Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Apr;131(1):84–91.

Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.

C A Hanson 1, G Frizzera 1, D F Patton 1, B A Peterson 1, K L McClain 1, K J Gajl-Peczalska 1, J H Kersey 1
PMCID: PMC1880570  PMID: 2833104

Abstract

Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation.

Full text

PDF
84

Images in this article

88Figure 1
on p.88

Selected References

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

  1. Andiman W., Gradoville L., Heston L., Neydorff R., Savage M. E., Kitchingman G., Shedd D., Miller G. Use of cloned probes to detect Epstein-Barr viral DNA in tissues of patients with neoplastic and lymphoproliferative diseases. J Infect Dis. 1983 Dec;148(6):967–977. doi: 10.1093/infdis/148.6.967. [DOI] [PubMed] [Google Scholar]
  2. Arnold A., Cossman J., Bakhshi A., Jaffe E. S., Waldmann T. A., Korsmeyer S. J. Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med. 1983 Dec 29;309(26):1593–1599. doi: 10.1056/NEJM198312293092601. [DOI] [PubMed] [Google Scholar]
  3. Artusi T., Bonacorsi G., Saragoni A., Spedicato M., Rinaldi G., Federico M., Silingardi V. Castleman's lymphoadenopathy: twenty years of observation. II. Generalized form. Haematologica. 1982 Feb;67(1):124–142. [PubMed] [Google Scholar]
  4. Bartoli E., Massarelli G., Soggia G., Tanda F. Multicentric giant lymph node hyperplasia. A hyperimmune syndrome with a rapidly progressive course. Am J Clin Pathol. 1980 Mar;73(3):423–426. doi: 10.1093/ajcp/73.3.423. [DOI] [PubMed] [Google Scholar]
  5. Birx D. L., Redfield R. R., Tosato G. Defective regulation of Epstein-Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders. N Engl J Med. 1986 Apr 3;314(14):874–879. doi: 10.1056/NEJM198604033141403. [DOI] [PubMed] [Google Scholar]
  6. Brown N. A., Liu C., Garcia C. R., Wang Y. F., Griffith A., Sparkes R. S., Calame K. L. Clonal origins of lymphoproliferative disease induced by Epstein-Barr virus. J Virol. 1986 Jun;58(3):975–978. doi: 10.1128/jvi.58.3.975-978.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CASTLEMAN B., IVERSON L., MENENDEZ V. P. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer. 1956 Jul-Aug;9(4):822–830. doi: 10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  8. Chan W. C., Hargreaves H., Keller J. Giant lymph node hyperplasia with unusual clinicopathologic features. Cancer. 1984 May 15;53(10):2135–2139. doi: 10.1002/1097-0142(19840515)53:10<2135::aid-cncr2820531024>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  9. Chen K. T. Multicentric Castleman's disease and Kaposi's sarcoma. Am J Surg Pathol. 1984 Apr;8(4):287–293. doi: 10.1097/00000478-198404000-00006. [DOI] [PubMed] [Google Scholar]
  10. Clark K. A., Keren D. F. Demonstration of monoclonal lymphoplasmacytic proliferations by immunofluorescence on routine formalin-fixed, paraffin-embedded tissue. Cancer. 1982 Jun 1;49(11):2376–2382. doi: 10.1002/1097-0142(19820601)49:11<2376::aid-cncr2820491126>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  11. Cleary M. L., Chao J., Warnke R., Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci U S A. 1984 Jan;81(2):593–597. doi: 10.1073/pnas.81.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Couch W. D. Giant lymph node hyperplasia associated with thrombotic thrombocytopenic purpura. Am J Clin Pathol. 1980 Sep;74(3):340–344. doi: 10.1093/ajcp/74.3.340. [DOI] [PubMed] [Google Scholar]
  13. Dambaugh T., Beisel C., Hummel M., King W., Fennewald S., Cheung A., Heller M., Raab-Traub N., Kieff E. Epstein-Barr virus (B95-8) DNA VII: molecular cloning and detailed mapping. Proc Natl Acad Sci U S A. 1980 May;77(5):2999–3003. doi: 10.1073/pnas.77.5.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Diebold J., Tulliez M., Bernadou A., Audouin J., Tricot G., Reynes M., Bilski-Pasquier G. Angiofollicular and plasmacytic polyadenopathy: a pseudotumourous syndrome with dysimmunity. J Clin Pathol. 1980 Nov;33(11):1068–1076. doi: 10.1136/jcp.33.11.1068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dorfman R. F., Cibull M. Castleman's disease. Recent Results Cancer Res. 1978;64:284–287. [PubMed] [Google Scholar]
