Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
letter
. 1993 Jun;142(6):1683–1688.

Association of Epstein-Barr Virus with Pediatric Hodgkin's Disease

A A Armstrong, F E Alexander, R Pinto Paes, N A Morad, A Gallagher, A S Krajewski, D B Jones, B Angus, J Adams, R A Cartwright, D E Onions, R F Jarrett
PMCID: PMC1886981  PMID: 8389527

Abstract

A bimodal age incidence curve has been shown for Hodgkin's disease (HD). In developing countries, the first age incidence peak occurs in childhood; however, this peak is delayed until young adulthood in developed countries. This difference may reflect differences in the age of exposure to infectious agents involved in the development of HD or may suggest different etiological agents. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a proportion of HD cases. In this study, EBV association was investigated in a series of 55 pediatric HD cases from three geographical locations (United Kingdom, Brazil, and Saudi Arabia) and the relationship between country, age, sex, histological subtype, and EBV positivity was evaluated. EBV was detected in 38 cases using RNA in situ hybridization, Southern blot, or immunohistochemical analysis. No significant difference in EBV positivity by country, age, or sex was observed; however, children under 10 years of age were particularly likely to be EBV-associated. The difference in EBV association in the pediatric group compared with that observed previously for young adult HD was highly statistically significant (P < 0.0001). These results are consistent with the hypothesis that pediatric and young adult HD have different etiologies and suggest that EBV is likely to be involved in the pathogenesis of pediatric HD.

