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Respiration; International Review of... 2017This review aims to describe some of the most frequent lymphoproliferative disorders arising from the lung: pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma,... (Review)
Review
This review aims to describe some of the most frequent lymphoproliferative disorders arising from the lung: pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma, lymphomatoid granulomatosis (LG), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and nodular lymphoid hyperplasia (NLH). Primary pulmonary lymphoma is defined as a clonal lymphoproliferative disorder affecting one or both lungs, without extrapulmonary involvement 3 months after diagnosis, and includes pulmonary MALT lymphoma and LG. MALT lymphoma is the most common pulmonary lymphoma. The disease is slow growing, most often asymptomatic, and revealed by chronic alveolar opacity on radiography. The diagnosis should involve minimally invasive techniques, and the prognosis is typically excellent. LG is a rare B-cell lymphoma driven by Epstein-Barr virus infection. The disease may mimic pulmonary vasculitis, often revealed by systemic signs. The diagnosis usually requires surgical lung biopsy. Its evolution is unpredictable, but median survival is poor and chemotherapy is usually proposed. MCD and PEL are both driven by Human herpesvirus 8 infection. Patients with MCD present with fever and lymphadenopathy associated with interstitial lung disease. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without any pleural mass on CT. Specific chemotherapy is urgent for both MCD and PEL. NLH is a benign lymphoproliferative disorder of the lung that is usually asymptomatic and revealed by a single nodular opacity. The prognosis is good, without recurrence after surgical resection.
Topics: Castleman Disease; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 8, Human; Humans; Lung Diseases; Lung Neoplasms; Lymphoma; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Primary Effusion; Lymphomatoid Granulomatosis; Lymphoproliferative Disorders
PubMed: 28609772
DOI: 10.1159/000477740 -
Blood Feb 2022Kaposi sarcoma (KS) herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of KS but is also pathogenetically related to several lymphoproliferative... (Review)
Review
Kaposi sarcoma (KS) herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of KS but is also pathogenetically related to several lymphoproliferative disorders, including primary effusion lymphoma (PEL)/extracavitary (EC) PEL, KSHV-associated multicentric Castleman disease (MCD), KSHV+ diffuse large B-cell lymphoma, and germinotropic lymphoproliferative disorder. These different KSHV-associated diseases may co-occur and may have overlapping features. KSHV, similar to Epstein-Barr virus (EBV), is a lymphotropic gammaherpesvirus that is preferentially present in abnormal lymphoid proliferations occurring in immunecompromised individuals. Notably, both KSHV and EBV can infect and transform the same B cell, which is frequently seen in KSHV+ EBV+ PEL/EC-PEL. The mechanisms by which KSHV leads to lymphoproliferative disorders is thought to be related to the expression of a few transforming viral genes that can affect cellular proliferation and survival. There are critical differences between KSHV-MCD and PEL/EC-PEL, the 2 most common KSHV-associated lymphoid proliferations, including viral associations, patterns of viral gene expression, and cellular differentiation stage reflected by the phenotype and genotype of the infected abnormal B cells. Advances in treatment have improved outcomes, but mortality rates remain high. Our deepening understanding of KSHV biology, clinical features of KSHV-associated diseases, and newer clinical interventions should lead to improved and increasingly targeted therapeutic interventions.
Topics: Epstein-Barr Virus Infections; Hematologic Diseases; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Lymphoproliferative Disorders; Sarcoma, Kaposi
PubMed: 34479367
DOI: 10.1182/blood.2020005470 -
Expert Review of Hematology Mar 2017Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both... (Review)
Review
Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional depth to this complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. The present review focuses on the classification of T-cell lymphomas, Hodgkin lymphomas, and histiocytic and dendritic cell neoplasms, summarizing changes reflected in the 2016 revision to the WHO classification. These changes are critical to hematologists and other clinicians who care for patients with these disorders. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revisions in the WHO classification particularly impact T-cell lymphomas, including a new umbrella category of T-follicular helper cell-derived lymphomas and evolving recognition of indolent T-cell lymphomas and lymphoproliferative disorders.