  16. Fauci A. S. The syndrome of Kaposi's sarcoma and opportunistic infections: an epidemiologically restricted disorder of immunoregulation. Ann Intern Med. 1982 Jun;96(6 Pt 1):777–779. doi: 10.7326/0003-4819-96-6-777. [DOI] [PubMed] [Google Scholar]
  17. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  18. Fishleder A., Tubbs R., Hesse B., Levine H. Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions. N Engl J Med. 1987 Apr 30;316(18):1118–1121. doi: 10.1056/NEJM198704303161803. [DOI] [PubMed] [Google Scholar]
  19. Frizzera G., Banks P. M., Massarelli G., Rosai J. A systemic lymphoproliferative disorder with morphologic features of Castleman's disease. Pathological findings in 15 patients. Am J Surg Pathol. 1983 Apr;7(3):211–231. doi: 10.1097/00000478-198304000-00001. [DOI] [PubMed] [Google Scholar]
  20. Frizzera G. Castleman's disease: more questions than answers. Hum Pathol. 1985 Mar;16(3):202–205. doi: 10.1016/s0046-8177(85)80002-2. [DOI] [PubMed] [Google Scholar]
  21. Frizzera G., Peterson B. A., Bayrd E. D., Goldman A. A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: clinical findings and clinicopathologic correlations in 15 patients. J Clin Oncol. 1985 Sep;3(9):1202–1216. doi: 10.1200/JCO.1985.3.9.1202. [DOI] [PubMed] [Google Scholar]
  22. Gaba A. R., Stein R. S., Sweet D. L., Variakojis D. Multicentric giant lymph node hyperplasia. Am J Clin Pathol. 1978 Jan;69(1):86–90. doi: 10.1093/ajcp/69.1.86. [DOI] [PubMed] [Google Scholar]
  23. Gajl-Peczalska K. J., Bloomfield C. D., Coccia P. F., Sosin H., Brunning R. D., Kersey J. H. B and T cell lymphomas. Analysis of blood and lymph nodes in 87 patients. Am J Med. 1975 Nov;59(5):674–685. doi: 10.1016/0002-9343(75)90228-4. [DOI] [PubMed] [Google Scholar]
  24. Greenberg J. M., Quertermous T., Seidman J. G., Kersey J. H. Human T cell gamma-chain gene rearrangements in acute lymphoid and nonlymphoid leukemia: comparison with the T cell receptor beta-chain gene. J Immunol. 1986 Sep 15;137(6):2043–2049. [PubMed] [Google Scholar]
  25. Hanto D. W., Frizzera G., Gajl-Peczalska K. J., Simmons R. L. Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation. 1985 May;39(5):461–472. doi: 10.1097/00007890-198505000-00001. [DOI] [PubMed] [Google Scholar]
  26. Hineman V. L., Phyliky R. L., Banks P. M. Angiofollicular lymph node hyperplasia and peripheral neuropathy: association with monoclonal gammopathy. Mayo Clin Proc. 1982 Jun;57(6):379–382. [PubMed] [Google Scholar]
  27. Ho M., Miller G., Atchison R. W., Breinig M. K., Dummer J. S., Andiman W., Starzl T. E., Eastman R., Griffith B. P., Hardesty R. L. Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: the role of primary infection. J Infect Dis. 1985 Nov;152(5):876–886. doi: 10.1093/infdis/152.5.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  29. Kadin M. E., Vonderheid E. C., Sako D., Clayton L. K., Olbricht S. Clonal composition of T cells in lymphomatoid papulosis. Am J Pathol. 1987 Jan;126(1):13–17. [PMC free article] [PubMed] [Google Scholar]
  30. Keller A. R., Hochholzer L., Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer. 1972 Mar;29(3):670–683. doi: 10.1002/1097-0142(197203)29:3<670::aid-cncr2820290321>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  31. Kessler E., Beer R. Multicentric giant lymph node hyperplasia clinically simulating angioimmunoblastic lymphadenopathy. Associated Kaposi's sarcoma in two of three cases. Isr J Med Sci. 1983 Mar;19(3):230–234. [PubMed] [Google Scholar]
  32. Korsmeyer S. J., Arnold A., Bakhshi A., Ravetch J. V., Siebenlist U., Hieter P. A., Sharrow S. O., LeBien T. W., Kersey J. H., Poplack D. G. Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins. J Clin Invest. 1983 Feb;71(2):301–313. doi: 10.1172/JCI110770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kyle R. A. 'Benign' monoclonal gammopathy. A misnomer? JAMA. 1984 Apr 13;251(14):1849–1854. [PubMed] [Google Scholar]
