These are relatively rare tumours that arise from the Interstitial cells of Cajal, the pacemaker cells located within the muscular layers of the gastrointestinal tract. They occur most commonly in the stomach but some arise from small bowel, colon or rectum.
Unlike the more common gastrointestinal cancers, they very seldom spread to lymph nodes. When they do metastasize, spread is usually via the blood to the liver or directly across the peritoneal cavity.
GISTs may present with gastrointestinal bleeding - vomiting blood (haematemesis), passing altered blood rectally as pitch black stools (melaena) or microscopic, occult bleeding that results in anaemia, which causes fatigue and lassitude. Alternatively, they may present with symptoms related to compression or obstruction by virtue of their large size. At presentation they can range in size from small nodular protrusions into the lumen of the stomach to huge masses protruding outside the outer wall of the stomach or intestine.
They are all potentially malignant but behaviour varies from very low risk of aggressive behavior to very high risk. Risk of aggressive malignant behaviour can be predicted from the size of the primary tumour, the number of mitotic figures that the pathologist sees and whether the tumour has ruptured, either spontaneously or during surgical removal.
Treatment for patients with gastrointestinal stromal tumors (GISTs) was revolutionized with the advent of imatinib, which targets mutated KIT and PDGFR gene products that drive growth in these rare cancers. Imatinib results in dramatic tumor response and protracted survival in patients with metastatic disease, and administration of adjuvant imatinib for 12 months after resection prolongs recurrence-free survival (RFS) compared with surgery alone. However, recurrence is common after discontinuation of adjuvant treatment.
Adjuvant Imatinib for 36 months has recently been shown to be superior to 12 months treatment in a randomised controlled trial.Imatinib, 400 mg per day, was administered orally for either 12 months or 36 months, starting within 12 weeks of surgery.Heikki Joensuu et alJAMA.2012;307(12):1265-1272. The5-year recurrence free survival (65.6% vs 47.9%) overall 5-year survival (92.0% vs 81.7%) were significantly superior in the group who received the drug for 3 years.