Epstein Barr Virus in Hodgkin’s Lymphoma a Path Less Treaded: An Observational Study
Keywords:
Hodgkin lymphoma, EBV, LMP1
Abstract
Background: Epstein-Barr virus (EBV) is a ubiquitous virus belonging to γ-Herpesvirus subfamily, infecting B cells, T cells, Natural killer (NK) cells & causes both benign and malignant diseases. It has been detected in large subset of Hodgkin lymphoma (HL) cases around the world, especially in countries with poor socioeconomic conditions and among younger age. Limited studies are available reflecting the Indian scenario of HL and EBV association. EBV positivity in Indian HL varies from 28-97% Majority of these studies employed Immunohistochemistry (IHC) for LMP1, a few performed In Situ Hybridisation (ISH) for EBER. Objective: To study the association of EBV in classical HL by immunohistochemical expression of latent membrane protein 1 (LMP1) antigen in North Indian population and to correlate it with different demographic variables & subtypes of HL. Materials and Methods: Observational study including 26 untreated HL cases diagnosed on lymph node excision biopsy. IHC was performed for EBV LMP1, CD15, CD30, CD45, CD3, CD20. Results: Patients ranged in age from 5-55years (median 18yrs), with M:F ratio of 3.3:1. Palpable lymphadenopathy was found in all cases followed by pallor (64%), B symptoms (50%), nodal pain (30.8%) & bulky disease (19.2%). Maximum number of patients were in Stage I (65.4%) followed by stage II&III (15.4% each) & stage IV (3.8%). Mixed cellularity HL comprised 77%, lymphocyte depleted 11.5%, nodular sclerosis 7.7% & lymphocyte rich 3.8%. IHC for EBV LMP1 was positive in 73.1% cases. Mixed cellularity HL showed an association in 70% cases. Conclusions: HL in India is a disease of young males, with mixed cellularity as the commonest subtype, highly associated with EBV and presentation at an early stage.References
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25. Zarate-Osorno A, Roman L, Kingma DW, Meneses-Garcia A, Jaffe ES. Hodgkin's disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype. Cancer.1995;75:1360-6.
26. Monterroso V, Zhou Y, Koo S, Glackin C, Bujan W, Medeiros LJ. Hodgkin's disease in Costa Rica: A report of 40 cases analyzed for Epstein-Barr virus. Am J Clin Pathol.1998;109(5):618-24.
27. Leoncini L, Spina D, Nyong'o A, Abinya O, Minacci C, Disanto A et al. Neoplastic cells of Hodgkin's disease show differences in EBV expression between Kenya and Italy. Int J Cancer.1996;65:781-4.
28. Weinreb M, Day PJ, Niggli F, Powell JE, Raafat F, Hesseling PB et al. The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas. Arch Dis Child.1996;74(1):27-31.
29. Tomita Y, Ohsawa M, Kanno H, Hashimoto M, Ohnishi A, Nakanishi H et al. Epstein-Barr virus in Hodgkin's disease patients in Japan. Cancer.1996;77:186-92.
30. Chan JK, Yip TT, Tsang WY, Lau WH, Wong CS, Ma VW. Detection of Epstein-Barr virus in Hodgkin's disease occurring in an Oriental population. Hum Pathol. 1995;26(3):314-8.
31. Belkaid MI, Briere J, Djebbara Z, Beldjord K, Andrieu JM, Colonna P. Comparison of Epstein-Barr virus markers in Reed-Sternberg cells in adult Hodgkin's disease tissues from an industrialized and a developing country. Leuk Lymph.1995;17:163-8.
32. Gulley ML, Eagan PA, Quintanilla-Martinez L, Picado AL, Smir BN, Childs C et al. Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin's disease: Association with mixed cellularity subtype and Hispanic American ethnicity. Blood.1994; 83(6):1595-602.
33. Gala R, Gandhi J, Gupta G, Grover S, Sharma A, Pasricha S et al. Study of association of Epstein-Barr virus in lymphomas by Epstein-Barr virus-encoded RNA in situ hybridization: An Indian perspective from a tertiary care cancer institute. Indian J Pathol Microbiol. 2017;60(3):341-9.
