eMedicine Specialties > Radiology > Gastrointestinal

Carcinoid, Gastrointestinal

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; David Sherlock, MBBS, FRCS, Consulting Staff, Department of Surgery, North Manchester General Hospital, Christie Hospital
Contributor Information and Disclosures

Updated: Apr 2, 2008

Introduction

Background

Gastrointestinal carcinoid, also called carcinoid tumor, is the most common primary tumor of the small bowel and appendix. Gastrointestinal carcinoid accounts for more than 95% of all carcinoids. The tumors arise from enterochromaffin cells of Kulchitsky, which are considered neural crest cells situated at the base of the crypts of Lieberkühn. Gastrointestinal carcinoids account for 1.5% of all gastrointestinal tumors. The tumors elaborate serotonin and other histaminelike substances that normally are transported to the liver, where they are metabolized.

Most tumors are clinically silent, but they may cause pain or intestinal obstruction, weight loss, a palpable mass, or, rarely, bowel perforation. Carcinoid syndrome occurs when the humoral load exceeds the capacity of monoamine oxidase (MAO) present in the liver and lung to metabolize serotonin. Most patients with carcinoid syndrome have liver metastases from a bowel carcinoid, although in rare cases, the humoral load from a primary tumor may overwhelm the liver and the capacity of the lungs to metabolize serotonin. Rarer still is carcinoid syndrome that develops in patients with noncarcinoid malignant tumors and dermatomyositis.

Pathophysiology

Carcinoids belong to a group of neoplasms known as neuroendocrine tumors (NETs). The NETs are composed of an interesting group of rare neoplasms that are derived from neuroendocrine cells interspersed within the gastrointestinal system and throughout the body. NETs are well known for producing various hormonal syndromes and for their indolent clinical course in most patients, although some of these tumors do not produce hormones of clinical significance.

Most gastrointestinal carcinoid tumors arise from neural crest cells, which are believed to be part of the amine precursor uptake and decarboxylation system and are programmed for endocrine function. On gross examination, tumors appear as firm, yellow submucosal nodules arising from argentophil Kulchitsky cells in the crypts of Lieberkühn. They grow through the muscularis mucosa and the bowel wall into the mesentery. Mesenteric invasion provokes an intense fibrotic reaction. If the tumors become large, they may present as intraluminal polypoid masses, and they occasionally are ulcerated.

Histologically, the tumors resemble adenocarcinomas, but they do not demonstrate the same aggressive behavior. Lesions of the foregut and foregut derivatives (bronchi, pancreas), as well as those of the hindgut, show a histologic pattern somewhat different from lesions of the midgut. The argentaffin reaction may be absent, and the histologic diagnosis is based on cell morphology and histologic patterns. This may explain some of the different behaviors of carcinoids found at different sites in the gastrointestinal tract.

The incidence of metastatic spread depends on the location of the primary tumor. Metastases are frequent from a midgut primary tumor, but are rare from an appendiceal carcinoid. Metastases also depend on the size of the primary tumor; tumors smaller than 1 cm metastasize in 2% of cases, tumors 1-2 cm in size metastasize in 50% of cases, and tumors larger than 2 cm metastasize in 85% of cases.

The small bowel is the most common primary site giving rise to carcinoid syndrome resulting from liver metastases. Gastrointestinal carcinoids metastasize to the lymph nodes and liver. Liver metastases may produce carcinoid syndrome, although most liver metastases are clinically silent and are usually found on images obtained before surgery or on images obtained for other reasons.¹

In carcinoid syndrome, deposition of fibrous tissue is found in the cardiac valves, particularly those of the right heart and endocardium, resulting in tricuspid stenosis/insufficiency stenosis of the pulmonary valve. Rarely, left-sided heart valves may be affected, with loss of trabeculation of the ventricle resulting from endocardial fibrosis.

