Intestinal Carcinoid Tumor Workup

Updated: Dec 20, 2021
  • Author: Rachel E Lewis, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Laboratory Studies

In patients with carcinoid syndrome, levels of urinary 5-hydroxyindoleacetic acid (5-HIAA) are usually significantly elevated. This is because tryptophan metabolism is diverted from protein and nicotinic acid metabolism to serotonin, with consequent breakdown to 5-HIAA. A very high (usually more than five times normal values) level of urinary 5-HIAA in a 24-hour collection is diagnostic, provided that foods and drugs that may interfere with test results are avoided before the test.

Foods that contain high levels of 5-HIAA precursor and should be excluded from the diet for at least 24 hours before the test include avocados, bananas, plums, walnuts, pineapples, tomatoes, and eggplants (aubergines). Drugs that may interfere with test results, and which typically should be excluded for at least 48 hours before the test, include cough medicines, antihistamines, acetaminophen, and monoamine oxidase inhibitors.

In very rare cases, usually in bronchial carcinoids or gastric tumors (derived from the foregut), the tumor cells lack the aromatic amino acid decarboxylase enzyme, and hence the secretion of 5-hydroxytryptophan (5-HTP) is increased. If this is the situation, then 5-HIAA urinary excretion would be normal. The diagnosis is confirmed by measuring total 5-hydroxyindole excretion. Such measurement includes 5-HTP, serotonin, and 5-HIAA.

Well-known biomarkers common to neuroendocrine tumors (NETs) include synaptophysin, chromogranin A (CgA), and neuron-specific enolase (NSE), among others. Of these neuroendocrine biomarkers, synaptophysin and CgA are recommended for routine use in practice because synaptophysin is considered the most sensitive and CgA the most specific in the evaluation of NETs. [43] Given the low specificity of NSE for NETs relative to synaptophysin and CgA, it is not recommended for routine use in practice.

Massironi and colleagues evaluated the diagnostic and prognostic value of plasma CgA in 181 patients with pancreatic or gastrointestinal neoplasms. CgA values at diagnosis were above the upper reference limit in 148 patients (82%). Median CgA levels were significantly higher in functioning tumors compared with non-functioning tumors and in patients with metastases compared with those without metastases. CgA levels were significantly associated with disease stage after adjustment for patient age, sex, and tumor site. An early decrease in CgA, a low Ki-67 index, and type of treatment were positively correlated with survival. Increased CgA levels predicted recurrence after radical surgery. [44]

In a study of 125 patients with neuroendocrine tumors, 29 patients without neuroendocrine tumors who were being treated with proton pump inhibitors, and 50 controls, a polymerase chain reaction (PCR)–based 51-transcript signature was significantly better than plasma CgA for detecting tumors, and was unaffected by the use of acid suppression therapy. PCR had a sensitivity of 98.4%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 97.8%; corresponding metrics for CgA were all less than 60 %. [45]


Imaging Studies


Ultrasound has limited use, particularly in lesions smaller than 1 cm.

Endoscopic ultrasound is useful for detecting gastric, duodenal, and pancreatic lesions; experience in this technique is mainly in detecting duodenal gastrinomas and is highly operator dependent. [46] It is also used to detect anal lesions.

Computed Tomography

Noncontrast CT scan is the investigation of choice for carcinoid tumors because metastatic carcinoid tumors are usually extremely vascular; consequently, they tend to become isodense in the presence of contrast. [47]

CT scan can also detect mesenteric involvement with tumor in 50% of patients with metastatic disease.

Magnetic Resonance Imaging

In the past, availability and the speed of the procedure initially limited use of this investigation. Another dilemma was the difficulty in distinguishing between small (< 2 cm) vascular intrahepatic lesions and benign hemangiomas. With technical improvements, MRIs are increasingly being used as the supplemental abdominal investigation of choice.

Radionucleotide Scans

Radionucleotides injected into the bloodstream can bind to the neuroendocrine tumor cells and thus help localize the site of the tumor.

Commonly, octreotide (an analogue of somatostatin) is labelled with a radioactive isotope and injected. Carcinoid tumors often have somatostatin receptors on their surface. The radio-labelled analogue (111In-octreotide) therefore binds to the tumor cells. Radiography then allows the tumor to be visualized. This test is particularly useful when other routine modalities have failed to localize the site of the carcinoid. Another compound used less commonly is I131 MIBG.

Positron Emission Tomography

This modality uses the ability of certain tumors to take up radiolabeled tracers and thus be used to assess the function of different metabolic pathways specific to the tissue being scanned. It is useful in those instances in which scintigraphy with In111 octreotide has been inconclusive.

FDG (F18 labelled deoxyglucose) is the tracer that is useful in detecting less-differentiated neuroendocrine tumors, as they have a higher metabolic rate. Well-differentiated tumors have slower metabolic rates and therefore do not take up FDG as avidly. These tumors are better visualized on PET scans, which use the tracer C15 5-HTP.

Recently, gallium-68 (68Ga)-DOTATATE PET/CT scanning has become the preferred modality for somatostatin receptor imaging due to its higher sensitivity and reduced exposure to radiation. It has a sensitivity greater than 94% and specificity greater than 92%. Use of 68Ga-DOTATATE PET/CT imaging has been reported for baseline staging, detection of metastases, and identification of the primary site. [4]


Other Tests

Gastric and anal carcinoid tumors can be evaluated by endoscopic techniques. Standard gastroscopy is of limited use except in patients with multiple gastric carcinoids.



There is no single system of classification and staging of carcinoid tumors. Different systems classify these tumors on the basis of site of origin (lung or gastrointestinal), malignant potential, and spread.

The World Health Organization (WHO) classifies carcinoids as neuroendocrine tumors (benign) or neuroendocrine cancers (malignant). Neuroendocrine cancers are further subclassified as either well differentiated (less aggressive) or poorly differentiated (aggressive).

Classification based on spread is as follows:

  • Localized - Limited to the organ of origin
  • Regional spread - Limited infiltration into surrounding tissues
  • Distant metastasis - Disease present in organs other than the primary

Histologic Findings

In general, gastrointestinal carcinoid tumors are described as submucosal or intramural lesions that are nodular or polypoid in shape with yellow-tan coloration. [48]  They may appear ulcerated in advanced lesions, indicated spread beyond the mucosa and submucosa. The typical histologic appearance of carcinoids is describe as a "salt-and-pepper" pattern, which is the chromatin within granules. They are small, with relatively uniform round to oval nuclei. They have an organoid shape with a nesting or trabecular like pattern. Carcinoids characteristically stain positive for CgA and synaptophysin.