Definition
Neuroendocrine tumors (NETs) are rare, typically slow-growing tumors that originate from neuroendocrine system cells. They occur in various organs, most commonly the gastrointestinal tract, pancreas, and lungs.

Pathogenesis
NETs arise from cells with both nervous and endocrine functions. Risk factors include:

  • Genetic syndromes: Such as multiple endocrine neoplasia type 1 (MEN1).
  • Chronic inflammation: E.g., chronic gastritis.

The tumors may be functional (secreting hormones and causing syndromes like carcinoid syndrome) or non-functional.

Diagnosis
Diagnosis is based on:

  • Laboratory tests: Detection of specific markers like chromogranin A (CgA) and hormones (e.g., serotonin, gastrin).
  • Imaging methods: CT, MRI, and PET-CT with Ga-68 DOTATATE for localization and staging.
  • Biopsy: Confirms diagnosis and histological grade (differentiation and Ki-67 expression).

Treatment
Treatment depends on the tumor’s location, functionality, and spread:

  • Surgical removal: The treatment of choice for localized disease.
  • Somatostatin analogs: (e.g., octreotide) to manage functional tumors and control growth.
  • Targeted therapies: (e.g., everolimus, sunitinib) for advanced stages.
  • Peptide receptor radionuclide therapy (PRRT): Used in functional tumors with positive somatostatin receptors.
  • Chemotherapy: For poorly differentiated, fast-growing tumors.

Prevention
Prevention includes managing predisposed conditions and closely monitoring individuals with genetic predisposition.

Early diagnosis and individualized therapeutic approaches significantly improve prognosis and quality of life, given the varied behavior of NETs.

Functional and non-functional tumours

This distinction determines the clinical picture. Non-functional tumours are the majority. They produce no hormones in symptomatic quantities and are often found incidentally during imaging or endoscopy performed for another reason.

Functional tumours secrete hormones and produce recognisable syndromes: carcinoid syndrome with flushing and diarrhoea, insulinoma with hypoglycaemia, gastrinoma with multiple refractory peptic ulcers.

Diagnosis is frequently delayed, because symptoms are attributed for years to irritable bowel syndrome, allergy or anxiety.

Grading is what matters

Not all neuroendocrine neoplasms behave alike, and this is the most important line in the pathology report. Tumours are graded by the Ki-67 proliferation index and mitotic count into G1, G2 and G3. Separately, neuroendocrine carcinomas are poorly differentiated, aggressive, and managed on entirely different principles.

A few-millimetre G1 tumour and a neuroendocrine carcinoma share a name but neither prognosis nor treatment.

Diagnosis

Endoscopic ultrasound is the modality of choice for pancreatic lesions. It detects tumours of a few millimetres that escape CT and allows targeted fine needle biopsy for histology and grading. Somatostatin receptor imaging identifies lesions missed by conventional modalities. Chromogranin A and urinary 5-HIAA serve as adjunctive biomarkers.

Treatment

Small, well-differentiated tumours of the stomach or rectum confined to the mucosa can be removed endoscopically. Surgical resection remains standard for most localised tumours. For very small non-functional pancreatic tumours, surveillance rather than resection is often the correct choice, when the risk of surgery exceeds the risk of the tumour. Somatostatin analogues, targeted agents and radionuclide therapy are used in advanced disease.

Pancreatic lesions are assessed with endoscopic ultrasound and fine needle biopsy. The key distinction is from pancreatic adenocarcinoma, which behaves very differently.

Frequently asked questions

Are neuroendocrine tumours cancer?

They span a very wide range of behaviour. Most are well differentiated and slow growing, and many patients live with the disease for years. At the other end are neuroendocrine carcinomas, which are poorly differentiated and aggressive. What determines prognosis is the grade based on the Ki-67 index, not the name of the disease.

Why is diagnosis often delayed?

Because symptoms are mild and non-specific. Flushing and diarrhoea from carcinoid syndrome are frequently attributed to irritable bowel syndrome, allergy or anxiety, while non-functional tumours produce no symptoms at all and are found incidentally. Suspicion is raised when symptoms persist without explanation.

How is a pancreatic neuroendocrine tumour diagnosed?

With endoscopic ultrasound and targeted fine needle biopsy. The method allows tissue sampling even from very small lesions, with accuracy that CT cannot match. Somatostatin receptor imaging is used as a complementary modality, and the final diagnosis and grade come from histology.

Sources


Content last updated: September 2026 (14/09/2026).