Distinguishing gastrointestinal stromal tumors from their mimics: An update
ABSTRACT Since the discovery of activating KIT mutations in gastrointestinal stromal tumors (GISTs) in 1998 and the subsequent demonstration that some malignant GISTs respond to targeted therapy with imatinib, it has become increasingly important for pathologists to correctly diagnose GISTs and separate them from their potential mimics in the gastrointestinal tract and abdominal cavity. Some mesenchymal tumors, such as leiomyomas of the muscularis mucosae, are easily distinguished from GIST on the basis of their anatomic location and morphologic appearance. Others, such as gastrointestinal schwannomas, can significantly overlap with GIST in their gross appearance and morphology and require a panel of immunostains for correct diagnosis. This article will review the most common mimics of GISTs: desmoid tumors, smooth muscle tumors (leiomyomas and leiomyosarcomas), gastrointestinal schwannomas, inflammatory fibroid polyps, and solitary fibrous tumors. Pertinent differences between each of these tumors and GIST in terms of gross appearance, histologic features, and immunophenotype will be emphasized. It is important to separate GISTs from these potential mimics because their treatment and prognosis can differ markedly.
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ABSTRACT: Duodenal gastrointestinal tumors represent an extremely rare subset of stromal tumors arising from interstitial cells of Cajal. In the last 30 years the comprehension of the pathophysiology and natural history of this previously misunderstood clinical entity, in association with developments in endoscopy, imaging technology, and immunohistochemistry has resulted in novel diagnostic and treatment approaches. This is a comprehensive review of the current data of the literature on the various aspects of the diagnosis and treatment of these tumors. The duodenum is the less commonly involved site for these tumors in the digestive tract. Endoscopy and computed tomography can usually establish the diagnosis, confirmed by immunohistochemical staining and occasionally molecular genetic analysis. Endoscopic ultrasound with fine needle aspiration has been recently found to be the gold diagnostic standard with high sensitivity and specificity rates, diagnosing GIST in up to 80% of patients. Due to the complex anatomy of the pancreatico-duodenal region optimal therapeutic strategy of duodenal GISTs are challenging. Nevertheless surgical resection with microscopically clear resection margins seems to be the only potentially curative treatment for non-metastatic primary GISTs of the duodenum. Imatinib mesylate plays a key role in the management of GISTs both as neoadjuvant therapy and in patients with recurrent and metastatic disease. Meanwhile, the advances in the comprehension of the pathophysiology and natural history of this previously misunderstood clinical entity as well as the treatment of these tumors may render feasible, in the near future, the advent of newer and more effective treatment options. Copyright © 2015 Elsevier Ltd. All rights reserved.European Journal of Surgical Oncology 04/2015; DOI:10.1016/j.ejso.2015.04.004 · 2.89 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumors are mesenchymal neoplasms with a spectrum of histologic appearances and biologic activity. The morphologic classification of these lesions has evolved over time, and molecular analysis has led to a better understanding of their nature. The histologic differential diagnosis for these lesions is broad and includes many spindle cell lesions of the gastrointestinal tract, including neoplasms of true smooth muscle and neural origin, proliferating fibrous lesions, metastatic neoplasms, and primary sarcomas of vascular and adipose origin. Immunohistochemical studies that include CD117 have become invaluable in the classification of mesenchymal lesions arising in the gastrointestinal tract. Treatment of gastrointestinal stromal tumors has historically been involved surgery, but the use of the chemotherapeutic agent imatinib mesylate for advanced disease has made accurate classification even more important. The molecular features have not only allowed us to understand the pathogenesis of these tumors but also have proven to be associated with response to kinase inhibitors.Archives of pathology & laboratory medicine 01/2010; 134(1):134-41. DOI:10.1043/2008-0083-RSR2.1 · 2.88 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumor (GIST) is a nonepithelial, mesenchymal tumor first described by Mazur and Clark in 1983. Since then, its molecular biology has been studied in great detail. Special interest in the role of tyrosine kinase in its regulation has been the target by different drug research. Mutation in c-kit exons 9, 11, 13, 17 and PDGFRA mutation in exons 12, 14, 18 are responsible for activation of gene signaling system resulting in uncontrolled phosphorylation and tissue growth. However, 5 to 15% of GISTs does not harbor these mutations, which raises additional questions in another alternate signaling pathway mutation yet to be discovered. Diagnosis of GISTs relies heavily on KIT/CD117 immunohistochemical staining, which can detect most GISTs except for a few 3% to 5% that harbors PDGFRA mutation. Newer staining against PKC theta and DOG-1 genes showed promising results but are not readily available. Clinical manifestation of GISTs is broad and highly dependent on tumor size. Surgery still remains the first-line treatment for GISTs. The advancement of molecular biology has revolutionized the availability of newer drugs, Imatinib and Sunitinib. Together with its advancement is the occurrence of Imatinib/Sunitinib drug resistance. With this, newer monoclonal antibody drugs are being developed and are undergoing clinical trials to hopefully improve survival in patients with GISTs.04/2012; 2012:595968. DOI:10.5402/2012/595968