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1/25. Molecular evidence of ocular Epstein-Barr virus infection.

    Ocular manifestations have been attributed to the Epstein-Barr virus (EBV), largely on the basis of seroepidemiologic data. Two patients who developed conjunctival disease as the presenting feature of EBV infection are reported, each confirmed by in situ hybridization of EBV genome in affected tissue biopsy specimens. Recognition of EBV-induced ocular disease as an initial presentation of clinical EBV infection is important to the practitioner because of the ubiquitous nature of this herpesvirus.
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ranking = 1
keywords = herpesvirus
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2/25. Epstein-Barr virus-targeted therapy for AIDS-related primary lymphoma of the central nervous system.

    Epstein-Barr virus (EBV) targeted therapeutic strategies for viral associated malignant diseases have received only perfunctory consideration, first, because latent herpesviruses have been intractable to antiviral chemotherapy and, second, because the role EBV has in maintenance of the malignant cell phenotype has been uncertain. Two patients with EBV related primary central nervous system lymphoma (PCNSL) in the setting of advanced AIDS, were treated with low dose hydroxyurea based on in vitro anti-EBV activity. The responses obtained here suggest the promise of antiviral approaches in select cancers.
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keywords = herpesvirus
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3/25. Simultaneous multiorgan presence of human herpesvirus 8 and restricted lymphotropism of Epstein-Barr virus dna sequences in a human immunodeficiency virus-negative immunodeficient infant.

    Because a profound dysregulation of the immune system occurs in primary immunodeficiencies, viral infections are not uncommon. Human herpesvirus (HHV)-8 dna was detected by polymerase chain reaction (PCR) analysis, Southern blotting, and in situ hybridization (ISH) in peripheral blood mononuclear cells and lymphoid organs (bone marrow, spleen, and lymph nodes) and endothelial and epithelial cells and macrophages from several organs (skin, lung, esophagus, intestine, choroid plexus [but not in brain or cerebellum], heart, striated muscle, liver, and kidney) of a human immunodeficiency virus-negative infant with DiGeorge anomaly who died of disseminated infection. Epstein-Barr virus dna sequences were detected in the spleen and lymph nodes (by PCR and ISH) and in bone marrow (only by ISH) but not in blood or nonlymphoid organs. This report is believed to be the first of multiorgan dissemination of HHV-8 in a primary immunodeficiency.
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ranking = 5
keywords = herpesvirus
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4/25. Monitoring four herpesviruses in unrelated cord blood transplantation.

    Cord blood transplantation, which has lower risk of graft-versus-host disease than bone marrow transplantation, might have higher risk of infections. A system to quantify four herpesviruses, CMV, human herpesvirus 6 (HHV6), EBV, varicella-zoster virus using the real-time PCR assay was established and applied for prospective viral load monitoring in three recipients undergoing cord blood transplantation. CMV and HHV6 were detected in peripheral blood from all three recipients, while EBV was detected in two. Varicella-zoster virus was not detected at all. At the peak of HHV6 or CMV, each patient showed virus-related symptoms. During the pre-transplant period, CMV dna was detected in two recipients who later developed CMV-related diseases. These observations indicate that our system is not only useful for managing herpesviruses infections in transplant recipients, but also a powerful method for clarifying the relationships between the viral load and clinical symptoms.
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ranking = 7
keywords = herpesvirus
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5/25. Pleural posttransplantation lymphoproliferative disorder following liver transplantation.

    A case of posttransplantation lymphoproliferative disorder (PTLD) involving the pleura is reported. The patient was a 57-year-old man who underwent liver transplantation 2 years prior to the development of PTLD. The PTLD was pleural-based and was first detected by radiologic studies as a pleural effusion. Transbronchial biopsy and cytologic examination of 2 pleural fluid specimens were nondiagnostic. Subsequent open-wedge biopsy revealed a monomorphic PTLD, composed of large immunoblasts with plasmacytoid differentiation. Immunohistochemical studies demonstrated B-cell lineage with expression of monotypic cytoplasmic immunoglobulin kappa light chain and CD79a, and absence of T-cell antigens. Immunohistochemical and in situ hybridization studies demonstrated Epstein-Barr virus protein and rna, respectively. No evidence of human herpesvirus 8 dna was detected by polymerase chain reaction. We report this case because pleural-based PTLD is rare. The diagnosis of this entity is made more difficult by the fact that PTLD is often underrepresented in pleural fluid cytology samples.
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ranking = 1
keywords = herpesvirus
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6/25. AIDS-related body cavity-based lymphoma. A case report.

