Carcinoid tumour

Introduction

Carcinoid tumours are a subset of neuroendocrine tumours (NETs) that arise from enterochromaffin cells and are capable of secreting biologically active substances, particularly serotonin. They are typically slow-growing and most commonly found in the gastrointestinal tract, especially the small intestine, appendix, rectum, and colon. In some cases, they produce a characteristic clinical syndrome known as carcinoid syndrome.

Peak Incidence

• Most frequently diagnosed in adults aged 50 to 70 years.
• Slightly more common in females and often discovered incidentally during surgery or imaging.

Pathophysiology

• Carcinoid tumours originate from neuroendocrine cells in the GI mucosa.
• These tumours secrete vasoactive substances such as serotonin, histamine, prostaglandins, and tachykinins.
• When confined to the GI tract, secreted substances are typically metabolised in the liver and do not enter systemic circulation.
• Carcinoid syndrome occurs only when liver metastases are present, allowing substances to bypass hepatic metabolism and enter systemic circulation.
• Right-sided heart involvement is typical due to first-pass pulmonary filtration; left-sided lesions are rare unless there is a right-to-left shunt or bronchial carcinoid.

Symptoms

• Diarrhoea and abdominal cramping.
• Wheezing or bronchospasm (due to serotonin or histamine release).
• Flushing – sudden and episodic, especially with alcohol, stress, or certain foods.
• Palpitations or dyspnoea (in cases of carcinoid heart disease).
• Weight loss, often despite normal or increased appetite.

Signs

• Cutaneous flushing – typically episodic and red–purple in colour.
• Pellagra – due to niacin deficiency (tryptophan is diverted to serotonin synthesis).
• Carcinoid heart disease – right-sided valvular fibrosis, commonly tricuspid regurgitation and pulmonary stenosis.
• Hepatomegaly – if liver metastases are present.

Diagnosis

Biochemical Markers

• 24-hour urinary 5-HIAA (5-hydroxyindoleacetic acid) – primary metabolite of serotonin; elevated in most symptomatic cases.
• Plasma chromogranin A – sensitive but non-specific marker for neuroendocrine activity.

Imaging Studies

• CT or MRI of abdomen and pelvis – to assess primary tumour and metastases.
• Somatostatin receptor imaging (e.g. Gallium-68 DOTATATE PET/CT) – highly sensitive for NETs expressing somatostatin receptors.
• Abdominal ultrasound – may detect hepatic metastases, but not first-line.

Histology & Biopsy

• Endoscopic or surgical biopsy for tissue diagnosis.
• Histopathology: small, uniform cells with “salt-and-pepper” chromatin pattern; immunohistochemistry positive for chromogranin A and synaptophysin.

Complications

• Carcinoid syndrome – only occurs with hepatic (or pulmonary) metastases.
• Carcinoid heart disease – progressive right-sided heart failure due to valvular fibrosis.
• Bowel obstruction or intestinal ischaemia due to mesenteric fibrosis or tumour bulk.
• Hormonal syndromes – rare secretion of ACTH (Cushing’s), GHRH (acromegaly), or insulin-like peptides.

Management

1. Surgical

• Surgical resection of primary tumour ± involved lymph nodes is first-line treatment when resectable.
• Appendiceal carcinoids <2 cm without high-risk features may not require further resection.

2. Medical (for unresectable or metastatic disease)

• Somatostatin analogues (e.g. octreotide, lanreotide)
  • Reduce hormone secretion, control symptoms, and may slow tumour progression.
• Tryptophan hydroxylase inhibitors (e.g. telotristat ethyl)
  • Used in combination with somatostatin analogues for refractory diarrhoea.
• Targeted therapies (e.g. everolimus, sunitinib)
  • Considered in progressive or high-grade tumours.
• Palliative chemotherapy
  • Reserved for poorly differentiated or aggressive neuroendocrine carcinomas.
• Peptide receptor radionuclide therapy (PRRT)
  • Delivers radiation to tumour cells via radiolabelled somatostatin analogues (e.g. Lutetium-177 DOTATATE).

3. Symptomatic Support

• Diuretics for carcinoid heart disease.

• Vitamin supplementation (e.g. niacin) to correct pellagra.

• Anti-diarrhoeal agents, nutritional support.