Epstein-Barr Virus-related Lymphoproliferative Disorder Research Articles

Epstein-Barr virus-related lymphoproliferative disorders of the skin

Epstein Barr Virus (EBV) is associated both solid (nasopharyngeal carcinoma, non-nasopharyngeal lymphoepithelioma- like carcinoma, gastric carcinoma, leiomyosarcoma) and hematolymphoid malignancies, some of the latter, however, spanning over a spectrum ranging from reactive and self-limiting to severe and life-threatening conditions. This review will focus on the disorder most commonly involving the skin, namely: EBVpositive mucocutaneous ulcer; lymphomatoid granulomatosis; EBV-positive diffuse large B cell lymphoma; plasmablastic lymphoma; post-transplant lymphoproliferative disorder; extranodal NK/T cell lymphoma, nasal type; angoimmunoblastic T cell lymphoma; severe mosquito bite allergy; hydroa vacciniformelike lymphoproliferative disorder. Given the uncommon occurrence of all these infiltrates in the skin, multidisciplinary approach, as well as referral to tertiary care centers are always advisable.

Post-transplant Epstein–Barr Virus-Related Lymphoproliferative Disorder: A Case Report and Review of Literature

AbstractPost transplant lympho-proliferative disorders (PTLD) are a serious complications of solid organ transplantation. Solid organ recipients have an increased risk of cancers related to immunosuppression and the Epstein-Barr virus (EBV)-in particular lymphomas and majority of PTLD are of B-cell origin. The occurrence of PTLD in solid organ recipients can have varied clinical presentation and histopathological features. Although lymphoproliferative disorders were initially reported to be rare complication of transplantation, observations in past decade shown that they are common and are associated with poor outcomes. We report the case of a patient with deceased donor liver transplantation for Budd-chiari syndrome, who presented, four years after liver transplantation, with an EBV-associated Burkitt lymphoma with gastrointestinal and extensive skeletal metastasis recovered completely after adjustment of immunosuppressive treatment and chemo-immunotherapy. Our suggestion is that patients with the risk factors like T-cell depleting agents or increasing immunosuppressive therapy must be closely monitored with quantitative EBV PCR. Improvements in immunosuppressive strategies for transplantation and advances in treatment resulted in improved outcomes and long term survival for patients with PTLD.

Epstein–Barr Virus: A Biological Overview and Clinicopathological Changes of Two Epstein–Barr Virus-Related Lymphoproliferative Disorders in a World Health Organization (WHO) 2017 Report

Epstein–Barr virus (EBV) is one of the most important viral causes for the development of tumours. The global geographical epidemiology of EBV shows prevalence differences between rich and poor countries across the world, and the impact on health suggests EBV should be an important target of research worldwide. This article will discuss the biology of the virus with an emphasis on its latency types, vital to understanding the possibilities of viral detection. The main objective is to discuss two lymphoproliferative diseases that are associated with EBV and appear in the World Health Organization (WHO) 2017 Classification of Tumours of Haematopoietic and Lymphoid Tissues: EBV-positive diffuse large B cell lymphoma and EBV mucocutaneous ulcer. The name of the former was changed to support the better understanding of infection pathology, while the second was recently described and made its debut in the WHO classification. Pathologists must have knowledge on these diseases and how to investigate them, and oncologists and clinical doctors must be informed on the guidelines.

An Autopsy Case of Peripheral T-cell Lymphoma Complicated by Epstein-Barr Virus-related Lymphoproliferative Disorders in the Central Nervous System

An Autopsy Case of Peripheral T-cell Lymphoma Complicated by Epstein-Barr Virus-related Lymphoproliferative Disorders in the Central Nervous System

A double-blind, placebo-controlled, crossover study of magnesium supplementation in patients with XMEN syndrome: preliminary results.

