Carcinoid Tumors

 

Clinical Background

Carcinoid tumors are rare, slow-growing neuroendocrine tumors (NETs).

Epidemiology

  • Incidence
    • 2-4/100,000 in U.S. (SEER database, 2003)
    • Most common gastrointestinal NET
  • Age – bimodal peaks
    • 15-25 years
    • 65-75 years
  • Sex – distribution inverts at 50 years
    • <50 years, M<F, 1:2
    • ≥50 years, M>F, 2:1
  • Occurrence – most frequently sporadic
  • Ethnicity – somewhat higher incidence in African Americans

Risk Factors

  • Multiple Endocrine Neoplasia type 1 (MEN1)
    • Neoplasia of the parathyroid, pancreas, anterior pituitary with 10% incidence of NETs of the lung, thymus and stomach
  • Von Hippel-Lindau 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 occur with liver metastases; rarely occur with lung tumor
      • May also produce adrenocorticotropic hormone (ACTH)
    • Symptoms include
      • Flushing, wheezing, diarrhea
      • Carcinoid heart disease
        • Typical symptoms include congestive heart failure (CHF), cardiac murmurs, jugular venous distension
        • Predominantly involves the right-side 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 (eg, blue cheese, chocolate, red wine)
  • Gastrointestinal manifestations
    • Diarrhea
    • Fibrosis and abdominal pain
    • Gastric carcinoids
      • Type 1 associated with chronic atrophic gastritis and pernicious anemia (75%)
      • Type 2 associated with Zollinger-Ellison syndrome and MEN1 (5%)
      • Type 3 sporadic, not associated with disease (20%)
  • Locating primary tumor may be difficult
    • Gastrointestinal tract – 65%
    • Bronchopulmonary tract – 35%
  • Metastatic disease – tumors less than 1 cm rarely metastasize