Topics: Histiocytic Disorders, Malignant; Hodgkin Disease; Humans; Lymphoma; Lymphoma, T-Cell; Neoplasm Grading; Prognosis; World Health Organization
PubMed: 28133975
DOI: 10.1080/17474086.2017.1281122 -
Hematology. American Society of... Dec 2016Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a specific, clonal lymphoproliferative B-cell bone marrow disorder... (Review)
Review
Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a specific, clonal lymphoproliferative B-cell bone marrow disorder results in autoimmune hemolytic anemia. The immune hemolysis is entirely complement-dependent, predominantly mediated by activation of the classical pathway and phagocytosis of erythrocytes opsonized with complement protein C3b. Typical clinical features in CAD have diagnostic and therapeutic implications. Pharmacologic treatment should be offered to patients with symptom-producing anemia or disabling circulatory symptoms. CAD should not be treated with corticosteroids. Based on an individualized approach, rituximab monotherapy or rituximab-fludarabine in combination is recommended as first-line therapy. Rituximab-bendamustine is still an investigational therapy. Although complement-modulating agents are still to be considered experimental in CAD, therapy with the anti-C1s monoclonal antibody TNT009 seems promising.
Topics: Anemia, Hemolytic, Autoimmune; B-Lymphocytes; Bendamustine Hydrochloride; Complement C3b; Humans; Lymphoproliferative Disorders; Rituximab
PubMed: 27913484
DOI: 10.1182/asheducation-2016.1.226 -
Haematologica Jul 2016Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing... (Review)
Review
Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.
Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.
Topics: Disease Management; Epstein-Barr Virus Infections; Hematopoietic Stem Cell Transplantation; Humans; Lymphoproliferative Disorders; Practice Guidelines as Topic; Risk Factors
PubMed: 27365460
DOI: 10.3324/haematol.2016.144428 -
American Journal of Transplantation :... Mar 2010Belatacept, a costimulation blocker, may preserve renal function and improve long-term outcomes versus calcineurin inhibitors in kidney transplantation. This Phase III... (Randomized Controlled Trial)
Randomized Controlled Trial
Belatacept, a costimulation blocker, may preserve renal function and improve long-term outcomes versus calcineurin inhibitors in kidney transplantation. This Phase III study (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) assessed a more intensive (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adults receiving a kidney transplant from living or standard criteria deceased donors. The co-primary endpoints at 12 months were patient/graft survival, a composite renal impairment endpoint (percent with a measured glomerular filtration rate (mGFR) <60 mL/min/1.73 m(2) at Month 12 or a decrease in mGFR > or =10 mL/min/1.73 m(2) Month 3-Month 12) and the incidence of acute rejection. At Month 12, both belatacept regimens had similar patient/graft survival versus cyclosporine (MI: 95%, LI: 97% and cyclosporine: 93%), and were associated with superior renal function as measured by the composite renal impairment endpoint (MI: 55%; LI: 54% and cyclosporine: 78%; p < or = 0.001 MI or LI versus cyclosporine) and by the mGFR (65, 63 and 50 mL/min for MI, LI and cyclosporine; p < or = 0.001 MI or LI versus cyclosporine). Belatacept patients experienced a higher incidence (MI: 22%, LI: 17% and cyclosporine: 7%) and grade of acute rejection episodes. Safety was generally similar between groups, but posttransplant lymphoproliferative disorder was more common in the belatacept groups. Belatacept was associated with superior renal function and similar patient/graft survival versus cyclosporine at 1 year posttransplant, despite a higher rate of early acute rejection.
Topics: Abatacept; Adult; Cyclosporine; Female; Glomerular Filtration Rate; Humans; Immunoconjugates; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphoproliferative Disorders; Male; Middle Aged; Risk Factors; Time Factors
PubMed: 20415897
DOI: 10.1111/j.1600-6143.2009.03005.x -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2017Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate... (Review)
Review
Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate is an anchor drug in the management of rheumatoid arthritis and become commonly used, MTX-LPD cases have increased. Many things has been unclear such as incidence, demographic characters, and risk factors. However, as the researches increased, several interesting topics has been demonstrated like associations with Epsteiin-Barr virus and with cell-mediated immunity. This report reviews newly the latest findings and future challenges on MTX-LPD.
