Diagnosis of Carcinoid Tumors

Clinical Evaluation and Laboratory Studies

Physical Examination

  • Medical history of the patient including any changes in symptoms or changes in health habits

  • Complete physical examination including palpation (in order to identify any masses or enlargement of any organs

Laboratory Studies

  • CBC (complete blood count)

    • number of red and white blood cells and number of platelets
    • amount of hemoglobin (oxygen) in the red blood cells
    • percentage of red blood cells in the blood sample (hematocrit)

  • Biochemical analysis which may include:

    • Chromogranin A (CgA) - this glycoprotein is stored in neuroendocrine cells and is released into the blood circulation in the presence of carcinoid tumors even if it is dormant. Chromogranin A is elevated in almost all types of neuroendocrine tumors regardless of organ of origin. Highest levels tend to appear in metastatic disease of midgut tumors. The level of CgA may be used to predict prognosis of carcinoid tumor and may also be a reliable marker for follow-up after treatment.

    • Neuron-specific enolase (NSE) - this is an enzyme that is present in enterochromaffin-like cells. In general, measurable increases in the level of NSE can be detected with metastatic spread of neuroendocrine tumors to the liver.

    • Serotonin - elevated levels may be present in midgut tumors with accompanying carcinoid syndrome

    • 5HTP (5-Hydroxytryptophan) - a substance utilized in the production of serotonin and frequently elevated in the presence of tumors of the foregut.

    • ACTH (adrenocorticotropic hormone) - elevated in the presence of tumors of the foregut.

    • Noradrenaline - this hormone may be elevated in midgut tumors

    • Growth hormone - may be elevated in foregut tumors

    • Ki-67 - detection of this antigen in the blood is a strong indicator of the malignant activity of a carcinoid tumor.

    • Urine sample - following a 24 hour urine collection, an elevated presence of 5-HIAA (5-hydroxyindole acetic acid, which is a serotonin metabolite) indicates either the presence of a GI tumor or carcinoid syndrome. 5-HIAA tends to be significantly elevated in the presence of tumors of the midgut but only mildly elevated with tumors of the foregut. Elevated levels of 5-HIAA is indicative of above normal amounts of serotonin.

    • Pentagastrin Provocative Test may be performed if the test for levels of 5-HIAA in the urine is not conclusive. This test induces flushing as well as other symptoms of carcinoid syndrome as well as an elevation of circulating serotonin in people with carcinoid syndrome.

Tumor markers are rarely elevated in hindgut carcinoid tumors even after they have spread. This is one of the reasons why hindgut carcinoid tumors tend to be discovered at a later stage of development. Tumor markers are usually not utilized as predictors or indicators of the level of disease activity.

Diagnostic Imaging

Radiologically identifiable pancreatic endocrine tumors and carcinoid tumors require further investigation in patients with NETs. Imaging is performed to permit the identification and localization of the primary tumor and to determine whether the patient has metastatic disease. Delay in identifying the site of primary tumor involvement may lead to up to a 30% to 50% incidence of metastases.

Various imaging modalities may be used either alone or in combination and may also be used in conjunction with fine needle biopsy. This involves inserting a thin needle into a tumor and extracting cells to be analyzed under a microscope in order to precisely characterize the type of cancer based on morphology. Computed Tomography (CT), Magnetic Resonance Imaging (MRI) or ultrasound may be used to guide the needle to the precise location of the tumor.

Somatostatin receptor scintigraphy (SRS), also called an octreotide scan, is a type of radionuclide scan used to detect carcinoid tumors. In a radionuclide scan, the patient is given an injection or swallows a small amount of radioactive material (a radionuclide). A scanner machine then measures the radioactivity in certain organs. This information is then used to produce an image of the internal organs.

In SRS, radioactive octreotide, a drug similar to somatostatin, is injected into a vein and travels through the bloodstream. The radioactive octreotide attaches to carcinoid tumor cells that have somatostatin receptors. A radiation-measuring device detects the radioactive material, showing where the carcinoid tumor cells are located in the body.

With the recent development of endoscopic ultrasonography (EUS), also called endoscopic ultrasound, as a sensitive imaging modality in the detection of primary neuroendocrine tumors of the duodenum and pancreas, the current recommendations are that patients undergo imaging with a combination of EUS, SRS, CT and MRI. By combining these imaging modalities, tumors can be detected in over 80% of cases.

Imaging alternatives for diagnosis of carcinoid tumors include:

  • Computerized Tomography (CT) with or without contrast dye. CT is reported to have a high sensitivity (up to 85%) for the identification of the spread of midgut tumors, however, the original tumor may not be visible if it is deep within the tissue. CT is effective for visualizing metastases to the liver and for determining lymph node involvement.

  • Magnetic Resonance Imaging (MRI) with or without contrast dye. MRI is helpful in confirming metastases of a carcinoid tumor to the liver. It is less sensitive than CT for identifying metastatic activity outside of the liver.

  • X-ray of the chest may be helpful in initially visualizing a lung carcinoid tumor.

  • Upper and lower GI series with contrast (barium) may be helpful in identifying abnormalities in lining of the gastrointestinal organs

  • Endoscopy (for foregut and upper midgut tumors), colonoscopy (for hindgut tumors) or bronchoscopy (for bronchial tumors) for identification of localized growths or polyps. Visualization is immediate and if certain abnormalities are found, the tissue can be excised during the test.

  • Ultrasound is helpful for visualizing liver metastases. It is also used for guiding fine needle biopsy for tumors in certain locations.

  • Radionuclide Imaging - Almost all carcinoid tumors have receptors for somatostatin which is a hormone-like substance secreted by the tumors. Somatostatin analogs, octreotide and lancreotide, have a strong affinity for the subtypes of somatostatin receptors expressed by carcinoid tumors. Radionuclide imaging scans include:

    • [111-In]-Octreotide Scintigraphy (Octreoscan) - When octreotide is attached to a radioactive isotope and injected into a patient, it bonds with the carcinoid cells thereby enabling the radioactive signal to be picked up and the area of the primary tumor to be identified (up to 95% sensitivity). Metastatic activity is also effectively identified with this technique. This is now considered to be the modality of choice for identifying and localizing carcinoid tumors. The effectiveness of [111-In]-octreotide scintigraphy is lower for hindgut tumors.

    • Iodine-131 Metaiodobenzylguanidine Scintigraphy - This test uses the same principle as octreotide scintigraphy but has a lower sensitivity for identifying metastatic carcinoids (approximately 80%). It has greater diagnostic value for other types of neuroendocrine tumors.

Bronchial tumors are usually identified with X-ray, CT, or MRI which may be combined with bronchoscopy, fine needle aspiration and biopsy.

Gastric tumors may be identified using endoscopy, endoscopic ultrasound, or an upper GI series. CT scans of the abdomen and pelvis help evaluate the spread of disease to the liver or surrounding lymph nodes.

Midgut tumors are usually diagnosed after they have metastasized and octreotide scintigraphy may be used to identify the lesion and determine its degree of spread. The diagnostic accuracy is very high as is its predictive value based on the degree of involvement. Additional studies may include upper or lower GI series, as well as CT scans of the abdomen and pelvis.

Liver metastases may be imaged by transabdominal ultrasound or by CT. Ultrasound may also be used to guide fine needle biopsy of the liver.

Hindgut tumors may be identified and evaluated by MRI, CT, colonoscopy, or scintigraphy.