Gastric neuroendocrine tumours (gastric carcinoids)
Gastric neuroendocrine tumours arise from hormone-producing cells in the stomach lining. They are uncommon, but they are being found increasingly often as endoscopy becomes more frequent and more careful. They are worth understanding properly because they are one of the few tumours where the classification alone almost dictates the treatment: three distinct types exist, they arise by quite different mechanisms, and they range from lesions that need nothing more than periodic observation to tumours requiring the same treatment as gastric cancer.
How they form
The relevant cells are the enterochromaffin-like (ECL) cells of the gastric body and fundus. Their normal job is to release histamine in response to gastrin, which then stimulates the parietal cells to secrete acid. They are under the direct control of gastrin, and that single fact explains almost everything about types 1 and 2.
Normally, acid in the stomach suppresses gastrin release through a negative feedback loop. If acid production fails, or is blocked, that brake is released. Gastrin rises, and persistently elevated gastrin acts as a growth stimulus on the ECL cells — producing first hyperplasia, then dysplasia, then multiple small tumours. This is a hormone-driven proliferation rather than a conventional cancer, which is why these lesions behave so indolently and why removing the source of the gastrin can make them regress.
Type 1 — the commonest, accounting for most cases
Arises in autoimmune atrophic gastritis. Autoimmune destruction of the parietal cells abolishes acid production; the antral G cells, sensing no acid, secrete gastrin continuously; the ECL cells proliferate in response. The result is multiple small polypoid tumours in the body and fundus, typically under 1cm, in a stomach with atrophic mucosa. These patients frequently also have pernicious anaemia from loss of intrinsic factor, and vitamin B12 deficiency.
Behaviour is indolent. Metastasis is rare and the outlook is essentially that of the underlying gastritis rather than of the tumours.
Type 2 — the rarest
Arises in Zollinger-Ellison syndrome, almost always in the context of multiple endocrine neoplasia type 1. Here a gastrinoma secretes gastrin autonomously, so gastrin is high and acid is high — the opposite biochemical picture from type 1, with the same trophic effect on the ECL cells. Tumours are again multiple and small, but behave somewhat more aggressively than type 1. Recognising type 2 matters because it identifies an underlying gastrinoma and an inherited syndrome requiring its own assessment.
Type 3 — sporadic
Arises independently of gastrin, in a normal stomach with normal acid and normal gastrin levels. This is a genuine neoplasm rather than a hormonally driven proliferation. It is typically solitary, larger, and occurs in an otherwise normal stomach, and it behaves like a malignant tumour: it invades, spreads to lymph nodes and metastasises to the liver. It is treated as such.
A fourth category — poorly differentiated neuroendocrine carcinoma, large-cell or small-cell — is a distinct and aggressive malignancy treated with chemotherapy along the lines of small-cell lung cancer, not as a carcinoid at all.
Grading
All are graded by how fast their cells divide, using the mitotic count and the Ki-67 proliferation index: G1 (low), G2 (intermediate) and G3 (high). Grade, type and size together determine treatment.
Symptoms
Most cause none and are found at endoscopy performed for anaemia or dyspepsia.
- symptoms of the underlying condition — fatigue and anaemia from B12 deficiency in type 1; severe ulcer disease and diarrhoea in type 2
- iron-deficiency anaemia or occult bleeding from an ulcerated lesion
- vague upper abdominal discomfort
- in advanced type 3 disease with liver metastases, features of carcinoid syndrome may occur, though the atypical gastric form — patchy flushing, itching and headache from histamine rather than serotonin release — differs from the classical picture seen with midgut tumours, and is uncommon
How the diagnosis is made
Classification is the work, and it requires more than looking at the lesion.
- Endoscopy — documenting the number, size and site of lesions, biopsying or removing them, and, critically, taking mapped biopsies of the background mucosa of antrum and body to establish whether atrophic gastritis is present. Whether the surrounding stomach is atrophic or normal is what separates type 1 from type 3.
- Fasting serum gastrin and gastric pH — together these distinguish the types: high gastrin with low acid indicates type 1; high gastrin with high acid indicates type 2; normal gastrin indicates type 3. Proton pump inhibitors raise gastrin and must be stopped before testing, or the result is uninterpretable.
- Chromogranin A — a tumour marker, though also raised by proton pump inhibitors and by renal impairment, which limits its usefulness.
- Anti-parietal cell and anti-intrinsic factor antibodies, vitamin B12 — confirming autoimmune gastritis.
- Histology with Ki-67 — confirming neuroendocrine differentiation (synaptophysin, chromogranin) and establishing grade.
- Endoscopic ultrasound for lesions above about 1cm, to assess depth of invasion and local nodes.
- CT, and functional imaging with Ga-68 DOTATATE PET for type 3 disease, larger lesions or suspected metastases.