    BACKGROUND: Body cavity-based lymphomas are rare malignancies in human immunodeficiency virus (hiv)-infected patients, but because of their unusual clinical, morphologic and immunophenotypic features, they are recognized as a distinct subgroup of lymphomas connected to human herpesvirus 8 (HHV-8) infection. CASE: A 39-year-old, hiv-positive, homosexual man was admitted to the hospital because of a left-sided pleural effusion that contained malignant lymphoid cells. He responded partially to a low-dose cyclophosphamide/doxorubycin/vincristine/prednisone regimen and died five months after the diagnosis of lymphoma. On cytology, the sediments contained exclusively large, round, neoplastic, lymphoid cells with abundant basophilic cytoplasm and large, round nuclei with prominent nucleoli. Many cells had immunoblastic features, and some had plasmocytoid differentiation. Mitotic figures were numerous. On flow cytometry, the homogeneous population of large cells expressed CD45, CD38, HLA-DR and CD7 positivity. Other specific T-, B- and NK-cell markers tested negative. polymerase chain reaction demonstrated Epstein-Barr virus (EBV) and HHV-8 in the malignant effusion. CONCLUSION: Primary effusion from lymphoma with molecular evidence of HHV-8 and EBV coinfection represents a distinct clinical and morphologic entity in AIDS patients. However, immunophenotypic markers of malignant clones can be diverse in different cases.
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ranking = 1
keywords = herpesvirus
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7/25. Epstein-Barr virus myeloradiculitis and encephalomyeloradiculitis.

    We provide a comprehensive clinical, radiological and virological analysis of four patients with Epstein-Barr virus (EBV) infection of the nervous system. One patient developed acute myeloradiculitis, one had acute encephalomyeloradiculitis, one had acute meningoencephalomyeloradiculitis and one had a subacute meningomyeloradiculitis. The ability of EBV to affect multiple parts of the entire neuraxis from meninges and brain to the spinal cord and peripheral nerves was evidenced by combinations of stiff neck and mental status changes, as well as patterns of weakness and sensory loss due to transverse myelitis or peripheral nerve disease. The CSF of all four patients contained a pleocytosis, predominantly mononuclear with elevated levels of protein, but a normal glucose level. In the two patients with acute myeloradiculitis and subacute meningomyeloradiculitis, the MRI revealed an increased signal in the spinal cord and lumbosacral roots, but in the two patients with acute encephalomyeloradiculitis and acute meningoencephalomyeloradiculitis, the brain and spinal cord MRIs were normal. In all four patients, EBV dna, but not cytomegalovirus (CMV), herpes simplex virus (HSV) or varicella-zoster virus (VZV) dna, was found in the CSF. The antibody pattern in serum was consistent with recent infection, and both EBV immunoglobulin (Ig) M and IgG antibodies, but not antibodies to HSV, VZV or CMV, were found in the CSF. Finally, there were reduced serum/CSF ratios of antibody to EBV, but not to total IgG or albumin, consistent with intrathecal antibody synthesis. None of the four patients died and none had brain swelling or focal changes according to brain MRI. Residual neurological deficits were evident. The two patients with acute myeloradiculitis and acute meningomyeloradiculitis had residual lower extremity weakness, and one of these patients later developed optic neuritis. The patient with acute encephalomyeloradiculitis had a moderate flaccid paraparesis, and the patient with subacute meningomyeloradiculitis was left with sensory loss in the feet. Compared with neurological disease caused by other herpes viruses, the clinical features of acute EBV myeloradiculitis, encephalomyeloradiculitis, encephalomyeloradiculitis and subacute meningomyeloradiculitis are distinctive. Of the eight human herpesviruses, EBV and VZV produce the most protean neurological syndromes. The mechanism by which EBV produces neurological disease is unknown. More correlative pathological, virological and immunological studies are needed in EBV-associated neurological disease.
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ranking = 1
keywords = herpesvirus
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8/25. HHV-8- and EBV-associated nonepidermotrophic large B-cell lymphoma presenting as a foot rash in a man with AIDS.

    Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is frequently identified in tumor tissue obtained from human immunodeficiency virus (hiv)-infected patients with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), or multicentric Castleman's disease. The association between HHV-8 and acquired immunodeficiency syndrome (AIDS)-associated solid lymphomas is less clear. Herein, I describe the case of a man with a CD4 count of 30 cells/microL, and hiv viral load of 90,000 copies/mL, multi-drug resistant hiv infection, and limited stage KS. biopsy of a progressive dorsal foot rash revealed a dense, deep, lymphoid infiltrate that extended into papillary dermis but without epidermotrophism. microscopy showed a homogeneous population of anaplastic large B cells that stained positive for CD20 (L26), CD30, and lambda light chain. in situ hybridization of tumor tissue identified Epstein-Barr virus (EBV)-encoded rna, and polymerase chain reaction amplification yielded HHV-8-specific gene products. Staging studies did not reveal lymphoma elsewhere, and the patient began chemotherapy, but died from septic complications. autopsy was notable only for the presence of a consolidative pneumonia. Although extranodal presentations are common in the setting of immunodeficiency, reports of AIDS-associated lymphoma presenting as a nonepidermotrophic foot lesion are rare. Such a presentation serves to broaden the differential of skin and foot lesions in the setting of hiv infection. More importantly, this case provides further support that HHV-8 can be associated with solid lymphomas that have an anaplastic large cell morphology.
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ranking = 2
keywords = herpesvirus
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9/25. Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient with acquired immunodeficiency syndrome.

    Tumours of smooth muscle origin, either solitary or multiple, are occasionally found in immunocompromised patients, particularly in children with acquired immunodeficiency syndrome (AIDS). Most of the reported AIDS-associated leiomyomatous neoplasms have been found in the visceral organs, and the tumour cells all possessed the Epstein-Barr virus (EBV) genome. Here we present a 32-year-old-man with AIDS who developed three skin nodules on his lower left extremity. No other tumorous lesions were found using computed tomography scans. Two of the three nodules were resected for pathological examination. Histologically, both tumours were well circumscribed and located in the subcutis. The tumours were composed of interlacing fascicles of spindle-shaped cells with prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or necrosis was seen. Immunohistochemically, the tumour cells were reactive to smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV-encoded small RNAs were also demonstrated in the nucleus of the tumour cells by in situ hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)-1 was found in the tumour cells. No human herpesvirus (HHV)-8 genome was detected in the lesion using polymerase chain reaction analysis. The results of this study indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm that must be considered in patients with human immunodeficiency virus infection who develop skin nodules. The role of EBV in the pathogenesis of this unique neoplasm is still unknown.
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ranking = 1
keywords = herpesvirus
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10/25. Epstein-Barr virus and human herpesvirus 8 coinfection and concomitant extranodal nasal-type NK/T cell lymphoma and Castleman disease: case report.

    We describe a 36-year-old man uninfected with human immunodeficiency virus who had confirmed concurrent infection with Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) and their respective lymphoproliferative manifestations, nasal-type NK/T cell lymphoma and Castleman disease. antibodies to HHV-8 and EBV dna were found in plasma and peripheral blood mononuclear cells. An EBV-positive nasal-type NK/T cell lymphoma infiltrated the splenic red pulp, whereas the white pulp contained HHV-8-positive plasmablasts, as found in Castleman disease.
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ranking = 5
keywords = herpesvirus
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