Gastrointestinal Stromal Tumors

Background: GISTs compromise 1% to 3% of all malignant GI tumors; however, they represent the most common mesenchymal tumor of the GI tract. Initially recognized histologically, a seminal discovery 20 years ago began elucidating the pathogenesis of most GISTs at the molecular level. Design and Methods: A comprehensive review of the literature was conducted in PubMed on GIST diagnosis, pathology, molecular pathology, epidemiology, prognosis, surgical management, and systemic treatment. Seminal papers on the disease and its management are included for a contemporary understanding of the disease. Information on rare subtypes of GIST, such as succinate dehydrogenase (SDH)-deficient tumors, is included. Primary Results: The majority of GISTs are present in the stomach or small bowel. Surgery remains the standard of care for management of primary disease. There is a benefit to the use of imatinib in the adjuvant setting for intermediate- to high-risk tumors. The management of advanced disease is primarily with tyrosine kinase inhibitor therapy with imatinib, sunitinib, and regorafenib; however, tumors with specific mutations such as PDGFRA D842V, NF-1-associated, or with SDHB deficiency require special considerations in their care. Surgery, radiation, or tumor embolization may be of benefit in appropriate patients. Principal Conclusions: The understanding of the molecular pathology of GIST has been translated into highly effective, molecularly targeted therapies that benefit most GIST patients.