Diagnosis of the carcinoid syndrome and tumor localization
- Jonathan R Strosberg, MD
Jonathan R Strosberg, MD
- Associate Professor
- Department of Gastrointestinal Oncology
- H. Lee Moffitt Cancer Center
- Section Editors
- Kenneth K Tanabe, MD
Kenneth K Tanabe, MD
- Section Editor — Gastrointestinal Malignancies
- Professor of Surgery
- Harvard Medical School
- David C Whitcomb, MD, PhD
David C Whitcomb, MD, PhD
- Section Editor — Pancreatic Diseases
- Professor of Medicine
- University of Pittsburgh School of Medicine
The term "carcinoid" is generally applied to neuroendocrine tumors (NETs) originating in the digestive tract, lungs, or rare primary sites, such as kidneys or ovaries. Use of the term carcinoid usually implies a well-differentiated histology, whereas the term "neuroendocrine carcinoma" is usually assigned to high-grade or poorly differentiated NETs. (See "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on 'Pathology, tumor classification, and nomenclature'.)
Carcinoid tumors can present in several different ways:
●As a result of the carcinoid syndrome: Chronic flushing and/or diarrhea are the typical manifestations of the carcinoid syndrome, which is the result of secretion of serotonin and other vasoactive substances into the systemic circulation. The carcinoid syndrome is primarily associated with metastatic tumors originating in the midgut (distal small intestine and proximal colon). In contrast, hindgut (distal colorectal) and foregut (gastroduodenal, bronchial) carcinoid tumors rarely produce the carcinoid syndrome (table 1). (See "Clinical features of the carcinoid syndrome" and "Bronchial neuroendocrine (carcinoid) tumors: Epidemiology, risk factors, classification, histology, diagnosis, and staging", section on 'Presenting signs and symptoms'.)
●As a result of tumor growth: Small bowel carcinoid tumors may cause chronic/recurrent abdominal pain, occasionally leading to bowel obstruction. Metastatic tumors in the liver can cause right upper quadrant pain, hepatomegaly, and early satiety. (See "Clinical characteristics of carcinoid tumors", section on 'Jejunoileal small bowel tumors' and "Metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: Presentation, prognosis, imaging, and biochemical monitoring", section on 'Clinical presentation'.)
●As an incidental finding: Many carcinoid tumors are discovered during endoscopic or radiographic procedures planned for other purposes; this is especially true of carcinoids of the stomach and rectum.
- Sjöblom SM. Clinical presentation and prognosis of gastrointestinal carcinoid tumours. Scand J Gastroenterol 1988; 23:779.
- O'Toole D, Grossman A, Gross D, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology 2009; 90:194.
- Modlin IM, Gustafsson BI, Moss SF, et al. Chromogranin A--biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol 2010; 17:2427.
- Feldman JM. Carcinoid tumors and syndrome. Semin Oncol 1987; 14:237.
- Feldman JM. Urinary serotonin in the diagnosis of carcinoid tumors. Clin Chem 1986; 32:840.
- Eriksson B, Arnberg H, Oberg K, et al. A polyclonal antiserum against chromogranin A and B--a new sensitive marker for neuroendocrine tumours. Acta Endocrinol (Copenh) 1990; 122:145.
- Campana D, Nori F, Piscitelli L, et al. Chromogranin A: is it a useful marker of neuroendocrine tumors? J Clin Oncol 2007; 25:1967.
- Nehar D, Lombard-Bohas C, Olivieri S, et al. Interest of Chromogranin A for diagnosis and follow-up of endocrine tumours. Clin Endocrinol (Oxf) 2004; 60:644.
- Stridsberg M, Oberg K, Li Q, et al. Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours. J Endocrinol 1995; 144:49.
- Granberg D, Stridsberg M, Seensalu R, et al. Plasma chromogranin A in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 1999; 84:2712.
- Fossmark R, Jianu CS, Martinsen TC, et al. Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition. Scand J Gastroenterol 2008; 43:20.
- Zatelli MC, Torta M, Leon A, et al. Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study. Endocr Relat Cancer 2007; 14:473.
- Stridsberg M, Eriksson B, Oberg K, Janson ET. A comparison between three commercial kits for chromogranin A measurements. J Endocrinol 2003; 177:337.
- Pregun I, Herszényi L, Juhász M, et al. Effect of proton-pump inhibitor therapy on serum chromogranin a level. Digestion 2011; 84:22.
