[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Endocrine system](https://durgical.com/en/general-pathology/areas/endocrine/) › Pancreatic neuroendocrine tumours

# Pancreatic neuroendocrine tumours

- Lesion

Rare pancreas tumours of hormone cells. Some make one hormone in excess and cause a striking syndrome; many make none and grow silently.

Updated Nov 12, 2026

## Key points

- Grading by Ki-67 and mitoses: G1 low, G2 intermediate, G3 high; neuroendocrine carcinoma is a separate, poorly differentiated, small or large cell tumour.
- Insulinoma: commonest functioning type, usually small, solitary and benign; Whipple triad, high insulin and C-peptide during hypoglycaemia; amyloid in stroma.
- Gastrinoma: often in the duodenum or pancreatic head (gastrinoma triangle), often malignant; Zollinger-Ellison syndrome with multiple, atypical peptic ulcers and diarrhoea.
- Glucagonoma: mild diabetes, necrolytic migratory erythema, anaemia, weight loss.
- VIPoma: watery diarrhoea, hypokalaemia, achlorhydria (WDHA).
- Somatostatinoma: diabetes, gallstones, steatorrhoea, hypochlorhydria.

## What it is

Pancreatic neuroendocrine tumours arise from islet-type cells and are graded by mitotic rate and Ki-67 into G1, G2 and G3 well-differentiated tumours, distinct from poorly differentiated neuroendocrine carcinomas. Most are non-functioning and discovered as masses or metastases; functioning tumours announce themselves by a hormone syndrome. Sporadic tumours often carry MEN1, DAXX or ATRX mutations and mTOR pathway changes; syndromic ones occur in MEN1, VHL, NF1 and tuberous sclerosis.

## Structure

- Gross: well-circumscribed, soft, red-tan nodules; larger tumours can invade or be cystic.
- Micro: nests, trabeculae or gyriform ribbons of uniform cells with salt-and-pepper chromatin.
- Immunohistochemistry: chromogranin A and synaptophysin; specific hormones by stain; Ki-67 for grade.
- Malignancy is judged by invasion and metastasis, mainly to liver; size and grade predict behaviour.

## Functioning pancreatic neuroendocrine tumours

| Tumour | Hormone | Syndrome | Behaviour |
| --- | --- | --- | --- |
| [Insulinoma](https://durgical.com/en/conditions/insulinoma/) | Insulin | Fasting hypoglycaemia: confusion, sweating, relief with glucose | Mostly benign |
| [Gastrinoma](https://durgical.com/en/conditions/zollinger-ellison-syndrome/) | Gastrin | Zollinger-Ellison: refractory, multiple or jejunal ulcers, diarrhoea | Often malignant; frequent in MEN1 |
| [Glucagonoma](https://durgical.com/en/conditions/pancreatic-neuroendocrine-tumours/) | Glucagon | Diabetes, necrolytic migratory erythema, anaemia, thrombosis | Usually malignant |
| [VIPoma](https://durgical.com/en/conditions/pancreatic-neuroendocrine-tumours/) | Vasoactive intestinal peptide | Watery diarrhoea, hypokalaemia, achlorhydria | Often malignant |
| [Somatostatinoma](https://durgical.com/en/conditions/pancreatic-neuroendocrine-tumours/) | Somatostatin | Diabetes, gallstones, steatorrhoea | Often malignant |
| [Non-functioning](https://durgical.com/en/conditions/pancreatic-neuroendocrine-tumours/) | None effective (often pancreatic polypeptide) | Mass, jaundice, liver metastases | Variable |

## Markers

- Chromogranin A
- Synaptophysin
- INSM1
- Ki-67
- Insulin, gastrin, glucagon stains
- Loss of DAXX or ATRX

## Clinical notes

- Islet cell hyperplasia, sulfonylurea use and factitious insulin are differentials for hypoglycaemia; C-peptide separates exogenous insulin.
- In MEN1, multiple small tumours throughout the pancreas and duodenum are typical.

## Memory aid

Each functioning islet tumour has a calling card: insulinoma faints, gastrinoma ulcerates, glucagonoma rashes, VIPoma floods and somatostatinoma blocks.

## Test yourself

Think of the answer, then tap the question to see it.

## What separates a G3 neuroendocrine tumour from a neuroendocrine carcinoma?

Both have a high proliferation index, but a G3 tumour is well differentiated, whereas a carcinoma is poorly differentiated (small or large cell).

## Which tumour causes multiple refractory peptic ulcers and diarrhoea?

Gastrinoma (Zollinger-Ellison syndrome).

## How does C-peptide help in hypoglycaemia caused by insulin?

It is high when insulin comes from the patient's beta cells (insulinoma, sulfonylurea) and low when insulin is injected.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/pancreatic-neuroendocrine-tumours/)

[More Pathology questions →](https://durgical.com/en/practice/?f=pathology)

## Elsewhere in DurgiPedia

- [Islets of Langerhans: α, β, δ cells](https://durgical.com/en/histology/islets-of-langerhans-cells/)
- [Grading and staging: what TNM means](https://durgical.com/en/general-pathology/grading-and-staging-what-tnm-means/)
- [Immunohistochemistry: the principle and the markers to know](https://durgical.com/en/general-pathology/immunohistochemistry-the-principle-and-the-markers-to-know/)

## Connections

## Related 5

- [Multiple endocrine neoplasia (MEN) syndromes](https://durgical.com/en/general-pathology/multiple-endocrine-neoplasia-syndromes/)
- [Gastrointestinal neuroendocrine (carcinoid) tumours](https://durgical.com/en/general-pathology/gastrointestinal-neuroendocrine-tumours/)
- [Peptic ulcer](https://durgical.com/en/general-pathology/peptic-ulcer/)
- [Pancreatic ductal adenocarcinoma](https://durgical.com/en/general-pathology/pancreatic-ductal-adenocarcinoma/)
- [Grading and staging: what TNM means](https://durgical.com/en/general-pathology/grading-and-staging-what-tnm-means/)

## Related conditions 7

- [Pancreatic neuroendocrine tumours (VIPoma, glucagonoma, somatostatinoma, non-functioning)](https://durgical.com/en/conditions/pancreatic-neuroendocrine-tumours/)
- [Insulinoma](https://durgical.com/en/conditions/insulinoma/)
- [Zollinger-Ellison syndrome (gastrinoma)](https://durgical.com/en/conditions/zollinger-ellison-syndrome/)
- [Multiple endocrine neoplasia (MEN 1, 2A, 2B)](https://durgical.com/en/conditions/multiple-endocrine-neoplasia/)
- [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/)
- [Hypoglycaemia (including insulin-induced)](https://durgical.com/en/conditions/hypoglycaemia/)
- [Renal cell carcinoma](https://durgical.com/en/conditions/renal-cell-carcinoma/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/pancreatic/hp/pnet-treatment-pdq) (National Cancer Institute, 2025); [Insulinoma: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000387.htm) (MedlinePlus, US National Library of Medicine, 2025); [Multiple endocrine neoplasia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia/) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/pancreatic-neuroendocrine-tumours/