Gastrointestinal stromal tumour (GIST) !

The most common sarcoma of the gut, usually in the stomach. It can bleed or grow silently, and most respond to a targeted pill called imatinib.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

A mesenchymal tumour of the digestive tract that arises from the interstitial cells of Cajal, the pacemaker cells of gut motility. Most are driven by activating mutations in KIT or PDGFRA, and their behaviour ranges from tiny harmless nodules to aggressive cancers that spread to the liver and peritoneum.

Who gets it

The most common mesenchymal tumour of the gut, though under 1% of digestive cancers. It occurs mainly in adults aged 50–70, equally in men and women. About 60% arise in the stomach and 30% in the small intestine, with the rest in the duodenum, rectum, colon or oesophagus. Small GISTs are often found by chance during endoscopy or surgery.

Causes

Activating KIT mutations (about 80%)
PDGFRA mutations (about 5–10%), including D842V, which resists imatinib
KIT/PDGFRA wild-type tumours: SDH-deficient GIST (children and young adults, Carney triad and Carney–Stratakis syndrome), NF1-associated GIST, BRAF-mutant
Rare familial germline KIT or PDGFRA mutations

Risk factors

Age 50–70
Neurofibromatosis type 1 (often multiple small-bowel GISTs)
Succinate dehydrogenase deficiency syndromes
No known environmental or dietary risk factors

Pathophysiology

KIT and PDGFRA are tyrosine kinase receptors that normally switch on only when their growth factor binds. Mutations keep them switched on, sending constant growth and survival signals to Cajal-cell precursors. The tumour grows outward from the muscle wall, so it often stays silent until it is large; it can ulcerate the mucosa and bleed, block the lumen or rupture into the abdomen. Spread is mainly to the liver and peritoneum; unlike carcinomas, lymph node spread is rare.

Classification

Risk of recurrence by tumour size, mitotic rate and site (gastric tumours are less aggressive than small-bowel or rectal ones)
Tumour rupture as a very high-risk feature
Molecular subtype: KIT exon 11 or 9, PDGFRA, SDH-deficient, NF1-associated
Localised, locally advanced or metastatic

Symptoms and signs

Often none; found incidentally
Gastrointestinal bleeding: melaena, vomiting blood or chronic occult bleeding with anaemia
Abdominal pain, fullness or early satiety
Palpable abdominal mass
Bowel obstruction or difficulty swallowing depending on site

Diagnosis

Clinical: Suspect it in a patient with gut bleeding or anaemia and a submucosal mass on endoscopy, or an intra-abdominal mass arising from the bowel wall on imaging.
Tests: Endoscopy shows a smooth submucosal bulge, sometimes with central ulceration; endoscopic ultrasound-guided biopsy (avoiding percutaneous biopsy that may seed the peritoneum). Histology shows spindle or epithelioid cells; immunohistochemistry is positive for CD117 (KIT) and DOG1. Mutation analysis of KIT and PDGFRA guides drug choice. Complete blood count for anaemia.
Imaging: Contrast CT of the abdomen and pelvis for staging and follow-up; MRI for rectal and liver lesions; FDG-PET can show early response to imatinib.

Differential diagnosis

Leiomyoma and leiomyosarcoma
Schwannoma
Gastric adenocarcinoma
Gastrointestinal lymphoma
Neuroendocrine tumour
Ectopic pancreas or other submucosal lesions

Goal of treatment

Remove localised tumours completely without rupture, lower recurrence in high-risk cases with targeted therapy, and control metastatic disease with tyrosine kinase inhibitors chosen by mutation.

Treatment

Surgical: Complete resection with an intact capsule and negative margins, often laparoscopic; routine lymph node dissection is not needed because nodal spread is rare. Very small gastric tumours may be followed endoscopically.
Medical: Imatinib, a tyrosine kinase inhibitor, is given for at least three years after surgery in high-risk tumours, before surgery to shrink large ones, and as first-line treatment for metastatic disease; avapritinib is used for PDGFRA D842V tumours.
Medical: After imatinib resistance: sunitinib, then regorafenib and ripretinib. Conventional chemotherapy and radiotherapy are largely ineffective.
Follow-up: CT follow-up for recurrence; nursing and pharmacy support for adherence and side effects of imatinib such as oedema, diarrhoea, nausea, fatigue and low blood counts, and for drug interactions.

Complications

Acute or chronic gastrointestinal bleeding
Tumour rupture with intra-abdominal haemorrhage and peritoneal seeding
Bowel obstruction
Liver and peritoneal metastases
Resistance to tyrosine kinase inhibitors

Prognosis

Small, low-mitotic gastric GISTs are usually cured by surgery. High-risk and metastatic tumours relapse often, but targeted therapy has turned metastatic GIST from a disease with survival of about a year and a half into one where many patients live five years or more.

Test yourself

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

From which cells do GISTs arise?

The interstitial cells of Cajal, the pacemaker cells of the gut.

Which two immunostains are typically positive in GIST?

CD117 (KIT) and DOG1.

What is the first-line drug for metastatic KIT-mutant GIST?

Imatinib, a tyrosine kinase inhibitor.

Why is routine lymphadenectomy not done in GIST surgery?

Because GISTs rarely spread to lymph nodes; they spread to liver and peritoneum.

What is the most common site of GIST?

The stomach (about 60%), followed by the small intestine.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Gastrointestinal Stromal Tumors Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).

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Representative model, for educational purposes only.

Stomach highlighted on the Durgical 3D model