Abstract Introduction X-linked immunodeficiency magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) syndrome is a primary immunodeficiency caused by the loss of expression of the magnesium transporter 1 (MAGT1). This syndrome is associated with CD4 lymphopenia, chronic EBV infection in most patients, and EBV related lympho proliferative disorders. The loss of MAGT1 leads to impaired T cell activation and decreased expression of the activator receptor, NKG2D on natural killer (NK) cells and CD8 T cells, leading to decreased EBV-specific cytolytic function of these cells. Results of previous studies suggest that magnesium supplementation may be a viable therapeutic option for patients with XMEN. Methods Patients ≥6 years of age with XMEN syndrome and persistent EBV viral load of ≥5,000 copies/mL by whole blood PCR are randomized to receive escalating doses of either placebo or oral magnesium L-threonate for 12 weeks. This is followed by crossover treatment for an additional 12 weeks. For patients who experience a 0.5-log decrease in the number of EBV-infected B cells by FISH with oral magnesium as compared to placebo, the study is complete. Patients who do not meet this outcome then undergo a 2-week washout period and proceed to Part II, an open-label, non-randomized evaluation of intravenous magnesium sulfate (MgSO4) followed by oral magnesium L-threonate. Results here we report the preliminary results for the first patient enrolled in the clinical trial, including changes in the number of EBV infected B cells and NKG2D expression with magnesium treatment.

HLA-mismatched haploidentical transplantation using low-dose anti-thymocyte globulin (ATG: thymoglobulin)

ABSTRACTObjectives: To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT).Methods: Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days −4 and −3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate.Results: The median age of the patients was 33 years. Six patients had previous allogeneic HSCT, and HSCT was performed in non-remission for nine patients. All patients but one, who died due to early infection, achieved neutrophil engraftment at a median of 17 days with complete donor-type chimerism. Acute and chronic GVHD were observed in six and five patients, respectively, but no patients died of GVHD-associated complication. No one developed cytomegalovirus disease, but Epstein–Barr virus-related lymphoproliferative disorder was observed in one patient. Long-term survival in remission without immunosuppressive agents are observed in two patients who underwent HSCT in remission, but the majority of patients who underwent HSCT in non-remission experienced disease progression.Conclusion: Haploidentical HSCT could be performed with thymoglobulin at 5 mg/kg, with the balance between GVHD and relapse rate. The dose reduction of thymoglobulin may be considered for advanced hematological malignancy.

Epstein-Barr ウイルスが関与した口腔内メトトレキサート関連リンパ増殖性疾患の4例

Epstein-Barr ウイルスが関与した口腔内メトトレキサート関連リンパ増殖性疾患の4例

Epstein-Barr Virus-Related Lymphoproliferative Disorder Caused by the Use of Antithymocyte Globulin and Cyclosporine for Aplastic Anemia

A 70-year-old woman with aplastic anemia treated by antithymocyte globulin (ATG), cyclosporine and prednisolone visited our hospital complaining of fever and general fatigue for a week. A chest computed tomography (CT) scan showed consolidation in both lungs, and histological analysis of the lung tissue showed Epstein-Barr virus-positive diffuse large B-cell lymphoma. We diagnosed immunodeficiency-associated lymphoproliferative disorder, and consolidation of the lung was reduced after the cessation of cyclosporine. We should consider the possibility of malignant lymphoma when CT scan showed multiple patchy consolidations with random pattern in both lungs as septic pulmonary emboli in patients with immunosuppressive treatment. J Med Cases. 2014;5(5):279-282 doi: http://dx.doi.org/10.14740/jmc1769w

Epstein-Barr Virus-Related Lymphoproliferative Disorder Caused by the Use of Antithymocyte Globulin and Cyclosporine for Aplastic Anemia

A 70-year-old woman with aplastic anemia treated by antithymocyte globulin (ATG), cyclosporine and prednisolone visited our hospital complaining of fever and general fatigue for a week. A chest computed tomography (CT) scan showed consolidation in both lungs, and histological analysis of the lung tissue showed Epstein-Barr virus-positive diffuse large B-cell lymphoma. We diagnosed immunodeficiency-associated lymphoproliferative disorder, and consolidation of the lung was reduced after the cessation of cyclosporine. We should consider the possibility of malignant lymphoma when CT scan showed multiple patchy consolidations with random pattern in both lungs as septic pulmonary emboli in patients with immunosuppressive treatment. J Med Cases. 2014;5(5):279-282 doi: http://dx.doi.org/10.14740/jmc1769w

Epstein-Barr Virus-related Lymphoproliferative Disorder Associated with X-linked Lymphoproliferative Syndrome: A Case Report

