Gastro Intestinal Stromal Tumors (GISTS)

Abstract

Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the GI tract with an estimated unadjusted incidence of around 1/100 000 / year. However, GISTs are the most common mesenchymal tumor of the gastrointestinal tract (80%). It represent about 1-3% of all gastrointestinal malignancies. GISTs account for 5% of all soft tissue sarcomas, predominantly occur in middle aged and older patients (fifth to seventh decades). These tumors start in very early forms of special cells found in the wall of the GI tract, called the interstitial cells of Cajal (ICCs). The neoplastic GIST cells appear to arise from a common precursor cell, which gives rise to the interstitial cells of Cajal in the normal myenteric plexus. GISTs may occur anywhere along the length of the digestive tract from the esophagus to the anus. Approximately 60-70% of the GISTs arise in the stomach, 20-30% in the small intestine, 5% in the colon and rectum, less than 5% in the esophagus and Sometimes develop outside the intestinal tract, in the abdominal cavity.

Grossly, GISTs vary greatly in size, ranging from 1-2 cm to >20 cm in diameter. GISTs are usually noncapsulated but well circumscribed masses, with a fibroid-like or a softer more fleshy appearance on cut surface. GISTs can be distinguished from other smooth muscle tumors by immunohistochemistry staining for c-kit (CD117), although a small entity of c-kit negative GISTs exists. The oncogenic development of GISTs involve the activating mutation of the c-kit gene and the homologous PDGFRα gene, which leads to ligand independent activation of receptor tyrosine kinase c-kit or exclusively PDGFRα, resulting in increased cell survival and proliferation. Clinical symptoms associated with GIST include abdominal pain, fatigue, dysphagia, satiety, and obstruction. Patients may present with chronic GI bleeding (causing anemia) or acute GI bleeding (caused by erosion through the gastric or bowel mucosa) or rupture into the abdominal cavity causing life-threatening intra-peritoneal hemorrhage. The main differential diagnosis of conventional GIST includes true smooth muscle tumours (leiomyomas and leiomyosarcomas), schwannoma, inflammatory fibroid polyp and desmoid fibromatosis. The management of GISTs should be undertaken by a multidisciplinary team (MDT) with experience in this disease. All patients with GISTs were considered for surgical resection, complete surgical excision of the primary GIST offers the best chance of cure. As with other soft-tissue sarcomas, a true capsule does not exist, the tumor should be removed en-bloc with its pseudocapsule and if possible, an adjacent margin of normal soft tissue or bowel. The tumor should be carefully dissected to avoid tumor rupture because of a risk of dissemination. Tyrosine kinase inhibitors are the mainstay of treatment for patients with metastatic GISTs. Treatment with Imatinib has increased the 2 years survival expectation of patients with advanced or metastatic GIST from less than 20% to approximately 70%. Imatinib mesylate is a selective inhibitor of tyrosine kinase c-kit/PDGFRα so it is a very effective treatment option for metastatic GIST, used as neoadjuvant (preoperative) therapy or adjuvant therapy.