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. Author manuscript; available in PMC: 2015 Jan 22.
Published in final edited form as: Niger J Surg Sci. 2014 Feb 14;23(1):6–8. doi: 10.4103/1116-5898.127096

EPSTEIN –BARR VIRUS ASSOCIATION WITH MALIGNANT LYMPHOMA SUBGROUPS IN ZARIA, NIGERIA

Yawale Iliyasu *, Leona W Ayers **, Almustapha A Liman *, Garba D Waziri *, Sani M Shehu *
PMCID: PMC4302412  NIHMSID: NIHMS647117  PMID: 25620871

SUMMARY

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 (BL), plasmablastic lymphoma, diffuse large cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL). We report the association of EBV with ML in a segment of our patient population.

Paraffin blocks from the archives of ABUTH, Zaria were used to construct tissue microarray sections stained using 30 monoclonal antibodies for common Non-Hodgkin's lymphoma/ Hodgkin's lymphoma antigen and chromogenic in situ hybridization (CISH) for EBV-encoded RNA were done.

Fewer associations of ML with EBV were found than reported from elsewhere in Africa.

INTRODUCTION

Epstein-Barr virus (EBV), a DNA virus belonging to the herpes group, has been incriminated in the aetiopathogenesis 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 disorders1.

EBV produces a protein, LMP-1, which activates the NFκB 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 life3.

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

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 Haematoxylin 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

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 (see Table 1).

Table 1.

Age and Sex Distribution of Malignant Lymphoma Cases

Age Group (years) Sex Total
M F
0-9 8 7 15
10-19 7 10 17
20-29 1 1 2
30-39 5 3 8
40-49 2 2 4
50-59 3 3 5
60-69 1 1 2
70-79 1 1 2

Total 28 27 55

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

Table 2.

Site Distribution of Malignant Lymphoma Cases

Site Number Percentage (%)
Abdomen 10 18.2
Jaw 18 32.7
Lymph Node 14 25.5
Bone Marrow 6 10.9
Others 7 12.7

Total 55 100

Burkitt's lymphomas were the commonest lymphoma type; and these accounted for 50.9% of all tumours studied. Of these 28 cases of BL, 23 (82.1%) were EBV positive and 7 cases 0r 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.

Table 3.

Diagnostic Subgroup with percentage of Subgroup with EBV Status

Subgroups EBV+ # (%) EBV-# (%) Total
Burkitt's Lymphoma 23 (82.1) 5 (17.9) 28
Hodgkin's Disease 6 (54.5) 5 (45.5) 11
Diffuse Large B Cell Lymphoma 1 (6.3) 15 (93.8) 16

Total 30 (54.5) 25 (45.5) 55

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

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 countries4,5. Epstein-Barr virus infection persists asymptomatically during the host's life maintaining a perpetual equilibrium between the immune response and this stealthy virus.

Incidentally, EBV was originally discovered because of isolation within a tumour 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 neoplasms6,7.

While the oncogenic potentials of EBV still remain hypothetical, the link between this virus and human tumours 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 events8.

The ranking lymphoma type in this study is by far the Burkitt's lymphoma with 28 out of 55 cases (Table 3).There are three variants this tumour; 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 variant9.

In this study however, 82% of BL cases had EBV positivity signifying thereby that, although we are in the endemic BL zone, some of the cases seen here must be set in the other 2 BL subtypes. It is of note though, that the immune status of our patients has not been determined. In addition, fewer associations of BL with EBV were found than reported recently from East Africa. Workers in Uganda reported 91.2% EBV positive BL against our 82.1% EBER positive cases10. EBV is purported to contribute to BL development by increasing the lymphomagenic potential of a cmyc translocation positive cell.

The link between EBV and Hodgkin's lymphoma had long been postulated on epidemiologic grounds, the key original findings yet were the detection of monoclonal viral genomes in some tumour biopsies via southern blotting, terminal repeat analysis and in situ hybridisation11. The association of HL with EBV in this survey was found to be 54.5% comparing less favourably with those of developing countries where HL is commonly noted as EBV positive in 90%-100% of cases12.

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 Tanzania13.

CONLUSION

It has been observed in this study that there were fewer associations of ML with EBV (EBER+) than were reported elsewhere including reports from other African centers for all the categories of MLs examined. Of interest also, that no plasmablastic lymphomas were present in this collection.

Further studies with larger samples and multi center efforts may be vital to confirm whether or not ML tumours in our region or if this is a result of the biopsy sample population.

ACKNOWLEDGEMENT

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, our participation in which enabled us to carry out this study.

APPENDIX

Figure.

Figure

EBER Positive Diffuse large B cell lymphoma (DLBC)

REFERENCES

  • 1.Dolcetti R, Masucci MG. Epstein-Barr virus: induction and control of cell transformation. J Cell Physiol. 196:207, 203. doi: 10.1002/jcp.10263. [DOI] [PubMed] [Google Scholar]
  • 2.Brennan P. Signalling events regulating lymphoid growth and survival. Cancer BIol. 2002;12:473. doi: 10.1006/scbi.2001.0408. [DOI] [PubMed] [Google Scholar]
  • 3.Prevot S. 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. 80:27–32. doi: 10.1111/j.1365-2141.1992.tb06396.x. [DOI] [PubMed] [Google Scholar]
  • 4.Henle G, Henle W, Diehl V. Relations of Burkitt's tumour associated herpes type virus to infectious mononucleosis. Proc. Natl. Acad. Sci. USA. 1968;59:94–101. doi: 10.1073/pnas.59.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Klunnb C, 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(1):66–70. doi: 10.1002/ijc.11443. [DOI] [PubMed] [Google Scholar]
  • 6.Epstein MA, Barr YM. Cultivation in vitro of human lymphoblasts from Burkitt's malignant lymphoma. Lancet. 1964;41:252–253. doi: 10.1016/s0140-6736(64)92354-2. [DOI] [PubMed] [Google Scholar]
  • 7.Epstein MA, Achong BG. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet. 1964;41:252–253. doi: 10.1016/s0140-6736(64)91524-7. [DOI] [PubMed] [Google Scholar]
  • 8.Rickinson A, Kieff E. Epstein-Barr virus. In: Fields BN, Knipe DM, Howley PM, editors. Fields’ Virology. 4th ed. Lippincott-Raven; Philadelphia: 2001. pp. 2511–73. [Google Scholar]
  • 9.Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Natl Rev Cancer. 2004;4:757–68. doi: 10.1038/nrc1452. [DOI] [PubMed] [Google Scholar]
  • 10.Tumwine LK, Orem J, Kerchan P, Buyarugaba W, Pileri S. EBV, HHV8 and HIV in B cell non-Hodgkin lymphomas in Kampala, Uganda. Infectious Agents and Cancer. 2010;5:12. doi: 10.1186/1750-9378-5-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Weiss LM, Movahed CA. In situ demonstration of Epstein-Barr viral genomes in Reed-Steinberg cells of Hodgkin's disease. N Eng J Med. 1989;320:502–506. doi: 10.1056/NEJM198902233200806. [DOI] [PubMed] [Google Scholar]
  • 12.Murray PG, Young LS. Hodgkin's lymphoma: Molecular pathogenesis and the contribution of Epstein-Barr virus. In: Robertson ES, editor. Epstein-Barr virus. Canister Academic Press; Norfolk: 2005. [Google Scholar]
  • 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. doi: 10.1186/1471-2407-10-344. [DOI] [PMC free article] [PubMed] [Google Scholar]

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