Epstein-Barr Virus-related Lymphoproliferative Disorder Associated with X-linked Lymphoproliferative Syndrome: A Case Report

Epstein–Barr virus‐related lymphoproliferative disorder, cytomegalovirus reactivation, and varicella zoster virus encephalitis during treatment of medulloblastoma

The case of a 14-year-old girl who developed Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and Varicella zoster virus encephalitis during treatment for medulloblastoma is described. The patient was diagnosed with a cerebral medulloblastoma and treated with systemic chemotherapy, intrathecal chemotherapy, and radiotherapy. Six months later, she developed persistent low-grade fever, abdominal pain, and vomiting. Several mucosal or ulcerated lesions of the stomach and colon were found on fiberscopy. The infiltrating cells were positive for CD20 and EBER1, and the diagnosis of lymphoproliferative disorder was made. CMV antigen was found in the peripheral lymphocytes at that time. At the same time, it was noted that the patient's language was inappropriate for her age, and a facial and abdominal rash, as well as a right facial palsy, had developed. She was then diagnosed as having VZV encephalitis, because VZV was detected in the CSF. She was treated subsequently with acyclovir and oral steroid, and the VZV encephalitis resolved. The lymphoproliferative disorder improved gradually with rituximab, ganciclovir, and total nutritional support. At the time of the development of the lymphoproliferative disorder and VZV encephalitis, the patient had severe lymphopenia and this may have caused these rare phenomena in a non-transplant setting.

Cutaneous hematologic disorders in children

To determine and list the clinical and pathological features of cutaneous hematologic diseases in childhood. We retrospectively analyzed the data for 51 patients up to 15 years of age, who presented with primary cutaneous hematologic disorders according to the WHO-EORTC classification, at Necker-Enfants Malades Hospital, Paris, France, over a 17-year period. The cases were classified into the following diagnostic categories: CD30+ T-cell lymphoproliferative disorders (24) all consisting of lymphomatoid papulosis (LyP, 24), lymphoblastic lymphoma (LL, 7), acute leukemias (AL, 7), mycosis fungoides (MF, 5), Epstein-Barr virus-related lymphoproliferative disorders (EBV-related LPD, 5), T/NK-cell lymphoma, nasal type (1), γ/δ T-cell lymphoma (1), and panniculitis-like T-cell lymphoma (1). We encountered a majority of LyP. No secondary lymphoma was found in LyP patients with a median follow-up of 8 years. 29% and 80% of LyP and MF patients, respectively, presented with pityriasis lichenoides chronica (PLC) before onset of disease. Owing to a frequently misleading clinicopathological presentation, MF patients were first underdiagnosed. Clinicopathological features of LL and AL were highly stereotypical, leading to the diagnosis being suspected and confirmed more promptly. In the latter patients and in EBV-related LPD patients, skin lesions usually led to the discovery of systemic disease. Distribution of cutaneous hematologic diseases seems to be different in adults and in children aged <15-year old. PLC was strongly correlated with MF and LyP. Physicians must be made aware of the stereotypical clinical presentations of LL and AL to allow prompt diagnosis and treatment.

Epstein–Barr virus-related lymphoproliferative disorder induced by equine anti-thymocyte globulin therapy

Post-transplant lymphoproliferative disorder (PTLD) is generally caused by an uncontrolled B-cell proliferation induced by Epstein-Barr virus (EBV) in the setting of impaired EBV-specific T-cell immunity. PTLD has been described in allogeneic hematopoietic stem cell transplant (HSCT) and rarely in autologous HSCT. Anti-thymocyte globulin (ATG) is being increasingly utilized for acute rejection in organ transplantation, severe autoimmune diseases and aplastic anemia. Mainly, the use of rabbit ATG has been associated with PTLD, which is considered to be more immunosuppressive than equine ATG. The sole administration of equine ATG has rarely been associated with PTLD. Due to the increased use of these potent and novel immunosuppressive agents, it is paramount to be aware of these complications. We present a 55-year-old man with an autologous HSCT who presented with an unusual case of monoclonal plasmacytic PTLD. His lymphoproliferative disorder occurred 3years after his HSCT and 1month after the use of equine ATG administered for severe aplastic anemia. We review current concepts of EBV-PTLD, including risk factors, the potential for preemptive therapy and various management strategies.

