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      Comparison Between Presence of Epstein Barr Virus in Nodal and Extra Nodal Diffuse Large B Cell Lymphoma of Head and Neck, an Iranian Experience

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          Abstract

          Background

          Epstein Barr Virus (EBV) is one of the most common viral infections in human population. EBV has a significant role in pathogenesis of Hodgkin's lymphoma, Burkitt's lymphoma and nasopharyngeal carcinoma. The role of EBV in non-Hodgkin’s lymphoma, diffuse large B cell (NHL - DLBL) in the head and neck is controversial.

          Objectives

          The purpose of this study is to find out the difference between the presence of Epstein Barr virus in nodal and extra nodal lymphoma of head and neck.

          Patients and Methods

          A total of 30 cases of DLBL in two separate groups were collected from pathology department. The first group was consisted of 15 patients with DLBL of neck lymph node and the other was consisted of 15 patients with extra nodal DLBL of head and neck mainly in palatine tonsil. Both immune-histo-chemical (IHC) study and polymerase chain reaction (PCR) for detection of late membrane antigen (LMP) were performed on formalin fixed paraffin embedded tissue.

          Results

          All 30 cases were negative for EBV in IHC method. But in PCR method, 10% of patients were positive for LMP gene. There were 2 positive cases in nodal lymphoma and 1 positive case in extra nodal lymphoma group.

          Conclusions

          Compare with PCR method, it seems that IHC is not a sensitive method for detection of EBV. Overall, the finding of EBV in NHL depends on site, type of lymphoma and the detection method.

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          Most cited references34

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          Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin.

          To study the main clinicobiologic features, response, and outcome of patients with diffuse large B-cell lymphoma (DLBCL) according to the primary site, lymph node, or different extranodal organs of the disease. We included 382 patients consecutively diagnosed with DLBCL in a single institution during a 13-year period. Morphology, immunophenotyping, proliferation index, differentiation profile, bcl-2/JH rearrangement, and clinical characteristics were analyzed according to the primary site of the lymphoma. Sites of the disease were: lymph node, 222 cases (58%); Waldeyer's ring (WR), 42 (11%); and extranodal sites, 118 (31%), including GI tract in 45 cases. Primary extranodal cases, particularly GI, showed a bcl-6 expression more frequently than nodal cases. Patients with primary WR or GI lymphomas presented with early-stage disease, no marrow infiltration, normal serum lactate dehydrogenase, and low- to low/intermediate-risk international prognostic index (IPI) more frequently than the remainder. Complete response (CR) rate was 63%, with WR and GI lymphomas having a higher CR rate (85% and 80%, respectively) than the other groups. In the whole series, 5-year overall survival (OS) was 52%. Patients with WR or GI lymphomas showed better OS (5-year OS: 77% and 68%, respectively) than patients with nodal or other extranodal sites. In the multivariate analysis, IPI, bulky disease, and beta2-microglobulin were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. In the present series, the primary site of disease was associated with particular clinicopathologic features and outcome, though the latter largely depended on other factors.
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            Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule.

            Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is an integral membrane protein which has transforming potential and is necessary but not sufficient for B-cell immortalization by EBV. LMP1 molecules aggregate in the plasma membrane and recruit tumour necrosis factor receptor (TNF-R) -associated factors (TRAFs) which are presumably involved in the signalling cascade leading to NF-kappaB activation by LMP1. Comparable activities are mediated by CD40 and other members of the TNF-R family, which implies that LMP1 could function as a receptor. LMP1 lacks extended extracellular domains similar to beta-adrenergic receptors but, in contrast, it also lacks any motifs involved in ligand binding. By using LMP1 mutants which can be oligomerized at will, we show that the function of LMP1 in 293 cells and B cells is solely dependent on oligomerization of its carboxy-terminus. Biochemically, oligomerization is an intrinsic property of the transmembrane domain of wild-type LMP1 and causes a constitutive phenotype which can be conferred to the signalling domains of CD40 or the TNF-2 receptor. In EBV, immortalized B cells cross-linking in conjunction with membrane targeting of the carboxy-terminal signalling domain of LMP1 is sufficient for its biological activities. Thus, LMP1 acts like a constitutively activated receptor whose biological activities are ligand-independent.
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              T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections.

              Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein-Barr virus (EBV) capsid antigen (greater than 10,000) and early antigen (greater than 640) but low titers to the EBV nuclear antigen (less than or equal to 40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95-8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell-receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections.
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                Author and article information

                Journal
                Iran Red Crescent Med J
                Iran Red Crescent Med J
                10.5812/ircmj
                Kowsar
                Iranian Red Crescent Medical Journal
                Kowsar
                2074-1804
                2074-1812
                06 December 2012
                December 2012
                : 14
                : 12
                : 764-770
                Affiliations
                [1 ]Transplant Research Center, Department of Pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, IR Iran
                [2 ]Department of Otolaryngology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, IR Iran
                Author notes
                [* ]Corresponding author: Negar Azarpira, Transplant Research Center, Department of Pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel.: +98-7116474331, Fax: +98-7116474331, E-mail: negarazarpira@ 123456yahoo.com .
                Article
                10.5812/ircmj.1302
                3587864
                23482890
                0cc5a5a9-51f6-435a-846c-41169e6b4cfe
                Copyright © 2012, Iranian Red Crescent Medical Journal

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 August 2011
                : 26 May 2011
                : 26 August 2011
                Categories
                Research Article

                Medicine
                epstein-barr virus infections,lymphoma, non-hodgkin,antigens,head and neck
                Medicine
                epstein-barr virus infections, lymphoma, non-hodgkin, antigens, head and neck

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