Carcinoid tumours

Question 1

Definition

Answer 1

Carcinoid tumours = malignant slow-growing tumours of enterochromaffin cells (type of neuroendocrine cell) which secrete serotonin (5-hydroxytryptamine) & other vasoactive peptides into systemic circulation. Thus carcinoid tumours are neuroendocrine tumours.
Carcinoid syndrome occurs when there is hepatic metastases (most common site of metastasis is the liver).

Question 2

Pathophysiology

Answer 2

Carcinoid tumour:

Neuroendocrine enterochromaffin cells mutate and divide uncontrollably, leading to a carcinoid tumour. Carcinoid tumours are malignant but slow growing.

Mainly occurs in the GI tract specifically the small intestine (ileum) & appendix. The most common site for metastasis from ileal tumours is the liver- when there is hepatic metastases this is referred to as carcinoid syndrome.

The cancerous neuroendocrine cells produce and secreting large amounts of hormones. Tumours can secrete:

Bradykinin, tachykinin, serotonin, substance P, VIP, gastrin, insulin, glucagon, ACTH, parathyroid and thyroid hormones.

Carcinoid syndrome:

Associated with hepatic involvement i.e. hepatic metastases.

Carcinoid syndrome occurs when there is a buildup of hormones produced by the neuroendocrine cells as the liver is no longer able to metabolise them.

• Increased histamine and bradykinin→ vasodilation leading to flushing
• Increased histamine → itching
• Increased serotonin: increases GI motility causing diarrhoea), bronchoconstriction leading to asthma, shortness of breath, and wheezing. **

Question 3

Which substances do carcinoid tumours secrete?

Answer 3

Carcinoid tumours are neuroendocrine tumours of enterochromaffin cells which mainly secrete serotonin (5-hydroxytryptamine) but also secrete: bradykinin, tachykinin, histamine, substance P, VIP, gastrin, insulin, glucagon, ACTH, thyroid & PTH

Histamine & bradykinin-> flushing due to vasdilation
Bradykinin-> bronchospasm & wheeze
Serotonin -> increases GI motility & causes diarrhoea

Question 4

What do carcinoid tumours express on their surface & implication?

Answer 4

Most carcinoid tumours express surface receptors for somatostatin. Hence somatostatin analogues e.g. Ocreotide can be given in treatment.
Octreoscan involves injecting radiolabelled somatostatin analogues to bind to somatostatin receptors on tumour cells.

Question 5

Symptoms

Answer 5

• Diarrhoea (serotonin increases GI motility)
• Shortness of breath, bronchospasm, wheeze (due to bradykinin)
• Flushing (histamine & bradykinin released from neuroendocrine cells cause vasodilation)
• Itching (due to histamine)
• Hepatic metastases: may cause RUQ pain

Question 6

Investigations

Answer 6

• 1st line = 24 hr urine 5-hydroxyindoleacetic acid - high (serotonin produced by enterochromaffin neuroendocrine cells travels to liver via portal vein where it is metabolised to 5-hydroxyindoleacetic acid for renal excretion; the remaining serotonin remains in the systemic circulation to exert its various effects).
• 1st line = CXR/ chest or pelvis MRI/ CT: to locate primary tumours (mainly in the GI tract- ileum & appendix but also in other sites)
• 1st line = Plasma chromogranin A: reflects tumour mass
• Ostreoscan: radiolabelled somatostatin analogue, octreotide is injected to bind to the increased number of somatostatin receptors on tumour cells.

Question 7

Management

Answer 7

For carcinoid tumours:

• Definitive Tx = Surgical resection of the tumour therefore essential to localise primary tumour. Also somatostatin analogues e.g. Ocreotide.

For carcinoid syndrome:

• Somatostatin analogues e.g. Ocreotide for metastatic disease (most carcinoid tumours express somatostatin receptors on their surface).
• Radiofrequency ablation to decrease symptoms.