Cutaneous Lymphoproliferative Disorder Complicating Infectious Mononucleosis in an Immunosuppressed Patient

Infectious mononucleosis is the syndrome produced by primary infection with Epstein-Barr virus during adolescence or early adulthood. In immunosuppressed individuals, depressed T-cell function allows the Epstein-Barr virus-driven B-cell proliferation to continue unabated, potentially leading to a lymphoproliferative disorder. A 15-year-old girl with a history of ulcerative colitis treated with 6-mercaptopurine and mesalamine presented with the acute onset of a rapidly enlarging, ulcerative nodule on her left lower eyelid 4 weeks following recovery from infectious mononucleosis. The biopsy revealed an Epstein-Barr virus-positive lymphoproliferative disorder. Systemic disease was absent. Following discontinuation of 6-mercaptopurine, the patient was treated with two courses of intravenous cyclophosphamide. The lesion resolved completely and she remains disease free at 14 months following diagnosis. We report a solitary cutaneous lesion of an immunosuppression-related lymphoproliferative disorder (IR-LPD) occurring as a complication of infectious mononucleosis, and review the pathogenesis and reported cases of Epstein-Barr virus-related immunosuppression-related lymphoproliferative disorder arising in the setting of inflammatory bowel disease. It is important for dermatologists and dermatopathologists to be aware of the occurrence of IR-LPD in patients being treated for inflammatory conditions, including inflammatory bowel disease. Given the role of primary infection with Epstein-Barr virus in the development of IR-LPD, consideration may be given to assessing Epstein-Barr virus status prior to initiating immunosuppressive therapy in young patients.

Difficult diagnosis of grade 1 lymphomatoid granulomatosis: a case report

<h3>Purpose</h3> Lymphomatoid granulomatosis (LYG) is a rare multisystem disease involving the lungs, skin, and nervous system.^1,2 Here we present a case of LYG diagnosed on omental biopsy taken at laparotomy suspecting a primary ovarian tumour. <h3>Methods</h3> Pieces of omentum were fixed in 10% neutral-buffered formalin, embedded in paraffin, and cut sections stained in haematoxylin and eosin. Mycobacterial, fungal and gram stains, TB PCR and immunohistochemical studies including EBER for Epstein-Barr virus, PCR for gene rearrangement studies and flow cytometry were performed. <h3>Results</h3> The omental biopsies showed diffuse infiltrate of small lymphocytes, some in an angiocentric pattern, poorly formed granulomas and patchy fat necrosis. The infiltrate consisted predominantly of T-cells with no aberrant staining and a minority (less than 1%) of mildly enlarged EBER positive B-lymphocytes, not readily apparent on H&E sections. No T or B-cell monoclonality was identified. TB PCR and antibody studies for ANA and ANCA were negative. <h3>Discussion</h3> LYG is an Epstein-Barr virus related lymphoproliferative disorder of B-cell lineage.³ Grading of LYG depends on the proportion of EBV-positive B-cells relative to reactive lymphocytic background.^1,4 Grade 1 lesion can be difficult to diagnose as only a few atypical large cells are present, highlighted on immunohistochemistry.^1,5

Epstein-Barr Virus Related Lymphoproliferations After Stem Cell Transplantation

Epstein-Barr virus related lymphoproliferative disorders are a rare but potentially fatal complication of allogeneic stem cell transplantation with an incidence of 1–3% and occurring within 6 months after transplantation. The most relevant risk factors include the use of in vivo T-cell depletion with antithymocyte globulin, HLA disparities between donor and recipient, donor type, splenectomy etc. The higher the numbers of risk factors the higher the risk of developing Epstein-Barr virus related lymphoproliferative disorders. Monitoring EBV viremia after transplantation is of value and it should be applied to high risk patients since it allows pre-emptive therapy initiation at specified threshold values and early treatment. This strategy might reduce mortality which was >80% prior to the implementation of anti-EBV therapy. Treatment of EBV-LPD after allogeneic SCT may consist of anti-B-cell therapy (rituximab), adoptive T-cell immunotherapy or both. Rituximab treatment should be considered the first treatment option, preferably guided by intensive monitoring of EBV DNA while reduction of immunosuppression should be carefully evaluated for the risk of graft versus host disease.

