Gastrointestinal Stromal Tumours

Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Gastrointestinal stromal tumours (GISTs) are soft tissue sarcomas. They are the most common mesenchymal neoplasm of the gastrointestinal tract.[1] Traditionally, they have been very difficult to treat due to resistance to conventional chemotherapy.

  • GISTs are rare. They represent 0.1-3% of all gastrointestinal cancers.[2]
  • However GISTs  are the most common primary mesenchymal tumours of the gastrointestinal tract.[3]
  • The estimated incidence of GISTs is around 15 per million of population per annum.[4]
  • There are approximately 900 new cases per year in the UK.[5]
  • The median age of presentation is 60–65 years, but with a wide range. Occurrence in children is very rare.[6]
  • There are oncogenic kinase mutations in most GISTs.
  • 75-80% of GISTs have mutations of the KIT receptor tyrosine kinase.[7] 10% have mutations in tyrosine kinase platelet-derived growth factor receptor alpha (PDGFRA).[8]
  • The different kinase mutations produce different clinical features and also have an impact on which part of the gastrointestinal tract the tumour affects, as well as how aggressive the tumour is.
  • GISTs can occur anywhere in the gastrointestinal tract.
  • 50% are found in the stomach, 25% in the small bowel and 10% in the colon and rectum.
  • They can also develop in the mesentery, omentum, retroperitoneum and pelvis.

Presenting symptoms

  • Nonspecific symptoms such as early satiety, bloating, fatigue (because of anaemia).
  • Fever, weight loss and night sweats.
  • Gastrointestinal bleeding (the most common presenting symptom).
  • Symptoms of abdominal mass and bowel obstruction.
  • They may also present as an incidental finding during investigation for other diseases.

GISTs should be differentiated from other gastrointestinal non-epithelial neoplasms such as leiomyomas, leiomyosarcomas and schwannomas by immunohistochemical staining.

  • GISTs are often discovered incidentally by computerised tomography (CT) scan or endoscopy.[1]
  • Endoscopic ultrasound helps to locate the lesions on the wall of the gastrointestinal tract accurately.
  • For large tumours, CT scanning of the chest, abdomen and pelvis is recommended to assess primary tumour extension and to stage for metastases.[9]
  • Positron emission tomography (PET) imaging is helpful in identifying small metastases.
  • Magnetic resonance imaging (MRI) can may help to provide greater anatomical detail in the anorectal region and help surgery planning.[1, 9]
  • Biopsy is only recommended for lesions of indeterminate type or unresectable and/or metastatic tumours.[9] If a GIST is highly suspected in a resectable tumour, biopsy should not be performed before resection because of the risk of tumour spread.
  • Pathological review of all cases should be made by a pathologist experienced in this tumour type. Specific immunohistochemical staining is used to support the diagnosis.[9]
  • People with neurofibromatosis type I have an increased risk of developing GISTs.
  • There is a familial gastrointestinal tumour syndrome.
  • GIST can also form part of Carney's triad tumour syndrome (the association of gastric stromal tumours, paraganglioma and pulmonary chondroma occurring mostly in girls and young women).
  • All GISTs have the potential to become malignant.
  • The National Institutes of Health workshop assessment criteria have been drawn up to predict tumour behaviour and assess prognosis.[9] These assessment criteria help to define the risk of aggressive behaviour based on tumour size and mitotic count. The criteria are stated in the Association of Upper Gastrointestinal Surgeons (AUGIS) Guidelines for the management of GISTs and may be used to determine subsequent follow-up and management.[9]
  • Aggressive GISTs tend to metastasise to the liver and/or throughout the abdomen. They rarely metastasise to the lymph nodes. Spread outside the abdominal cavity is unusual but, when it occurs, is usually to the lungs and bone.
  • Other work to produce staging systems for GISTs is ongoing with the aim of using these to provide prognostic information.[10]

Localised tumours

  • Complete surgical resection is the principal treatment. Careful handling is needed so as to avoid tumour rupture and intra-abdominal dissemination. Open, trans-sacral or endoscopic surgery are treatment options. Laparoscopic surgery may also be used for some tumours.[11, 12]
  • Subsequent management depends on the risk of recurrence according to the prediction of tumour behaviour.
  • Adjuvant imatinib (a tyrosine kinase inhibitor):
    • Prolongs recurrence-free survival after resection of localised primary GISTs.[13, 14, 15]
    • The availability of imatinib followed by other tyrosine kinase inhibitors has dramatically improved the outcome of GISTs.[16]
    • Side-effects include anaemia, neutropenia, oedema, fatigue, nausea, diarrhoea, skin rashes and liver toxicity.[9, 17]
  • A follow-up CT scan should be performed at three months after surgery.[9]
  • AUGIS has produced an algorithm of overall care which may be followed.[9]

Advanced disease

  • Some metastatic GISTs may be technically resectable.
  • In unresectable and metastatic disease that is KIT-positive, the National Institute for Health and Care Excellence (NICE) recommends that imatinib should be used.[18]
  • Imatinib controls disease in 70-85% of patients with advanced GIST, with an estimated median overall survival time >36 months in all large clinical studies.[19, 20]
  • If patients respond to imatinib, they should remain on it unless or until the tumour becomes unresponsive (as imatinib interruption results in rapid progression in most patients with advanced GIST).[21] Unresponsiveness is indicated by radiological and/or symptomatic progression.[1, 9]NICE does not recommend increasing the dose of imatinib at this stage.[17]
  • CT scanning is used to detect recurrence and is recommended at three-monthly intervals in patients treated with imatinib for unresectable/metastatic disease.[9] Patients should be closely followed up and surgical resection should be performed if the tumour becomes resectable.[9]
  • Sunitinib, another kinase inhibitor, has also been approved by NICE as a treatment option for people with unresectable and/or metastatic malignant GIST if:
    • Imatinib treatment has failed because of resistance or tolerance; and
    • The drug cost of sunitinib (excluding any related costs) for the first treatment cycle will be met by the manufacturer.[22]
  • Other alternative agents to treat imatinib-resistant tumours are also being studied.[1]

Did you find this information useful?

Original Author:
Dr Michelle Wright
Current Version:
Dr Colin Tidy
Peer Reviewer:
Dr Adrian Bonsall
Document ID:
7092 (v4)
Last Checked:
28 May 2014
Next Review:
27 May 2019

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