Gastrointestinal stromal tumors are soft tissue sarcomas that originate from the Cajal cells, the pacemaker cells of the gastrointestinal tract, or their precursor cells.
GISTs are rare, accounting for only 1% of all gastrointestinal malignancies, yet they are the most common mesenchymal tumors of the gastrointestinal tract. The incidence is estimated at about 15 cases per 1 million inhabitants. The median age at onset is between 55 and 65 years. There is no gender-specific predisposition.
A mutation in the Kit or PDGF receptor, leading to continuous activity of the receptor tyrosine kinase, is crucial for pathogenesis. Therefore, GISTs are paradigmatic for successful therapy with tyrosine kinase inhibitors. Since the approval of the TKI Imatinib in 2002, the overall survival of patients with metastatic GIST has tripled. The adjuvant use of TKI has also significantly extended the survival of patients with localized GIST. The therapy strategy for GIST is determined by its molecular characterization. The mutation status has high predictive significance. GISTs with KIT exon 11 mutation, for example, have the best response with partial remission rates of 80%. For KIT exon 9 mutation, doubling the dose to 800 mg Imatinib is standard to enhance response. A PDGFRA exon 18 mutation results in primary resistance. In about 10% of cases, no mutation of the KIT or PDGFRA gene, so-called wild type, is detectable. For these reasons, a mutation analysis must always be initiated when drug treatment is indicated.
GISTs most commonly occur in the stomach (33-63%), followed by manifestations in the small intestine (23-38%). The colon and rectum are affected in 5-32% of cases. GISTs are very rarely found in the esophagus, duodenum, and extraintestinal locations.
About half of the patients with newly diagnosed GIST already have metastases. The most common sites of metastasis are the liver (up to 65%) and the peritoneum (20%).
GISTs exhibit heterogeneous biological behavior. Cytomorphological malignancy criteria for clear classification as “benign – malignant” are lacking. Even tumors of very small size and with very low mitotic count occasionally metastasize, so all GISTs must be considered potentially malignant. Classification into different risk levels of malignant transformation is based on the parameters of tumor size and mitotic index in the categories “very low, low, intermediate, and high risk.”
Furthermore, risk/prognosis depends on the tumor's location. A gastric GIST has a better survival prognosis than a small intestine GIST of the same tumor size and mitotic count, with colorectal GISTs showing the worst course.
The median survival time for advanced and metastatic GISTs is about five years due to the use of targeted therapies.