Bone metastases from gastrointestinal carcinoids are highly unusual and rarely occur in the more commonly occurring midgut carcinoids. Most osseous metastases have been reported from carcinoids of the stomach or rectum. Most bone metastases are osteoblastic, but rarely, lytic or mixed lesions occur. With increasing use of somatostatin receptor scintigraphy in the diagnosis of carcinoid tumors, more metastatic bony lesions are being identified.

Regarding their biochemistry, carcinoid tumors secrete the following:

• Serotonin (5-hydroxytryptophan)
• Adrenocorticotropic hormone
• Histamine
• Bradykinin
• Kallikrein

Serotonin is metabolized in the liver by MAO into 5-hydroxyindole acetic acid (5-HIAA) and is excreted in urine; 5-hydroxytryptophan is destroyed in the lungs.

Carcinoids have various pathophysiologic features, as follows:

• Biliary carcinoid - Tumors arising from enterochromaffin cells within the biliary tree are exceptionally rare, and only 15 cases have been reported in the world literature. They may arise from either an intrahepatic or extrahepatic location. Extrahepatic tumors have been reported more frequently because of the presentation (obstructive jaundice). Fibrosing hilar tumor mimicking a Klatskin tumor has been reported.
• Colon carcinoid - Of carcinoid tumors, 5% occur in the colon and account for 0.3% of colon tumors. The cecum is affected most frequently, and 75% of colon carcinoid tumors occur in the ascending colon. Tumors frequently have an extraluminal component and often metastasize. A carcinoid tumor is an occasional incidental finding on histologic examination of a removed appendix.
  • Colon tumors are implicated in the pathogenesis of appendicitis when the tumor is located at the base of the appendix, where it may obstruct the lumen of the appendix.
  • In patients with tumor at the base of the appendix or tumors larger than 2 cm, a right hemicolectomy is indicated.
  • In patients with carcinoid tumor at the appendix tip, removal of the appendix usually is adequate treatment.
  • In more than 70% of patients, the nodule is smaller than 1 cm in size and is located at the tip of the appendix. In 10%, the lesion is located at the base of the appendix.
  • Appendiceal carcinoids follow a benign course.
  • Appendiceal carcinoids are found mostly in younger patients, usually in patients aged 20-40 years, while other carcinoids occur in patients older than 50 years. Appendiceal carcinoids have been reported in children as young as 3 years.
  • Malignant appendiceal carcinoids are an exception to the general rule.
• Duodenal carcinoid - Duodenal carcinoid is rare, and the duodenum is the second – least common site for carcinoid tumors, which are seen with decreasing frequency from the first to the third part of the duodenum. The tumors usually are slow growing and benign. An association with Zollinger-Ellison syndrome has been described.²
• Gastric carcinoid - These are rare tumors, making up 0.5% of gastric tumors. Multiple gastric carcinoid tumors are associated with enterochromaffin-like cell hyperplasia, chronic atrophic gastritis, and pernicious anemia, and they have a low risk of malignancy. A higher potential for metastatic disease is found in solitary gastric carcinoid tumors and/or in carcinoid tumors that are associated with multiple endocrine neoplasia type 1 (MEN-1) and Zollinger-Ellison syndrome. Through clinicopathologic characterization of gastric carcinoid neoplasia, the following 3 subtypes, each with a unique endoscopic appearance and clinical outcome, have been found¹ :
  • Type I gastric carcinoids are small, benign tumors associated with chronic atrophic gastritis and chronic hypergastrinemia.³
  • Type II gastric carcinoids may be large and polypoid. They are usually associated with MEN-1 and Zollinger-Ellison syndrome and are prone to lymph node metastases.
  • Type III gastric carcinoids usually are large, solitary, sporadic tumors unassociated with hypergastrinemic states. They are prone to carcinoid syndrome, as well as to lymph node and liver metastases.
• Hepatic carcinoid - The liver is frequently involved as a result of metastatic disease from a gastrointestinal carcinoid; in fact, a liver metastatic deposit may be the presenting feature of a carcinoid. Although rare, primary hepatic carcinoid does occur and is classified as a foregut tumor that is presumed to arise from the biliary mucosa. Carcinoids metastatic to the liver are often multiple in number. They may be hypervascular, may become calcified, and are frequently associated with carcinoid syndrome.
• Esophageal carcinoid - Carcinoids of the esophagus are exceptionally rare. A dozen or so esophageal carcinoids have been reported. On the whole, prognosis is poor, and most tumors metastasize.⁴
• Pancreatic carcinoid - Pancreatic carcinoid tumors are rare; most occur in the tail of the pancreas. They frequently metastasize to the regional lymph nodes and liver. They often become calcified, whereas islet cell tumors usually do not.
• Rectal carcinoid - Most rectal carcinoids are asymptomatic and are discovered incidentally during proctoscopy and/or sigmoidoscopy. Carcinoids represent 1.3% of rectal tumors. They are usually benign, and they seldom metastasize to the regional lymph nodes or the liver. Rarely, liver metastasis does occur (1%), causing carcinoid syndrome. However, as in other tumors, metastases are correlated directly with the size of the tumor. The incidence of metastases increases sharply in tumors larger than 2 cm.
• Small-bowel carcinoid - One third of gastrointestinal carcinoids involve the small bowel, with these neoplasms being the most commonly occurring tumor of the small bowel. The ileum is the most common site (91%). Incidence of tumors increases with proximity to the cecum. Small-bowel tumors are multiple in number in 15-35% of cases. Liver metastases and carcinoid syndrome occur in 25-30% of cases. The tumor often infiltrates the mesentery, provoking an intense fibrotic reaction that results in kinking of the bowel segments, which may cause intestinal obstruction. A finding of kinking of the small-bowel loops is considered the hallmark of a carcinoid tumor on a small-bowel barium series.

