Introduction to Carcinoid Tumors

Neuroendocrine tumors (NETs) include both carcinoid tumors and pancreatic endocrine tumors (PETs). Carcinoid tumors, representing the largest number of cases, pose a significant challenge to the clinician because they produce a unique clinical syndrome. Consequently, their diagnosis is difficult and often delayed. The clinician requires a high index of suspicion and confirmation with biochemical tests in order to establish their diagnosis. Because the majority of neuroendocrine tumors of the pancreas and carcinoid tumors that involve the wall of the gut have similar biological characteristics, the approach to diagnosis and treatment can be applied broadly to all classes of NETs.

The origins of NETs are thought to occur in the enterchromaffin-like cells, which are present in the wall of the gastrointestinal tract, pancreas, and lung. Enterochromaffin-like cells are neuroendocrine cells in the gastric mucosa that control acid secretion by releasing histamine. In normal physiology these cells regulate secretion and motility (movement of food through the digestive tract).

There are many types of tumors that arise from the neuroendocrine system of which carcinoid tumors are the most common. Carcinoid tumors were initially identified in 1888 and were thought to clinically and histologically (cellular appearance under a microscope) resemble carcinoma cells (highly malignant cancer cells) but behave in a more benign fashion than true cancer cells. Over the years it became clear that carcinoid tumors can be quite aggressive, can metastasize, and can cause carcinoid syndrome. Most carcinoid tumors are now known to be slow growing malignant tumors that have their own specific biological and clinical characteristics.

Like many types of cells in the body, neuroendocrine cells can begin to reproduce out of control and cause cancer. This occurs more commonly as part of the Multiple Endocrine Neoplasia (MEN) Type I Syndrome which is characterized by a genetic mutation as described later. Carcinoid tumors share some properties with other cancer cells such as uncontrolled, overproduction of the cells that results in tumor formation and malignant potential. However, carcinoid tumor cells are distinguished from most other types of tumors in that they secrete various hormone-like substances (e.g., serotonin, noradrenalin, histamines) which may cause symptoms throughout the body rather than symptoms localized to the organ where the tumor originates.

Carcinoid tumors can appear anywhere neuroendocrine cells are present including the gastrointestinal (GI) tract, lungs, ovaries, pancreas, appendix, small and large intestine, testes, and rectum. The location of origin of carcinoid tumors is divided into three categories:

  • Foregut Carcinoid Tumors - These tumors originate in the lungs, thymic gland, pancreas, stomach, and duodenum (lung and stomach are most common locations)
  • Midgut Carcinoid Tumors - These tumors originate in the small intestines, appendix, and cecum (small intestines and appendix are most common locations)
  • Hindgut Carcinoid Tumors - These tumors originate in the colon (large intestine) and rectum

The largest number of neuroendocrine cells is found in the gastrointestinal tract, since it is the largest endocrine organ in the body. Indeed, according to the National Cancer Data Registry, approximately 70% of carcinoid tumors arise from locations within the gastrointestinal tract and up to 25% arise from the lungs.

Carcinoid tumors of the lung can be divided into two types:

  • Typical carcinoids which grow slowly and only rarely spread beyond the lungs. They are usually found along the major airways and, according to the American Cancer Society, are approximately nine times more common than atypical carcinoids.

  • Atypical carcinoids are faster growing tumors and are more likely to spread to other organs. They are also more likely to be located in the peripheral areas of the lung.

Although estimates vary, studies indicate that the incidence of carcinoid tumor by area of involvement is as follows:

  • Small intestines - up to 30% of carcinoids
  • Lungs - up to 25% of carcinoids
  • Appendix - approximately 20%
  • Rectum -12 to15%
  • Colon - 10%
  • Stomach - 3%

Other locations for carcinoid tumors (e.g., testis, ovary, larynx) are infrequent or rare and account for only about 3 to 5% of all carcinoid tumors. It is estimated that in up to 15% of patients with carcinoid tumors, distant metastases have developed by the time they are diagnosed with a carcinoid tumor.

The potential for malignant growth of carcinoid tumors appears to be related to several factors including:

  • The site at which the tumor originates
  • The depth of tumor invasion into adjacent tissue
  • The size of the tumor

It is estimated that approximately 10% of patients with carcinoid tumors develop carcinoid syndrome that manifests itself with symptoms related to the various substances produced by the tumors. A more detailed description of carcinoid syndrome follows later in this section.