Pancreatic neuroendocrine tumours
Pancreatic neuroendocrine tumours arise from the hormone-producing cells of the pancreas rather than the digestive ones. They are far less common than ductal adenocarcinoma and behave very differently — most grow slowly, many are curable by surgery, and even patients with spread to the liver may live for many years with active treatment. They should not be confused with pancreatic cancer in the usual sense, and the distinction is frequently the most reassuring thing a patient hears.
How they form
Scattered through the pancreas are the islets of Langerhans, clusters of endocrine cells producing insulin, glucagon, somatostatin and other hormones. Neuroendocrine tumours arise from these cells or their precursors. Because the cells they come from are secretory, some of these tumours continue to produce hormones in excess — and when they do, the hormone, rather than the tumour's size, causes the symptoms.
They divide into two groups:
- Non-functioning — the majority. They produce no clinically active hormone and present as a mass, or incidentally.
- Functioning — producing a recognisable syndrome. Insulinoma causes hypoglycaemia; gastrinoma causes severe peptic ulceration and diarrhoea (Zollinger–Ellison syndrome); glucagonoma causes a characteristic rash, diabetes and weight loss; VIPoma causes profuse watery diarrhoea and potassium loss; somatostatinoma causes diabetes, gallstones and steatorrhoea.
Most occur sporadically. A minority arise within inherited syndromes — multiple endocrine neoplasia type 1 (MEN1), von Hippel–Lindau disease, neurofibromatosis type 1 and tuberous sclerosis. This matters practically: tumours in these settings are often multiple, occur in younger patients, and require both genetic counselling and screening of relatives.
Behaviour is graded by how fast the cells divide, measured by the Ki-67 proliferation index and mitotic count. Grade 1 tumours are indolent; grade 2 intermediate; grade 3 aggressive. Poorly differentiated neuroendocrine carcinoma is a separate and far more aggressive disease treated quite differently, more like small-cell carcinoma. Grade drives prognosis and treatment more than size does.
Symptoms
Non-functioning tumours may cause abdominal or back pain, jaundice if in the head, or nothing at all. A growing proportion are found incidentally on imaging.
Functioning tumours present through their hormone. Insulinoma is the classic example: episodes of confusion, sweating, palpitations or loss of consciousness, relieved by eating, and often present for years before the diagnosis is made because the symptoms are attributed to something else.
How the diagnosis is made
Pancreatic protocol CT and MRI identify and stage the tumour. Neuroendocrine tumours are typically hypervascular, enhancing briskly in the arterial phase — the opposite of adenocarcinoma, and a useful distinguishing feature.
Endoscopic ultrasound is highly sensitive for small tumours and allows biopsy, which is important because grade cannot be determined without tissue.
Functional imaging is central. Somatostatin receptor PET-CT (Ga-68 DOTATATE) detects well-differentiated tumours with high sensitivity and identifies disease elsewhere; it also predicts whether receptor-targeted treatment will work. FDG-PET is more useful for high-grade disease.
Biochemical testing is directed by the clinical picture: chromogranin A as a general marker, and specific tests such as supervised fasting with paired insulin and C-peptide for suspected insulinoma, or fasting gastrin for gastrinoma.
Treatment
Surgery
Surgery is the only curative treatment and is the mainstay for localised disease.
- Enucleation — shelling the tumour out while preserving the rest of the gland. Suitable for small, superficial, low-grade tumours at a safe distance from the main pancreatic duct.
- Distal pancreatectomy, with spleen preservation where oncologically appropriate, for tumours of the body and tail.
- Pancreaticoduodenectomy for tumours of the head requiring formal resection.
- Liver resection or ablation for metastatic disease. Unlike most cancers, removing or debulking liver metastases from a neuroendocrine primary is worthwhile, both for survival and for controlling hormonal symptoms.
Small, non-functioning, low-grade tumours — conventionally those under 2cm — may reasonably be observed rather than resected, particularly in older patients or where the operation would be a Whipple. This is an area where the guideline threshold is genuinely a starting point: the patient's age, fitness, the tumour's position, its growth on serial imaging and their own attitude to living with an unresected tumour all bear on the recommendation.
Medical treatment
- Somatostatin analogues (octreotide, lanreotide) control hormonal symptoms and slow tumour growth in receptor-positive disease.
- Peptide receptor radionuclide therapy (Lu-177 DOTATATE) delivers targeted radiation to receptor-positive tumours and is effective in progressive metastatic disease.
