Introduction

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours that can occur anywhere in the gastrointestinal tract, although most commonly in the stomach or small intestine. GISTs have been difficult to diagnose in the past, which, along with their rarity, means their true incidence is hard to determine and probably underestimated. Until relatively recently, there were very few treatment options for patients with GIST and the prognosis for patients with advanced disease was extremely poor. However, this has changed markedly over the past decade with increases in understanding of molecular pathology. These developments have made diagnosis more accurate and have led to effective treatments with molecular-targeted therapies. As research continues, it is likely that more therapies will become available for this condition.

GISTs probably originate from the interstitial cells of Cajal (ICC) – pacemaker cells that control gut motility. The tumours are diagnosed by a combination of morphological features and immunohistochemistry staining. Oncogenesis appears to be related to dysregulation of the proto-oncogenes KIT or PDGFRA, which encode growth factor receptor tyrosine kinases. Most tumours harbour an activating mutation in KIT or less commonly PDGFRA.

Types of tumour

There are a number of gastrointestinal mesenchymal (non-epithelial) tumours which include smooth muscle tumours, schwannomas and intra-abdominal fibromatosis. GIST is the most common of the gastrointestinal soft tissue tumours.

Incidence and epidemiology

The annual incidence in the UK is between 10 and 20 per million; it is difficult to obtain an accurate count because of the cancer's rarity and because of previous difficulty in diagnosis. There are 600–1200 new cases reported per year in England and 30–60 new cases per year in Wales.

GISTs have become more reliably diagnosable since KIT expression has become detectable by immunohistochemistry, which may have changed the perceived incidence. GIST is rare before age 40; the median age at diagnosis is 60–65 years. It is rarely seen in patients < 20 years and in these cases is usually associated with a syndrome. Most studies show an equal gender distribution of the disease.

GISTs represent 1% or fewer of all primary tumours of the GI tract and 5% of soft tissue sarcomas (Duffaud and Blay, 2003).