Carcinoid Tumours

These neuroendocrine tumours of predominantly enterochromaffin cell origin (Kulchitsky cells) often appear in the GI tract (90%) especially appendix (35%), ilium (20%) and rarely the gall bladder.¹ They may also appear in the bronchus (10%) or gonads. Carcinoid tumours are often indolent asymptomatic tumours. However, a small but significant proportion are malignant and difficult to manage.² Metastases to the mesenteric lymph nodes, liver, ovaries, peritoneum and spleen may occur.

• The incidence of neuroendocrine tumours diagnosed during life is increasing, with the majority being gastrointestinal carcinoid tumours. Recent studies have estimated an annual incidence of approximately 3 per 100,000 per year.³
• Carcinoid tumours may be found as an incidental finding in up to 10% of post-mortem examinations.³
• The risk is increased if there is a family history involving a first-degree relative.³

• Carcinoid syndrome occurs in approximately 10% of carcinoid tumours. The amount of serotonin secreted exceeds the capacity of the liver and lung to metabolise to metabolise it. Most patients with carcinoid syndrome have liver metastases from a bowel carcinoid.
• Features are caused by the release of pharmacologically active mediators 5-hydroxytryptamine, prostaglandins, kinins, substance P, gastrin, somatostatin, corticotrophin and neuron-specific enolase into the peripheral circulation.
• Presentation:
  • Flushing (after alcohol, coffee, various foods or drugs - present in 90%).
  • Other features include diarrhoea, abdominal pain, palpitations, hypotension, wheezing and right-sided heart disease (tricuspid incompetence or pulmonary stenosis).
• There may rarely cause additional features such as Cushing's syndrome.
• Pellagra may occur because the tumour consumes tryptophan.⁴

• Most tumours are clinically silent, but they may cause pain, weight loss or present as a palpable mass.
• Carcinoid tumours may produce vague right-sided abdominal discomfort but any symptoms are usually mild and have often been present for a number of years before a diagnosis is made.
• Diagnosis may be made after urgent surgery, e.g. for gastrointestinal obstruction.
• Examination is often normal but may find a right-sided abdominal mass, hepatomegaly, telangiectasia, pellagra, tricuspid regurgitation.

• Other possible causes of site-related tumours.
• Other causes of flushing (carcinoid syndrome), e.g.:
  • Systemic mastocytosis
  • Anaphylaxis
  • Alcohol ingestion
  • Menopause
  • Hyperthyroidism
  • Vipoma
  • Thyroid Medullary carcinoma

• 24 hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA): 24 hour excretion greater than 15mg is highly suggestive. Fruits (eg bananas, avocados) and some cough remedies give false positive results. Several drugs eg. L-dopa, aspirin and phenothiazines may cause false negative results.
• Other baseline investigations, considering possible associated neuroendocrine neoplasia or bowel adenocarcinoma, include thyroid function tests, parathyroid hormone, calcium, calcitonin, prolactin. alpha-fetoprotein, carcinoembryonic antigen (CEA) and beta-HCG.
• Gastric and intestinal tumours may be diagnosed by endoscopy or endoscopic ultrasound; barium studies may demonstrate polyps.
• CT or MRI and laparotomy may be needed for localization.
• Scintigraphic imaging with labelled somatostatin can provide accurate information on the site and dissemination of the tumour.⁵
• In a young person whose pneumonia is slow to resolve a bronchoscopy may reveal a carcinoid tumour.

• Carcinoid tumours are associated with MEN (multiple endocrine neoplasia) type 1 in about 10% of cases. MEN I is the association of parathyroid adenoma, pancreatic islet cell tumour and pituitary adenoma. Associated endocrine neoplasia should be sought in all patients presenting with carcinoid tumours.
• Adenocarcinoma in 10-20% (usually colorectal adenocarcinoma).

• Treatment is usually based on the size of the tumor. Surgical resection (local resection with node clearance) when possible is the treatment of choice. Surgery should be considered for patients with liver metastases and potentially resectable disease.^3,6
• For advanced metastatic disease, somatostatin analogue therapy and surgical debulking provide the best symptomatic relief and may improve survival.⁷
• If metastases are present, avoid precipitating factors, e.g. alcohol, chocolate, spicy foods, strenuous exercise.
• Options for non-resectable disease include somatostatin analogues, e.g. octreotide (which blocks 5-HT release), biotherapy, targeted radionuclide therapy, radiofrequency ablation therapy and chemotherapy.³
• External beam radiotherapy may relieve bone pain from metastases.³
• Hepatic artery embolisation works well for liver metastases, but may precipitate a carcinoid crisis (preventable with intravenous infusion of somatostatin analogues).⁸
• Receptor-targeted therapy (e.g. using yttrium-90-labelled octreotide) is likely to be the treatment of the future.
• Liver transplantation has been used successfully in carefully selected patients.⁹

• Gastrointestinal carcinoid tumours may cause appendicitis, intussusception, bowel obstruction or bowel perforation (rare).
• The tendency for metastatic spread increases with tumour size, and is substantially higher in lesions larger than 2.0 cm.¹⁰
• Carcinoid crisis: the tumour may outgrow its blood supply and release large amounts of mediators. May dramatically worsen symptoms and be life-threatening.

• Advances in diagnostic methods and surgical techniques have allowed more active management and improved prognosis.¹¹
• The prognosis for patients with completely resected localized disease is excellent, but patients with metastases have poor outcome.
• Prognosis depends on site. One large report from the United States found 5-year survival rates for stomach (75%), small intestine (76%), appendix (76%) and rectum (87%).¹²
• Median survival 5-8 years, bit if metastases are present the mean is 38 months (8% survival at 4 years).
• If patient is suitable for liver transplant and donor available, 5 year survival may be increased to 69%.⁹
• 5-year survival for carcinoid tumours of the lung has been reported as 96% in one study (14% had lymph node involvement and none had carcinoid syndrome).¹²