Although they comprise fewer than 1% of all gastrointestinal (GI) tumors, gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the GI tract. It has been estimated that there are 3,300 to 6,000 new GIST cases per year in the United States. A study based on Surveillance, Epidemiology and End Results (SEER) registry data found that the age-adjusted yearly incidence of GIST in the United States was 6.8 per million from 1992 to 2000. However, the true incidence is not known, in part because many tumors have not been tested for the characteristic KIT or platelet-derived growth factor receptor alpha (PDGFRA) gene mutations. In addition, small, indolent GIST, only a few millimeters in diameter, are common in the general population and are not included in cancer registries.[4,5] GIST are equally distributed across all geographic and ethnic groups and men and women are equally affected. Most patients present between the ages of 50 and 80. The vast majority of GIST are sporadic, but there are rare familial forms associated with the characteristic heritable mutations in the KIT gene (or, rarely, in succinate dehydrogenase genes in Carney-Stratakis syndrome). Familial GIST may present as multiple primary tumors.
Clinical Presentation and Diagnostic Evaluation
GIST can occur anywhere along the GI tract, but most often are found in the stomach or small intestine. The American Joint Committee on Cancer (AJCC) Cancer Staging Manual lists the following approximate distributions:
- Stomach (60%).
- Small intestine (30%).
- Rectum (3%).
- Colon (1–2%).
- Esophagus (<1%).
- Omentum/mesentery (rare).
Gastrointestinal stromal tumors (GISTs) may be found anywhere in or near the gastrointestinal tract.
Less frequently, GIST may arise in the appendix, gallbladder, pancreas, retroperitoneum, and paravaginal and periprostatic tissues. Approximately 20% to 25% of gastric GIST and 40% to 50% of small intestinal GIST are clinically aggressive.[9,10] It has been estimated that approximately 10% to 25% of patients present with metastatic disease.[9,11]
The clinical presentation of patients with GIST varies depending on the anatomic location of the tumor and the tumor size and aggressiveness. The most common presentation of GIST is GI bleeding, which may be acute (melena or hematemesis) or chronic and results in anemia.
GIST patients may also present with:
- An acute abdomen caused by tumor rupture.
- GI obstruction.
- Appendicitis-like pain.
Other clinical symptoms include the following:
Smaller lesions may be incidental findings during surgery, radiologic studies, or endoscopy. The natural history of these incidental tumors and the frequency of progression to symptomatic disease are unknown. There may be a substantial reservoir of small GIST tumors that do not progress to symptomatic stages. For example, a series of 98 consecutive systematic autopsies on adults who died of unrelated causes revealed grossly recognizable gastric tumors (1 mm–6 mm) that were histologically diagnosed as GIST in 22.5% of cases. Sufficient DNA was available for analysis in 26 patients, revealing 13 patients with mutations in KIT exon 11 and one in PDGFRA.