A 45-year-old woman presents to your general surgical colleague with vague abdominal symptoms and a computed tomography (CT) scan shows a large mass involving the stomach, spleen and left kidney. The surgeon has arranged a percutaneous Tru-cut biopsy and the report indicates a gastrointestinal stromal sarcoma. The surgeon discusses the patient with you and asks if she should attempt to resect this mass.
What are gastrointestinal stromal tumours (GISTs)?
How are they diagnosed?
How should patients with GIST be managed?
What are gastrointestinal stromal tumours (GIST)?
GISTs are soft tissue sarcomas of mesenchymal origin arising in the gastrointestinal tract and account for 5% of soft tissue sarcomas overall. Historically these tumours were thought to be of smooth muscle origin and were regarded as leiomyomas or leiomyosarcomas. However, with advances in electron microscopy and immunohistochemical techniques, it was seen that they lacked the features of smooth muscle differentiation typical of leiomyomas occurring elsewhere in the body. It was later identified that these tumours specifically express CD34 and KIT (CD117) establishing the group as a separate entity.
KIT, the product of the proto-oncogene c-KIT, is a tyrosine kinase growth factor receptor. It is expressed on interstitial cells of Cajal (ICC) which act as pacemaker cells for intestinal motility and GISTs probably develop from ICC precursors. The receptor is activated by stem cell factor leading to homodimerization of adjacent receptors and activation of the intracellular KIT kinase domain. This ultimately activates the cell-signalling cascades involved in tumorigenesis - cell proliferation, adhesion and differentiation. Mutations of the c-KIT gene occur in up to 90% GISTs resulting in gain of function activation of the KIT receptor and unopposed cellular proliferation.1
In the UK the incidence of GIST is in the region of 15/100 100 which equates to approximately 900 new cases per year.2 The median age at diagnosis is 60 years and they are rare before the age of 40. They can occur anywhere in the gastrointestinal tract from the oesophagus to the rectum but up to 90% occur in the stomach or small intestine. The size of tumour can vary from ≤2 cm to over 20 cm. Smaller tumours are often identified incidentally on upper gastrointestinal imaging whereas larger tumours can present with gastrointestinal bleeding, abdominal pain, obstruction or non-specific vague symptoms as in this case.
GISTs can be difficult to diagnose and the pathology sample should always be reviewed by a pathologist experienced in the tumour type. If a tumour is resectable the diagnosis should be made after surgery. Biopsy should not be attempted in such circumstances due to a risk of tumour rupture or seeding, unless there is a possibility of an alternative diagnosis, such as lymphoma or germ cell tumour, the management of which would be entirely different. In ...