GIST: gastrointestinal stromal tumour

GIST: Gastrointestinal Stromal Tumour

GIST stands for gastrointestinal stromal tumour and is a rare but distinct type of tumour found in the wall of the gastrointestinal tract. It develops from the Cajal cells, which act as pacemaker cells for gut movements. GIST differs from both mucosal cancers and common soft tissue tumours, and therefore requires a different treatment approach. Some are benign or very slow-growing, while others are aggressive. This depends on the tumour's size, location, cell division activity, and molecular profile.

In Denmark, approximately 100-150 new cases are diagnosed annually. While not a large number, it is increasing as gastroscopy and CT scans more frequently detect small tumours incidentally.

What are the symptoms?

GIST often causes few or no symptoms, especially when small. Typical presentations include:

• Vague bloating, discomfort, or a feeling of heaviness in the abdomen
• Early satiety, as the stomach cannot expand normally
• Bleeding from the gastrointestinal tract, often slow and chronic, leading to iron deficiency anaemia, but also acutely as vomiting blood or black stools
• A palpable lump in the abdomen if the tumour is large
• Sudden severe abdominal pain due to bleeding into the tumour or rupture
• Fatigue due to anaemia

Many small GISTs are found incidentally during a gastroscopy or CT scan ordered for entirely different reasons.

Where is it located?

GIST can arise anywhere in the gastrointestinal tract, but the distribution is:

• Stomach: 60 percent
• Small intestine: 25 percent
• Large intestine and rectum: 5-10 percent
• Oesophagus and other locations: rare

Why does it occur?

GIST is most often caused by an acquired mutation in one of two genes:

• KIT gene (approximately 80 percent)
• PDGFRA gene (approximately 5-10 percent)

A small group are considered wild-type and lack these mutations. These are more often seen in younger patients and can be associated with syndromes such as Carney triad or neurofibromatosis type 1. Familial GIST is rare but does exist.

The mutation causes Cajal cells to grow uncontrollably. The rate of growth depends on the type and location of the mutation. This is why molecular analysis is central to modern treatment.

How is the diagnosis made?

1. Gastroscopy or colonoscopy typically shows a smooth, rounded bulge beneath the mucosa, often with a small ulcer on top. Standard biopsies often miss the tumour because it lies in the muscle layer.
2. Endoscopic ultrasound (EUS) with fine-needle biopsy is the reference standard for obtaining tissue samples from gastric GISTs. It provides information on size, layer involvement, and diagnostic tissue.
3. CT scan of the abdomen and pelvis with contrast is used to determine the extent of the disease and check for spread (typically to the liver and peritoneum).
4. Immunohistochemistry shows positivity for CD117 (KIT) and DOG1. This distinguishes GIST from other soft tissue tumours.
5. Molecular analysis of KIT and PDGFRA is mandatory for tumours that require surgery or medical treatment. The mutation profile guides the choice of medication.

The risk of the tumour being aggressive is assessed based on size, mitotic activity, and location. This is called risk stratification according to the Miettinen criteria.

Treatment

Treatment is highly specialised and takes place at highly specialised centres. The surgeon, oncologist, and pathologist work closely together.

Surgery is the cornerstone for localised GIST. The tumour is removed without being opened, and without extensive lymph node removal, as lymph node spread is rare. For small gastric GISTs, surgery can be very minimally invasive, often laparoscopic.

Imatinib (Glivec) is a tyrosine kinase inhibitor that has substantially changed the treatment of GIST. It is used:

• Adjuvantly after surgery for 3 years in high-risk cases
• As standard treatment for locally advanced, inoperable and metastatic disease. Per the ESMO guideline, treatment is continued for as long as it is tolerated and effective, and the choice requires biopsy with mutational analysis, not least because certain mutations call for a different dose
• As neoadjuvant treatment before surgery to shrink large tumours

Second-line treatments include sunitinib and regorafenib, and for specific mutations, avapritinib (PDGFRA D842V) or ripretinib are used. Wild-type GIST has its own treatment strategies.

Active observation may be appropriate for small gastric GISTs under 2 cm without risk factors. This requires close follow-up with EUS.

Prognosis

The prognosis is generally good. The five-year survival rate is over 80 percent for localised disease and has significantly improved for metastatic disease since the introduction of imatinib. Many patients live a normal life on maintenance treatment.

When should you see a doctor?

Contact your GP if you have:

• Persistent discomfort, early satiety, or a lump in your abdomen
• Black stools, vomiting blood, or unexplained iron deficiency anaemia
• Unexplained weight loss or exhaustion
• An incidental finding on a scan or gastroscopy that does not have a follow-up plan

Call 112 for heavy bleeding, fainting, cold clammy skin or reduced consciousness. Contact the acute medical helpline (1813 in the Capital Region of Denmark, otherwise your local out-of-hours doctor) straight away and ask for urgent hospital assessment for intense abdominal pain or black stools when you are otherwise stable.

Frequently Asked Questions

Is GIST cancer? Yes, it is considered a form of cancer with varying aggressiveness. Some GISTs are very slow-growing, while others spread quickly. The classification guides treatment.

Can GIST be cured? Localised GIST that is completely surgically removed has a high chance of cure. Even with metastatic disease, medical treatment can keep the tumour stable for many years.

Should the whole family be tested? Familial GIST is rare. Genetic evaluation is only recommended for very young patients, multiple GISTs, or specific syndromes.

What follow-up should I expect? After surgery, CT scans are typically performed every six months for the first few years, then less frequently. Maintenance treatment with a tyrosine kinase inhibitor requires regular blood tests.

Do I need to change my diet or lifestyle? No, there is no specific diet for GIST. A healthy lifestyle reduces treatment side effects and general risks but has no direct impact on the tumour.

References

1. Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guideline. Ann Oncol. 2022;33(1):20-33. PubMed
2. Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable GIST: 10-year follow-up of the SSGXVIII/AIO randomized trial. JAMA Oncol. 2020;6(8):1241-1246.
3. Sundhed.dk. Gastrointestinal stromal tumor (lægehåndbogen).
4. Blay JY, Kang YK, Nishida T, von Mehren M. Gastrointestinal stromal tumours. Nat Rev Dis Primers. 2021;7(1):22. PubMed

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This article provides general information and does not replace a medical consultation. Contact your GP if you experience symptoms.