Frequency

United States

Gastrointestinal carcinoids are the most common primary tumors of the small bowel and appendix. They account for more than 95% of all carcinoids. The overall frequency is not known.

International

Gastrointestinal carcinoids are the most common primary tumors of the small bowel and appendix. They account for more than 95% of all carcinoids. The overall frequency is not known.

Mortality/Morbidity

Patients with malignant carcinoid syndrome frequently have symptoms for several years before it is diagnosed. Survival of 10-15 years is not unusual. When a gastrointestinal carcinoid is diagnosed without lymph node or liver metastases, the prognosis is excellent.

Sex

The male-to-female ratio is 2:1.

Age

Most carcinoids occur in patients older than 50 years; appendiceal carcinoids occur in patients aged 20-40 years. The youngest reported patient with an appendix carcinoid was aged 3 years.

Anatomy

Anatomic locations of gastrointestinal carcinoid tumors are as follows:

• Esophageal - Exceptionally rare
• Gastric - 0.5%
• Small bowel - 25-35%
  • Duodenum - 2%
  • Jejunum - 7%
  • Ileum - 91%
  • Multiple sites - 15-35%
• Appendix - 30-45% (most benign)
  • Base - 10%
  • Middle - 20%
  • Tip - 70%
• Colon - 5% (most in ascending colon)
• Rectum - 10-15%
• Pancreas - Rare
• Liver - Primary, exceptionally rare
• Biliary tract - Rare

Presentation

Most patients with gastrointestinal carcinoids are asymptomatic (66%), but patients with bowel carcinoids may present with pain, intestinal obstruction (19%), weight loss (16%), palpable mass (14%), or perforation or gastrointestinal hemorrhage (rare). Excess serotonin levels cause carcinoid syndrome.