34. Glaser SL, Gulley ML, Clarke CA, Keegan TH, Chang ET, Shema SJ et al. Racial/ethnic variation in EBV-positive classical Hodgkin lymphoma in California populations. Int J Cancer.2008;123(7):1499-507.
35. Cickusic E, Mustedanagic-Mujanovic J, Iljazovic E, Karasalihovic Z, Skaljic I. Association of Hodgkin’s Lymphoma with Epstein Barr Virus Infection. Bosnian Journal of Basic Medical Sciences. 2007;7(1):58-65.
2. Anagnostopoulos I, Herbst H, Niedobitek G, Stein H. Demonstration of monoclonal EBV genomes in Hodgkin’s disease and Ki-1 positive anaplastic large cell lymphoma by combined Southern and in situ hybridisation. Blood.1989;74:810-6.
3. Radha K, Shanthi P, Madhavan M, Senthamarai A. Study of association of Epstein-Barr virus with Hodgkin’s disease. Indian J Pathol Microbiol. 1997;40(3):351–4.
4. Naresh KN, Johnson J, Srinivas V, Soman C, Saikia T, Advani S et al. Epstein-Barr virus association in classical Hodgkin’s disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells. Annals of Oncology.2000;11:91–6.
5. Karnik S, Srinivasan B, Nair S. Hodgkin’s lymphoma: Immunohistochemical features and its association with EBV LMP-1. Experience from a South Indian hospital. Pathology. 2003;35(3):207–11.
6. Rajalakshmi T, Payal K, Makhija P, Karuna V. Epstein- Barr virus in Hodgkin’s lymphoma–Incidence and prognostic implications. Indian Journal of Medical and Paediatric Oncology. 2006;27(1):23-6.
7. Dinand V, Dawar R, Arya LS, Unni R, Mohanty B, Singh R et al. Hodgkin’s lymphoma in Indian children: prevalence and significance of Epstein-Barr virus detection in Hodgkin’s and Reed-Sternberg cells. Eur J Cancer. 2007;43(1):161-8.
8.Gulley M, Glaser S, Craig F, Borowitz M, Mann R, Shema S et al. Guidelines for interpreting EBER in Situ Hybridisation and LMP1 immunohistochemical tests for detecting Epstein-Barr virus in Hodgkin lymphoma. Am J Clin Pathol.2002;117:259-67.
9. Jain H, Sengar M, Nair R, Menon H, Laskar S, Shet T et al. Treatment results in advanced stage Hodgkin’s lymphoma: A retrospective study. J Postgrad Med.2015;61(2):88-91.
10. Goswami B, Sarkar S, Chakraborti S, Mondal S, Roy A, Deb A. Clinicopathologic profile of Hodgkin’s lymphoma in a rural medical college. Indian J Hematol Blood Transfus.2008;24(4):166-9.
11. Patkar N, Mehta J, Kulkarni B, Pande R, Advani S, Borges A. Immunoprofile of Hodgkin’s lymphoma in India. Indian Journal of Cancer. 2008;45(2):59-63.
12. Au WY, Gascoyne RD, Gallagher RE, LeN, KlasaRD, Liang R. Hodgkin’s lymphoma in Chinese migrants to British Columbia: a 25-year survey. Annals of Oncology. 2004;15(4):626–30.
13. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001.Blood. 2006;107(1):265-76.
14. Shimabukuro-Vornhagen A, Haverkamp H, Engert A, Balleisen L, Majunke P, Heil G et al. Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials. J Clin Oncol. 2005;23(24):5739-45.
15. Slack GW, Ferry JA, Hasserjian RP, Sohani AR, Longtine JA, Harris NL et al. Lymphocyte depleted Hodgkin lymphoma: an evaluation with immunophenotyping and genetic analysis. Leuk Lymphoma. 2009;50(6):937-43.
16. Swerdlow AJ. Epidemiology of Hodgkin’s disease and non-Hodgkin’s lymphoma. Eur J Nucl Med Mol Imaging.2003;30 Suppl 1:3-12.
17.Jarrett R, Krajewski A, Angus B, Freeland J, Taylor P, Taylor G et al. The Scotland and Newcastle epidemiological study of Hodgkin’s disease: Impact of histopathological review and EBV status on incidence estimates. J Clin Pathol.2003;56(11):811-6.
