Carcinoid Tumours

What Is a Carcinoid Tumour?

A carcinoid tumour is a type of neuroendocrine tumour (NET) that arises from specialised hormoneproducing cells of the diffuse neuroendocrine system. These tumours most commonly develop in the gastrointestinal tract (especially the small intestine, appendix and rectum) and the lungs, but they can occur anywhere in the body.

Historically considered benign, carcinoid tumours are now known to have a broad spectrum of behaviour ranging from indolent, slowgrowing lesions to aggressive cancers that can metastasise and cause lifethreatening complications.

Epidemiology

• Incidence: ~12 cases per 100,000 persons per year in Western countries.
• Peak age at diagnosis: 5060years.
• Gender: Slight male predominance for bronchial carcinoids; gastrointestinal carcinoids are roughly equal.
• Increasing detection due to improved imaging and endoscopic techniques.

Classification

Modern classification systems combine tumour grade (based on proliferation) and stage (extent of spread). The most widely used are the WHO 2019 classification and the TNM system.

Grade

Stage (TNM)

StageIIV reflects tumour size (T), nodal involvement (N) and distant metastasis (M). Detailed tables are available from the AJCC and ENETS guidelines.

Clinical Presentation

The symptoms depend on tumour location and whether the tumour secretes biologically active hormones.

Locationrelated symptoms

• Small intestine: intermittent abdominal pain, bowel obstruction, obscure gastrointestinal bleeding.
• Appendix: often discovered incidentally during appendectomy; may present as acute appendicitis.
• Rectum: rectal bleeding or change in bowel habits.
• Lung (bronchial): cough, wheeze, recurrent pneumonia, or haemoptysis.

Hormonerelated syndrome Carcinoid Syndrome

Only tumours that have metastasised to the liver (or arise outside the portal system) can release serotonin and other vasoactive substances into the systemic circulation.

• Flushing (warm, redpurple face and neck)
• Diarrhoea
• Asthmalike wheezing
• Rightsided valvular heart disease (tricuspid regurgitation, pulmonary stenosis)
• Niacin deficiency pellagra (dermatitis, dementia)

Approximately 10% of patients present with carcinoid syndrome at diagnosis.

Diagnostic Workup

Laboratory Tests

• 24hour urinary 5HIAA metabolite of serotonin; elevated in most patients with carcinoid syndrome.
• Plasma Chromogranin A (CgA) a general NET marker; can be raised by protonpump inhibitors.
• Serum pancreastatin, neuronspecific enolase (NSE), and gastrin may be useful in selected cases.

Imaging

• Crosssectional CT or MRI firstline for localisation and staging.
• Somatostatin receptor imaging (68GaDOTATATE PET/CT) most sensitive for detecting primary and metastatic disease.
• Octreotide scintigraphy (Octreoscan) alternative when PET is unavailable.
• Endoscopic ultrasound (EUS) useful for pancreatic and duodenal lesions.

Histopathology

Biopsy samples are examined for morphology, immunohistochemical markers (chromogranin A, synaptophysin, CD56) and proliferation indices (Ki67). Accurate grading guides treatment decisions.

Treatment Options

Management is multidisciplinary and must be personalised according to tumour grade, stage, functional status and patient fitness.

Surgical Resection

• Curative intent for localized disease segmental resection of smallbowel lesions, right hemicolectomy for ileal tumours, appendectomy for appendiceal carcinoids 2cm.
• Debulking surgery (70% tumour reduction) can improve symptoms and prolong survival in metastatic disease.

Medical Therapy

• Somatostatin analogues (octreotide, lanreotide) firstline for symptom control and tumour growth inhibition.
• PeptideReceptor Radionuclide Therapy (PRRT) 177LuDOTATATE for patients with high somatostatinreceptor expression; demonstrated progressionfree survival benefit.
• Targeted agents everolimus (mTOR inhibitor) and sunitinib (tyrosinekinase inhibitor) for pancreatic NETs; offlabel use in some carcinoids.
• Chemotherapy limited role; reserved for highgrade (G3) or rapidly progressive disease.
• Interferon modest efficacy for carcinoid syndrome when somatostatin analogues are insufficient.

Management of Carcinoid Syndrome

• Somatostatin analogues (longacting formulations) are the cornerstone.
• Telotristat ethyl a tryptophan hydroxylase inhibitor that reduces diarrhoea in refractory cases.
• Diuretics and cardiac monitoring for valvular disease.

Followup

After initial treatment, patients are usually monitored every 36months with clinical review, biochemical markers (5HIAA, CgA) and imaging (CT or MRI). Lifelong surveillance is recommended because late recurrences are common.

Prognosis

Prognosis varies dramatically with grade and stage.

• Localized, lowgrade (G1) tumours: 5year survival >90% after complete resection.
• Metastatic disease, especially with high Ki67 (>20%): 5year survival 3050%.
• Presence of carcinoid heart disease reduces survival; early detection and valve surgery improve outcomes.

Current Research Directions

Key areas of investigation include:

• New radiolabelled agents for PRRT (e.g., 225AcDOTATATE) aiming at higher tumourkilling potency.
• Combination regimens (PRRT+checkpoint inhibitors) in clinical trials.
• Genomic profiling to identify actionable mutations (e.g., MEN1, DAXX/ATRX) and guide personalised therapy.
• Improved biomarkers for early detection of recurrence.

Patients are encouraged to discuss clinical trial participation with their oncology team.

Key Takeaways

1. Carcinoid tumours are neuroendocrine neoplasms most often found in the gut and lungs.
2. Classification by grade (Ki67) and stage determines prognosis and treatment.
3. Somatostatinreceptor imaging is essential for localisation, staging, and planning PRRT.
4. Surgery remains the only curative option for localized disease; systemic therapies control symptoms and growth in advanced cases.
5. Longterm followup is crucial because disease can recur many years after apparent cure.