Skip to main content

Advertisement

SpringerLink
Log in

Reversible Epstein-Barr Virus-Negative Lymphadenopathy and Bone Marrow Involved by Hodgkin’s Lymphoma in a Rheumatoid Arthritis Patient Undergoing Long-term Treatment with Low-Dose Methotrexate: A Case Report and Review of the Literature

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

We report a case of spontaneous regression of Epstein-Barr virus (EBV)-negative methotrexate-associated lymphadenopathy occurring with Hodgkin’s lymphoma in the bone marrow of a 48-year-old woman with rheumatoid arthritis. Following 10 years of treatment with low-dose methotrexate, the patient developed pancytopenia, hypercalcemia, and elevated levels of liver enzymes over the course of 2 months. A computed tomography scan of the abdomen revealed splenomegaly and enlarged abdominal lymph nodes. A bone marrow biopsy demonstrated cellular marrow with 2 paratrabecular granuloma-like lesions composed of histiocytes, fibroblasts, small lymphocytes, a few plasma cells, and scattered CD30+CD15+ Hodgkin’s cells, including a classic Reed-Sternberg cell. The results of EBV studies of the bone marrow were negative. Within a month from withdrawal of methotrexate treatment, the patient’s symptoms and the abnormalities in the laboratory results had regressed completely. A positron emission tomography scan failed to detect lymphadenopathy. Twelve months later, the patient remains free of symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Harris NL, Swerdlow SH. Methotrexate-associated lymphoprolif- erative disorders. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours. Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues. 1st ed. Lyon, France: IARC Press; 2001:270–271.

    Google Scholar 

  2. Salloum E, Cooper DL, Howe G, et al. Spontaneous regression of lymphoproliferative disorders in patients treated with methotrex- ate for rheumatoid arthritis and other rheumatic diseases. J Clin Oncol. 1996;14:1943–1949.

    Article  PubMed  CAS  Google Scholar 

  3. Kono H, Inokuma S, Matsuzaki Y, et al. Two cases of methotrexate induced lymphomas in rheumatoid arthritis: an association with increased serum IgE. J Rheumatol. 1999;26:2249–2253.

    PubMed  CAS  Google Scholar 

  4. Moder KG, Tefferi A, Cohen MD, Menke DM, Luthra HS. Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study. Am J Med. 1995;99: 276–281.

    Article  PubMed  CAS  Google Scholar 

  5. Kremer JM. Safety, efficacy, and mortality in a long-term cohort of patients with rheumatoid arthritis taking methotrexate: followup after a mean of 13.3 years. Arthritis Rheum. 1997;40: 984–985.

    Article  PubMed  CAS  Google Scholar 

  6. Weinblatt ME, Maier AL, Fraser PA, Coblyn JS. Longterm prospective study of methotrexate in rheumatoid arthritis: conclusion after 132 months of therapy. J Rheumatol. 1998;25:238–242.

    PubMed  CAS  Google Scholar 

  7. Mariette X, Cazals-Hafem D, Warszawki J, Liote F, Balandraud N, Sibilia J, and the investigators of the Club Rhumatismes et Inflammation. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood. 2002;99: 3909–3915.

    Article  PubMed  CAS  Google Scholar 

  8. Georgescu L, Quinn GC, Schwartzman S, Paget SA. Lymphoma in patients with rheumatoid arthritis: association with the disease state or methotrexate treatment. Semin Arthritis Rheum. 1997;26: 794–804.

    Article  PubMed  CAS  Google Scholar 

  9. Kamel OW, Weiss LM, van de Rijn M, Colby TV, Kingma DW, Jaffe ES. Hodgkin’s disease and lymphoproliferations resembling Hodgkin’s disease in patients receiving long-term low-dose methotrexate therapy. Am J Surg Pathol. 1996;20:1279–1287.

    Article  PubMed  CAS  Google Scholar 

  10. Padeh S, Sharon N, Schiby G, Rechavi G, Passwell JH. Hodgkin’s lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate. J Rheumatol. 1997;24: 2035–2037.

    PubMed  CAS  Google Scholar 

  11. Ferracciloi GF, Casatta L, Bartoli E, et al. Epstein-Barr virus-associated Hodgkin’s lymphoma in a rheumatoid arthritis patient treated with methotrexate and cyclosporin A. Arthritis Rheum. 1995;38:867–868.

    Article  Google Scholar 

  12. Kamel OW, van de Rijn M, Weiss LM, et al. Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med. 1993;328:1317–1321.

    Article  PubMed  CAS  Google Scholar 

  13. Londino AV Jr, Blatt J, Knisely AS. Hodgkin’s disease in a patient with juvenile rheumatoid arthritis taking weekly low dose methotrexate. J Rheumatol. 1998;25:1245–1246.

    PubMed  Google Scholar 

  14. Chang KL, Chen YY, Shibata D, Weiss LM. Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues. Diagn Mol Pathol. 1992;1: 246–255.

    Article  PubMed  CAS  Google Scholar 

  15. Lukes RJ. Criteria for involvement of lymph node, bone marrow, spleen and liver in Hodgkin’s disease. Cancer Res. 1971;31: 1755–1767.

    PubMed  CAS  Google Scholar 

  16. Feng W, Cohen JI, Fischer S, et al. Reactivation of latent Epstein- Barr virus by methotrexate: a potential contributor to methotrexate-associated lymphomas. J Natl Cancer Inst. 2004;96:1691–1702.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA

    Annika M. Svensson, Erica R. Jacobson & Barbara H. indle

  2. Department of Pathology and Laboratory Medicine, Fletcher Allen Health Care, Burlington, Vermont, USA

    Annika M. Svensson, Erica R. Jacobson & Barbara H. indle

  3. Central Vermont Medical Center, Berlin, Vermont, USA

    David Ospina

Authors
  1. Annika M. Svensson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erica R. Jacobson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barbara H. indle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Ospina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Annika M. Svensson.

About this article

Cite this article

Svensson, A.M., Jacobson, E.R., indle, B.H. et al. Reversible Epstein-Barr Virus-Negative Lymphadenopathy and Bone Marrow Involved by Hodgkin’s Lymphoma in a Rheumatoid Arthritis Patient Undergoing Long-term Treatment with Low-Dose Methotrexate: A Case Report and Review of the Literature. Int J Hematol 83, 47–50 (2006). https://doi.org/10.1532/IJH97.NA0503

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1532/IJH97.NA0503

Key words

Search

Navigation