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      Bone metastasis of a gastrointestinal stromal tumor: A report of two cases

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          Abstract

          Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal tumors of the GI tract. GISTs usually arise from the stomach, followed by the small intestine, rectum and other locations in the GI tract. The most common metastatic sites are the liver and peritoneum, whereas GISTs rarely metastasize to the bone. Although a small number of previous studies have described bone metastases originating from GISTs, the true prevalence is yet to be elucidated. The present study describes two cases of bone metastasis in patients with GISTs and reviews the relevant literature. Case one was of a 78-year-old male who presented with bone metastasis to the femoral neck five years after the resection of a GIST. The metastasis was completely resected and the patient remains alive nine years after the initial diagnosis of the GIST. Case 2 was of a 41-year-old male who presented with bone metastases to the ribs following resection of GISTs seven and 17 years earlier. The metastases were completely resected and the patient remains alive 17 years after the initial diagnosis. In total, only 10 cases of GISTs with metastases to the bone have been reported in the English literature. The possibility of bone metastases originating from a GIST should be considered during clinical follow-up, particularly in the presence of liver metastases. If feasible, bone metastases should be completely surgically excised.

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          Most cited references18

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          Diagnosis of gastrointestinal stromal tumors: A consensus approach.

          As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time. Copyright 2002, Elsevier Science (USA). All rights reserved.
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            Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis.

            Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. They are defined here as KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasms primary in the GI tract, omentum, and mesentery. GISTs typically present in older individuals and are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). Benign tumors outnumber the malignant ones by a wide margin. Approximately 70% of GISTs are positive for CD34, 20-30% are positive for smooth muscle actin (SMA), 10% are positive for S100 protein and <5% are positive for desmin. The expression of CD34 and SMA is often reciprocal. GISTs commonly have activating mutations in exon 11 (or rarely exon 9 and exon 13) of the KIT gene that encodes a tyrosine kinase receptor for the growth factor named stem cell factor or mast cell growth factor. Ligand-independent activation of KIT appears to be a strong candidate for molecular pathogenesis of GISTs, and it may be a target for future treatment for such tumors. Other genetic changes in GISTs discovered using comparative genomic hybridization include losses in 14q and 22q in both benign and malignant GISTs and occurrence in various gains predominantly in malignant GISTs. GISTs have phenotypic similarities with the interstitial cells of Cajal and, therefore, a histogenetic origin from these cells has been suggested. An alternative possibility, origin of pluripotential stem cells, is also possible; this is supported by the same origin of Cajal cells and smooth muscle and by the common SMA expression in GISTs. GISTs differ clinically and pathogenetically from true leiomyosarcomas (very rare in the GI tract) and leiomyomas. The latter occur in the GI tract, predominantly in the esophagus (intramural tumors) and the colon and rectum (muscularis mucosae tumors). They also differ from schwannomas that are benign S100-positive spindle cell tumors usually presenting in the stomach. GI autonomic nerve tumors (GANTs) are probably a subset of GIST. Other mesenchymal tumors that have to be separated from GISTs include inflammatory myofibroblastic tumors in children, desmoid, and dedifferentiated liposarcoma. Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs.
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              Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review.

              This paper reviews data on the prognosis of gastrointestinal stromal tumors (GISTs). These tumors are specific KIT-expressing and KIT-signaling-driven mesenchymal tumors, many of which have KIT-activating mutations. GISTs occur in the entire gastrointestinal (GI) tract and may also arise from the omentum, mesenteries, and retroperitoneum. They range from small benign tumors to sarcomas at all sites of occurrence. A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Understanding the natural history of GIST before introduction of STI-571 will help assess the impact and position of this new treatment. The frequency of benign versus malignant GISTs varies between sites. Benign GISTs outnumber malignant GISTs in the stomach, whereas malignant GISTs are more common in the intestines. Tumors that have metastasized at presentation have a very poor prognosis. Traditionally, the 3 key prognostic factors have been mitotic rate, tumor size, and site. Tumors that are small ( 5/50 HPFs usually have a malignant behavior. The Ki67 index may help identify tumors with malignant potential, but large site-specific series are not yet available. Genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential. Copyright 2002, Elsevier Science (USA). All rights reserved.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                April 2015
                17 February 2015
                17 February 2015
                : 9
                : 4
                : 1814-1818
                Affiliations
                [1 ]Department of Orthopedic Surgery, University of Toyama, Toyama, Toyama 930-0194, Japan
                [2 ]Department of Orthopedic Surgery, Iiyama Red Cross Hospital, Iiyama, Nagano 389-2295, Japan
                [3 ]Department of Human Science, University of Toyama, Toyama, Toyama 930-0194, Japan
                Author notes
                Correspondence to: Dr Taketoshi Yasuda, Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan, E-mail: yasuda@ 123456med.u-toyama.ac.jp
                Article
                ol-09-04-1814
                10.3892/ol.2015.2976
                4356394
                25789048
                ff22db43-d351-4565-b178-632250c08d39
                Copyright © 2015, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 15 May 2014
                : 22 January 2015
                Categories
                Articles

                Oncology & Radiotherapy
                gastrointestinal stromal tumor,bone metastasis,surgery,imatinib
                Oncology & Radiotherapy
                gastrointestinal stromal tumor, bone metastasis, surgery, imatinib

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