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

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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A Case of Methotrexate-associated Lymphoproliferative Disorder Developed as Diffuse Large B Cell Lymphoma on the Lower Leg with Reactivated Epstein-Barr Virus

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.80.214 ◽

2018 ◽

Vol 80 (3) ◽

pp. 214-218 ◽

Cited By ~ 1

Author(s):

Naoya MURAYAMA ◽

Yuta KOIKE ◽

Noriko TASAKI ◽

Yutaka KUWATSUKA ◽

Saori TOMIMURA ◽

...

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lower Leg ◽

Barr Virus ◽

Large B Cell Lymphoma ◽

Epstein Barr ◽

Large B Cell

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Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma arising in patient with a history of EBV-positive mucocutaneous ulcer and EBV-positive nodal polymorphous B-lymphoproliferative disorder

Pathology International ◽

10.1111/pin.12738 ◽

2018 ◽

Vol 69 (1) ◽

pp. 37-41 ◽

Cited By ~ 6

Author(s):

Teerada Daroontum ◽

Kei Kohno ◽

Yoko Inaguma ◽

Akinao Okamoto ◽

Masataka Okamoto ◽

...

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Barr Virus ◽

Large B Cell Lymphoma ◽

History Of ◽

Epstein Barr ◽

Large B Cell

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The potential usefulness of sputum cytology in the conclusive diagnosis of methotrexate-associated lymphoproliferative disorders: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x19836017 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1983601 ◽

Cited By ~ 1

Author(s):

Seiya Mizuguchi ◽

Kenichi Mizutani ◽

Manabu Yamashita ◽

Hiroshi Minato ◽

Sohsuke Yamada

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Epstein Barr Virus ◽

B Cell Lymphoma ◽

Lymphoid Cells ◽

Sputum Cytology ◽

Barr Virus ◽

Large B Cell Lymphoma ◽

Epstein Barr ◽

Conclusive Diagnosis

Background: Methotrexate has been used as an anchor drug for the treatment of rheumatoid arthritis and is considered to be a cause of methotrexate-associated lymphoproliferative disorder. Spontaneous regression can occur after withdrawal of methotrexate and may be associated with Epstein–Barr virus positivity and non-diffuse large B cell lymphoma histological type. Methotrexate-associated lymphoproliferative disorders are often diagnosed pathologically by lung biopsy. To the best of our knowledge, there have been no studies on the cytological diagnosis of methotrexate-associated lymphoproliferative disorder using sputum smears. Case: A 70-year-old man, who was diagnosed with rheumatoid arthritis 13 years previously and who had been treated with methotrexate, presented shortness of breath and productive cough. Methotrexate-associated lymphoproliferative disorder was suspected as the sputum cytology showed many atypical lymphoid cells with hyperchromatic enlarged nuclei, foamy cytoplasm and distinct nucleoli. Chest computed tomography revealed multiple nodular shadows with interstitial pneumonia in the bilateral lower lung field. A lung biopsy specimen contained atypical lymphoid cells that were immunohistochemically positive for CD20 and MUM-1, and weakly positive for bcl-6, but negative for CD3 and CD10. There were no Epstein–Barr virus-infectious lymphoid cells by ISH-EBER. He was finally diagnosed with methotrexate-associated lymphoproliferative disorder (non-germinal center B-cell-like diffuse large B cell lymphoma histological type). Most of the nodules disappeared spontaneously following the withdrawal of methotrexate. Discussion and conclusion: A cytologically conclusive diagnosis of methotrexate-associated lymphoproliferative disorder may be reached using sputum smears and clinical information.

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

Blood ◽

10.1182/blood-2008-06-164806 ◽

2009 ◽

Vol 113 (12) ◽

pp. 2629-2636 ◽

Cited By ~ 113

Author(s):

Naoko Asano ◽

Kazuhito Yamamoto ◽

Jun-Ichi Tamaru ◽

Takashi Oyama ◽

Fumihiro Ishida ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Epstein Barr Virus ◽

Age At Onset ◽

B Cell Lymphoma ◽

Female Ratio ◽

Barr Virus ◽

Age Related ◽

Classic Hodgkin Lymphoma ◽

Epstein Barr

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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A case of age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorder which presented with encephalitis-like images

Rinsho Shinkeigaku ◽

10.5692/clinicalneurol.51.207 ◽

2011 ◽

Vol 51 (3) ◽

pp. 207-210

Author(s):

Yoshikatsu Noda ◽

Yoshihisa Ohtsuka ◽

Naoko Yasui ◽

Kenji Sekiguchi ◽

Aya Kawakami ◽

...

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Epstein Barr Virus ◽

Barr Virus ◽

Age Related ◽

Epstein Barr

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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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