GISTs are primary mesenchymal tumours of the gastrointestinal tract previously thought to be gastric or intestinal smooth muscle tumours.1
Recent advances in immunohistochemistry has enabled specific identification of these tumours, which were found to be c-KIT (CD117) positive. GISTs are rare benign or malignant tumours accounting for less than 1% of gastrointestinal neoplasms. Often they arise from the stomach but they can involve any part of the gastrointestinal tract and can also involve the mesentery and omentum. Distant metastases appear late and lymph nodes are not usually involved. The most common metastatic sites are the liver and peritoneum.
The presentation of these tumours depends on the pattern of growth, which may be intra- or extra-luminal. With extra-luminal growth it may take an extended period of time for symptoms to develop with patients often presenting with a large abdominal mass. Upper gastrointestinal bleeding is the most common presentation of intraluminal GISTs because of a tendency of ulceration of the overlying mucosa. Our patient presented with intra-abdominal bleeding. This is rare but has been reported before in GISTs of the stomach,2
or ileal mesentery.4
An acute surgical abdomen can also be caused by acute intratumoural bleeding without haemoperitoneum5
or sudden tumour perforation.3 6
Presenting symptoms in the elective situation may include nausea, vomiting, anorexia, weight loss and abdominal pain. Physical examination is rarely revealing although advanced extra-luminal tumours may have a palpable mass. GISTs can also be an incidental finding in upper gastrointestinal endoscopies and postmortem examinations.
The differential diagnosis of spontaneous intra-abdominal bleeding is wide and includes unnoticed minor trauma (in susceptible patients, such as haemophiliacs) with bleeding from the mesentery, liver or spleen; spontaneous splenic rupture (in patients with pathologically enlarged spleens); ruptured ectopic pregnancy; spontaneous rupture of liver lesions (such as a large hepatocellular carcinoma or haemangioma) or other intra-abdominal tumours; ruptured abdominal aortic aneurysm and other rarer causes.
Surgery is the only curative treatment for GIST lesions.7 8
However, treatment needs to be tailored to the individual patient. Consideration should be given to the location, size and presence of distant metastases. The main treatment for localised GIST is surgical removal of the entire tumour along with the pseudocapsule without rupturing it. Removal of lymph nodes is not necessary when removing a GIST as these tumours do not spread via the lymphatic route.
Imatinib (Glivec) was the first medication approved for the treatment of GIST and represents a major breakthrough in the management of these tumours.9
Imatinib is an orally administered selective inhibitor of ABL tyrosine kinase, platelet-derived growth factor and c-KIT. A small minority of GISTs possess mutations of these tyrosine kinase enzymes, which render the tumour resistant or poorly responsive to imatinib. Tumour mutational status predicts response to imatinib and survival. Results from the MetaGIST study of 1640 patients showed that patients with a KIT exon 11 mutation had the longest progression-free survival, while those with KIT exon 9 mutation had the worst survival.10
Other poor prognostic factors from this study included poor performance status, high neutrophil counts, low haemoglobin level, male sex and small bowel GISTs. Imatinib is currently licensed in the UK for treatment of metastatic or locally advanced and irresectable GISTs. However, there is intense research interest in to defining its role in the neo-adjuvant and adjuvant setting.11
Other drugs with similar mechanisms of action to imatinib, such as sumatinib, are emerging as useful second-line treatment options.
Features that are associated with a poor prognosis include large tumour size, high mitotic count and the presence of metastases. GISTs should be classified into very low, low, intermediate and high risk categories to aid in treatment and follow-up strategies (). Tumour rupture (either spontaneously or at surgery) has recently been shown to increase the risk of tumour recurrence and adjuvant treatment should be considered in such cases.12 13
There has been a suggestion that tumour site and whether the tumour ruptured should be incorporated into a prognostic classification system.14
The presence of tumour rupture or a non-gastric GIST with a size greater than 2 cm would be categorised as high risk for tumour recurrence.
Table 1 NIH consensus classification criteria for defining risk of aggressive clinical course of primary gastrointestinal stromal tumours (adapted from Fletcher15)
It is difficult to quantify the risk of tumour recurrence in this particular case. The tumour size is less than 5 cm and it had a low mitotic rate consistent with low risk tumour. However, the precise tumour dimensions were difficult to measure due to haematoma formation. Because the tumour ruptured, there is a risk of seeding to the peritoneum and so we considered it to be a tumour at intermediate risk of recurrence. It is reassuring that the postoperative CT scan performed 3 months after surgery showed no evidence of tumour recurrence. The patient will continue to be followed up on a regular basis.
In summary, GISTs are rare gastrointestinal tumours that usually present in adult life. They most commonly present with upper gastrointestinal bleeding and some are found incidentally; rarely they can present with acute bleeding into the abdominal cavity and should be considered in the differential diagnosis of spontaneous intra-abdominal bleeding. The primary and only curative treatment is complete surgical excision. However, these tumours carry a risk of recurrence and metastases and they should be classified into very low, low, intermediate or high risk categories to determine intensity of follow-up and the place for additional treatment. Primary or adjuvant treatment with imatinib, a tyrosine kinase inhibitor, is a valuable treatment option in certain patient groups.
- GISTs are rare causes of intra-abdominal bleeding and may present with surgical abdominal signs.
- The prognosis of GISTs is based on a classification by tumour size and number of mitoses present.
- GIST rupture may indicate an increased risk of disease recurrence and adjuvant treatment with the tyrosine kinase inhibitor, imatinib (Glivec), should be considered.