Carcinoid tumors arise from enterochromaffin cells.  These tumors may appear in various organ systems to include the lungs, stomach, small intestine, appendix, colon or rectum.  The tumors may be either malignant or benign and metastasis may occur.  The majority of tumors arise from the gastrointestinal tract and approximately 85% of carcinoid tumors are benign.  Histologic examination shows a positive reaction to silver stains and neuroendocrine markers (neuron-specific enolase, synatophysin, and chromogranin), and when viewed under an electron microscope, the cells of carcinoid tumors are found to contain numerous neurosecretory granules.  These granules contain various hormones and biogenic amines (serotonin, corticotropin, histamine, dopamine, substance P, neurotensin, prostaglandins, and kallikrein) which cause many of the various symptoms associated with carcinoid syndrome (paroxysmal or chronic flushing, wheezing, diarrhea, oliguria, hypotension, abdominal pain, periorbital or facial edema,and right-sided cardiac valvular disease).  Pellagra (dermatits, diarrhea, mental status changes, and mucus membrane inflammation causing sore tongue, odynophagia, abdominal pain, urethritis and vaginitis) occurs in some patients as a result of disturbed tryptophan metabolism with resultant niacin (nicotinic acid/ nicotinamide) deficiency.

     Carcinoid tumors are categorized by location and serotonin secretion as serotonin is responsible for symptom manifestation. Foregut tumors secrete low levels of serotonin and may present with the classic symptoms without associated hepatic metastasis. Midgut tumors secrete high levels of serotonin that are inactivated by hepatic enzymes; therefore, symptoms only manifest when there is associated hepatic metastasis. Most hindgut carcinoids do not secrete serotonin and are without the characteristic symptoms. Carcinoid tumors may be a component of multiple endocrine neoplasia type 1, von Hippel-Lindau disease, or neurofibromatosis type 1. Patients with carcinoid tumors are also at risk for other malignancies of the genitourinary, gastrointestinal, and respiratory tracts. Carcinoid tumors are often indolent, but when metastasis does occur (less than 15% of cases), the mediastinal lymph nodes, liver, bone, or skin may be affected.


     Pulmonary carcinoid tumors are often located in the perihilar region and present during the fifth decade of life in most patients.  Patients often present with recurrent pneumonia, cough, chest pain, or hemoptysis.  Cushing’s syndrome and acromegaly may result from ectopic secretion of corticotropin and growth hormone-releasing factor, respectively. 

     Gastric carcinoid tumors are divided into three groups based on clinical and histologic findings.  The three groups include those associated with chronic atrophic gastritis type A (most common form), those associated with the Zollinger-Ellison syndrome (associated with MEN I: pituitary, pancreatic islet cell, and parathyroid gland tumors), and sporadic tumors.  Metastasis is uncommon but does occur.  The sporadic form of gastric carcinoid tumors are often metastatic and associated with a poor outcome.  These sporadic tumors often manifest as flushing, and radical gastrectomy is the preferred treatment due to their aggressive nature. Gastric carcinoid tumors may manifest as pernicious anemia.


          Small intestinal carcinoid tumors are most common in the distal ileum and are often multicentric.  Patients are often between 50 to 70 years of age at initial presentation.  Metastasis to the liver or lymph nodes is common. 

     The most common cancers of the appendix are carcinoid tumors.  Patients are generally between the ages of 30 to 50 years at the time of diagnosis.  Metastasis is uncommon when tumor size is less than 2 centimeters in diameter, but becomes more common (approximately 33% of cases) with larger tumors.  When there is hepatic metastasis, the symptoms of the carcinoid syndrome may manifest.  Tumors less than 2 centimeters are treated by appendectomy.  Larger tumors are treated with right colectomy.

     The majority of carcinoid tumors of the colon are located on the right side and are considered midgut tumors.  Metastasis is common, and most cases are treated with radical colectomy.


     Carcinoids from the transverse colon to the rectum are not associated with symptoms of the carcinoid syndrome and often manifest as rectal bleeding, pain or constipationIron deficiency anemia may be a manifestation of carcinoid tumors of the bowel. When metastasis occurs it is generally to local lymph nodes or to the liver.  Surgical resection includes local resection (tumors less than 1 centimeter), and either low anterior resection or abdominoperineal resection (tumors greater than 2 centimeters).  Treatment for tumors between 1 to 2 centimeters is controversial and may include either local resection or more extensive procedures.

     Patients with the carcinoid syndrome often develop right sided cardiac valvular disease.  Tricuspid regurgitation is the most common abnormality, but tricuspid stenosis or pulmonic valve pathology (stenosis or regurgitation) may also occur.  Left-sided disease occurs less frequently and may be associated with pulmonary metastasis. Tumor-induced fibrosis may also manifest as hydronephrosis, mesenteric ischemia, and Peyronie disease. When a carcinoid tumors is suspected based on symptoms and screening labs (elevated levels of 24 hour urinary 5-hydroxy-indoleacetic acid, serum serotonin, or serum chromagranin A), somatostatin receptor scintigraphy with radiolabeled octreotide is most useful for localizing both primary and metastatic tumors.

     Patients with the symptoms of the carcinoid syndrome with metastatic disease localized to a single hepatic lobe may be treated with surgical resection. Other patients, those with hepatic metastasis in multiple hepatic lobes or those who are deemed to be poor surgical candidates, may obtain relief through therapy with interferon alfa, octreotide (150 micrograms subcutaneously TID), or both.  H-1 and H-2 receptor antagonists used in combination may be effective at controlling flushing as may phenoxybenzamine HCl.  Symptoms of dyspnea and wheezing may be controlled with the use of methylxanthines, bronchodilators or glucocorticoids.  Diarrhea may respond to cyproheptadine HCl or methysergide maleate.  Hepatic artery embolization with or without chemotherapy may be effective when there is extensive liver metastasis. Radiation therapy with meta-iodo-benzylguanidineiodine 131 is an option in patients whose tumors express receptors for MIBG (approximately 70%). Prognosis varies depending on the location of the tumor and the presence of metastasis. Carcinoid tumors of the appendix and rectum have the best prognosis, whereas carcinoids of the small intestine have the worst. Carcinoid crisis may occur and manifests as hypo or hypertension, tachycardia, and altered mental status (shock). Crisis may occur spontaneously or during manipulation of the tumor via surgery, chemotherapy, or hepatic artery embolization. Catecholamines and calcium therapy should be avoided, instead patients should be treated with intravenous octreotide and plasma. Intravenous octreotide may be used before chemotherapy, surgery, or arterial embolization as prophylaxis against carcinoid crisis.