gastrointestinal stromal tumors ( gist ) are the most common mesenchymal tumor of the human gastrointestinal tract , which arise from intestinal cells of cajal . before the imatinib ( glivec , novartis korea , seoul , korea ) era , surgery was the only therapeutic treatment for gist . even after the complete resection of gist , however , most patients with advanced disease relapsed making the prognosis of patients with metastatic and/or recurrent gist extremely poor .
although a number of experiences have been reported with imatinib mesylate ( i m ) in patients with unresectable or metastatic gists without operation , there were few reports about neoadjuvant experience in those cases .
we report a case of unresectable gastric gist who underwent neoadjuvant therapy followed by surgical resection .
a 53-year - old female was admitted to our department of general surgery because of dyspepsia and vomiting during the previous month . for her past history ,
contrast - enhanced abdominal computed tomography ( ct ) and f-18 fluorodeoxyglucose positron emission tomography ( fdg - pet ) ct showed an approximately 12 cm sized heterogeneous mass located from fundus to mid body of stomach , which seemed to invade pancreas , spleen and left adrenal gland ( fig .
endoscopic biopsy performed in our institution and pathologic report revealed a spindle cell tumor consistent with gist ( figs . 2 , 3 ) .
results of immunohistochemical stain : the tumor cell was positive for cd34 and c - kit ( cd117 ) , weak positive for smooth muscle actin ; whereas s-100 was negative ( fig .
two weeks later , we performed laparotomy , but the mass was huge and invaded the pancreas and retroperitoneum very tightly so that it could n't be resected .
ten days after the operation , the patient was started on imatinib therapy , a daily dose of 400 mg , maintained for 4 months .
a follow - up ct , 2 months after the start of imatinib , showed a dramatic reduction in the size of the tumor . and
4 months after follow - up ct , there was no evidence of mass lesion in the stomach ( fig .
5 ) ; on the gastroduodenoscopy , the mass lesion was invisible with only an ulcerative lesion observed in the same location ( fig .
although the mass lesion was not revealed clearly at the follow - up imaging study ( fig .
5 months after the treatment with imatinib , the patient underwent total gastrectomy and splenectomy .
the stomach was adhered to the spleen , tightly , and the lesion was found between stomach and spleen , firm and white , having irregular margin .
pathologically , very few tumor cells were in the fibrotic tissue ; residual tumor size was 0.3  0.2 cm and 0.2  0.2 cm , respectively .
the tumor consisted of spindle cells with a mitotic activity index of 1/50 hpf on microscopy . around the residual tumor , hyalinized fibrosis , inflamed granulation tissue , dystrophic calcification , and necrosis and abscess
gist is the most common mesenchymal tumor of the gastrointestinal tract . up to two - thirds of gists show malignant behavior with high recurrence rates .
therefore , improving the rate of complete resection is a key challenge in the treatment of gists .
neoadjuvant therapy with tyrosine kinase inhibition has potential usefulness in primary gist , although not yet as a standard of care .
several retrospective studies suggested that resection of residual lesions could prolong progression - free survival if it is done while the tumors are under control with imatinib .
it is also emphasized that imatinib should be continued even after complete resection of all visible disease .
however , the role of resection of residual tumors after imatinib therapy has not been established , and several phase iii clinical trials to investigate the role of surgical resection in this setting are ongoing or planned worldwide .
there is no disagreement on the benefit of treatment with imatinib for malignant gists , but the clinical outcome of neoadjuvant treatment with imatinib is not well established . in our case , we could perform complete resection of the gist by down - sizing of the tumor after treatment with imatinib . the duration of neoadjuvant therapy with imatinib may vary according to response to the treatment , but surgery may be performed after sufficient shrinkage of tumors is observed ; typically after 4 to 6 months and within 12 months of imatinib treatment . the standard initial dose of imatinib is 400 mg per day in patients with unresectable or metastatic gists . in a randomized phase iii trial that compared 400 mg daily with 800 mg daily , the 800 mg daily was a more toxic but not more effective dose .
the goal of surgery is complete resection of tumor , possibly avoiding the occurrence of tumor rupture and achieving negative margins . in our case ,
there was no tumor rupture during the operative procedure and pathologically negative margins were obtained .
radiographic tumor response to preoperative imatinib correlated significantly with complete resection , with 91% of patients with partial responses achieving complete resection , versus 4% of patients with progressive disease .
radiographic and metabolic complete response based upon fdg - pet are not always concordant with a pathologic complete response ; therefore , it should be born in mind that the pathological evaluation on the surgically resected materials obtained from patients treated with i m might be indispensable for the elucidation of the therapeutic effect of i m on gist . in our case , follow - up pet showed a hypermetabolic lesion around medial side of the spleen ; residual tumor was observed in that site on microscopy , but follow - up ct showed no evidence of mass lesion in the stomach . in the surgical findings , the lesion had extensive areas of fibrotic changes and there were severe adhesions between the lesion and spleen , so it was suspected to be invasion , thus we performed total gastrectomy and splenectomy .
first , the patient 's follow - up period is short and will not be an accurate prognostic assessment .
suspected to be in an inoperable state , neoadjuvant chemotherapy should take precedence over surgical procedure . in summary
, we report a case of gist in an unresectable state , initially , who underwent complete surgical resection following imatinib treatment . in cases of advanced gists , neoadjuvant treatment with imatinib may provide an opportunity for surgeons to perform a complete resection .
 a 53-year - old woman was diagnosed with gastrointestinal stromal tumor ( gist ) of the stomach . computed tomography ( ct ) revealed a huge mass ( 12 cm in diameter ) , likely to invade pancreas and spleen . in the operation field , 
 the tumor was in an unresectable state . 
 the patient was then started on imatinib therapy for 4 months . on follow - up imaging studies , 
 the tumor almost disappeared . 
 we performed total gastrectomy and splenectomy upon which two small - sized residual tumors were found on microscopy . in this paper , we describe a case of clinicopathologic change in unresectable gist after neoadjuvant imatinib mesylate . 
INTRODUCTION
CASE REPORT
DISCUSSION