Apart from minor exceptions, carcinoid syndrome is regarded as evidence of malignancy. Clinical manifestations of carcinoid syndrome include the following:

• Episodes of diarrhea and abdominal cramps (70%)
• Bowel obstruction
• Gastrointestinal bleeding, either occult or apparent
• Malabsorption syndromes (eg, pellagra)
• Flushing of skin, telangiectasia of the face, and neck and skin desquamation
• Right-sided heart failure - The result of right-sided endocardial fibro-elastosis, which leads to tricuspid regurgitation and pulmonary valve stenosis
• Attacks of wheezing resulting from bronchospasm (15%)
• Fever

An association with scleroderma has been described. Hydroxytryptamine (serotonin) secreted by the carcinoid tumor is degraded in the liver to 5-HIAA and excreted in urine. Significantly higher levels of 5-HIAA are found in carcinoid syndrome. Calculations are performed by using a 24-hour collection of urine.

Preferred Examination

Diagnosis is usually achieved by using several complementary imaging techniques.

The most promising imaging technique is somatostatin receptor scintigraphy.^5,6,7 The technique can aid diagnosis by localizing primary and metastatic sites of gastro-enteropancreatic endocrine tumors. The degree of radionuclide uptake is related to somatostatin receptor density. In gastrointestinal carcinoids, the concentration at the receptor sites is high (90%).

Plain radiographic findings (eg, soft-tissue mass, punctate calcification within a mass, signs of intestinal obstruction) are not specific for carcinoids. Plain radiographs are usually obtained in an acute setting, being taken, for example, in patients presenting with intestinal obstruction or perforation.

Results of barium studies are nonspecific, and these tests are usually performed in patients presenting with nonspecific gastrointestinal symptoms. Clinical correlation is required.

Ultrasonography is performed to investigate a variety of abdominal complaints. The radiologist must be aware of the ultrasonographic appearances of a carcinoid. Although these are nonspecific, they may lead to the most appropriate investigation and result in a diagnosis.

Computed tomography (CT) scan findings in a malignant carcinoid depend on its size, degree of mesenteric invasion and desmoplastic reaction, and the presence of regional lymph node invasion. In the appropriate setting, the appearance of a malignant carcinoid on a CT scan may be highly suggestive of a diagnosis of carcinoid.

Angiography is essential in interventional procedures involving liver metastases.

Somatostatin receptor scintigraphy and endoscopic ultrasonography have a direct clinical impact, because they influence individual therapeutic strategies

Limitations of Techniques

None of the radiologic techniques can provide a specific diagnosis; therefore, clinical input is obviously important. All of the imaging techniques listed above provide anatomic information, with the exception of radionuclide studies.

A carcinoid is a functioning tumor, which means that clinical correlation is important. Indications for performing various imaging studies are dependent on the initial presentation. Two techniques stand out: CT scanning is better at providing anatomic information than are barium studies, and radionuclide studies add a functional element, which is obviously important in the context of carcinoid syndrome.

Differential Diagnoses

Biliary Obstruction
Colonic Obstruction
Liver, Metastases

Other Problems to Be Considered

Islet cell tumors of the pancreas
Other bowel neoplasms
Nongastrointestinal carcinoids
Abdominal desmoid tumors

• Search for CME/CE on This Topic »

• Carcinoid Tumor, Intestinal (Oncology)
• Gastrointestinal Neoplasms (Pediatrics: Surgery)
• Malignant Carcinoid Syndrome (Oncology)
• Lower Gastrointestinal Bleeding (Gastroenterology)

• Recommendations Issued for Use of Gastrointestinal Surgery to Treat Type 2 Diabetes
• Puzzling Gastrointestinal Symptoms Common in Abused Children
• Capsule Endoscopy Does Not Improve GI Bleeding Outcomes

• Alterations in the p16INK4a/Cyclin D1/RB Pathway in Gastrointestinal Tract Endocrine Tumors
• Intra-operative Application of Real-Time Tissue Elastography for the Diagnosis of Liver Tumors
• Pellagra Associated with Esophageal Carcinoma and Alcoholism

• Noncolorectal Gastrointestinal Cancer Resource Center
• Minimally Invasive Gastrointestinal Surgery Resource Center
• IBS and Chronic Constipation Resource Center