Diagnosis of Neuroendocrine cancer

Summary

The diagnosis of neuroendocrine tumors (NETs) involves the combined diagnostic result of pathology test, biochemistry test, hormonal tests, diagnostic imaging and endoscopic imaging for getting a comprehensive clinical picture.

Introduction

The neuroendocrine tumors (NETs) diagnosis requires coordinated, multidisciplinary action involving oncologists, interventional radiologists, surgeons, and pathologists. The results of pathology tests, diagnostics, hormonal tests, and functional imaging are integrated to form a comprehensive clinical picture.

Pathology

Tissue collection is essential for NET diagnostics, pathological examination. If surgical resection is not possible, core needle biopsy should be preferred over fine-needle aspiration to assess tumor structure fully​1,2​.

Syndrome-specific biochemical testing

In patients with presenting NET symptoms, biochemical tests target a specific syndrome. A 24-hour urinary 5-hydroxyindole acetic acid (5-HIAA) test should be recorded in patients with small bowel masses or symptoms suggestive of carcinoid syndrome. The sensitivity of this test is reported to be 35-73%​3,4​. Patients should avoid eating foods rich in serotonin (such as pineapples, bananas, kiwis, avocados, or nuts) before three days of testing.

Nonsyndrome-specific biochemical testing

Chromogranin A is the NET diagnostic marker of choice​5​. It has high sensitivity (53%–91%) but low specificity (<50%). Reasons for false elevations include obstructive, renal failure, adenocarcinoma, proton-pump inhibitors and severe arterial hypertension​6​.

Diagnostic imaging

There are two general types of diagnostic imaging modalities used in conjunction with NET diagnostics.

The first method is standard cross-sectional imaging using magnetic resonance imaging (MRI) or computed tomography (CT). Canadian consensus guidelines suggest that all patients with suspected NETs should have chest, abdominal, and pelvic CT scans to determine the stage and consider an MRI of the liver or pancreas if a more detailed definition is needed​1,2​.

The second method is functional imaging using overexpression of normal somatostatin receptors in NETs. The radiolabeled somatostatin analog is administered intravenously and is focused on the NET, and the radiation emitted is detected to localize the tumor. 111Indium (In)-labelled pentetreotide- is a commonly used radioactive tracer in Canada. A recent meta-analysis of NET molecular imaging methods showed that scintigraphic imaging of 111 In-label pentetreotide somatostatin receptors with 46–100% sensitivity for abdominal NET, 46–83% for pancreatic NET and 71% for bronchial NET​7​.

The new radioactive isotope 68Ga (gallium) is a positron emitter that can be attached to somatostatin analogs and localized by positron emission tomography (PET)/CT imaging. NETs were imaged using 111In-label pentoxide scanning and 68Ga-DOTATATE PET/CT​8​. The sensitivity of 68Ga-DOTATATE PET/CT compared to 111In-labeled pentoxide was 96% (95%CI= 86%-100%) versus 72% (95% CI= 58%-84%). Access to 68Ga-based imaging is currently limited in specialized centres in Canada but is expected to become widespread soon.

It is important to note that imaging methods based on somatostatin analogs have low sensitivity in poorly differentiated cancers, as cells often lack somatostatin receptors. Thus, poorly differentiated tumors can be better characterized by fluorodeoxyglucose (18FDG) PET/CT scanning, which localizes the tumor by uptake of radiolabeled glucose molecules​8​.

Endoscopic imaging

Endoscopic ultrasound is a very sensitive test for diagnosing pancreatic NETs (sensitivity 82%–93%)​9​. Endoscopic ultrasound is beneficial for identifying tumors smaller than 2 cm and localizing insulinomas.

References

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    Singh S, Asa S, Dey C, et al. Diagnosis and management of gastrointestinal neuroendocrine tumors: An evidence-based Canadian consensus. Cancer Treat Rev. 2016;47:32-45. doi:10.1016/j.ctrv.2016.05.003
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    Singh S, Dey C, Kennecke H, et al. Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group. Ann Surg Oncol. 2015;22(8):2685-2699. doi:10.1245/s10434-014-4145-0
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    Feldman J, O’Dorisio T. Role of neuropeptides and serotonin in the diagnosis of carcinoid tumors. Am J Med. 1986;81(6B):41-48. doi:10.1016/0002-9343(86)90583-8
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    Bajetta E, Ferrari L, Martinetti A, et al. Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer. 1999;86(5):858-865. doi:
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    Modlin I, Gustafsson B, Moss S, Pavel M, Tsolakis A, Kidd M. Chromogranin A–biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol. 2010;17(9):2427-2443. doi:10.1245/s10434-010-1006-3
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    Koopmans K, Neels O, Kema I, et al. Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results. Crit Rev Oncol Hematol. 2009;71(3):199-213. doi:10.1016/j.critrevonc.2009.02.009
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    Squires M, Volkan A, Schuster D, et al. Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach. Ann Surg Oncol. 2015;22(7):2295-2301. doi:10.1245/s10434-015-4471-x
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    Anderson M, Carpenter S, Thompson N, Nostrant T, Elta G, Scheiman J. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol. 2000;95(9):2271-2277. doi:10.1111/j.1572-0241.2000.02480.x