Full text

PDF
1683

Images in this article

1685Figure 2
on p.1685

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abramson J. H., Pridan H., Sacks M. I., Avitzour M., Peritz E. A case-control study of Hodgkin's disease in Israel. J Natl Cancer Inst. 1978 Aug;61(2):307–314. [PubMed] [Google Scholar]
  2. Alexander F. E., McKinney P. A., Williams J., Ricketts T. J., Cartwright R. A. Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease. Int J Epidemiol. 1991 Jun;20(2):354–361. doi: 10.1093/ije/20.2.354. [DOI] [PubMed] [Google Scholar]
  3. Alexander F. E., Ricketts T. J., McKinney P. A., Cartwright R. A. Community lifestyle characteristics and lymphoid malignancies in young people in the UK. Eur J Cancer. 1991;27(11):1486–1490. doi: 10.1016/0277-5379(91)90037-e. [DOI] [PubMed] [Google Scholar]
  4. 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 blot and in situ hybridization. Blood. 1989 Aug 1;74(2):810–816. [PubMed] [Google Scholar]
  5. Armstrong A. A., Gallagher A., Krajewski A. S., Jones D. B., Wilkins B. S., Onions D. E., Jarrett R. F. The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin's disease. Histopathology. 1992 Jul;21(1):72–73. doi: 10.1111/j.1365-2559.1992.tb00346.x. [DOI] [PubMed] [Google Scholar]
  6. Armstrong A. A., Weiss L. M., Gallagher A., Jones D. B., Krajewski A. S., Angus B., Brown G., Jack A. S., Wilkins B. S., Onions D. E. Criteria for the definition of Epstein-Barr virus association in Hodgkin's disease. Leukemia. 1992 Sep;6(9):869–874. [PubMed] [Google Scholar]
  7. Boiocchi M., Carbone A., De Re V., Dolcetti R. Is the Epstein-Barr virus involved in Hodgkin's disease? Tumori. 1989 Aug 31;75(4):345–350. doi: 10.1177/030089168907500409. [DOI] [PubMed] [Google Scholar]
  8. Correa P., O'Conor G. T. Epidemiologic patterns of Hodgkin's disease. Int J Cancer. 1971 Sep 15;8(2):192–201. doi: 10.1002/ijc.2910080203. [DOI] [PubMed] [Google Scholar]
  9. Evans A. S., Gutensohn N. M. A population-based case-control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings. Int J Cancer. 1984 Aug 15;34(2):149–157. doi: 10.1002/ijc.2910340203. [DOI] [PubMed] [Google Scholar]
  10. Glaser S. L., Swartz W. G. Time trends in Hodgkin's disease incidence. The role of diagnostic accuracy. Cancer. 1990 Nov 15;66(10):2196–2204. doi: 10.1002/1097-0142(19901115)66:10<2196::aid-cncr2820661026>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  11. Gledhill S., Gallagher A., Jones D. B., Krajewski A. S., Alexander F. E., Klee E., Wright D. H., O'Brien C., Onions D. E., Jarrett R. F. Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples. Br J Cancer. 1991 Aug;64(2):227–232. doi: 10.1038/bjc.1991.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gutensohn N. M. Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis". Cancer Treat Rep. 1982 Apr;66(4):689–695. [PubMed] [Google Scholar]
  13. Gutensohn N., Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med. 1981 Jan 15;304(3):135–140. doi: 10.1056/NEJM198101153040302. [DOI] [PubMed] [Google Scholar]
  14. Gutensohn N., Cole P. Epidemiology of Hodgkin's disease. Semin Oncol. 1980 Jun;7(2):92–102. [PubMed] [Google Scholar]
  15. Gutensohn N., Cole P. Epidemiology of hodgkin's disease in the young. Int J Cancer. 1977 May 15;19(5):595–604. doi: 10.1002/ijc.2910190502. [DOI] [PubMed] [Google Scholar]
  16. Herbst H., Dallenbach F., Hummel M., Niedobitek G., Pileri S., Müller-Lantzsch N., Stein H. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4766–4770. doi: 10.1073/pnas.88.11.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jarrett R. F., Gallagher A., Jones D. B., Alexander F. E., Krajewski A. S., Kelsey A., Adams J., Angus B., Gledhill S., Wright D. H. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age. J Clin Pathol. 1991 Oct;44(10):844–848. doi: 10.1136/jcp.44.10.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Khan G., Coates P. J., Gupta R. K., Kangro H. O., Slavin G. Presence of Epstein-Barr virus in Hodgkin's disease is not exclusive to Reed-Sternberg cells. Am J Pathol. 1992 Apr;140(4):757–762. [PMC free article] [PubMed] [Google Scholar]
  19. MacMahon B. Epidemiology of Hodgkin's disease. Cancer Res. 1966 Jun;26(6):1189–1201. [PubMed] [Google Scholar]
  20. McKinney P. A., Alexander F. E., Ricketts T. J., Williams J., Cartwright R. A. A specialist leukaemia/lymphoma registry in the UK. Part 1: Incidence and geographical distribution of Hodgkin's disease. Leukaemia Research Fund Data Collection Study Group. Br J Cancer. 1989 Dec;60(6):942–947. doi: 10.1038/bjc.1989.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Merk K., Björkholm M., Rengifo E., Gavilondo J., Holm G., Rivas H. Epidemiological study of Hodgkin's disease in Cuba and Sweden. Oncology. 1990;47(3):246–250. doi: 10.1159/000226824. [DOI] [PubMed] [Google Scholar]
  22. Mueller N. An epidemiologist's view of the new molecular biology findings in Hodgkin's disease. Ann Oncol. 1991 Feb;2 (Suppl 2):23–28. doi: 10.1007/978-1-4899-7305-4_3. [DOI] [PubMed] [Google Scholar]
  23. Murray P. G., Young L. S., Rowe M., Crocker J. Immunohistochemical demonstration of the Epstein-Barr virus-encoded latent membrane protein in paraffin sections of Hodgkin's disease. J Pathol. 1992 Jan;166(1):1–5. doi: 10.1002/path.1711660102. [DOI] [PubMed] [Google Scholar]
  24. Muñoz N., Davidson R. J., Witthoff B., Ericsson J. E., De-Thé G. Infectious mononucleosis and Hodgkin's disease. Int J Cancer. 1978 Jul 15;22(1):10–13. doi: 10.1002/ijc.2910220104. [DOI] [PubMed] [Google Scholar]
  25. Paffenbarger R. S., Jr, Wing A. L., Hyde R. T. Characteristics in youth indicative of adult-onset Hodgkin's disease. J Natl Cancer Inst. 1977 May;58(5):1489–1491. doi: 10.1093/jnci/58.5.1489. [DOI] [PubMed] [Google Scholar]
  26. Pallesen G., Hamilton-Dutoit S. J., Rowe M., Young L. S. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991 Feb 9;337(8737):320–322. doi: 10.1016/0140-6736(91)90943-j. [DOI] [PubMed] [Google Scholar]
  27. Roberts G. T., Aur R. J., Sheth K. V. Immunophenotypic and age patterns of childhood acute lymphoblastic leukemia in Saudi Arabia. Leuk Res. 1990;14(7):667–672. doi: 10.1016/0145-2126(90)90023-3. [DOI] [PubMed] [Google Scholar]
  28. Staal S. P., Ambinder R., Beschorner W. E., Hayward G. S., Mann R. A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease. Am J Clin Pathol. 1989 Jan;91(1):1–5. doi: 10.1093/ajcp/91.1.1. [DOI] [PubMed] [Google Scholar]
  29. Weiss L. M., Chen Y. Y., Liu X. F., Shibata D. Epstein-Barr virus and Hodgkin's disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol. 1991 Dec;139(6):1259–1265. [PMC free article] [PubMed] [Google Scholar]
  30. Weiss L. M., Movahed L. A., Warnke R. A., Sklar J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl J Med. 1989 Feb 23;320(8):502–506. doi: 10.1056/NEJM198902233200806. [DOI] [PubMed] [Google Scholar]
  31. Weiss L. M., Strickler J. G., Warnke R. A., Purtilo D. T., Sklar J. Epstein-Barr viral DNA in tissues of Hodgkin's disease. Am J Pathol. 1987 Oct;129(1):86–91. [PMC free article] [PubMed] [Google Scholar]
  32. Wu T. C., Mann R. B., Charache P., Hayward S. D., Staal S., Lambe B. C., Ambinder R. F. Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease. Int J Cancer. 1990 Nov 15;46(5):801–804. doi: 10.1002/ijc.2910460509. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES