Here, we report a case of resistance to imatinib in a patient with metastatic GIST of gastric origin. The tumour relapsed during Sutent imatinib treatment after showing a very good clinical response. We also present a c-kit mutation analysis of the primary and metastatic tumours of the patient. CASE REPORT A 64-year-old Japanese man underwent a proximal gastrectomy for a KIT-positive gastric GIST. At 8 months after the gastric resection, the patient underwent a palliative resection for peritoneal metastases (more than 10foci with the largest being 6.5cm in diameter). At 11 months after initial resection, computed tomography (CT) revealed a solitary liver metastasis measuring 3.1cm in diameter and multiple peritoneal metastases, of which the largest was 5.5cm in diameter (Figure 1A).

The patient was referred to Niigata University Medical and Dental Hospital for imatinib treatment of the recurrent GISTs. Figure 1 Response to imatinib treatment. Computed tomographic examination before imatinib treatment: a solitary liver metastasis (arrow) and multiple peritoneal metastases (arrowheads) (A), CT scan after 6 months of imatinib treatment showing a partial response … Imatinib treatment with four capsules of 100mg imatinib mesylate (Glivec?, Novartis Pharma, Basel, Switzerland) once daily was started. After 3 months of imatinib treatment, abdominal CT scans showed that the liver and peritoneal metastatic tumours had reduced in size to 2.5 and 3.4cm in diameter, respectively. Computed tomography scans conducted a further 3 months later showed that the antitumour effect of imatinib had continued, confirming a partial response (PR) (Figure 1B).

However, 9 months after imatinib treatment was initiated, CT and magnetic resonance imaging (MRI) revealed disease progression at the metastatic site in the liver (Figure 1C). The peritoneal metastases had reduced to smaller lesions with an irregular shape and the intensity of soft tissue. Positron-emission tomography (PET) with [18F] fluorodeoxyglucose ([18F]FDG) as a tracer revealed increased uptake only in the liver metastasis (Figure 1D), suggesting that the liver tumour was active and insensitive to imatinib. At 12 months after the start of imatinib treatment, the relapsing tumour in the liver was excised with extended left hepatectomy. The patient is alive with no evidence of disease relapse 2 months after the liver resection.

PATHOLOGICAL EXAMINATION The resected liver specimen contained a metastatic GIST measuring 5.0 �� 3.2cm. The peripheral tumour showed a solid margin and there was central necrosis with cystic change. Viable spindle-shaped tumour cells were observed in the solid part by histology, and immunohistochemistry revealed that the tumour cells were KIT-positive. The proliferative activity of the tumour cells was approximately 80% in the regrowing focus, as evaluated by the Ki-67 labelling index (MIB1; Immunotech, Batimastat Marseille, France).