Carcinoid Tumors

Carcinoid tumor is defined as malignant proliferation of well-differentiated neuroendocrine cells (cells that generate bioactive compounds).

Tumors contain neuroendocrine secretory granules (positive form Chromogranin).

The Tumor

Carcinoid tumors can make serotonin (5HT), histamine, VIP. These tumors are located primarily along the GIT and other part of the body. The most common location is the appendix. Other common places include the small intestine (especially the terminal ileum). They grow as submucosal polypolike nodules. Sometimes, carcinoid tumor can also be found in the ovary and lungs (bronchial carcinoids), rectum (often small and benign), stomach (3 settings possible).

Carcinoid tumor of the stomach:

• Type 1: Gastric Atrophy and Achlorhydria
  • Hypergastrinemia due to ECL (stomach Neuroendocrine cell) cell hyperplasia.
  • May be multiple tumor but usually benign lesion.
• Type 2: Gastrinoma (Zollinger Ellison Syndrome)
  • Usually in MEN 1 syndrome, Hypergastrinemia
• Type 3: (sporadic)
  • Usually aggressive with metastasis, known as sporadic carcinoids that are not due to ZES or MEN1

Tumor Biology

• Secretes Serotonin into the portal circulation and metabolized by liver MAO to 5-HIAA
• 5-HIAA excreted in the urine. Hence diagnosed with 5-HIAA in urine

Metastasis of Carcinoid Tumor to Liver

• Allows Serotonin to bypass liver metabolism and hence serotonin is in the circulation and cause Carcinoid syndrome and Carcinoid heart

Carcinoid syndrome

• Bronchospasm, Diarrhea, (vasodilation of vessel symptoms: flushing of skin, hypotension with tachycardia)
• Niacin deficiency symptoms (Rash – dermatitis), dementia diarrhea. Because niacin and 5HT are both made from Tryptophan and being shunt away during Carcinoid syndrome.
• Symptoms may be triggered by alcohol, emotional stress which activate serotonin release from tumor.
• Diagnosis: urinary 5-HIAA level.
• Treatment: somatostatin analog

Carcinoid Heart

• Right sided valvular fibrosis (increased collagen) leading to tricuspid valve regurgitation, pulmonary valve stenosis.
• Left sided valvular lesion are not seen due to presence of MAO in the lung which will metabolize the serotonins.