  34. Lipford E. H., Smith H. R., Pittaluga S., Jaffe E. S., Steinberg A. D., Cossman J. Clonality of angioimmunoblastic lymphadenopathy and implications for its evolution to malignant lymphoma. J Clin Invest. 1987 Feb;79(2):637–642. doi: 10.1172/JCI112860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mufarrij A., Fazzini E., Feiner H. D. Giant lymph node hyperplasia. An immunopathologic and ultrastructural study of a case of the multicentric plasma cell variant. Arch Pathol Lab Med. 1982 Feb;106(2):92–95. [PubMed] [Google Scholar]
  36. Nathwani B. N., Rappaport H., Moran E. M., Pangalis G. A., Kim H. Malignant lymphoma arising in angioimmunoblastic lymphadenopathy. Cancer. 1978 Feb;41(2):578–606. doi: 10.1002/1097-0142(197802)41:2<578::aid-cncr2820410226>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  37. Okuda K., Himeno Y., Toyama T., Ohta M., Kitagawa M., Sugai S. Gamma heavy chain disease and giant lymph node hyperplasia in a patient with impaired T cell function. Jpn J Med. 1982 Apr;21(2):109–114. doi: 10.2169/internalmedicine1962.21.109. [DOI] [PubMed] [Google Scholar]
  38. Pelicci P. G., Knowles D. M., 2nd, Arlin Z. A., Wieczorek R., Luciw P., Dina D., Basilico C., Dalla-Favera R. Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis. J Exp Med. 1986 Dec 1;164(6):2049–2060. doi: 10.1084/jem.164.6.2049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pelicci P. G., Knowles D. M., 2nd, Dalla Favera R. Lymphoid tumors displaying rearrangements of both immunoglobulin and T cell receptor genes. J Exp Med. 1985 Sep 1;162(3):1015–1024. doi: 10.1084/jem.162.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Penn I. Kaposi's sarcoma in organ transplant recipients: report of 20 cases. Transplantation. 1979 Jan;27(1):8–11. doi: 10.1097/00007890-197901000-00003. [DOI] [PubMed] [Google Scholar]
  41. Pérez Peña F., Tejero Lamarca J., Martin Rodilla C., de la Peña Mayor M., Sanz Ortega F., Murie Carrillo M., González N., Schuller Pérez A. Enfermedad de Castleman: linfoma difuso histiocítico en la evolución de la hipepplasia linfonodular hialino-vascular es una entidad benigna? Rev Clin Esp. 1980 Jul 15;158(1-2):83–86. [PubMed] [Google Scholar]
  42. Rambaldi A., Pelicci P. G., Allavena P., Knowles D. M., 2nd, Rossini S., Bassan R., Barbui T., Dalla-Favera R., Mantovani A. T cell receptor beta chain gene rearrangements in lymphoproliferative disorders of large granular lymphocytes/natural killer cells. J Exp Med. 1985 Dec 1;162(6):2156–2162. doi: 10.1084/jem.162.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schlosnagle D. C., Chan W. C., Hargreaves H. K., Nolting S. F., Brynes R. K. Plasmacytoma arising in giant lymph node hyperplasia. Am J Clin Pathol. 1982 Oct;78(4):541–544. doi: 10.1093/ajcp/78.4.541. [DOI] [PubMed] [Google Scholar]
  44. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  45. Tawa A., Hozumi N., Minden M., Mak T. W., Gelfand E. W. Rearrangement of the T-cell receptor beta-chain gene in non-T-cell, non-B-cell acute lymphoblastic leukemia of childhood. N Engl J Med. 1985 Oct 24;313(17):1033–1037. doi: 10.1056/NEJM198510243131701. [DOI] [PubMed] [Google Scholar]
  46. Thomsen D. R., Stinski M. F. Cloning of the human cytomegalovirus genome as endonuclease XbaI fragments. Gene. 1981 Dec;16(1-3):207–216. doi: 10.1016/0378-1119(81)90077-9. [DOI] [PubMed] [Google Scholar]
  47. Weisenburger D. D., Nathwani B. N., Winberg C. D., Rappaport H. Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases. Hum Pathol. 1985 Feb;16(2):162–172. doi: 10.1016/s0046-8177(85)80065-4. [DOI] [PubMed] [Google Scholar]
  48. Weiss L. M., Wood G. S., Ellisen L. W., Reynolds T. C., Sklar J. Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease). Am J Pathol. 1987 Mar;126(3):417–421. [PMC free article] [PubMed] [Google Scholar]
  49. Weiss L. M., Wood G. S., Trela M., Warnke R. A., Sklar J. Clonal T-cell populations in lymphomatoid papulosis. Evidence of a lymphoproliferative origin for a clinically benign disease. N Engl J Med. 1986 Aug 21;315(8):475–479. doi: 10.1056/NEJM198608213150802. [DOI] [PubMed] [Google Scholar]

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

RESOURCES