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      Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Involving the Colon in a Patient With Ulcerative Pancolitis and Polymyositis on Long-Term Methotrexate Therapy

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          Abstract

          The link between immunosuppressive therapy and increased lymphoma risk is well established in patients with solid organ transplantation. Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLBCL) is known to be a complication in patients receiving methotrexate for rheumatoid arthritis, and the risk of lymphoma in inflammatory bowel disease (IBD) has raised concerns regarding the lymphoproliferative potential of immunomodulatory therapy. In this report, we describe a case of EBV-positive DLBCL arising within the colon of a patient affected by ulcerative pancolitis. The patient is a 73-year-old man with a history of IBD and polymyositis on long-term methotrexate therapy. Increasing age and long-term methotrexate therapy may simulate post-transplantation immunosuppression and contribute to lymphoma tumorigenesis in a segment of chronically inflamed colon.

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          Most cited references16

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          EBV-positive diffuse large B-cell lymphoma of the elderly.

          Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008 World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in patients >50 years of age and in whom there is no known immunodeficiency or history of lymphoma. These tumors are more common in Asia but also occur in North America and Europe at a low frequency. These neoplasms exhibit a morphologic continuum, from polymorphous to monomorphous, but morphologic features do not correlate with prognosis as all patients have a clinically aggressive course. Most EBV-positive DLBCL of the elderly patients have an activated B-cell immunophenotype and are characterized by prominent nuclear factor-κB activation. Cytogenetic complexity is usually low. In this review, we comprehensively delineate the data emerging from analyses of EBV latency program, microRNA-mediated EBV viral oncogenesis, functional genomics of EBV and its biology, and differential diagnosis challenge for EBV-positive DLBCL of the elderly. It is hoped that the improved understanding of these tumors will lead to the development of novel therapeutic approaches, enhance the effectiveness of clinical trials, and improve prognosis.
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            Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication.

            Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.
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              Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients.

              Twenty-two Epstein-Barr virus-associated B-cell lymphoproliferative disorders (LPDs) without predisposing immunodeficiencies were evaluated clinically and pathologically. All patients were Japanese and negative for anti-human immunodeficiency virus antibody. They were all more than 60 years old with a median age of 75.5 years. Eighteen (82%) patients showed extranodal involvement. Biopsied specimens contained variable numbers of centroblasts, immunoblasts, and Reed-Sternberg-like giant cells often with necrosis and an angiocentric pattern. The 13 cases showing polymorphous composition and inflammatory background were categorized as polymorphic LPD subtype. The other nine cases contained diffuse proliferative lesions of large lymphoid cells and were categorized as large cell lymphoma subtype. Tumor cells expressed CD20 and/or CD79a, and in situ hybridization showed them to be associated with Epstein-Barr virus. LMP1 was detected in all cases and EBNA2 in seven. Eighteen patients initially received combination chemotherapy, and 12 achieved complete remission. However, six patients were refractory to chemotherapy and four patients with complete remission later relapsed. Eight of the 18 patients who received chemotherapy showed an aggressive disease course within a year after the diagnosis. There was a significant difference in prognosis between the group with polymorphic LPDs and the one with large cell lymphomas (p = 0.003). Although the disease profile of the 22 cases was analogous to that of immunodeficiency-associated B-cell LPDs, none of the patients showed evidence of underlying immunodeficiency-related diseases. These findings suggest that Epstein-Barr virus-associated LPD without immunodeficiency mainly occurs in elderly patients. Further investigations are needed to clarify the pathogenesis of this disease and to determine the optimal treatment strategy.
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                Author and article information

                Journal
                Gastroenterology Res
                Gastroenterology Res
                Elmer Press
                Gastroenterology Research
                Elmer Press
                1918-2805
                1918-2813
                October 2016
                20 September 2016
                : 9
                : 4-5
                : 83-86
                Affiliations
                [a ]Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
                [b ]Division of Hematology & Oncology, College of Medicine, University of Florida, Gainesville, FL, USA
                Author notes
                [c ]Corresponding Author: Xiuli Liu, Department of Anatomic Pathology, Immunology and Laboratory Medicine, University of Florida, PO Box 100275, Gainesville, FL 32610, USA. Email: xiuliliu@ 123456ufl.edu
                Article
                10.14740/gr720e
                5040551
                70ba6254-43f8-4357-a0b2-080cff9edd35
                Copyright 2016, Chang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 September 2016
                Categories
                Case Report

                epstein-barr virus,b-cell lymphoma,colon,ulcerative pancolitis,polymyositis,methotrexate

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