- Korse CM, Muller M, Taal BG. Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours. Br J Cancer 2011; 105:1173.
- Vezzosi D, Walter T, Laplanche A, et al. Chromogranin A measurement in metastatic well-differentiated gastroenteropancreatic neuroendocrine carcinoma: screening for false positives and a prospective follow-up study. Int J Biol Markers 2011; 26:94.
- Richter G, Stöckmann F, Conlon JM, Creutzfeldt W. Serotonin release into blood after food and pentagastrin. Studies in healthy subjects and in patients with metastatic carcinoid tumors. Gastroenterology 1986; 91:612.
- Allen KR, Degg TJ, Anthoney DA, Fitzroy-Smith D. Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5-hydroxyindoleacetic acid: three case examples. Ann Clin Biochem 2007; 44:300.
- Tellez MR, Mamikunian G, O'Dorisio TM, et al. A single fasting plasma 5-HIAA value correlates with 24-hour urinary 5-HIAA values and other biomarkers in midgut neuroendocrine tumors (NETs). Pancreas 2013; 42:405.
- Sundin A, Vullierme MP, Kaltsas G, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. Neuroendocrinology 2009; 90:167.
- Consensus-based guidelines from the National Comprehensive Cancer Network are available online at http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on March 29, 2016).
- Ganeshan D, Bhosale P, Yang T, Kundra V. Imaging features of carcinoid tumors of the gastrointestinal tract. AJR Am J Roentgenol 2013; 201:773.
- Paulson EK, McDermott VG, Keogan MT, et al. Carcinoid metastases to the liver: role of triple-phase helical CT. Radiology 1998; 206:143.
- Dromain C, de Baere T, Lumbroso J, et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol 2005; 23:70.
- Pisegna JR, Doppman JL, Norton JA, et al. Prospective comparative study of ability of MR imaging and other imaging modalities to localize tumors in patients with Zollinger-Ellison syndrome. Dig Dis Sci 1993; 38:1318.
- Elias D, Lefevre JH, Duvillard P, et al. Hepatic metastases from neuroendocrine tumors with a "thin slice" pathological examination: they are many more than you think... Ann Surg 2010; 251:307.
- Dromain C, de Baere T, Baudin E, et al. MR imaging of hepatic metastases caused by neuroendocrine tumors: comparing four techniques. AJR Am J Roentgenol 2003; 180:121.
- Strosberg J, Nasir A, Coppola D, et al. Correlation between grade and prognosis in metastatic gastroenteropancreatic neuroendocrine tumors. Hum Pathol 2009; 40:1262.
- Schillaci O, Corleto VD, Annibale B, et al. Single photon emission computed tomography procedure improves accuracy of somatostatin receptor scintigraphy in gastro-entero pancreatic tumours. Ital J Gastroenterol Hepatol 1999; 31 Suppl 2:S186.
- Krausz Y, Keidar Z, Kogan I, et al. SPECT/CT hybrid imaging with 111In-pentetreotide in assessment of neuroendocrine tumours. Clin Endocrinol (Oxf) 2003; 59:565.
- Reidy-Lagunes DL, Gollub MJ, Saltz LB. Addition of octreotide functional imaging to cross-sectional computed tomography or magnetic resonance imaging for the detection of neuroendocrine tumors: added value or an anachronism? J Clin Oncol 2011; 29:e74.
- Janson ET, Westlin JE, Eriksson B, et al. [111In-DTPA-D-Phe1]octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment. Eur J Endocrinol 1994; 131:577.
- Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26:2124.
- Sadowski SM, Neychev V, Millo C, et al. Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites. J Clin Oncol 2016; 34:588.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm504524.htm (Accessed on June 07, 2016).
- Strosberg JR, Shibata D, Kvols LK. Intermittent bowel obstruction due to a retained wireless capsule endoscope in a patient with a small bowel carcinoid tumour. Can J Gastroenterol 2007; 21:113.
- BIOCHEMICAL TESTING FOR THE CARCINOID SYNDROME
- Urinary excretion of 5-HIAA
- Urinary excretion of serotonin
- Chromogranin concentration
- Blood serotonin concentration
- Plasma 5-HIAA concentration
- TUMOR LOCALIZATION AND STAGING
- Computed tomography
- Magnetic resonance imaging
- Indium-111 pentetreotide (OctreoScan)
- Functional PET imaging with 68-Ga DOTATATE
- Bronchial carcinoids
- SUMMARY AND RECOMMENDATIONS