Gastrointestinal stromal tumour (GIST)
- Lesion
The most common sarcoma-type tumour of the gut grows from the gut's pacemaker cells and is driven by an overactive growth receptor.
What it is
GIST is the commonest mesenchymal tumour of the abdomen, and more than half arise in the stomach. It derives from the interstitial cells of Cajal, the pacemaker cells of gut motility. About three quarters carry activating mutations of the receptor tyrosine kinase KIT and fewer carry PDGFRA mutations; the two are mutually exclusive. Tumours lacking both often have loss of succinate dehydrogenase. Kinase-inhibitor therapy made GIST a model of targeted cancer treatment.
Structure
- Gross: solitary, well-circumscribed, fleshy mass, which can be very large; whorled cut surface; overlying mucosa often ulcerated.
- Metastases: multiple serosal nodules in the peritoneum and liver; spread beyond the abdomen is uncommon.
- Micro: spindle-cell type (bundles of thin cells) or epithelioid type (plump cells that can mimic carcinoma), often mixed.
Step by step
- A Cajal cell gains a gain-of-function mutation in KIT or PDGFRA.
- The receptor signals constantly without its ligand.
- Downstream growth pathways drive a clonal spindle or epithelioid proliferation.
- Further chromosomal losses (9, 14, 22) accompany progression.
- Kinase inhibitors block the receptor; new mutations later restore signalling.
Markers
- KIT (CD117)
- DOG1
- SDHB loss (SDH-deficient)
Clinical notes
- Mass effects and bleeding from mucosal ulceration; about half present with anaemia.
- Complete resection for localized tumours; kinase inhibitors for unresectable or metastatic disease.
Test yourself
Think of the answer, then tap the question to see it.
From which cell does a GIST arise?
The interstitial cell of Cajal, the pacemaker cell of gut motility.
Which two genes are most often mutated in GIST?
KIT (most) and PDGFRA, mutually exclusive activating mutations of receptor tyrosine kinases.
Which marker helps when a GIST is KIT-negative?
DOG1, positive in nearly all GISTs including epithelioid ones.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Gastrointestinal Stromal Tumors Treatment (Adult) (PDQ®)–Patient Version (National Cancer Institute, 2025).
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Representative model, for educational purposes only.