Epstein-Barr virus-related lymphoproliferative disorders

Esptein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that persists in carriers as a lifelong, mostly asymptomatic infection. EBV is associated with a variety of lymphomas and lymphoproliferative disorders. In this review we provide an update of the relevant literature on EBV-associated lymphoproliferative disorders, with particular emphasis on epidemiology, pathogenesis, and novel treatment approaches.

Primary cutaneous Epstein-Barr virus–related lymphoproliferative disorders in 4 immunosuppressed children

Primary cutaneous Epstein-Barr virus-related lymphoproliferative disorders are rare. We describe 4 cases in children: two with acquired immunodeficiencies (HIV infection, heart transplantation) and two with congenital immunodeficiencies (ataxia-telangiectasia and an undetermined disease affecting the T lymphocytes). Two of the lymphoproliferative disorders were T-cell types and two were B-cell types. The two T-cell types were also Epstein-Barr virus positive, which is extremely rare. Three of the patients developed extracutaneous disease with poor outcome, resulting in death.

Posttransplant Epstein-Barr virus related lymphoproliferative disorder with a primary cutaneous presentation

Posttransplant lymphoproliferative disorder is a rare and often difficult diagnosis in patients with only cutaneous symptoms. A stepwise approach to diagnosis and classification can lead to successful treatment. We report a case of an EBV-associated posttransplant lymphoproliferative disorder (PTLD) occurring on the face with a primary cutaneous presentation. The appropriate diagnosis was made only after multiple biopsies and special stains. There was near complete resolution with decreased levels of iatrogenic immunosuppression. The diagnosis of Posttransplant lymphoproliferative disorder can be difficult to establish. A proper workup will aid in making an accelerated diagnosis and choosing appropriate treatment options.

Bone Marrow Transplantation from Alternative Donors in Children Receiving Rabbit ATG for Prophylaxis of Graft-Versus-Host Disease.

Rabbit antithymocyte globulin (ATG) has been used in allogeneic stem cell transplantation to facilitate engraftment as well as prevent graft-versus-host disease (GVHD). ATG can reduce the incidence of acute and chronic GVHD, but it prolongs the period of immunodeficiency and increases the incidence of infectious complications such as Epstein-Barr virus-related lymphoproliferative disorders (EBV-LPD). To evaluate the advantages and disadvantages of incorporating ATG into the preconditioning regimen, we reviewed records of 70 children with malignant (n=16) or non-malignant disease (n=54) who received unmanipulated bone marrow transplant (BMT) from alternative donors at our hospitals. Eleven patients (15.7%) received BMT from an HLA-mismatched related donor and 59 (84.3%) received BMT from an unrelated voluntary donor. The median age was 9 years (range, 0–21 years). The ratio of boys to girls was 2:1. The serological compatibility of HLA was as follows: 6/6 matched (n=43), 5/6 matched (n=21), 4/6 matched (n=5), and 3/6 matched (n=1). Fifty-one patients (72.9%) received a preconditioning regimen including total body irradiation, 15 (21.4%) received busulfan-based regimens, and 4 (5.7%) received other regimens. ATG (2.5mg/kg/day) was administered for 4 days (day -5, -4, -3, and -2) in all patients. For prophylaxis against GVHD, cyclosporine + methotrexate (MTX) was administered to 34 (48.6%) patients and tacrolimus + MTX to 36 (51.4%). Stable engraftment was not achieved in 2 of 70 (2.9%) patients. Both patients were rescued by second transplants from another donor. Acute GVHD (grade 2–4) developed in 13 of 68 (19.1%) evaluable patients and chronic GVHD in 16 of 62 (25.8%) evaluable patients (limited type, 4; extensive type, 12). Six patients (8.8%) suffered from interstitial pneumonitis and 5 patients (7.4%) developed EBV-LPD. Ten patients died of regimen-related toxicities and 3 died due to relapse of malignant disease. The estimate for 5-year survival from BMT was 88.5% for patients with non-malignant disease and 51.1% for patients with malignant disease. Our dose schedule of ATG appeared to be well tolerated and effective at reducing the incidence of acute and chronic GVHD in high-risk recipients.