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1/169. Malignant gastrointestinal stromal tumor of the ampulla of vater: a case report.

    GIST is a rare neoplasm, the majority of GISTs are located in the stomach and small intestine. Most GISTs are diagnosed histopathologically after resection because of submucosal location. A 37-year-old female patient presented with a 2-weeks history of generalized weakness, nausea accompanied by intermittent passage of black, tarry stools. Esophagogastroduodenoscopy and ERCP showed a large round mass measuring 5 cm in diameter in the ampulla of vater with ulcer crack. Endoscopic multiple biopsies from the mass including ulcer base were taken. light microscopic findings showed spindle-shaped and epitheloid tumor cells having high cellularity and frequent mitotic figures. On immunohistochemical stainings, the tumor cells were positive for CD34 and smooth muscle actin. Based on these preoperative findings, a diagnosis of malignant GIST of the ampulla of vater was made probably. After operation, immunohistochemical studies revealed positive reaction for c-kit and vimentin, as well as focally reactive for CD34 and smooth muscle actin. We report a case of GIST in the ampulla of vater presenting with melena that was diagnosed preoperatively and postoperatively. ( info)

2/169. Immunohistopathological and molecular genetic features of a case in which gastrointestinal stromal tumor recurred five times.

    Gastrointestinal stromal tumor (GIST) is a distinct group of mesenchymal neoplasms recently shown to exhibit differentiation toward interstitial cells of Cajal. Although previous studies have shown that the clinical outcome of patients with GIST is associated with mitotic activity, the proliferation index determined by the Ki-67 labeling index, immunophenotype (CD34 and/or p53) and mutation in exon 11 of the c-kit, a definitive discrimination between benign and malignant GIST has not yet been established. We report a patient in whom malignant GIST in the abdomen recurred five times. In this case, the primary GIST and the five recurrent GIST were associated with c-kit immunoreactivity, but the mitotic index of the GIST tended to be increasingly higher with subsequent recurrences. Mutational analysis of the c-kit revealed that the primary and recurrent GIST were mutant-negative. These data indicated that 'morphologically appearing benign' tumors with lower proliferative parameters may also have the capacity of metastasis and recurrence. ( info)

3/169. Gastrointestinal stromal tumor of the retroperitoneum: CT and MR findings.

    Gastrointestinal stromal tumor (GIST) is a non-epithelial neoplasm arising from the wall of the gastrointestinal (GI) tract. Although the majority of GISTs are located in the GI tract, some GISTs occur in the omentum, mesentery and retroperitoneum. GIST arising in the retroperitoneum is extremely rare, and its radiological findings have not been well described. We report a case of primary retroperitoneal GIST and discuss its imaging findings. ( info)

4/169. Separate occurrence of extra-adrenal paraganglioma and gastrointestinal stromal tumor in monozygotic twins: probable familial Carney syndrome.

    The nonfamilial Carney triad includes paraganglioma, gastrointestinal stromal tumor (GIST), and pulmonary chondroma. Some paraganglioma-GIST diads are familial and inherited in an apparent autosomal dominant manner. The familial paraganglioma-GIST syndrome differs from the Carney triad by the absence of female predilection and predominance of paragangliomas. We report the cases of a 12-year-old boy with a paraganglioma of the organ of Zuckerkandl, and his 13-year-old monozygotic twin with a gastric GIST. These two patients, to our knowledge, are the first to be reported as likely having the familial paraganglioma-GIST syndrome following its description by Carney and Stratakis (Am J Med Genet 2002;108:132-139) in 12 patients from five families. A lifetime follow-up and a periodic search for both tumors are indicated in these patients and their families. ( info)

5/169. Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans.

    Imatinib mesylate, licensed to treat chronic myelogenous leukemia and gastrointestinal stromal tumors, is metabolized by cytochrome P450 3A and undergoes little renal excretion, but its biliary excretion by humans is uncharacterized. Liquid chromatography-mass spectrometry was used to quantitate imatinib and its metabolite CGP 74588 in the bile of two patients with biliary stents; the ratio of imatinib:CGP 74588 in each was approximately 9:1. In the first patient, who was receiving long-term therapy with imatinib 400 mg/day and had normal liver function tests, biliary imatinib accounted for 17.7% of the daily dose and CGP 74588 accounted for 2.1%. In the second patient, who had elevated liver function tests and was studied after his first dose of imatinib 300 mg, biliary imatinib accounted for only 1.8% of the daily dose and CGP 74588 accounted for 0.2%. These data show both the qualitative similarities and the quantitative variability in biliary excretion of imatinib and its principal metabolite. ( info)

6/169. Gastrointestinal stromal tumor of the stomach with rhabdoid phenotype: immunohistochemical, ultrastructural, and immunoelectron microscopic evaluation.

