Summary
Fourteen examples of non-Hodgkin’s lymphoma (NHL) and four of Hodgkin’s disease in patients with AIDS as well as lymph nodes exhibiting changes related to the lymphadenopathy syndrome (LAS) from 11 HIV-positive individuals were studied for the presence of Epstein-Barr virus (EBV) genome both by in situ DNA hybridization and blotting techniques. Both methods were performed using formalin-fixed paraffin-embedded material. All the NHLs were of high malignancy and all but one were of the B-cell type. Of the four examples of Hodgkin’s disease, two were lymphocytic predominant, one of mixed cellularity and one of the nodular sclerosing variety. The lymph nodes of patients with LAS were mostly stage I with marked follicular hyperplasia. In 7 of the 14 NHLs the presence of EBV-DNA was clearly demonstrated by dot-blotting and by in situ hybridization. All lymph nodes from the patients with LAS and AIDS-related Hodgkin’s disease were negative for EBV by dot-blot and in situ hybridization assays. We conclude that EBV plays a role in the development of AIDS-related lymphomas, but the fact that half these lymphomas are EBV-negative suggests that other mechanisms such as polyclonal stimulation of B-cells by HIV products may also be important.
Similar content being viewed by others
References
Blattner WA, Marks G, Gallo RC, Mann DL (1986) HTLV-I associated B cell chronic lymphocytic leukemia: a model for indirect retroviral leukemogenesis. Clin Res 34:690 A
Dubeau L, Weinberg K, Jones PA, Nichols PW (1988) Studies on immunoglobulin gene rearrangement in formalin-fixed, paraffin-embedded pathology specimens. Am J Pathol 130:588–594
Filipovich AH, Spector JH, Kersey JH (1980) Immunodeficiency in humans as a risk factor in the development of malignancy. Prev Med 9:252–259
Filipovich AH, Zerbe DA, Spector DB, Kersey JH (1984) Lymphomas in persons with naturally occuring immunodeficiency disorders. In: McGrath JB, Ramot B (eds) The influence of the environment of leukemia and lymphoma subtypes. Raven Press, New York, pp 225–234
Goelz SE, Hamilton SR, Vogelstein B (1985) Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun 130:118–126
Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, Saxon A (1981)Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. Evidence of a new acquired cellular immunodeficiency. N Engl J Med 305:1425–1431
Hamilton-Dutoit SJ, Pallesen G, Karkov J, Skinhoj P, Franzman MB, Pedersen P (1989) Identification of EBV-DNA in tumour cells of AIDS-related lymphomas by in-situ hybridisation. Lancet 1:555
Hanto DW, Frizzera G, Gajl-Peczalska KJ, Simmons RL (1985) Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation 39:461–472
Herbst H, Anagnostopoulos I, Niedobitek G, Kratzsch H-C, Stein H (1989) Hodgkin’s disease: genotype, phenotype and association with viral genomes (abstract). Pathol Res Pract 185/1:73
Kalter SP, Riggs SA, Cabanillas F, Butler JJ, Hagemeister FB, Mansell PW, Newell GR, Velasquez WS, Salvador P, Barlogie B, Rios A, Hersh EM (1985) Agressive non-Hodgkin’s lymphomas in immunocompromised homosexual males. Blood 66:655–659
Klein G (1989) Viral latency and transformation: the strategy of Epstein-Barr virus. Cell 58:5–8
Klein G, Klein E (1985) Evolution of tumors and the impact of molecular oncology. Nature 315:190–195
Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS (1983) Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 309:453–458
Levine AM (1987) Non-Hodgkin’s lymphomas and other malignancies in the acquired immune deficiency syndrome. Semin Oncol 14 [Suppl 3]: 24–29
Levine AM, Meyer PR, Begandy MK, Parker JW, Taylor CR, Irwin L, Lukes RJ (1984) Development of B-cell lymphoma in homosexual men. Ann Intern Med 100:7–13
