Carcinoid Tumors

Clinical Background

Carcinoid tumors are rare, slow-growing neuroendocrine tumors.

Epidemiology

Incidence
- 1-2 per 100,000 in U.S.
Age (2 peaks)
- 15-25 years
- 65-75 years
Gender (distribution inverts at 50 years)
- <50 years, females outnumber males 2:1
- greater than or equal to 50 years, males outnumber females 2:1
Occurrence
- Most frequently sporadic

Risk Factors

Multiple Endocrine Neoplasia 1 (MEN1)
- Neoplasia of the parathyroid, pancreas, anterior pituitary with 10% incidence of neuroendocrine tumors of the lung, thymus and stomach
Von Hippel-Landau syndrome
- Pancreatic neoplasia of neuroendocrine origin occurs in 15% of cases
Neurofibromatosis type 1 (von Recklinghausen disease)
- Infrequent carcinoids of the duodenum (somatostatinomas)

Pathophysiology

Tumor derived from enterochromaffin cells (Kulchitsky cells)
Symptoms due to secretion of neuroendocrine substances such as serotonin and kallikreins
Classified by tumor location
- Foregut - pancreas, duodenum, bronchus, thymus, stomach
- Midgut - jejunum, ileum, ascending colon
- Hindgut - ascending colon, rectum

Clinical Presentation

Relatively slow growing tumor with nonspecific presentation
- May be found coincidentally during surgery for appendicitis or bowel obstruction
Symptoms of typical carcinoid syndrome (occur in ~10% of patients)
- Usually occurs with liver metastases
- Rarely occurs with lung tumor
  - May produce ACTH
- Include
  - Flushing, wheezing, diarrhea
  - Carcinoid heart disease
    - Involves the heart valves - causes fibrosis, thickening
    - Develops in 45-60% of patients with metastatic disease
    - Late complication of metastatic disease
- May be precipitated by certain foods or drinks high in tyramine
  - Blue cheese, chocolate, red wine
Gastrointestinal manifestations
- Diarrhea
- Fibrosis and abdominal pain
- Gastric carcinoids
  - Type 1 is associated with chronic atrophic gastritis and pernicious anemia (75%)
  - Type 2 is associated with Zollinger-Ellison and MEN 1 (5%)
  - Type 3 is sporadic without disease association (20%)
Locating primary tumor may be difficult
- Gastrointestinal tract - 65%
- Bronchopulmonary tract - 35%
Metastatic disease
- Tumors less than 1 cm rarely metastasize

See Also

Lung Cancer

Multiple Endocrine Neoplasias - MEN

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: 5-Hydroxyindoleacetic Acid (HIAA), Urine

ARUP #: 0080420

Methodology: High Performance Liquid Chromatography

Use:

Diagnose carcinoid tumors

Monitor disease

Limitations:

Influenced by foods rich in serotonin (avocado, bananas, eggplant, kiwi, pineapple, plums, tomatoes, walnuts) and medications that may affect metabolism

Serotonin must be avoided 72 hours before and during collection of urine specimen

Follow-up:

Confirm results by repeating 24 hour urine test

CT/MRI to identify tumor location

Test name: Serotonin, Whole Blood

ARUP #: 0080395

Methodology: High Performance Liquid Chromatography

Use:

Diagnose carcinoid tumors

Preferred test since most of the blood serotonin resides in the platelets

Limitations:

Certain medications may affect serotonin

Foods that contain serotonin do not interfere significantly

Slight increases may be seen in acute intestinal obstruction, acute myocardial infarction, cystic fibrosis, dumping syndromes and nontropical sprue

Follow-up:

Test name: Serotonin, Serum

ARUP #: 0080397

Methodology: High Performance Liquid Chromatography

Use:

Diagnose carcinoid tumors

Limitations:

Certain medications may affect serotonin

Foods that contain serotonin do not interfere significantly

Slight increases may be seen in acute intestinal obstruction, acute myocardial infarction, cystic fibrosis, dumping syndromes and nontropical sprue

Follow-up:

Test name: Chromogranin A

ARUP #: 0080469

Methodology: Enzyme Immunoassay

Use:

Monitor carcinoid tumors

Limitations:

Nonspecific tumor marker

Results obtained with different assay methods or kits cannot be used interchangeably

Follow-up:

Test name: Neuron Specific Enolase

ARUP #: 0098198

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Not recommended as a test for carcinoid tumors

Limitations:

Not useful in diagnosis or monitoring of carcinoid tumors

Follow-up:

Test name: Immunohistochemistry Stain Offering

ARUP #: arup005

Methodology: Immunohistochemistry

Use:

For fixed tissue samples, consultative services as well as immunohistochemical staining for NSE, Cam5.2 (LMW), PGP9.5, synaptophysin and chromogranin A are available

References

Guidelines

Ramage JK, Davies AH, Ardill J, Bax N, Caplin M, Grossman A, Hawkins R, McNicol AM, Reed N, Sutton R, Thakker R, Aylwin S, Breen D, Britton K, Buchanan K, Corrie P, Gillams A, Lewington V, McCance D, Meeran K, Watkinson A. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54 Suppl 4:iv1-16.

General References

de Herder WW. Biochemistry of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21(1):33-41.

Dierdorf SF. Carcinoid tumor and carcinoid syndrome. Curr Opin Anaesthesiol. 2003;16(3):343-347.

Kulke MH. Clinical presentation and management of carcinoid tumors. Hematol Oncol Clin North Am. 2007;21(3):433-455.

Lips CJ, Lentjes EG, Hoppener JW. The spectrum of carcinoid tumours and carcinoid syndromes. Ann Clin Biochem. 2003;40(Pt 6):612-627.

Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128(6):1717-1751.

Robertson RG, Geiger WJ, Davis NB. Carcinoid tumors. Am Fam Physician. 2006;74(3):429-434.

Rockall AG, Reznek RH. Imaging of neuroendocrine tumours (CT/MR/US). Best Pract Res Clin Endocrinol Metab. 2007;21(1):43-68.

Schnirer II, Yao JC, Ajani JA. Carcinoid--a comprehensive review. Acta Oncol. 2003;42(7):672-692.

Sippel RS, Chen H. Carcinoid tumors. Surg Oncol Clin N Am. 2006;15(3):463-478.

Zuetenhorst JM, Taal BG. Metastatic carcinoid tumors: a clinical review. Oncologist. 2005;10(2):123-131.

Medical Reviewers

Frank, Elizabeth L. , Ph.D. Medical Director, Analytic Biochemistry and Calculi at ARUP Laboratories; Associate Professor, Clinical Pathology, University of Utah

Grenache, David G., Ph.D. Medical Director, Special Chemistry at ARUP Laboratories; Assistant Professor, Clinical Pathology, University of Utah

Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah

Comprehensive Review: January 2008
Last Update: March 2008