    A variety of neoplasms with rhabdoid differentiation have been reported in many sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of the stomach that exhibited prominent rhabdoid features. Immunohistochemically, the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells revealed paranuclear whorls of intermediate filaments, which were immunoreactive for vimentin by both light microscopic immunohistochemical and protein A gold immunoelectron microscopic techniques. On H&E light microscopic examination alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal, or other neoplasms that may show rhabdoid features. One report of GIST with a rhabdoid histologic phenotype has been described. This is the second known report of such a case with immunophenotypic and ultrastructural evaluation, and the first case with immunoelectron microscopic examination. ( info)

7/169. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: case report.

    BACKGROUND: The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. CASE PRESENTATION: A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial.The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. CONCLUSION: This case illustrates that the brain can be a sanctuary site to treatment of GISTs with imatinib. Maintaining dosing of imatinib in the face of isolated sites of disease progression is also important, as other metastatic sites may still be sensitive. ( info)

8/169. Malignant gastrointestinal stromal tumor of the gallbladder.

    gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of an extremely rare group of tumors. We have encountered a patient with a malignant GIST of the gallbladder and presented it with a review of some articles. A 72-yr-old woman initially presented with right upper quadrant abdominal pain, fever and chills. Emergency cholecystectomy was performed under the impression of gallbladder empyema. Liver metastasis was found at 7 months postoperatively and the patient expired 9 months after the surgery. At the time of cholecystectomy, the gallbladder showed a necrotic serosal surface with an irregular thickened wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the neck and upper body of the gallbladder. Microscopic findings revealed frequent mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic, pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern of short fascicles infiltrated the entire layer of the gallbladder. The tumor cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the c-kit proto-oncogene were not found in this case. These findings were sufficient to provide enough clinical, histopathological and immunohistochemical evidence in diagnosing our case as a malignant GIST. ( info)

9/169. gastrointestinal stromal tumors arising from the stomach: a report of three children.

    BACKGROUND: gastrointestinal stromal tumors (GIST) are a unique subset of intestinal mesenchymal tumors that behave in an aggressive fashion. They have been commonly described in adults but have been rarely observed in children. methods: The authors review the presentation, diagnostic workup, operative records, pathologic specimens, and outcomes of 3 children with GISTs that originated from the stomach. RESULTS: All 3 children presented after upper gastrointestinal bleeding from the gastric tumor. The first was a 10-year-old girl who underwent partial gastrectomy but had recurrence 8 years later requiring a second resection. She subsequently had a hepatic metastasis 8 years later requiring a third resection. The second patient was a 9-year-old girl who had an antrectomy with a Bilroth I reconstruction and was noted to have a synchronous liver metastasis that was also resected. Despite Imatinib Mesylate, she had further hepatic metastases. The third child was a 4-year-old boy who recently underwent a partial gastrectomy and has no signs of metastatic disease at this time. CONCLUSIONS: GISTs are unusual tumors that have been rarely described in children. When they arise in the stomach, they often present after upper gastrointestinal bleeding. diagnosis can be made by endoscopy and biopsy. GISTs require resection and close observation for hepatic metastases. Current studies are ongoing for the potential role of Imatinib Mesylate for GISTs in children. ( info)

10/169. Gastrointestinal stromal tumour of the duodenum in a 7-year-old boy.

    We report a 7-year-old boy presenting with an acute upper gastrointestinal (GI) haemorrhage subsequently diagnosed to have a very rare duodenal gastrointestinal stromal tumour (GIST). endoscopy, pertechnetate and red cell scans were negative. Abdominal US detected a 17-mm mass lesion of the third part of the duodenum. This was confirmed on CT and shown to be hypervascular on selective angiography. At laparotomy, a 20-mm submucosal duodenal lesion was found associated with mucosal ulceration. Immunohistochemical analysis revealed it to be positive for CD117 (c-KIT protein) consistent with a GIST. We emphasize the importance of a thorough abdominal US examination in children with GI haemorrhage and the consideration of GIST in the diagnosis after the common causes have been excluded. ( info)
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