Treatment
Type 1
The guiding principle is restraint. These are indolent lesions in a stomach that will continue to produce them, and over-treatment has historically been a greater problem than under-treatment.
- Lesions under 1cm, few in number: endoscopic surveillance alone is appropriate, with removal of larger lesions as they appear.
- Lesions of 1–2cm, or increasing in number: endoscopic resection.
- Lesions above 2cm, invading the muscle layer, or with higher grade: local surgical resection.
- Antrectomy — removing the source of gastrin — is an option for recurrent multifocal disease and can cause the remaining tumours to regress, though it is used selectively.
- Somatostatin analogues suppress gastrin and can reduce tumour number and size; used in troublesome recurrent disease.
- Lifelong vitamin B12 replacement and attention to iron.
- Gastrectomy for type 1 disease is rarely justified.
Type 2
Treatment is directed at the gastrinoma as much as at the gastric lesions: localisation and resection of the gastrinoma where possible, high-dose proton pump inhibitors, endoscopic management of the gastric tumours, and full assessment for MEN1 including parathyroid and pituitary, with genetic counselling.
Type 3
Treated as a malignant gastric tumour: partial or total gastrectomy with lymphadenectomy, as for gastric adenocarcinoma. Small, low-grade, superficial type 3 lesions may occasionally be managed by endoscopic resection in carefully selected cases, but the default is oncological surgery.
Metastatic disease is managed with somatostatin analogues, peptide receptor radionuclide therapy (PRRT), targeted agents such as everolimus and sunitinib, liver-directed treatment, and chemotherapy for high-grade disease — through a specialist neuroendocrine tumour service.
Recovery
Endoscopic resection is a day-case or overnight procedure, with a soft diet for a few days. Surgical resection follows the usual course for the operation performed — a local gastric resection typically three to five days in hospital, a formal gastrectomy considerably longer, with the dietary adjustments described on the gastric cancer page.
Follow-up
Type 1 requires long-term endoscopic surveillance at intervals of one to two years, with B12 monitoring, and awareness that atrophic gastritis itself carries an increased risk of gastric adenocarcinoma — which is arguably the more important reason for continued surveillance. Type 2 follows the MEN1 protocol. Type 3 is followed with imaging as for gastric malignancy.
When to seek an opinion
A diagnosis of gastric carcinoid or neuroendocrine tumour without a clear statement of which type it is, or of pernicious anaemia or atrophic gastritis without endoscopic assessment. These tumours are uncommon enough that management benefits from a unit familiar with them.
Common questions
I was told I have carcinoid tumours in my stomach. Is this cancer?
It depends which type. By far the commonest type arises because of a long-standing change in the stomach lining, consists of several very small growths, and behaves gently — it rarely spreads and is usually managed by watching and removing the larger ones. A less common type occurs in an otherwise normal stomach and does behave like a cancer. Establishing which you have is the first and most important step.
How do you tell the types apart?
Chiefly by two things: whether the surrounding stomach lining is normal or has the changes of long-standing inflammation, and a blood test measuring the hormone gastrin. High gastrin with a stomach that makes no acid points to the common, gentle type; a normal result in a normal stomach points to the type that needs proper surgery.
Why do I need to stop my acid tablets before the blood test?
Because acid-suppressing tablets raise the gastrin level themselves, which would make the result impossible to interpret. They are usually stopped for a couple of weeks beforehand, provided it is safe to do so.
Do they all need removing?
No. Small lesions of the common type are often simply monitored by endoscopy, with removal of any that grow beyond a certain size. Removing every small lesion repeatedly achieves little and is not the recommended approach.
Why do I need vitamin B12 injections?
Because the same condition that causes these tumours — loss of the acid-producing cells — also removes the substance the stomach makes to absorb vitamin B12 from food. Without replacement, this causes anaemia and, over time, nerve damage. Replacement is lifelong and straightforward.
Will I need regular endoscopies for life?
Usually yes, for the common type, though at intervals of a year or two rather than frequently. There are two reasons: to check the tumours, and — the more important one — because the underlying change in the stomach lining carries a small increased risk of stomach cancer, which surveillance is designed to catch early.
Is it inherited?
The common type is not inherited, though the autoimmune condition behind it can run in families alongside other autoimmune disorders such as thyroid disease. One rare type occurs as part of an inherited syndrome affecting several hormone glands, and where that is suspected, genetic testing and family assessment are offered.
Related conditions
Other conditions of the stomach covered on this site:
- Peptic ulcer disease
- Perforated and bleeding peptic ulcer
- Gastric outlet obstruction
- Gastric polyps
- Gastrointestinal stromal tumour (GIST)
- Stomach cancer (gastric cancer)
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, investigations and discussion in a multidisciplinary meeting.