Epidemiology

Etiology

Carcinoid tumors are neuroendocrine tumors that arise from amine precursor uptake and decarboxylation cells (APUD cells).
- A group of endocrine cells that secrete peptide hormones (e.g., secretin, cholecystokinin)
- These cells take up amine precursors (e.g., 5-hydroxytryptophan) and decarboxylate them to form amines.
Neuroendocrine cells (including β cells in the pancreas or enterochromaffin cells in the GI tract) belong to the APUD series and share a common biologic function despite their different embryologic origins, anatomic sites, and secretory products (e.g., serotonin, histamine).

GI tract (55% of cases):
- Small intestine (esp. the ileum): 45%
- Rectum: 20%
- Appendix: 17%
Pancreas (15% of cases)
- Insulinoma
- Glucagonoma
Bronchopulmonary system (10% of cases)
- Carcinoid lung tumor
- Small cell carcinoma
Thyroid: medullary carcinoma
Adrenal glands: pheochromocytoma

Carcinoid tumors can synthesize different hormones (most commonly serotonin).
Serotonin is degraded via the following mechanisms:
- First-pass metabolism in the liver
- Monoamine oxidases in the lung
Serotonin can reach systemic circulation under the following conditions:
- Intestinal carcinoid tumors with liver metastases
- Extraintestinal carcinoid tumors
↑ Serotonin in systemic circulation can lead to:
- Carcinoid syndrome
- Carcinoid heart disease
- Pellagra due to increased serotonin metabolism

Carcinoid syndrome
- Diarrhea and abdominal cramps
- Cutaneous flushing
  - Caused by vasodilation of small arteries and arterioles
  - Possible triggers: alcohol consumption, food intake, stress
  - In severe cases, may be accompanied by tachycardia and fluctuating blood pressure
- Dyspnea, wheezing (asthma-like attacks)
- Palpitations
- Possible weight loss despite normal appetite
Carcinoid heart disease
- Liver metastases of the carcinoid tumor produce serotonin which travels to the right heart via the IVC.
- Endocardial fibrosis that especially affects the right heart
- Tricuspid insufficiency and/or pulmonary stenosis
- Symptoms of right-sided heart failure
Other symptoms: abdominal pain

Tip

In a patient presenting with secretory diarrhea, episodic flushing, wheezing, and cardiac valvular abnormalities, consider a carcinoid tumor.

↑ 5-hydroxyindoleacetic acid (5-HIAA) in 24-hour urine collection
- A degradation product of serotonin metabolism. Elevated levels in 24-hour urine are seen in carcinoid tumor.

Histology
- Can show a variety of architectural patterns (e.g., islands, nests, trabeculae)
- Prominent rosettes composed of numerous small monomorphic cells with salt-and-pepper chromatin
Immunohistochemistry: immunostaining with synaptophysin, chromogranin A, and neuron-specific enolase (NSE) to confirm neuroendocrine origin

Somatostatin analogs (e.g., octreotide) to relieve symptoms
- ↓ 5-HIAA levels in the urine
- High-dose treatment slows progression and increases survival time
Tryptophan hydroxylase inhibitors (e.g., telotristat) as adjunctive therapy if diarrhea is not controlled with somatostatin analogs
- rate-limiting step of serotonin synthesis