Association between Epstein-Barr virus and Hodgkin's lymphoma in Belgium: A pathological and virological study

Epstein–Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV. Methods such as the heterophile antibody test, immunofluorescence assays, enzyme immunoassays, Western blot, and polymerase chain reaction (PCR) are also employed in the detection of EBV in different types of samples. The determination of EBV viral load using PCR, however, is gaining more prominence in the diagnosis of EBV-associated diseases. Given the challenge of false positive/negative results that are sometimes experienced during the detection of EBV, variability in results from different laboratories, and the impact of factors such as sample type and the immunological status of patients from whom samples are collected, the need to critically examine these present methods is invaluable. This review thus presents current advances in the detection of EBV, detailing the advantages and disadvantages of the various techniques. In addition, fundamental virological concepts are highlighted to enhance the greater understanding, the proper application, and the interpretation of EBV tests.

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Epstein-Barr Virus–Negative Hodgkin's Lymphoma After Mycosis Fungoides: Molecular Evidence for Distinct Clonal Origin

Modern Pathology ◽

10.1038/modpathol.3880262 ◽

2001 ◽

Vol 14 (2) ◽

pp. 91-97 ◽

Cited By ~ 15

Author(s):

Marcus Kremer ◽

Michael Sandherr ◽

Birgit Geist ◽

Antonello D Cabras ◽

Heinz Höfler ◽

...

Keyword(s):

Mycosis Fungoides ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Molecular Evidence ◽

Barr Virus ◽

Clonal Origin ◽

Epstein Barr

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Positive Correlation between Epstein-Barr Virus Viral Load and Anti-Viral Capsid Immunoglobulin G Titers Determined for Hodgkin's Lymphoma Patients and Their Relatives

Journal of Clinical Microbiology ◽

10.1128/jcm.44.1.47-50.2006 ◽

2006 ◽

Vol 44 (1) ◽

pp. 47-50 ◽

Cited By ~ 22

Author(s):

C. Besson ◽

C. Amiel ◽

C. Le-Pendeven ◽

P. Brice ◽

C. Ferme ◽

...

Keyword(s):

Viral Load ◽

Immunoglobulin G ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Viral Capsid ◽

Positive Correlation ◽

Barr Virus ◽

Epstein Barr

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Arginine Methyltransferases Are Regulated by Epstein-Barr Virus in B Cells and Are Differentially Expressed in Hodgkin’s Lymphoma

Pathogens ◽

10.3390/pathogens1010052 ◽

2012 ◽

Vol 1 (1) ◽

pp. 52-64 ◽

Cited By ~ 6

Author(s):

Sarah Leonard ◽

Naheema Gordon ◽

Nikki Smith ◽

Martin Rowe ◽

Paul G. Murray ◽

...

Keyword(s):

B Cells ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Differentially Expressed ◽

Hodgkin's Lymphoma ◽

Barr Virus ◽

Epstein Barr

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Latent Epstein-Barr Virus Infection of Tumor Cells in Classical Hodgkin's Lymphoma Predicts Adverse Outcome in Older Adult Patients

Journal of Clinical Oncology ◽

10.1200/jco.2008.20.5138 ◽

2009 ◽

Vol 27 (23) ◽

pp. 3815-3821 ◽

Cited By ~ 58

Author(s):

Arjan Diepstra ◽

Gustaaf W. van Imhoff ◽

Michael Schaapveld ◽

Henrike Karim-Kos ◽

Anke van den Berg ◽

...

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Older Adult ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Adult Patients ◽

Hodgkin's Lymphoma ◽

Barr Virus ◽

Epstein Barr ◽

The Impact

Purpose In classical Hodgkin's lymphoma (cHL), the impact of tumor cell Epstein-Barr virus (EBV) status on clinical outcome is controversial. Patients and Methods We assessed failure-free survival (FFS) and relative survival (RS) in 412 patients with cHL and age-defined subgroups in a population-based study in the northern Netherlands. Tumor cell EBV status was positive in 34%, and the median follow-up time was 7.1 years. Patients' median age at diagnosis was 35 years (range, 7 to 91 years), and 63% had Ann Arbor stage I or II, 24% had stage III, and 12% had stage IV disease. Results EBV status influenced 5-year FFS and RS only in patients from the age group 50 to 74 years. Five-year FFS was 60% in patients with EBV-positive versus 85% in EBV-negative tumors (P = .01). Five-year RS was 69% in patients with EBV-positive versus 82% in EBV-negative tumors (P = .03). After adjusting for histology, HLA class II expression by tumor cells, stage, presence of extranodal localizations and treatment, and the effect of positive EBV tumor status remained significant in FFS multivariate analysis (hazard ratio, 3.11; 95% CI, 1.28 to 7.53; P = .01). Conclusion This study indicates that treatment failure in older adult patients with cHL is associated with positive tumor cell EBV status.

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The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.3121.3121 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3121-3121

Author(s):

Alexander Claviez ◽

Markus Tiemann ◽

Heike Lueders ◽

Reza Parwaresch ◽

Guenther Schellong ◽

...

Keyword(s):

Overall Survival ◽

Children And Adolescents ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Barr Virus ◽

Ebv Infection ◽

Nodular Sclerosis ◽

Epstein Barr ◽

The Impact

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.

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