcinoid and pancreatic endocrine tumors:recent advances in molecular pathogenesis, local ization, and treatment." Current Opinions in Oncology 12 (July 2000):368-377.

Rougier, P., E. Mitry. "Chemotherapy in the treatment of neu roendocrine malignant tumors." Digestion 62 (2000)Suppl.1:73-78.

Vuitch, F., Y. Sekido, K. Fong, B. Mackay, J. D. Minna, A. F. Gazdar. "Neuroendocrine tumors of the lung." Chest Sur gical Clinics North America 7 (1997):21-25.

Warner, R. R. P., L. P. Angel, C. M. Divino, S. T. Brower, T. Damani. "Pancreatic Neuroendocrine Tumors: A Ten Year Experience." Regulatory Peptides 94 (October 2000):51-56.

Warner, R. R. P. "Exploring Carcinoid Tumors." Coping with Cancer Magazine (January-February 2001):49-50.

ORGANIZATIONS

The Carcinoid Cancer Foundation, Inc. 1751 York Avenue, New York, NY 10128. Phone:(888)722-3132 or (212)722-3132. Web site: <http://www.carcinoid.org/>.

OTHER

European Neuroendocrine Tumor Network. Web site: <http://www.tentelemed.com/eunet/home.html>.

The Carcinoid Cancer Online Support Group. To subscribe: <http://[email protected]>.

Monique Laberge, Ph.D.

KEY TERMS

Apudoma

—A tumor capable of Amine Precursor Uptake and Decarboxylation (APUD).

Bronchi

—Air passages to the lungs.

Diffuse neuroendocrine system

—Concept developed by Feyrter, a German pathologist, more than 60 years ago, to unify tumors that occur in various parts of the body and possess secretory activity as well as similar properties when examined under a microscope.

Epithelial cells

—Cells that cover the surface of the body and line its cavities.

Gastrointestinal tract

—The GI tract, also called the digestive tract, starts from the oral cavity (mouth) and proceeds to the esophagus, the stomach, the duodenum, the small intestine, the large intestine (colon), the rectum and the anus. It processes all the food we eat. Along its way, food is digested, nutrients are extracted and waste is eliminated from the body in the form of stool and urine.

Gland

—An organ that produces and releases substances for use in the body, such as fluids or hormones.

Hormone

—Chemical substances produced by endocrine glands and transported by the bloodstream to the organs which require them to regulate their function.

Ileum

—The last portion of the small intestine.

Metastasis

—The transfer of cancer from one location or organ to another one not directly related to it.

Nervous system

—The network of nerve tissue of the body. It includes the brain, the spinal cord and the ganglia (group of nerve cells).

Neurohormone

—A hormone produced by specialized neurons or neuroendocrine cells.

Neuron

—Specialized cell of the nervous system, that transmits nervous system signals. It consists of a cell body linked to a long branch (axon) and to several short ones (dendrites).

Syndrome

—A series of symptoms or medical events occurring together and pointing to a single disease as the cause.

Neuroendocrine Tumors

Definition

Neuroendocrine tumor refers to the type of cell that a tumor grows from rather than where that tumor is located. Neuroendocrine cells produce hormones or regulatory proteins, and so tumors of these cells usually have symptoms that are related to the specific hormones that they produce.

Description

Neuroendocrine cells have roles both in the endocrine system and the nervous system. They produce and secrete a variety of regulatory hormones, or neuropeptides, which include neurotransmitters and growth factors. When these cells become cancerous, they grow and overproduce their specific neuropeptide. Neuroendocrine tumors are generally rare. One type of neuroendocrine tumor is a carcinoid tumor. This type of tumor can occur in the intestinal tract, appendix, rectum, bronchial tubes, or ovary. Most carcinoid tumors secrete serotonin. When the blood concentration of this hormone is high enough, it causes carcinoid syndrome. This syndrome refers to a variety of symptoms that are caused by the excessive amount of hormone secreted rather than the tumor itself.

The total incidence of neuroendocrine tumors is thought to be between five and nine million people in the United States. It is possible that these tumors are underreported because they grow slowly and do not always produce dramatic symptoms.