Topics: Age Factors; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Herpesvirus 4, Human; Humans; Immunity, Cellular; Lymphoproliferative Disorders; Male; Methotrexate; Prognosis; Risk Factors
PubMed: 28747604
DOI: 10.2177/jsci.40.174 -
Journal of Hematology & Oncology Sep 2023Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from... (Observational Study)
Observational Study
Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring.
Topics: Humans; DNA Copy Number Variations; Epigenesis, Genetic; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoproliferative Disorders; Cell-Free Nucleic Acids; Genomics
PubMed: 37705050
DOI: 10.1186/s13045-023-01500-x -
Archives of Pathology & Laboratory... Sep 2019Pulmonary nodular lymphoid hyperplasia is an uncommon reactive lymphoproliferative disorder that presents as an asymptomatic lung mass. The histopathologic diagnosis of... (Review)
Review
Pulmonary nodular lymphoid hyperplasia is an uncommon reactive lymphoproliferative disorder that presents as an asymptomatic lung mass. The histopathologic diagnosis of pulmonary nodular lymphoid hyperplasia may be challenging because of its morphologic overlap with other diseases, such as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and immunoglobulin G4-related sclerosing disease. Despite the similarities, there are distinctive morphologic and phenotypic features that allow for the correct diagnosis in the majority of cases. This review aims to discuss the clinicopathologic features of pulmonary nodular lymphoid hyperplasia and contrast them with its histopathologic mimickers.
Topics: Adult; Aged; Aged, 80 and over; Chromosome Aberrations; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunoglobulin G4-Related Disease; Lung; Lymphoma, B-Cell, Marginal Zone; Lymphoproliferative Disorders; Male; Middle Aged; Solitary Pulmonary Nodule
PubMed: 30720334
DOI: 10.5858/arpa.2018-0188-RS -
The Journal of Dermatology Sep 2021Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare cutaneous disease associated with Epstein-Barr virus infection. We retrospectively analyzed the...
Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare cutaneous disease associated with Epstein-Barr virus infection. We retrospectively analyzed the clinical presentation, histopathological characteristics, and prognostic study of HV-LPD in 24 Chinese patients. All patients presented with recurrent papulovesicular and necrotic eruptions on the face, neck, and extremities, with 11 showing systemic symptoms. Twenty patients were diagnosed with HV-LPD in childhood (age < 18 years) and four in adulthood (age ≥ 18 years). The median age at diagnosis was 8.5 years old (range, 2-50). Histopathology revealed variably dense lymphocyte infiltration throughout the dermis. All cases were strongly positive for CD3 and Epstein-Barr encoding region based on in situ hybridization. Of 18 cases with a T-cell phenotype, 15 harbored monoclonal rearrangements in T-cell receptor (TCR) genes. Four cases with a natural killer cell phenotype carried polyclonal rearrangements in TCR genes. Among 24 patients, eight (33.3%) received chemotherapy, two (8.3%) allogeneic hematopoietic stem cell transplantation, and both are currently alive without disease. The median follow-up period was 24 months (range, 7-120) and 23 patients were available: 15 (62.5%) were alive, and eight (33.3%) had died. Fourteen cases had a relapse of disease and three developed lymphoma within 24 months of diagnosis. The mean survival time of childhood-onset patients was longer than that of adult-onset patients (36.4 vs. 20.8 months). In summary, the wide clinical course and representative presentation of cases in our center reflect the pedigree characteristics of HV-LPD. Allogeneic hematopoietic stem cell transplantation should be a preferred choice for relapse and refractory patients due to the poor effect of chemotherapy. Adult-onset and high serum EBV DNA loads may indicate an increased risk of aggressive disease in patients with HV-LPD.
Topics: Adolescent; Adult; Child; China; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Hydroa Vacciniforme; Lymphoma; Lymphoproliferative Disorders; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies
PubMed: 33982815
DOI: 10.1111/1346-8138.15944