18. Chandi L, Kumar L, Kochupillai V, Dawar R, Singh R. Hodgkin's disease: a retrospective analysis of 15 years experience at a large referral centre. Natl Med J India.1998;11(5):212-7.
19. Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin's Disease. N Engl J Med.2003;348:2386-95.
20. Herling M, Rassidakis G, Medeiros L, Vassilakopoulos T, Kliche K, Nadali G et al. Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome. Clin Cancer Res. 2003;9(6):2114-20.
21. Jarrett RF, Stark GL, White J, Angus B, Alexander FE, Krajewski AS et al. Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study. Blood. 2005;106(7):2444-51.
22. Glaser SL, Lin RJ, Stewart SL, Ambinder RF, Jarrett RF, Brousset P et al. Epstein Barr virus associated Hodgkin's disease: Epidemiologic characteristics in international data. Int J Cancer.1997;70:375-82.
23. Jarrett AF, Armstrong AA, Alexander E. Epidemiology of EBV and Hodgkin's lymphoma. Ann Oncol. 1996; 7 Suppl4: 5-10.
24. Huh J, Park C, Juhng S, Kim CE, Poppema S, Kim C. A pathologic study of Hodgkin's disease in Korea and its association with Epstein-Barr virus infection. Cancer.1996;77:949-55.
25. Zarate-Osorno A, Roman L, Kingma DW, Meneses-Garcia A, Jaffe ES. Hodgkin's disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype. Cancer.1995;75:1360-6.
26. Monterroso V, Zhou Y, Koo S, Glackin C, Bujan W, Medeiros LJ. Hodgkin's disease in Costa Rica: A report of 40 cases analyzed for Epstein-Barr virus. Am J Clin Pathol.1998;109(5):618-24.
27. Leoncini L, Spina D, Nyong'o A, Abinya O, Minacci C, Disanto A et al. Neoplastic cells of Hodgkin's disease show differences in EBV expression between Kenya and Italy. Int J Cancer.1996;65:781-4.
28. Weinreb M, Day PJ, Niggli F, Powell JE, Raafat F, Hesseling PB et al. The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas. Arch Dis Child.1996;74(1):27-31.
29. Tomita Y, Ohsawa M, Kanno H, Hashimoto M, Ohnishi A, Nakanishi H et al. Epstein-Barr virus in Hodgkin's disease patients in Japan. Cancer.1996;77:186-92.
30. Chan JK, Yip TT, Tsang WY, Lau WH, Wong CS, Ma VW. Detection of Epstein-Barr virus in Hodgkin's disease occurring in an Oriental population. Hum Pathol. 1995;26(3):314-8.
31. Belkaid MI, Briere J, Djebbara Z, Beldjord K, Andrieu JM, Colonna P. Comparison of Epstein-Barr virus markers in Reed-Sternberg cells in adult Hodgkin's disease tissues from an industrialized and a developing country. Leuk Lymph.1995;17:163-8.
32. Gulley ML, Eagan PA, Quintanilla-Martinez L, Picado AL, Smir BN, Childs C et al. Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin's disease: Association with mixed cellularity subtype and Hispanic American ethnicity. Blood.1994; 83(6):1595-602.
33. Gala R, Gandhi J, Gupta G, Grover S, Sharma A, Pasricha S et al. Study of association of Epstein-Barr virus in lymphomas by Epstein-Barr virus-encoded RNA in situ hybridization: An Indian perspective from a tertiary care cancer institute. Indian J Pathol Microbiol. 2017;60(3):341-9.
34. Glaser SL, Gulley ML, Clarke CA, Keegan TH, Chang ET, Shema SJ et al. Racial/ethnic variation in EBV-positive classical Hodgkin lymphoma in California populations. Int J Cancer.2008;123(7):1499-507.
35. Cickusic E, Mustedanagic-Mujanovic J, Iljazovic E, Karasalihovic Z, Skaljic I. Association of Hodgkin’s Lymphoma with Epstein Barr Virus Infection. Bosnian Journal of Basic Medical Sciences. 2007;7(1):58-65.
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07-07-2020
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