Loureiro C, Parkash SG, Meyer PR, Rhodes R, Rarick MU, Levine AM (1988) Autopsy findings in AIDS-related lymphoma. Cancer 62:735–739
Mathur-Wagh U, Enlow RW, Spigland I, Sacks HS, Yancovitz SR, William DC, Enlow RW, Winchester RJ, Rorat E, Klein MJ, Mildvan D (1984) Longitudinal study of persistent generalized lymphadenopathy in homosexual men: relation to acquired immunodeficiency syndrome. Lancet 1:1033
Metroka CE, Cunningham-Rundles S, Pollack MS, Sonnabend JA, Davis JM, Gordon B, Fernandez RD, Mourdian J (1983) Generalized lymphadenopathy in homosexual men. Ann Intern Med 99:585–591
Montagnier L, Gruest J, Chamaret S, Daugnet C, Axler C, Guetard D, Nugeyre MT, Barré-Sinoussi F, Cherman JC, Brunet JB, Klatzman D, Gluckman JC (1984) Adaption of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines. Science 225:63–66
Müller H, Falk S, Stutte HJ (1987) Immunohistochemical studies of lymph nodes from LAV and AIDS patients. Cancer Detect Prev [Suppl 1]: 577–588
Nalesnik MA, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowa L, Ho M, Locker J (1988) The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. Am J Pathol 133:173–192
Niedobitek G, Hamilton-Dutoit SJ, Herbst H (1989) Identification of Epstein-Barr virus infected cells in tonsills of acute infectious mononucleosis by in-situ hybridisation. Hum Pathol 20:796–799
Öst A, Baroni CD, Biberfeld P, Diebold J, Morgas A, Noel H, Pallesen G, Racz P, Schipper M, Tenner-Racz K, Van den Tweel JG (1989) Lymphadenopathy in HIV infection: histological classification and staging. APMIS [Suppl] 8:7–15
Schnittman SM, Lane HC, Higgins SE, Folks T, Fauci S (1986) Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus. Science 233:1084–1086
Siegal F, Lopez C, Hammer GS, Brown A, Kornfeld SJ, Gold J, Hasett TJ, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR, Parham DM, Siegal M, Cunningham-Rundles S, Armstrong D (1981) Severe acquired immunodeficiency in male homosexuals manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med 305:1425–1431
Staal SP, Ambinder R, Beschorner WE, Hayward GS, Mann R (1989) A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin’s disease. Am J Clin Pathol 91:1–5
Tenner-Racz K, Racz P, Dietrich M, Kern P (1985) Altered follicular dendritic cells and virus like particles in AIDS and AIDS-related lymphadenopathy. Lancet 1:105–106
Uccini S, Vitolo D, Monardo F, Faggioni A, Monarca B, Vitale A, Ruco LP, Baroni CD (1989) Interaction of HIV and EBV at lymphoid tissue level: immunohistochemistry and in situ hybridization. APMIS [Suppl] 8:28–32
Weiss LM, Movahed LA (1989) In situ demonstration of Epstein-Barr viral genomes in viral-associated B cell lymphoproliferations. Am J Pathol 134:651–659
Weiss LM, Strickler JG, Warnke RA, Purtilo DT, Sklar J (1987) Epstein-Barr viral DNA in tissues of Hodgkin’s disease. Am J Pathol 129:86–91
Weiss LM, Movahed LA, Warnke RA, Sklar J (1989) Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med 320:502–506
Yarchoan R, Redfield RR, Broder S (1986) Mechanisms of B cell activation in patients with the acquired immunodeficiency syndrome and related disorders. J Clin Invest 78:439–447
Ziegler JL, Miner RC, Rosenbaum E, Lenette E, Shillitoe E, Casvant C, Drew WL, Mintz L, Gershow J, Greenspan J, Beckstead J, Yamamoto K (1982) Outbreak of Burkitt’s-like lymphoma in homosexual men. Lancet 11:631–633
Author information
Authors and Affiliations
Additional information
This study was supported by the DFG, SFB 172 to BBC and HKMH and by the BMFT grant 01KI 88061 to BBC
Rights and permissions
About this article
Cite this article
Chappuis, B.B., Müller, H., Stutte, J. et al. Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS. Virchows Archiv B Cell Pathol 58, 199–205 (1989). https://doi.org/10.1007/BF02890072
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02890072