Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 23  |  Issue : 1  |  Page : 6-8

Epstein-Barr virus association with malignant lymphoma subgroups in Zaria, Nigeria


1 Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Pathology, Ohio State University, Columbus, Ohio, USA

Date of Acceptance05-Sep-2013
Date of Web Publication14-Feb-2014

Correspondence Address:
Yawale Iliyasu
Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1116-5898.127096

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  Abstract 

Epstein-Barr virus (EBV) is said to infect more than 90% of humans worldwide with latent infection for life. A recognized carcinogen, EBV is linked to malignant lymphoma (ML) subtypes of Burkitt's lymphoma, plasmablastic lymphoma, diffuse large cell lymphoma and Hodgkin's lymphoma. We report the association of EBV with ML in a segment of our patient population. Paraffin blocks from the archives of Ahmadu Bello University Teaching Hospital Zaria were used to construct tissue microarray. Sections were stained using 30 monoclonal antibodies for common non-Hodgkin's lymphoma/Hodgkin's lymphoma antigen. Chromogenic in situ hybridization for EBV-encoded RNA was done. Fewer associations of ML with EBV (54-5%) were found than reported elsewhere in Africa.

Keywords: Epstein-Barr virus, lymphoma, malignancy, Northern Nigeria


How to cite this article:
Iliyasu Y, Ayers LW, Liman AA, Waziri GD, Shehu SM. Epstein-Barr virus association with malignant lymphoma subgroups in Zaria, Nigeria. Niger J Surg Sci 2013;23:6-8

How to cite this URL:
Iliyasu Y, Ayers LW, Liman AA, Waziri GD, Shehu SM. Epstein-Barr virus association with malignant lymphoma subgroups in Zaria, Nigeria. Niger J Surg Sci [serial online] 2013 [cited 2019 Aug 22];23:6-8. Available from: http://www.njssjournal.org/text.asp?2013/23/1/6/127096


  Introduction Top


Epstein-Barr virus (EBV), a DNA virus belonging to the herpes group, has been incriminated in the etiopathogenesis of several malignant B cell lymphomas especially in the immunocompromised individuals. These include endemic Burkitt lymphoma, Hodgkin's disease (HD) and B cell lymphomas of immunosuppression such as HIV-associated lymphomas, plasmablastic lymphomas and many post-transplant lymphoproliferative disorders. [1]

EBV produces a protein, LMP-1, which activates the NFkB and JAK/STAT signaling pathways. In addition, the EBV-encoded EBNA-2 gene transactivates some host genes such as cyclin D. All these, lead to dysregulation of the normal proliferative and survival signals of latently infected cells thereby immortalizing them. [2] The virus is ubiquitous and is believed to have infected nearly 100% of humans worldwide with established latent infection for life. [3]

The prevalence of malignant lymphoma (ML) subgroups throughout Africa, particularly among persons with HIV/AIDS is not known. The Sub-Saharan Africa lymphoma Consortium (SSALC) and Cancer Specimen Resource (ACSR/NCI) Project seeks to define indigenous Sub-Saharan non-Hodgkin lymphoma (NHL) subtypes using the World Health Organisation Classification of Tumours of the Lymphoid Tissues, 2008.

We report the association of EBV with ML in our patient population.


  Materials and Methods Top


Demographic data from 57 cases seen at the Department of Pathology, Ahmadu Bello University Teaching hospital (ABUTH), Zaria was retrieved from the Surgical Pathology records of the department. Paraffin-embedded tissue blocks from the 55 cases were used to construct a tissue microarray (TMA) and whole tissue sections were stained with hematoxylin and eosin for morphology. Of the 57 cases, 2 were found unsuitable for the construction of TMAs.

