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Neuroendocrine Tumours

Neuroendocrine tumours (NETs) are neoplasms arising from cells of the endocrine and nervous systems. They commonly occur in the intestine, pancreas, and lungs but can be found throughout the body. These tumours share histological features, secretory granules, and often produce hormones.

Micrograph of a neuroendocrine tumour. H&E stain.
Micrograph of a neuroendocrine tumour. H&E stain.

Classification

The World Health Organisation (WHO) classifies NETs into three categories based on tumour grade rather than anatomical origin: well-differentiated NETs, well-differentiated neuroendocrine carcinomas, and poorly differentiated neuroendocrine carcinomas. This classification considers factors like tumour size, lymphovascular invasion, mitotic count, Ki-67 index, and metastatic presence. NETs of the gastrointestinal tract, pancreas, upper aerodigestive tract, and salivary glands are graded into three tiers based on proliferation rates.

Signs and Symptoms

Gastroenteropancreatic

NETs within the gastroenteropancreatic category include those of gastrointestinal origin and pancreatic origin. Carcinoid tumours are the most common, often affecting the small bowel and appendix. Symptoms may include flushing, diarrhoea, asthma, congestive heart failure, abdominal cramping, peripheral oedema, and heart palpitations. Pancreatic neuroendocrine tumours (PanNETs) may be nonfunctional or functional, secreting hormones like insulin or glucagon, leading to clinical syndromes.

Other

NETs can also arise in the lung, thymus, and parathyroid. They may cause symptoms like airway obstruction, pneumonia, pleurisy, difficulty breathing, cough, hemoptysis, and Cushing's syndrome. Familial syndromes like multiple endocrine neoplasia types 1 and 2, von Hippel-Lindau disease, and neurofibromatosis type 1 are associated with NETs.

Diagnosis

Markers

Symptoms from secreted hormones may prompt measurement of hormones in the blood or associated urinary products. Important markers include chromogranin A, urine 5-hydroxyindoleacetic acid, neuron-specific enolase, and synaptophysin.

Synaptophysin immunohistochemistry of neuroendocrine tumour, staining positively.
Synaptophysin immunohistochemistry of neuroendocrine tumour, staining positively.

Imaging

CT scans, MRIs, sonography, and endoscopy (including endoscopic ultrasound) are commonly used for morphological imaging. Advances in nuclear medicine allow for somatostatin receptor scintigraphy using octreotide and positron emission tomography (PET) with Gallium-68 for higher resolution imaging.

Histopathology

NETs show common phenotypic characteristics, including immunoreactivity for neuroendocrine markers. Typical histological features include small, yellow or tan masses located submucosally, often with a desmoplastic reaction.

Nuclei of neuroendocrine tumours often show granular "salt-and-pepper" chromatin, as seen here on H&E stain and Pap stain.
Nuclei of neuroendocrine tumours often show granular "salt-and-pepper" chromatin, as seen here on H&E stain and Pap stain.
Small intestinal neuroendocrine tumour at bottom third of image, showing the typical intramural (within the wall) location, and overlying intact epithelium. H&E stain.
Small intestinal neuroendocrine tumour at bottom third of image, showing the typical intramural (within the wall) location, and overlying intact epithelium. H&E stain.

Treatment

Surgery

Surgery is often a key treatment, even when curative surgery is not possible. It may help relieve symptoms and extend lifespan. Cholecystectomy is recommended if long-term somatostatin analogue treatment is considered.

Symptomatic Relief

Somatostatin analogues alleviate symptoms by blocking hormone release. These medications may also stabilise or shrink tumours. The PROMID and CLARINET studies have demonstrated the effectiveness of somatostatin analogues like octreotide and lanreotide in stabilising tumour growth.

Chemotherapy

Interferon and chemotherapy agents like everolimus and sunitinib are used in treating PanNETs. Poorly differentiated NETs may respond better to chemotherapy combinations.

Radionuclide Therapy

Peptide receptor radionuclide therapy (PRRT) uses radiolabelled hormones to target tumour cells, delivering targeted radiation with minimal side effects.

Hepatic Artery Treatments

Hepatic artery embolisation, chemoembolisation, and selective internal radiation therapy are used to treat liver metastases by occluding blood flow to tumours or delivering targeted radiation.

Lymph node metastasis of a neuroendocrine tumour.
Lymph node metastasis of a neuroendocrine tumour.

Self-assessment MCQs (single best answer)

Neuroendocrine tumours (NETs) most commonly occur in which of the following locations?



The World Health Organisation (WHO) classifies NETs based on which of the following criteria?



Which of the following is a common symptom of carcinoid tumours in the gastroenteropancreatic category?



Which marker is commonly measured to help diagnose NETs?



What imaging modality is commonly used for higher resolution imaging of NETs involving somatostatin receptors?



Which histopathological feature is typical of neuroendocrine tumours?



Which treatment is often recommended if long-term somatostatin analogue treatment is considered?



Which therapy uses radiolabelled hormones to target tumour cells in NETs?



Which of the following is NOT a common location for NETs to arise?



Which familial syndrome is associated with the development of NETs?



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