Gastric Neuroendocrine Tumours

Gastric neuroendocrine tumours (NETs), also known as gastric carcinoid tumours, are rare cancers that develop in the stomach, an organ in the upper abdomen that stores and digests food. They are known as a type of gastrointestinal carcinoid tumour, also known as gastroenteropancreatic NETs (GEP-NETs).

The stomach has four tissue layers: the mucosa, submucosa, muscle layer and outer layer. The mucosa is the inner-most layer that produces digestive juices (specifically hydrochloric acid and pepsin) to break down food, and mucus to protect the lining of the stomach. The second inner-most layer, the submucosa, supports the mucosa layer, and provides blood and nutrients to the stomach. It contains a variety of blood vessels, lymphatic vessels, and nerves. The next layer is the muscle layer, also known as the muscularis externa, which is responsible for producing contractions to further help break down food and push it to the small intestine. The outer-most layer is the serosa, which is a smooth, protective membrane that surrounds the stomach.

Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreas, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.

Gastric NETS are generally diagnosed in people over the age of 50, with gender predilection varying by subtype. However, anyone can develop this disease.

Types of Gastric Neuroendocrine Tumours

There are three primary types of gastric NETs, which are classified by associated conditions and the hormones they produce. Some experts argue that there is a fourth subtype, however more research into this area is required.

Type I

Type I gastric NETs are the most common subtype of this disease, and often begin as benign growths – or polyps – in the lining of the stomach, which can become cancerous if left untreated. Type I gastric NETs are often associated with atrophic gastritis (chronic inflammation of the stomach), autoimmune gastritis and/or infection with helicobacter pylori bacteria, as well as an overproduction of the hormone gastrin. This type of gastric NET is slightly more common in women and is likely to recur, but often has a good prognosis.

Type II

Type II gastric NETs are a less common subtype of this disease, and often occur as a result of multiple endocrine neoplasia type 1 (MEN 1) and/or Zollinger-Ellison syndrome. It may cause the overproduction of the hormone gastrin by a tumour called gastrinoma, which can cause an over-production of stomach acid. These tumours are often quite small, and can have a good prognosis.

Type III

Type III gastric NETs are the second most common type of gastric NETs. These tumours are usually larger that types I and II, and are not related to the overproduction of gastrin. These tumours are slightly more common in males and are likely to metastasise, but can have a good prognosis when caught early.

Treatment

If a gastric NET is detected, it will be staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system:

  • T (tumour) indicates the size and depth of the tumour.
  • N (node) indicates whether the cancer has spread to nearby lymph nodes.
  • M (metastasis) indicates whether the cancer has spread to other parts of the body.

This system can also be used in combination with a numerical value, from stage 0-IV:

  • Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
  • Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
  • Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
  • Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
  • Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.

Cancers can also be graded based on the rate of growth and how likely they are to spread:

  • Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
  • Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
  • Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. This is often performed after a biopsy, and can help guide treatment options for you.

Treatment is dependent on several factors, including location, stage of disease and overall health.

Treatment options for gastric NETs may include:

  • Surgery, potentially including:
    • Endoscopic mucosal resection.
    • Gastrectomy.
    • Surgery to insert a feeding tube (often required after surgery on the stomach), such as a gastronomy tube (G-tube) or nasogastric tube (NG tube).
  • Somatostatin analogues (SSAs).
  • Chemotherapy.
  • Radiation therapy, potentially including peptide receptor radionuclide therapy (PRRT).
  • Targeted therapy.
  • Ablation therapy.
  • Watch and wait (for slow growing tumours).
  • Clinical trials.
  • Palliative care.

Risk factors

While the cause of gastric NETs remains unknown, the following factors may increase the likelihood of disease:

  • Chronic inflammation of the stomach, often associated with atrophic or autoimmune gastritis.
  • Having multiple endocrine neoplasia syndrome type 1 (MEN1).

Symptoms

Some people with gastric NETs will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:

  • Abdominal discomfort and/or pain.
  • Nausea and/or vomiting.
  • Reflux, heartburn and/or indigestion.
  • Feeling full after eating little food.
  • Unexplained weight loss/loss of appetite.
  • Anaemia.
  • Zollinger-Elison syndrome, which carries its own set of symptoms:
  • Abdominal pain.
  • Nausea and/or vomiting.
  • Weight loss.
  • Diarrhoea.
  • Darkening of stool colour/rectal bleeding.
  • Carcinoid syndrome (rare), which carries its own set of symptoms:
    • Facial flushing (usually red or purple in the face, neck, and/or upper chest).
    • Diarrhoea.
    • Wheezing.
    • Abdominal pain.
    • Carcinoid heart disease (plaques on the heart muscle caused by excess hormone production).
    • Fatigue.
    • Skin changes, such as red or purple spots on the face, neck, and/or upper chest.
  • Paraneoplastic syndromes (rare).
  • Hypercalcaemia (rare).

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have a gastric NET, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment:

  • Physical examination.
  • Imaging tests, potentially including:
    • Ultrasound/endoscopic ultrasound.
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
    • PET (positron emission tomography) scan.
    • MIBG scan.
  • Blood tests.
  • Urine tests.
  • Exploratory surgery, such as a gastroscopy.
  • Biopsy.

References

Keep up with Rare Cancers Australia

Inside Rare is a monthly newsletter that shares the latest news, events and stories connecting the rare community.