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International Journal of Hematology

, Volume 79, Issue 3, pp 260–265 | Cite as

Epstein-barr virus-associated composite lymphoma composed of peripheral t-cell lymphoma and an anaplastic variant of a diffuse large b-cell type of non-hodgkin’s lymphoma and strongly expressing P53 protein

  • Yuko Hirose
  • Toshihiro Fukushima
  • Yasufumi Masaki
  • Kumiko Shimoyama
  • Hiromi Karasawa
  • Noriyoshi Ogawa
  • Yuji Wano
Case Report

Abstract

We report a case of composite lymphoma consisting of peripheral T-cell lymphoma and an anaplastic variant of diffuse large B-cell lymphoma (DLBCL) and associated with Epstein-Barr virus (EBV) infection and strong p53 expression. A 65-year-old Japanese woman developed fever and generalized lymphadenopathy.A biopsy of the cervical node revealed the morphology of malignant lymphoma with 2 kinds of lymphoma coexisting in 1 lymph node. One lymphoma type consisted of immunoblastic large cells with the T-cell marker phenotype CD3+, CD45RO/UCHL-1+, CD20/L26-, CD79-, CD10-, CD30-, and CD15-; the other type consisted of large cells with abundant cytoplasm and pleomorphic nuclei with the marker phenotype CD79+, CD20/ L26+, CD45RO/UCHL-1-, CD3-, CD10-, CD30+, NPM/ALK-, and CD15-. Therefore, the diagnosis was composite lymphoma of peripheral T-cell lymphoma and an anaplastic variant of DLBCL, stage IVB, because the patient had bone marrow involvement with peripheral T-cell lymphoma. The biopsy led to findings of latent type II EBV-associated lymphoma in both the peripheral T-cell lymphoma and the anaplastic variant of DLBCL as the result of positive signals for EBV small RNAs by in situ hybridization, positive immunostaining results for EBV latent membrane protein 1 antibody, and negative immunostaining results for EBV nuclear antigen 2. Immunostaining of the mass with p53 antibody also yielded positive results for both types of lymphoma cells. This case suggests that the immunocompromised state of this patient with EBV-related peripheral T-cell lymphoma allowed the emergence of an EBV-related anaplastic variant of DLBCL and suggests a close relationship between p53 expression and latent EBV infection.

Key words

Epstein-Barr virus Composite lymphoma Peripheral T-cell lymphoma Anaplastic variant of diffuse large B-cell lymphoma p53 protein 

