Gastrointestinal stromal tumors (GISTs)
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that arise in the connective tissue of the gastrointestinal tract, most commonly found in the stomach and small intestine. They are distinguished by the overexpression of the C-KIT protein, which plays a key role in cell proliferation. Although the exact risk factors for GISTs are not well-defined, certain genetic conditions, such as neurofibromatosis and familial gastrointestinal stromal tumor syndrome, can increase the likelihood of developing these tumors. GISTs can be benign or malignant, with around 20 to 30 percent diagnosed as malignant. Symptoms may vary depending on tumor size, with possible manifestations including abdominal pain, intestinal bleeding, nausea, and weight loss. Diagnosis often occurs incidentally during surgery or routine screenings, with imaging tests playing a role in detection. Treatment primarily involves surgical removal of the tumor, and targeted therapy with imatinib has emerged as a significant advancement in managing GISTs. The prognosis for patients depends on tumor size, grade, and spread, with better outcomes generally associated with localized tumors.
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Gastrointestinal stromal tumors (GISTs)
ALSO KNOWN AS: Gastrointestinal sarcomas, gastrointestinal stromal neoplasm, gastrointestinal stromal sarcoma
RELATED CONDITIONS: Soft-tissue sarcomas
DEFINITION: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that form in the connective tissue of the gastrointestinal system. The most common forms of GISTs occur in the stomach, although tumors may also develop in the small intestine, the esophagus, and the colon or rectum. GISTs are differentiated from similar gastrointestinal tumors by overexpression of the C-KIT protein, a tyrosine kinase receptor protein that, on activation, triggers protein-signaling pathways that initiate cell proliferation.
Risk factors: No well-defined risk factors exist for developing gastrointestinal stromal tumors. Neurofibromatosis, a disease characterized by numerous benign tumors in nerves throughout the body, may be associated with the formation of GISTs. Most GISTs occur sporadically, but a few reported cases of these tumors developing in members of the same family, perhaps due to the inheritance of a mutation within the C-KIT or PDGFRA genes. Additionally, familial gastrointestinal stromal tumor syndrome is an inherited disorder that predisposes individuals to the formation of GISTs. This rare condition is caused by mutations in the C-KIT gene. However, unlike people with sporadic GIST in which only the tumor expresses C-KIT mutations, individuals with gastrointestinal stromal tumor syndrome have C-KIT mutations in all the cells of their bodies.
Etiology and the disease process: Gastrointestinal stromal tumors arise because of activating mutations of one of two tyrosine kinase proteins essential for triggering cell proliferation. Around 80 percent of GISTs occur after mutations within the gene encoding for the C-KIT protein, and around 10 percent of cases are associated with mutations in the gene encoding the platelet-derived growth factor receptor PDGFRA genes. The specific type of cell in which GISTs originate is what differentiates a GIST from similar gastrointestinal tumors. Most investigators believe that GISTs begin in particular cells within the connective tissue of the gastrointestinal tract, called interstitial cells of Cajal. Many GISTs are benign growths within the gastrointestinal system and are not malignant.
Incidence: A gastrointestinal stromal tumor is considered to be a relatively rare cancer and is estimated to occur in 10 to 20 individuals per 1 million people. Each year, approximately 4,500 to 6,000 Americans have a GIST. Of these cases, 20 to 30 percent of the tumors are diagnosed as malignant. Most GISTs occur in people over the age of fifty, with the majority of tumors diagnosed between the ages of fifty-five and sixty-five. GISTs rarely occur in children or people younger than forty years. While GISTS are thought to affect both genders equally, some studies have suggested that there may be a slight prevalence of GIST development in men.
Symptoms: Depending on the size of the gastrointestinal stromal tumor, an individual may or may not experience any symptoms. As the tumor enlarges, patients often feel abdominal pain or develop intestinal bleeding. Upon examination, a GIST may be found to cause these symptoms. Other symptoms associated with GISTs include nausea, vomiting, and appetite or weight loss.
Screening and diagnosis: No effective screening tests for gastrointestinal stromal tumors exist. Some GISTs are diagnosed by chance, during abdominal surgery, or a routine colonoscopy. Also, GISTs may be identified by radiological screening tests, such as a computed tomography (CT) scan, a barium X-ray, or magnetic resonance imaging (MRI). Sometimes, a doctor may perform a biopsy if a mass is detected. However, biopsies are often impractical, and instead, surgery is performed to remove the mass. At this time, a biopsy of the tumor tissue is removed to determine if it is malignant or benign. Using a biopsy sample, GISTs are histologically graded to determine the malignant potential of the tumor.
Treatment and therapy: The primary treatment for GIST is surgery, in which the goal is to remove as much of the tumor as possible. Surgery is more likely to be successful when the GIST is small. Most general anticancer chemotherapeutics previously used to treat GISTs were largely ineffective. The approval of the targeted therapy imatinib (Gleevec) has caused this drug to become part of the front-line therapy for the treatment of GISTs. Imatinib specifically inhibits both C-KIT and PDGFR, the two main proteins responsible for the development and survival of GIST cells. Although imatinib does not necessarily cure the GIST, it is often used to shrink the tumor size.
Prognosis, prevention, and outcomes: The prognosis for patients diagnosed with a GIST depends on several factors. These include the size and grade of the tumor and the degree to which the tumor has spread, if at all. For people diagnosed and treated between 1992 and 2000, the overall five-year survival rate of patients with GIST was approximately 45 percent. This survival rate increased to 64 percent if the tumor remained localized but decreased to 13 percent if it spread to distant sites.
However, these survival rates increased because of the addition of new therapies to treat GIST. Individuals with localized tumors that have not spread outside their original location have a five-year survival rate of 93 percent. Those whose tumors metastasize to distant organs have a 55 percent five-year survival rate.
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