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.
"They compared primary tumor tissues of leiomyosarcoma with those of GIST. These two soft tissue sarcomas are the most common mesenchymal tumors and share remarkably similar phenotypic features although they are molecularly and clinically distinct . It is important to separate leiomyosarcoma from GIST because their treatment and prognosis differ significantly. "
[Show abstract][Hide abstract] ABSTRACT: Soft tissue sarcomas are rare and account for less than 1% of all malignant cancers. Other than development of intensive therapies, the clinical outcome of patients with soft tissue sarcoma remains very poor, particularly when diagnosed at a late stage. Unique mutations have been associated with certain soft tissue sarcomas, but their etiologies remain unknown. The proteome is a functional translation of a genome, which directly regulates the malignant features of tumors. Thus, proteomics is a promising approach for investigating soft tissue sarcomas. Various proteomic approaches and clinical materials have been used to address clinical and biological issues, including biomarker development, molecular target identification, and study of disease mechanisms. Several cancer-associated proteins have been identified using conventional technologies such as 2D-PAGE, mass spectrometry, and array technology. The functional backgrounds of proteins identified were assessed extensively using in vitro experiments, thus supporting expression analysis. These observations demonstrate the applicability of proteomics to soft tissue sarcoma studies. However, the sample size in each study was insufficient to allow conclusive results. Given the low frequency of soft tissue sarcomas, multi-institutional collaborations are required to validate the results of proteomic approaches.
"The most common metastatic sites include the abdominal cavity, liver, and rarely bones and soft tissues. GISTs very rarely, if not, metastasize to the lymph nodes and the skin [9, 43]. In the case reports that we reviewed, abdominal cavity was the most common metastatic site followed by the liver and the pancreas. "
[Show abstract][Hide abstract] 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.
"In FAP, desmoid tumors arise from mutations in the adenomatous polyposis coli (APC) gene, located on chromosome 5q21-22, which encodes a tumor suppressor protein, although its function may be more complex than simply a tumor suppressor . Inactivation of APC leads to nuclear accumulation of β-catenin, causing increased transcription and cell proliferation . Most APC mutations associated with desmoid tumors are found 3′ to codon 1400 [8, 9]. "
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal (GI) mesenchymal tumors other than gastrointestinal stromal tumor (GIST) are rare neoplasms, but they often enter the differential diagnosis of more common GI lesions. Some of these mesenchymal tumors in the GI tract have well understood molecular pathologic aspects, including desmoid tumors, inflammatory myofibroblastic tumor (IMT), clear cell sarcoma (CCS), inflammatory fibroid polyp (IFP), and synovial sarcoma (SS). Molecular pathology is fast becoming a mainstream focus in laboratories because it aids in the precise classification of tumors, may be prognostic, and may help predict response to therapy. The following review is not intended as an exhaustive summary of all mesenchymal tumors that have been reported to involve the GI tract, but instead will highlight the current knowledge of the most important non-GIST GI mesenchymal neoplasms, focusing on those tumors with well-characterized molecular pathology and how the molecular pathologic features impact current diagnostic, therapeutic, and prognostic standards.
Pathology Research International 02/2011; 2011:952569. DOI:10.4061/2011/952569
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