Carcinoid Tumor Workup: Laboratory Studies, Imaging Studies, Procedures (original) (raw)

Laboratory Studies

Laboratory diagnosis of carcinoid tumors depends on the identification of the characteristic biomarkers of the disease. Measurement of biogenic amines levels (eg, serotonin, 5-HT, catecholamines, histamine) and its metabolites in the platelets, plasma, and urine of patients can be helpful in diagnosis.

Urinary 5-HIAA levels are usually increased and aid in the assessment of carcinoid tumors. [80, 81, 82, 83, 84, 85] Measurement of urinary 5-HIAA levels can help in diagnosing carcinoid syndrome but may not help in detecting tumors at an early stage of development when they are potentially curable with resection. Although the detection of urinary 5-HIAA is the single best screening method for carcinoid tumors, the level is not always elevated, and the measurement of other peptides (eg, SP, neuropeptide K, chromogranin) may be necessary for diagnosis and follow-up.
Fasting plasma 5-HIAA assay is more stable than whole-blood serotonin assay and is more convenient than 24-hour urine collection. [86] Substances produced by carcinoid tumors are listed in Pathophysiology above.
In one study, CDX2 was highly indicative of GI carcinoid tumor, whereas TTF-1 had high specificity for pulmonary tumors. [87] One (17%) of 6 gastric carcinoids stained with CDX2, whereas 8 (53%) of 15 pulmonary carcinoids stained with TTF-1. None of the GI tumors stained with TTF-1.

Imaging Studies

Numerous imaging modalities have been used to detect carcinoid tumors. These modalities include plain radiography, upper-GI and lower-GI radiography with the use of oral contrast agents, CT, MRI, angiography, positron emission tomography (PET), scintigraphy with metaiodobenzylguanidine (MIBG) and octreotide, [23, 24] radionuclide imaging with somatostatin analogs attached to the radioactive tracer, and technetium-99m bone scanning. Depending on the location of the tumor and metastasis, a combination of these may be used.

A study sought to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumors. The study found that PET-CT has a poor sensitivity but good specificity to detect the presence of mediastinal lymph node metastases in pulmonary carcinoid tumors. Mediastinal lymph node metastases cannot be ruled out with negative PET-CT uptake, and if the absence of mediastinal lymph node disease is a prerequisite for directing management, tissue sampling should be undertaken. [88, 89]

GI series, CT, and MRI may be helpful in some situations.
- For the diagnosis of chest tumors, CT combined with scintigraphy with octreotide is preferred.
- In the large bowel, the disease is often detected with colonoscopy and does not provide an imaging challenge. Imaging diagnosis of small-bowel carcinoids is relatively difficult. Small tumors in this location are difficult to detect on upper-GI series and CT scans, and other techniques are required.
- Mesenteric invasion and liver metastasis are often detected on CT scans. MRI can also be helpful in the diagnosis of hepatic disease but is less sensitive than CT in detection of extrahepatic lesions.
With advances in imaging studies, angiography is rarely used and is reserved for equivocal situations.
PET scanning can be helpful and is increasingly used for diagnosis and follow-up of the tumors.
Scintigraphy with MIBG and octreotide scanning have been used to successfully detect carcinoid tumors. [90] Octreotide scanning appears to be more sensitive than MIBG imaging.
Radionuclide imaging with somatostatin analogs attached to radioactive tracer can be used to advantage for diagnosis of carcinoid tumors.
- Radiotracers currently used include indium-111 diethylenetriamine pentaacetic acid (111 In-DTPA) and yttrium. Most neuroendocrine tumors have receptors for somatostatins. Five somatostatin receptor subtypes, designated SSTR-1 to SSTR-5, are identified. Binding affinity of somatostatin analogs to these subtypes may vary depending on the type and primary site of the tumor. In general, the highest affinity is for SSTR-2, medium affinity for SSTR-3 and SSTR-5, and lowest affinity for SSTR-1 and SSTR-4. Carcinoid tumors often express SSTR-1 to SSTR-3 and, infrequently, SSTR-2. Nevertheless, for tumors that measure less than 1 cm in diameter, the sensitivity of 111 In-DTPA octreotide imaging reaches 80-90%. [91]
- This technique can be used to identify primary and metastatic disease and is approved for radionuclide scanning of carcinoid tumors. An advantage is that, if the result is positive, this technique can be used as a treatment modality.
- In a study of 40 patients, somatostatin-receptor scintigraphy (SRS) helped in detecting localized tumors in 78% of patients versus 82% with CT scanning. However, SRS helped in identifying primary tumors in 2 patients missed on CT scanning. In 16% of patients, SRS depicted lesions not found with other modalities. No false-positive results were observed.
- Overall, SRS appears to be the imaging method of choice for localizing and evaluating the extent of carcinoid tumor.
- Bone metastasis is not uncommon in carcinoid tumors. In a study of 12 patients, 11 of whom had liver metastasis, 8 had bone involvement, as detected on SRS.
- 6-Fluoro-[18F]L-dihydroxyphenylalanine positron emission/computed tomography for imaging carcinoid tumor has been reported. [92]
- Technetium-99m bone scanning can aid in the detection of metastases.

Procedures

Endoscopy, including bronchoscopy, esophagogastroscopy, gastroscopy, and colonoscopy, can be used for biopsy and diagnosis. Functional imaging with somatostatin receptor-specific radiotracers with fused functional as well as anatomic imaging have significantly improved the diagnosis and follow up of carcinoid tumors. [93]

Histologic Findings

Please see Pathophysiology above.

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Author

Cameron K Tebbi, MD Director, Children's Cancer Research Group Laboratories

Cameron K Tebbi, MD is a member of the following medical societies: International Society of Pediatric Oncology