What are the GISTs

The acronym GIST means gastrointestinal stromal tumors. GISTs are the most common mesenchymal neoplasia of the gastrointestinal tract. GISTs result from the transformation of the interstitial cells of Cajal, the intestinal pacemaker cells of the myenteric plexus that control intestinal motility. Their annual incidence is 10-20 new cases per million of people. The median age of incidence is 40-60 years old. Nevertheless sporadic GISTs also affect children and young-adults (pediatric GIST). There is a slightly higher incidence in men than in women. Till the mid-1990s, GISTs were classified as leiomyoma, leiomyosarcoma. At the present time, GISTs are recognized and considered a clinicopathologically distinct entity. GISTs arise predominantly in the stomach (50%) and small intestine (25%) and they rarely occur in colon(10%), mesentery (7%), esophagus (5%). Metastatic spread affect most commonly abdomen and liver, less frequently in lymph nodes, lung or extra-abdominal sites. GISTs have typical immunohistochemical features which are essentials for diagnosis. About 95% of GISTs are positive for c-KIT expression (CD117 antigen), a transmembrane tyrosine kinase receptor which activation leads to cell proliferation. Prognostic factors are substantially two: mitotic index and tumour size. The combination of these parameters permits the stratification of primary tumours into three classes of risk (high, intermediate and low). A high mitotic index and/or tumor size ≥ 10 cm are negative prognostic factors for predicting disease recurrence. GIST diagnosis might be incidental or due to the appearance of aspecific symptoms such as abdominal pain, early surfeit, abdominal mass, gastrointestinal bleeding, or fatigue related to anaemia. Computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) are the most important instrumental exams for diagnosis. Surgery is the treatment of choice for resectable tumours, whereas for unresectable tumours the standard treatment is the administration of imatinib (Glivec), a c-KIT/PDGFRA competitive inhibitor. Response rate to imatinib treatment is about 80%. The recommended daily dose at the start of treatment is 400mg. At disease progression the daily dose of imatinib can be increased to 800 mg. Sunitinib (sutent) administration; a tyrosine kinase inhibitor with antiangiogenic properties which has been approved as the standard treatment after imatinib resistance or intolerance. Clinical controlled trials to evaluate drugs to use in third and more line therapy are still ongoing.