Age-related Epstein-Barr virus (EBV)–associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic Hodgkin lymphoma in elderly patients

Abstract Age-related Epstein-Barr virus–associated B-cell lymphoproliferative disorder (aEBVLPD) is a disease group characterized by EBV-associated large B-cell lymphoma in elderly without predisposing immunodeficiency. In nearly one- third of cases, aEBVLPD occurs as a polymorphous subtype with reactive cell-rich components, bearing a morphologic similarity to classic Hodgkin lymphoma (cHL). The aim of this study was to clarify clinicopathologic differences between the polymorphic subtype of aEBVLPD (n = 34) and EBV+ cHL (n = 108) in patients aged 50 years or older. Results showed that aEBVLPD was more closely associated with aggressive clinical parameters than cHL, with a higher age at onset (71 vs 63 years); lower male predominance (male-female ratio, 1.4 vs 3.3); and a higher rate of involvement of the skin (18% vs 2%), gastrointestinal tract (15% vs 4%), and lung (12% vs 2%). aEBVLPD was histopathologically characterized by a higher ratio of geographic necrosis, greater increase (> 30%) in cytotoxic T cells among background lymphocytes, higher positivity for CD20 and EBNA2, and absence of CD15 expression. As predicted by the clinical profile, aEBVLPD had a significantly poorer prognosis than EBV+ cHL (P < .001). The polymorphous subtype of aEBVLPD constitutes an aggressive group with an immune response distinct from EBV+ cHL, and requires the development of innovative therapeutic strategies.

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Epstein-Barr Virus-Positive Large B-Cell Lymphoma Mimicking Hodgkin Lymphoma in a 28-Year-Old Man

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqw151.016 ◽

2016 ◽

Vol 146 (suppl_1) ◽

Author(s):

Yi Sun ◽

Steve Xie

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Barr Virus ◽

Large B Cell Lymphoma ◽

Epstein Barr ◽

Large B Cell

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Epstein-Barr Virus Positive B-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract

Cancers ◽

10.3390/cancers13153815 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3815

Author(s):

Eri Ishikawa ◽

Akira Satou ◽

Masanao Nakamura ◽

Shigeo Nakamura ◽

Mitsuhiro Fujishiro

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Epstein Barr Virus ◽

B Cell Lymphoma ◽

Biological Behavior ◽

Routine Practice ◽

Gi Tract ◽

Barr Virus ◽

Age Related ◽

Epstein Barr

Epstein-Barr virus positive B-cell lymphoproliferative disorder (EBV+ B-LPD) encompasses a broad clinicopathological spectrum and distinct clinical behavior that relatively favors the gastrointestinal (GI) tract. In this review, we provide an update on the clinicopathological features and biological behavior of EBV-positive mucocutaneous ulcer (EBVMCU) and primary EBV+ diffuse large B-cell lymphoma (DLBCL) of the GI tract. EBVMCU is a newly recognized entity but well known as an indolent and self-limited EBV+ B-LPD occurring in various immunodeficiencies. In contrast, EBV+ DLBCL constitutes the largest group of EBV+ B-LPDs and is regarded as an aggressive neoplasm. These two distinct diseases have historically been distinguished in the reappraisal of age-related EBV-associated B-LPDs but are challenging in routine practice regarding their differential diagnostic and therapeutic approaches. An increasing number of reports indicate that they are epidemiologically prevalent beyond western and eastern countries, but their comprehensive analysis is still limited. We also describe the PD-L1 positivity of tumorous large cells and non-malignant immune cells, which is relevant for the prognostic delineation among patients with primary DLBCL of the GI tract with and without EBV on tumor cells.

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Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck

Journal of Oncology ◽

10.1155/2015/605750 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Kentaro Kikuchi ◽

Toshiyuki Ishige ◽

Fumio Ide ◽

Yumi Ito ◽

Ichiro Saito ◽

...

Keyword(s):

B Cell ◽

Epstein Barr Virus ◽

Somatic Hypermutation ◽

Cytidine Deaminase ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Barr Virus ◽

Age Related ◽

Activation Induced Cytidine Deaminase ◽

Epstein Barr

Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated withc-myctranslocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs.

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Co-Expression of the Epstein-Barr Virus-Encoded Latent Membrane Proteins and the Pathogenesis of Classic Hodgkin Lymphoma

Cancers ◽

10.3390/cancers10090285 ◽

2018 ◽

Vol 10 (9) ◽

pp. 285 ◽

Cited By ~ 4

Author(s):

Katerina Vrzalikova ◽

Maha Ibrahim ◽

Eszter Nagy ◽

Martina Vockerodt ◽

Tracey Perry ◽

...

Keyword(s):

Membrane Proteins ◽

B Cell ◽

Hodgkin Lymphoma ◽

Epstein Barr Virus ◽

Tumour Cells ◽

Nuclear Antigen ◽

Barr Virus ◽

Classic Hodgkin Lymphoma ◽

Epstein Barr ◽

Cellular Transcription

The Epstein-Barr virus (EBV) is present in the tumour cells of a subset of patients with classic Hodgkin lymphoma (cHL), yet the contribution of the virus to the pathogenesis of these tumours remains only poorly understood. The EBV genome in virus-associated cHL expresses a limited subset of genes, restricted to the non-coding Epstein-Barr virus-encoded RNAs (EBERs) and viral miRNA, as well as only three virus proteins; the Epstein-Barr virus nuclear antigen-1 (EBNA1), and the two latent membrane proteins, known as LMP1 and LMP2, the latter of which has two isoforms, LMP2A and LMP2B. LMP1 and LMP2A are of particular interest because they are co-expressed in tumour cells and can activate cellular signalling pathways, driving aberrant cellular transcription in infected B cells to promote lymphomagenesis. This article seeks to bring together the results of recent studies of the latent membrane proteins in different B cell systems, including experiments in animal models as well as a re-analysis of our own transcriptional data. In doing so, we summarise the potentially co-operative and antagonistic effects of the LMPs that are relevant to B cell lymphomagenesis.

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