Gastrointestinal stromal tumours (GIST)

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•75• Chapter 7 Gastrointestinal Stromal Tumours (GIST) B. Baako Epidemiology GIST is the commonest mesenchymal neoplasm of the gastrointestinal tract. European incidence1 per annum has been estimated at 10-20/ million and a prevalence of 129/million. Malignant transformation is seen in 20-30 percent of newly diagnosed cases per year. One surgical unit in Korle Bu Teaching Hospital saw 8 cases over a 6-year period (unpublished data) with only one case less than 5cm in the widest diameter. It is seen commonly in the over 50 years age group with a median between 55 and 65 years 2 . The gender preference in not settled, but there may be a slight male preponderance. Ethnicity, race, geographical location, and environmental factors are not known to influence the incidence. Rarely, GISTs may arise from other organs, extragastro intestinal GIST (eGIST). This may be from the mesentery, omentum, and the peritoneal surface. Cases have been reported arising from the gall bladder, liver, pancreas and the urinary bladder. Distribution of GISTs in the GIT Oesophagus Stomach Duodenum and Small Intestine Colon and Rectum 5% 50-60% 30-40% 5% GIST may occur in the paediatric age group but the incidence is not known. Familial GIST - an autosomal dominant trait was described in 1998.3 There are germ line mutations in addition to kit mutation. Neurofibromatosis (von Recklinghausen disease), extraadrenal para-ganglionoma and oesophageal leiomyoma (Carney triad) are associated with gastric GISTs .4 •76• Chapter 6 Histopathology (pathogenesis) GISTs are mesenchymal tumours that show differentiation towards the Carjal cells or their progenitor stem-cells. The main event is the mutation of the kit CD117 or the PDGFRA genes. This then promotes the uncontrolled activation of the protein kinase site to produce tumour protein thus enhancing cell proliferation and tumour growth5 . Furthermore, approximately 50 percent to 70 percent of GISTS, especially of the small bowel, express the CD34 on the cell surface. Secondary mutations may occur during treatment with tyrosine kinase inhibitors resulting in drug resistance 9606 . The site and type of mutation may affect prognosis. Gastric GIST arising from deletion behave more aggressively than those from duplication. Kit mutations affecting codons 557-558 also have unfavourable outcomes. GISTs that do not have KIT mutations, PDGFRA mutations, (20 to 30 percent gastric) often have primary resistance to imatinib. Histologically there are the spindle, epithelioid and the mixed epitheliod and spindle cell types. Site specific GISTs tend to have variations in cell types. Stomach GISTs are more epithelioid than spindle cells. Intestinal ones have more spindle cells. Prognosis Unlike most malignancies, GISTs have no grading/staging systems. The risk of recurrence of completely excised GIST with healthy margins is determined/predicted by the mitotic rate/50hpf, tumour size and tumour site. 7 Risk group Mitotic rate Tumour size (cm) Very low 5 > 5 Any >10 >10 any Tumours of similar size and mitotic index have poorer prognosis if in the small bowel than in the stomach. Poor performance status, high •77• Gastrointestinal Stromal Tumours (GIST) white cell count with absolute neutrophilia and low haemoglobin are clinical indicators of poor prognosis. Distribution of GISTs in gastrointestinal tract Oesophageal GISTs occur most commonly in the distal third and constitute only 5 percent of all GISTs. Most are greater than 5cm in diameter. The commonest site is the stomach (70 percent) and can grow exophytically up to more than 40cm in diameter. They commonly show epithelioid cell type with better prognosis. Duodenal GISTs, 4 to 5 percent of all GISTs, tend to show histologically a spindle cell differentiation with poorer prognosis. Like the duodenal type, the other small bowel GISTs are morphologically spindle cell type with similar prognosis. Clinical diagnosis Most GISTs present with abdominal mass, GIT bleeding with anaemia, or obstructive bowel symptoms. Some present with nonspecific symptoms, and others are found incidentally while investigating for other conditions by endoscopy, radiological imaging or even laparotomy for other reasons. Those incidental findings are usually small in size. CT scan of the abdomen and pelvis shows an inhomogeneously enhanced mass lesion. They may show polypoid exophytic or endophytic growth although the swellings are generally centered on the bowel wall. Lymph nodes are rarely involved. There may be liver secondaries and/or serosal nodules. Gastric lesions are visualised as submucosal protruberances with central necrosis on endoscopy. Endoscopic US may be helpful. Biopsy for histological confirmation of the diagnosis may not be necessary before surgical intervention for fear of spillage. In those cases that will need neoadjuvant...