Gastrointestinal stromal tumour (GIST)

• gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract
  • term GIST defines a unique group of mesenchymal neoplasms that are distinct from true smooth muscle and neural tumors [1].
• GISTs display spindle cell or epithelioid morphologic characteristics and specific immunohistochemical properties
  • most specific and important immunohistochemical marker is the c-kit (CD117) protein, a tyrosine kinase growth factor receptor
  • many tumors previously diagnosed as leiomyomas, leiomyoblastomas, or leiomyosarcomas have been found to be positive for CD117 and are now considered GISTs
    • includes tumors involving most sites in the gastrointestinal tract except the oesophagus, where true leiomyomas are more common than GISTs. All GISTs should be considered as having malignant potential, although they display varying degrees of aggressiveness [2]
• some families with hereditary GISTs have been described, most cases are sporadic. GISTs occur in 10-20 per one million people
  
  • true incidence might be higher, as new laboratory methods are much more sensitive in diagnosing GISTs
    
    
• GISTs can occur anywhere in the gastrointestinal (GI) tract from the oesophagus to the rectum, as well as the omentum, mesentery, and retroperitoneum
  • approximately 60-70% of GISTs occur in the stomach, and 25-35% arise in the small intestine. Colon, rectum, appendix (together 5%) and oesophagus (2-3%) are rare site
  • less commonly, GISTs may arise in the mesentery, or omentum [1]
  • GISTs are usually solitary tumors
  • GISTs in the oesophagus and colon are relatively more frequently showing a malignant behaviour
  • GIST may spread intra-abdominally to the omentum and peritoneum or reoccur locally after nonradical resection of the primary tumor. Metastasis can be found in liver and only very rarely in lungs, bones and subcutis
  • spleen involvement is a rare finding
• most individuals are over 50 years of age at the time of presentation, and GISTs are rarely seen in patients younger than 40 years, although there are several reports in the paediatric population
• patients with neurofibromatosis type 1 (NF1) have an increased prevalence of GISTs. Classically, patients with NF1 have multiple small intestinal GISTs
  
  
• clinical manifestations of GISTs depend on the location and size of the tumors and are often nonspecific
  • size of the GISTs may vary from small (1-2 cm) to more than 20 cm
  • clinical presentation, such as pain, nausea, vomiting, bleeding, obstruction, anaemia, melaena depends on the tumor size and localization
    
    
• treatment of localized GISTs is surgical resection and that of advanced or unresecable GISTs is based on the use of targeted therapy, imatinib, which is a pharmacological antagonist of the c-kit protein
  • NICE have stated that sunitinib is recommended, within its licensed indication, as a treatment option for people with unresectable and/or metastatic malignant gastrointestinal stromal tumours if imatinib treatment has failed because of resistance or intolerance (4)

Reference:

• 1. Miettinen M, Lasota J. Gastrointestinal stromal tumors: definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001; 438: 1-12.
• 2. Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 2008; 53: 245-266.
• 3. Blanke C, Eisenberg BL, Heinrich M. Epidemiology of GIST. Am J Gastroenterol 2005; 100: 2366
• 4. NICE (September 2009). Sunitinib for the treatment of gastrointestinal stromal tumours