Carcinoid Tumors

Carcinoid Tumors

 

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
    • ≥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

Diagnosis

  • Carcinoid syndrome is an indication for testing
  • Laboratory testing
    • Urinary 5-hydroxyindoleacetic acid (5-HIAA) - metabolic product of serotonin
    • Serotonin – whole blood preferred to serum
    • Chromogranin A – sensitive, but not specific
  • Imaging studies
    • CT/MRI
    • If CT/MRI negative, consider somatostatin receptor scintigraphy
      • Indium-111 labelled octreotide
      • Superior to metaiodobenzylguanidine (MIBG) scanning

Differential Diagnosis

  • Flushing – pheochromocytoma, menopause, medullary carcinoma of the thyroid, mastocytosis
  • Wheezing – asthma, anaphylaxis, foreign body, pulmonary edema
  • Diarrhea – infections, inflammatory bowel disease, laxative abuse
  • Heart valve disease – rheumatic heart diseases, endocarditis, cardiomyopathy

Disease Monitoring

  • Chromogranin A
    • Useful as a marker of relapse
  • Neuron specific enolase – nonspecific

See Also