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References

  1. 1.
    Kim H, Hendrickson MR, Dorfman RF. Composite lymphoma. Cancer. 1977;40:959–976.CrossRefPubMedGoogle Scholar
  2. 2.
    Kim H. Composite lymphoma and related disorders. Am J Clin Pathol. 1993;99:445–451.CrossRefPubMedGoogle Scholar
  3. 3.
    Gonzalez CL, Meroides LJ, Jaffe ES. Composite lymphoma: a clinicopathologic analysis of nine patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Am J Clin Pathol. 1991;96:81–89.CrossRefPubMedGoogle Scholar
  4. 4.
    Tobinai K, Ohtsu T, Hayashi M, et al. Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma. Leuk Res. 1991;15:837–846.CrossRefPubMedGoogle Scholar
  5. 5.
    Strickler JG, Amsden TW, Kurtin PJ. Small B-cell lymphoid neoplasms with coexisting T-cell lymphomas. Am J Clin Pathol. 1992; 98:424–429.CrossRefPubMedGoogle Scholar
  6. 6.
    Liu YC, Tomashefski JF Jr, Cleveland RP, et al. Composite cutaneous T-cell lymphoma and small B-cell lymphocytic lymphoma: morphologic, and molecular genetic documentation of concurrent lymph node involvement. Mod Pathol. 1994;7:641–646.PubMedGoogle Scholar
  7. 7.
    Zettl A, Lee SS, Rudiger T, et al. Epstein-Barr virus associated B-cell lymphoproliferative disorders in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Am J Clin Pathol. 2002;117:368–379.CrossRefPubMedGoogle Scholar
  8. 8.
    Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe ES. Anaplastic large cell lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. WHO Classification:Tumors of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:230–235.Google Scholar
  9. 9.
    Borisch B, Finke J, Hennig I, et al. Distribution and localization of Epstein-Barr virus subtypes A and B in AIDS-related lymphomas and lymphatic tissue of HIV-positive patients. J Pathol. 1992;168: 229–236.CrossRefPubMedGoogle Scholar
  10. 10.
    Hamilton-Dutroit SJ, Raphael M, Audouin J, et al. In situ demonstration of Epstein-Barr virus small RNAs (EBER) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site. Blood. 1993;82:619–624.Google Scholar
  11. 11.
    Hanto DW, Frizzera G, Purtilo DT, et al. Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Res. 1981;41:4253–4261.PubMedGoogle Scholar
  12. 12.
    Penn I. Malignant lymphomas in organ transplant recipients. Transplant Proc. 1981;13:736–738.PubMedGoogle Scholar
  13. 13.
    Kamel OW, van de Riin M, Weiss LM, et al. Brief report: reversible lymphoma associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med. 1993;328:1317–1321.CrossRefPubMedGoogle Scholar
  14. 14.
    Dawson TM, Starkebaum G, Wood BL, Wilkins RF, Gown AM. Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjögren’s syndrome: case series. J Rheumatol. 2001;28:47–53.PubMedGoogle Scholar
  15. 15.
    Hirose Y, Masaki Y, Okada J, et al. Epstein-Barr virus associated B-cell type non-Hodgkin’s lymphoma with concurrent p53 protein expression in a rheumatoid arthritis patient treated with methotrexate. Int J Hematol. 2002;75:412–415.CrossRefGoogle Scholar
  16. 16.
    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;74:810–816.Google Scholar
  17. 17.
    Herbst H, Dallenbach F, Hummel M, et al. Epstein-Barr virus DNA and latent gene products in Ki-1 (CD30)-positive anaplastic large cell lymphomas. Blood. 1991;78:2666–2673.Google Scholar
  18. 18.
    Shimakage M, Nakamine H, Tamura S, Takenaka T, Yutsudo M, Hakura H. Detection of Epstein-Barr virus transcript in anaplastic large-cell lymphomas by mRNA in situ hybridization. Hum Pathol. 1997;28:1415–1419.CrossRefGoogle Scholar
  19. 19.
    Hirose Y, Masaki Y, Shimoyama K, et al. Epstein-Barr virus-associated anaplastic large cell variant of diffuse large B-cell-type non-Hodgkin’s lymphoma with concurrent p53 protein expression. Int J Hematol. 2003;77:499–502.CrossRefGoogle Scholar
  20. 20.
    Szekely W, Selivanova G, Magnusson KP, et al. EBNA-5, an Epstein- Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins. Proc Natl Acad Sci U S A. 1993;90:5455–5459.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Chen W, Cooper NR. Epstein-Barr virus nuclear antigen 2 and latent membrane protein independently transactivate p53 through induction of NF-βB activity. J Virol. 1996;70:4849–4853.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Shibata D, Weiss LM, Nathwani BN, et al. Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin’s lymphoma. Blood. 1991;77: 1527–1533.PubMedGoogle Scholar
  23. 23.
    Hirose Y, Masaki Y, Shimizu S, et al. Association of Epstein-Barr virus with human immunodeficiency virus-negative T cell lymphomas in Japan, in situ hybridization, polymerase chain reaction and immunohistochemical studies. Leukemia. 1996;10:1673–1675.PubMedGoogle Scholar
  24. 24.
    Khan G, Norton AJ, Slavin G. Epstein-Barr virus in angioimmunoblastic T-cell lymphomas. Histopathology. 1993;22:145–149.CrossRefPubMedGoogle Scholar
  25. 25.
    Menke DM, Griesser H, Moder KG, et al. Lymphomas in patients with connective tissue disease: comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate. Am J Clin Pathol. 2000; 113:212–218.CrossRefPubMedGoogle Scholar
  26. 26.
    Bartek J, Bartkova J, Vojtesek B, et al. Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene. 1991;6:1699–1703.PubMedGoogle Scholar
  27. 27.
    Edwards RH, Raab-Traub N. Alterations of p53 gene in Epstein- Barr virus-associated immunodeficiency-related lymphomas. J Virol. 1994;68:1309–1315.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Cesarman E, Inghirami G, Chadburn A, et al. High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma. Am J Pathol. 1993;143:845–856.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Szekely L, Selivanova G, Magnusson KP, et al. EBNA-5, an Epstein- Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins. Proc Natl Acad Sci U S A. 1993;90:5459–5459.CrossRefGoogle Scholar
  30. 30.
    Chen W, Cooper NR. Epstein-Barr virus nuclear antigen-2 and latent membrane protein independently transactivate p53 through induction of NF-βB activity. J Virol. 1996;70:4849–4853.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Oyama T, Ichimura K, Suzuki R, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27:16–26.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Yuko Hirose
    • 1
  • Toshihiro Fukushima
    • 1
  • Yasufumi Masaki
    • 1
  • Kumiko Shimoyama
    • 1
  • Hiromi Karasawa
    • 1
  • Noriyoshi Ogawa
    • 1
  • Yuji Wano
    • 1
  1. 1.Division of Hematology and Immunology, Department of Internal MedicineKanazawa Medical UniversityIshikawaJapan

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