Carcinoid Tumors of the Small and Large Intestines

Relevant Physiology and Pathophysiology

Carcinoid tumors are an interesting group of neoplasms that have their origin in the endocrine argentaffin cells in the small intestinal mucosa (argentaffinomas). They are found incidentally in 0.50% to 0.75% of autopsies. Carcinoid tumors occur frequently in the ileum, where argentaffin cells are more abundant, and 20% of these tumors are multifocal. Histologic criteria do not help the physician to distinguish benign from malignant carcinoid tumors. The tumors are invariably small. About 80% of tumors more than 2 cm in diameter metastasize; those less than 1 cm are almost always benign. Metastases are to local lymph nodes, liver, lung, and bone. Carcinoid tumors may induce a reactive fibrosis in the bowel mesentery, sometimes creating an angulated intestinal segment. Even malignant and metastatic carcinoid tumors are indolent. More than 50% of patients with unresectable local metastases survive 5 years, as do about 30% of those with liver metastases. About 10% of individuals with liver metastases survive more than 10 years.

Laboratory and Other Diagnostic Tests

The biochemical marker for the carcinoid syndrome is increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). More than 30 mg of 5-HIAA is usually excreted in 24 hours by patients with carcinoid syndrome. Less striking increases in urinary 5-HIAA may be found in some patients with malabsorption such as occurs in celiac disease and bacterial overgrowth syndromes. Blood serotonin and 5-hydroxytryptophan levels can now be determined; the latter is helpful if gastric carcinoid is suspected. When urinary 5-HIAA excretion is being tested, patients should avoid drugs that may produce false-positive test results, most notably glyceryl guaiacolate, phenothiazines, and methenamine mandelate. Foods rich in serotonin should also be avoided. These include pineapples, bananas, avocados, and walnuts.

Carcinoid tumors may secrete a variety of other hormones, including insulin, adrenocorticotropic hormone, melanocyte-stimulating hormone, gastrin, and glucagon. The endocrine cells from which carcinoid tumors originate are part of the amine content, precursor uptake, and decarboxylation (APUD) family. Foregut carcinoid tumors have also been associated with pluriglandular adenomatoses (e.g., pituitary, adrenal, and parathyroid tumors) and with pancreatic gastrinomas.

Differential Diagnosis

Carcinoid tumors of the small bowel seldom ulcerate and bleed and are usually too small to cause obstruction. They may, however, produce transient intussusceptions and cause cramping abdominal pain and diarrhea. These symptoms may be long standing and intermittent, suggesting irritable bowel syndrome or Crohn's disease.

In about one third of patients with liver metastases, carcinoid syndrome, which occurs rarely with only nodal metastases, develops. Carcinoid syndrome is characterized primarily by episodes of flushing and diarrhea. The flush may produce a cyanotic appearance, and if attacks are prolonged, facial edema and telangiectasis may develop. The mediator of the carcinoid flush is unknown. Kallikrein, bradykinin, other kinin peptides, substance P, prostaglandins, serotonin, and histamine have been implicated. The flush has been precipitated by ingestion of a meal and by administration of ethanol, calcium, epinephrine, isoproterenol, and pentagastrin. The diarrhea and cramps in this syndrome appear to be related to the production of serotonin (5-hydroxytryptamine).