TMA sections were stained using 30 monoclonal antibodies for common NHL/HD antigens and Lana-1 for HHV-8 immunohistochemical (IHC); chromogenic in situ hybridization (CISH) for EBV-encoded RNA (EBER), Kappa/lambda light chains (Ventana, Tucson, AZ); and fluorescent in situ hybridization (FISH), c-myc t (8;14) (Abbot/Vysis, Downers' Grove, IL). A prior ethical clearance was sought for and obtained from the ABUTH Ethical Clearance Committee.


  Results Top


Of the 55 cases of malignant lymphomas examined, 28 were male (50.9%) and 27 (49.1%) were female with a male to female ratio of almost 1:1. Thirty two cases (58.2%) were mainly from children and adolescents with a slight female preponderance (53.1%) in this age group [Table 1].
Table 1: Age and sex distribution of malignant lymphoma cases

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The distribution of lesions as per primary anatomic site of disease showed that jaw tumors constitute 32.7% of all cases. These were followed by diseases of the lymph nodes from various sites in the body (25.5%), abdominal tumors (18.2%), with bone marrow involvement seen in 10.9% and the remaining 12.7% from other sites [Table 2].
Table 2: Site distribution of malignant lymphoma cases

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Burkitt's lymphomas were the commonest lymphoma sub-type; and these accounted for 50.9% of all tumors studied. Of these 28 cases of BL, 23 (82.1%) were EBV positive and 7 cases or 17.9% EBV negative [Table 3]. Diffuse large B cell lymphoma constituted the next frequent group with a total of 16 (29.1%) cases. Of these however, 15 (93.8%) were EBV negative and only one case (6.3%) was EBV positive [Figure 1].
Figure 1: EBER-positive diffuse large B cell lymphoma

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Table 3: Diagnostic subgroup with percentage of subgroup with EBV status

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Hodgkin's lymphoma comprised 11 (20%) of the 55 cases surveyed and greater than half of them all; 6 (54.5%) had a positive EBV results [Table 3].


  Discussion Top


Epstein-Barr virus, a member of the gamma subfamily of herpes viruses is present in all human populations, infecting greater than 95% of mankind within the first decade of life. Infections in Africa and other developing areas are characterized by primary exposure in early childhood; perhaps due to certain cultural practices, than in the developed countries. [4],[5] Epstein-Barr virus infection persists asymptomatically during the host's life maintaining a perpetual equilibrium between the immune response and this stealth virus.

Incidentally, EBV was originally discovered because of isolation within a tumor cell; the Burkitt's lymphoma cell and has since been extensively characterized because of ostensive linkage with a spectrum of human diseases including BL, HL, post-transplant and AIDS-related lymphomas, nasopharyngeal carcinoma, and a small subset of other epithelial and mesenchymal neoplasms. [6],[7]

While the oncogenic potentials of EBV still remain hypothetical, the link between this virus and human tumors is undeniable. Firm epidemiological associations and genetic studies with recombinant DNA, EBV has demonstrated its influences on cell proliferation and survival which are traits that may contribute to carcinogenesis or at least increase the potential for genetic transformation events. [8]

The commonest lymphoma type in this study is by far the Burkitt's lymphoma with 28 out of 55 cases [Table 3]. There are three variants of this tumor; endemic, sporadic and immunodeficiency associated types. Epstein-Barr virus has been detected in virtually all cases of the endemic type BL, 15-20% of the sporadic and 30-40% of immunodeficiency-related variant. [9]

EBV is believed to contribute to BL development by increasing the lymphomagenetic potential of a c-myc translocation positive B cell. In this study, 82% of BL cases are EBV positive. This figure is relatively lower to that found in Uganda where 91.2% of their tumors were EBV positive. The relative discrepancy in these figures is probably due to the fact that the immune status of our patients was not determined unlike the Ugandan study where more than 80% of the patients were HIV positive. In addition, our sample size was relatively lower to theirs. [10]

The link between EBV and Hodgkin's lymphoma had long been postulated on epidemiologic grounds; the key original findings were the detection of monoclonal viral genomes in some tumor biopsies via southern blotting, terminal repeat analysis and in situ hybridization. [11] The association of HL with EBV in this survey was found to be 54.5% comparing less favorably with those of developing countries where HL is commonly noted as EBV positive in 90-100% of cases. [12]

In the diffuse large B cell lymphoma category of our MLs, only one case (6.3%) out of 16 showed EBV positivity as against about 44.4% recorded in Tanzania. [13]


  Conclusion Top


This study revealed fewer associations of ML with EBV (EBER+) compared to what was previously reported from Africa and elsewhere. Further studies with larger samples involving various centers are required to determine the exact prevalence of EBV-associated ML in our environment.