Causes and symptoms

Many of the symptoms of carcinoid tumor are due to the hormones that the tumor secretes. These hormones can affect the whole body and cause what is referred to as carcinoid syndrome. The most common symptom of carcinoid syndrome is flushing, a sudden appearance of redness and warmth in the face and neck that can last from minutes to hours. Other symptoms of carcinoid syndrome are diarrhea, asthma-like symptoms and heart problems. Since most carcinoid tumors are found in the appendix, the symptoms are often similar to appendicitis, primarily pain in the abdomen. When these tumors are found in the small intestine, they can cause abdominal pain that is often initially diagnosed as bowel obstruction. Many patients have no symptoms and the carcinoids are found during routine endoscopy of the intestines.

Diagnosis

The diagnosis of carcinoid syndrome is made by the measurement of 5-hydroxy indole acetic acid (5-HIAA) in the urine. 5-HIAA is a breakdown (waste) product of serotonin. If the syndrome is diagnosed, the presence of carcinoid tumor is a given. When the syndrome is not present, diagnosis may be delayed, due to the vague symptoms present. Diagnosis can sometimes take up to two years. It is made by performing a number of tests, and the specific test used depends on the tumor's suspected location. The tests that may be performed include gastrointestinal endoscopy, chest x ray, computed tomography scan (CT scan), magnetic resonance imaging, or ultrasound. A biopsy of the tumor is performed for diagnosis. A variety of hormones can be measured in the blood as well to indicate the presence of a carcinoid.

Treatment

The only effective treatment for carcinoid tumor as of the early 2000s is surgical removal of the tumor. Although chemotherapy is sometimes used when metastasis has occurred, it is rarely effective. The treatment for carcinoid syndrome is typically meant to decrease the severity of symptoms. Patients should avoid stress as well as foods that bring on the syndrome. Some medications can be given for symptomatic relief; for example, tumors of the gastro-intestinal tract may be treated with octreotide (Sandostatin) or lanreotide (Somatuline) to relieve such symptoms as diarrhea and flushing. These drugs are known as somatostatin analogs.

Liver transplantation is a treatment option for patients with neuroendocrine tumors that have metastasized only to the liver. As of 2004, this approach is reported to offer patients long disease-free periods and relief of symptoms.

Prognosis

The prognosis of carcinoid tumors is related to the specific growth patterns of that tumor, as well as its location. For example, a group of researchers at the University of Wisconsin reported in 2004 that patients with gastrointestinal tumors in the hindgut had longer periods of disease-free survival than those with foregut or midgut cancers. For localized disease the five-year survival rate can be 94%, whereas for patients where metastasis has occurred, the average five-year survival rate is 18%. It is not unusual for patients with carcinoid tumors to live ten or fifteen years after the initial diagnosis.

Prevention

Neuroendocrine tumors such as carcinoid tumors are rare, and no information consequently is yet available on cause or prevention.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Carcinoid Tumors." Section 2, Chapter 17 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Ahlman, H., S. Friman, C. Cahli, et al. "Liver Transplantation for Treatment of Metastatic Neuroendocrine Tumors." Annals of the New York Academy of Sciences 1014 (April 2004): 265-269.

Oberg, K., L. Kvols, M. Caplin, et al. "Consensus Report on the Use of Somatostatin Analogs for the Management of Neuroendocrine Tumors of the Gastroenteropancreatic System." Annals of Oncology 15 (June 2004): 966-973.

Singhal, Hemant, MD, and Alan A. Saber, MD. "Carcinoid Tumor, Intestinal." eMedicine April 13, 2004. 〈http://www.emedicine.com/med/topic271.htm〉.

Van Gompel, J. J., R. S. Sippel, T. F. Warner, and H. Chen. "Gastrointestinal Carcinoid Tumors: Factors That Predict Outcome." World Journal of Surgery 28 (April 2004): 387-392.

ORGANIZATIONS

Carcinoid Cancer Foundation, Inc. 1751 York Ave., New York, NY 10128. (212) 722-3132. 〈http://www.carcinoid.org〉.

KEY TERMS

Appendicitis— Inflammation of the appendix.

Growth factor— A local hormone produced by some cells that initiates growth.

Metastasis— The spread of disease from one part of the body to another, as when cancer cells appear in parts of the body remote from the site of the primary tumor.

Neurotransmitter— A chemical messenger used to transmit information in the nervous system.