- Targeted agents such as everolimus and sunitinib.
- Chemotherapy, more useful in higher-grade tumours.
- Symptom-specific treatment — proton pump inhibitors at high dose for gastrinoma, diazoxide for insulinoma pending surgery.
Liver-directed therapy
Embolisation, chemoembolisation and radioembolisation are useful for liver-predominant disease, particularly for controlling hormone-related symptoms.
Recovery
Enucleation involves a shorter recovery than formal resection, though it carries a recognised risk of pancreatic fistula. Formal resections follow the recovery pattern described for other pancreatic surgery. Patients with functioning tumours often notice immediate resolution of their hormonal symptoms — a patient whose hypoglycaemic episodes stop the day after removal of an insulinoma is a striking example.
Follow-up
Long-term, with imaging, biochemical markers and clinical review. Intervals are set by grade and stage. In patients with MEN1 or another inherited syndrome, follow-up covers the other organs at risk, and family members are offered genetic assessment.
When to seek a specialist opinion
Any pancreatic mass that enhances briskly in the arterial phase should raise the possibility of a neuroendocrine tumour rather than adenocarcinoma, and be assessed accordingly — the two carry entirely different prognoses and the distinction should not be assumed. Unexplained recurrent hypoglycaemia, or severe or atypical peptic ulceration, warrants investigation for a functioning tumour. And patients with metastatic disease should be assessed by a unit that offers the full range of treatments, since "metastatic" here does not carry the meaning it does in most other cancers.
Common questions
Is this the same as pancreatic cancer?
No, and the difference matters enormously. These tumours arise from the hormone-producing cells of the pancreas rather than from the duct lining, they usually grow far more slowly, and the outlook is very much better — often measured in many years even when they have spread. They are a different disease that happens to occur in the same organ.
What does "functioning" mean?
That the tumour produces a hormone in excess, causing recognisable symptoms — low blood sugar from an insulinoma, severe ulcers and diarrhoea from a gastrinoma, and so on. Most of these tumours are non-functioning, producing no hormone and causing symptoms only through their size, or being found incidentally on a scan.
Do small tumours need removing?
Not always. Small, non-functioning, low-grade tumours — generally under two centimetres — can reasonably be monitored with scans, as many never grow or cause trouble, and pancreatic surgery carries real risks. Functioning tumours, larger tumours, higher-grade tumours and those that grow are removed.
What is the grade and why does it matter?
It is a measure of how rapidly the tumour cells divide, assessed from the mitotic count and a marker called Ki-67. It predicts behaviour more reliably than size and determines both how the tumour is treated and how closely it is followed. It is worth asking what your grade is, because it shapes everything else.
Can the tumour be removed without taking out much pancreas?
Often yes. A small tumour sitting away from the main duct can be shelled out, preserving the whole gland and its function. Where that is not safe, a limited resection of the affected part is used. Preserving pancreatic tissue matters because it protects against diabetes and digestive problems later.
It has spread to my liver. What can be done?
A great deal. Unlike most cancers, liver deposits from these tumours are often slow-growing and can be removed surgically, destroyed with heat, or treated by blocking the artery supplying them. Long-acting hormone injections control both growth and symptoms, and targeted radiotherapy delivered to the tumour through the bloodstream is highly effective. Patients frequently live well for many years.
What is the injection I am being offered?
A somatostatin analogue — a long-acting version of a natural hormone that both suppresses excessive hormone production and slows tumour growth. It is given every few weeks and is generally well tolerated, with gallstones being the main long-term side effect to watch for.
Is it inherited?
Usually not, but a proportion occur within inherited syndromes, particularly multiple endocrine neoplasia type 1 and von Hippel-Lindau disease. Genetic assessment is considered where the tumours are multiple, occur at a young age, or occur alongside parathyroid or pituitary problems, and it has implications for relatives.
Related conditions
Other conditions of the pancreas covered on this site:
- Pancreatic ductal adenocarcinoma
- Acute pancreatitis
- Chronic pancreatitis and its complications
- Pancreatic cysts — IPMN and MCN
- Solid pseudopapillary neoplasm and other rare pancreatic tumours
- Periampullary lesions
- Pancreas divisum
- Annular pancreas
This page provides general information and does not replace an individual medical consultation. Assessment and treatment are decided for each patient after review of their history, examination and imaging, and in the setting of a multidisciplinary team.