  Acknowledgment Top


We wish to acknowledge the Ohio State University Research Foundation and the National Institute of Health/National Cancer Institute for their generous funding of the Sub-Saharan Africa Lymphoma Consortium which enabled us to carry out this study.

 
  References Top

1.Dolcetti R, Masucci MG. Epstein-Barr virus: Induction and control of cell transformation. J Cell Physiol 1996;196:207-18.  Back to cited text no. 1
    
2.Brennan P. Signalling events regulating lymphoid growth and survival. Semin Cancer Biol 2002;11:415-21.  Back to cited text no. 2
    
3.Prevot S, Hamilton-Dutoit S, Audouin J, Walter P, Pallesen G, Diebold J. Analysis of African Burkitt′s and high grade B cell non-Burkitt′s lymphoma for Epstein-Barr virus genome using in situ hybridization. Br J Haematol 1992;80:27-32.  Back to cited text no. 3
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4.Henle G, Henle W, Diehl V. Relations of Burkitt′s tumour associated herpes type virus to infectious mononucleosis. Proc Natl Acad Sci U S A 1968;59:94-101.  Back to cited text no. 4
[PUBMED]    
5.Klunnb CE, Hussain R, De-Oliveira DE, De-Resende LM, Camico MK, Dobbin De-Almeida J, et al. Geographic variation in Epstein-Barr virus associated Burkitt′s lymphoma in children from Brazil. Int J Cancer 2004;108:66-70.  Back to cited text no. 5
    
6.Epstein MA, Barr YM. Cultivation in vitro of human lymphoblasts from Burkitt′s malignant lymphoma. Lancet 1964;41:252-3.  Back to cited text no. 6
    
7.Epstein MA, Achong BG. Virus particles in cultured lymphoblasts from Burkitt′s lymphoma. Lancet 1964;1:702-3.  Back to cited text no. 7
    
8.Rickinson A, Kieff E. Epstein-Barr virus. In: Fields BN, Knipe DM, Howley PM, editors. Fields′ Virology. 4 th ed. Philadelphia: Lippincott- Raven; 2001. p. 2511-73.  Back to cited text no. 8
    
9.Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Natl Rev Cancer 2004;4:757-68.  Back to cited text no. 9
    
10.Tumwine LK, Orem J, Kerchan P, Buyarugaba W, Pileri SA. Epstein Barr Virus, Human Herpes Virus8 and Human Immunodeficiency Virrus in B cell non-Hodgkin lymphomas in Kampala, Uganda. Infect Agents Cancer 2010;5:12.  Back to cited text no. 10
    
11.Weiss LM, Movahed CA. In situ demonstration of Epstein-Barr viral genomes in Reed-Steinberg cells of Hodgkin′s disease. N Engl J Med 1989;320:502-6.  Back to cited text no. 11
    
12.Murray PG, Young LS. Hodgkin′s lymphoma: Molecular pathogenesis and the contribution of Epstein-Barr virus. In: Robertson ES, editor. Epstein-Barr virus. Norfolk: Canister Academic Press; 2005.  Back to cited text no. 12
    
13.Mwakigonja AR, Kaya EE, Helden T, Wannhoff G, Castro J, Oak F, et al. Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBVassociation. BMC Cancer 2010;10:344.  Back to cited text no. 13
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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Abstract
Introduction
Materials and Me...
Results
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