gastrointestinal stromal tumors ( gists ) are rare , but are the most common mesenchymal neoplasm of the gastrointestinal tract , with an incidence of 1020 cases per million7 ) . these tumors can arise from anywhere in the gastrointestinal tract , and are thought to originate from interstitial cells of cajal . the stomach is the most common site of origin ( 6070% ) , and the small intestine ( 2025% ) and the large intestine ( 510% ) are other usual sites7 ) . it can present as localized disease , however , metastasis at presentation occurs in up to 50% of cases . the most common sites to which gastrointestinal tumors metastasize are liver and peritoneum , while lung , bone , or lymph node metastases are rare13 ) . surgical removal is the only curative option for localized gist . in cases of metastasis , discovery of a gain - of - function mutation in the c - kit protooncogene in gist and development of imatinib , a tyrosine kinase inhibitor against the mutation , resulted in a dramatic change of the prognosis of this disease13 ) . as a consequence , median overall survival for metastatic gist in the imatinib era is approximately five years14 ) . due to introduction of very effective target agents , we now encounter metastases of gist , which used to be regarded as unusual sites of metastasis . here report on a patient with skull metastasis of gist after seven years of imatinib treatment who underwent successful metastasectomy . ten years before the skull metastasis occurs , a 50-year old female patient complaining of dyspepsia was diagnosed with a gist on the high body posterior wall of the stomach . the tumor measured 976 cm in size with a mitotic rate of 52/50 high power field ( hpf ) , less than 10% of necrosis , clear resection margin , and no lymph node metastasis . on immunohistochemical ( ihc ) staining , cd34 and c - kit were positive , while smooth muscle actin ( sma ) and s-100 were focally positive . at that time , neither mutation analysis nor adjuvant imatinib treatment was a routine practice ; therefore , she was followed - up with regular examination with out adjuvant treatment . nine years before the skull metastasis occurs , recurrence was observed in the abdominal wall and peritoneum . she started 400 mg / day of imatinib , and very good partial response ( pr ) was achieved and maintained . although recurred gist responded well to imatinib , she was suffering from grade 3 anorexia and lethargy , therefore , she took imatinib intermittently . the tumor grew during the imatinib - off period , but shrank again when she resumed imatinib treatment . her tumor was under control for seven years , until the peritoneal mass in the right lower quadrant showed progression and invasion of adjacent small bowel and ascending colon . she underwent debulking surgery ( small bowel resection and reanastomosis , right hemicolectomy ) , and the mass measured 118 cm in size with 1013/50 hpf and positive radial resection margin . after surgery , no gross mass was observed ; how ever , the dose of imatinib was increased to 600 mg / day . the mass continued to grow , and ct scan of brain and abdomen which were taken three months later showed a large mass located in the parietal cranial vault suppressing adjacent brain and a small single liver metastasis ( fig . 1 ) . subsequent mri revealed a heterogeneously enhancing mass of approximately 7.7 cm ex tent involving the right parietal bone , parietal scalp , and parietal convexity with a heterogeneous signal intensity on a t1/t2 weighted image , multiple signal void on a t2 weighted image , and fatty marrow signal loss with enhancement ( fig . she underwent craniectomy with excision of the mass , cranioplasty , and hepatic resection . on surgical field , about 1010 cm sized yellowish , relatively soft mass originating from skull was com pressing dura and brain parenchyma . because mass adhered to the dura and invasion with seeding was grossly suspected , the bone , tumor , and dura were removed as a unit . she experienced left hemiparesis postoperative day 1 , and ct scan indicated intracerebral hemorrhage in the right temporoparietal lobe . this delayed subcortical hemorrhagic trans formation was thought to result from drainage vein sacrifice during the operation . after conservative management and re habilitation , she recovered and was discharged from the hospital . because the role of adjuvant radiotherapy for gist is not established , we did not administer adjuvant radiotherapy . in stead , her imatinib dose was elevated to 800 mg / day thereafter , which she was not able to tolerate . after three months of rest , huge masses were found in the liver and peritoneal cavity . unfortunately , she was not able to tolerate sunitinib due to nausea and fatigue ; there fore , after 1.5 month of sunitinib treatment , she rested for three months . as the masses progressed , she resumed sunitinib , when 1 year has passed since metastasectomy . a month after sunitinib resumption , she was admitted to the hospital via the emergency department for fever and dyspnea , and diagnosed with pneumonia . she died of acute respiratory distress syndrome one month later , when 14 months has passed since skull metastasectomy . this case illustrates a woman who had skull metastasis of imatinib - resistant gist , which was treated by surgical removal . she lived for one year after craniectomy without evidence of cranial recurrence , and her cause of death was not disease progression itself but infection and respiratory failure . although malignant gists can theoretically metastasize any organ , they obviously have some tropism for specific organs . only a few papers have reported bone metastases of gist1,5,6,8,10 ) , and the most frequent site of bone metastases re ported were spine and pelvis5,6 ) . presenting symptoms depended on the location of metastasis , with skull base or periorbital metastases being more symptomatic24,11,15 ) . management of metastatic gist should be customized according to symptom , location of disease , available treatment modalities , and condition of the patient . our patient underwent debulking craniectomy , because we believed that previous long - term imatinib treatment produced a resistant clone , a huge metastatic mass would soon provoke neurologic symptoms , and en - bloc resection would be possible . debulking surgery is a viable option even in patients with metastatic gist , especially when disease status is stable or shows limited progression12 ) . our patient survived 10 years after recurrence . considering that median overall survival of metastatic or recurrent gist receiving imatinib treatment is five years and nine - year overall survival rate is 34%14 ) we believe that appropriate metastasectomy ( peritoneal , hepatic , and skull metastasis ) during the treatment course had an important role in her long - term survival . traditionally , bone metastasis of gist was thought to be very rare ; however , long - term survival of our patient enabled the disease to metastasize to an uncommon site . likewise , with the much prolonged survival of gist patients by virtue of effective target agents and multidisciplinary approach , medical and surgical oncologists will encounter more and more unusual presentations and complications of this disease . for resistant clones , lo cal treatment such as surgery or radiofrequency ablation has a critical role . therefore , identification of rare but complicated metastasis is essential for clinicians in order to ensure prompt administration of a precise treatment modality . we present the case of a female with skull metastasis of gist after a long term treatment with imatinib successfully managed by metastasectomy . symptomatic skull metastasis from gist is very rare , and an aggressive multidisciplinary approach including surgery and chemotherapy plays an important role in its management .
gastrointestinal stromal tumors ( gists ) are rare , but are the most common mesenchymal neoplasm of the gastrointestinal tract . 
 the most common sites of metastasis are liver and peritoneum , while bone metastasis is rare . 
 we report on a patient with skull metastasis after seven years of treatment with imatinib for metastatic gist . 
 she underwent metastasectomy consisting of craniectomy with excision of the mass , and cranioplasty and continued treatment with imatinib and sunitinib , without evidence of cranial recurrence . 
 she died of pneumonia sepsis one year after metastasectomy . 
 skull metastasis of gist is a very rare presentation , and an aggressive multidisciplinary approach should be considered whenever possible .