Correspondence
Reversible Lymphomas
N Engl J Med 1993; 329:1657-1658November 25, 1993
- Article
To the Editor:
Kamel et al. (May 6 issue)1 reported two cases of reversible lymphomas associated with methotrexate therapy for rheumatic diseases. As they noted, several years ago we made a similar observation2. Unlike their cases, the lymphoma we described originated in T lymphocytes. Although we did not report viral data at that time, we have examined specimens from this patient for viral genomic material using the polymerase chain reaction. We found that the samples contained copies of the cytomegalovirus genome but not of the Epstein-Barr virus or human herpesvirus 6 genome3.
We have subsequently seen a second patient with rheumatoid arthritis who had a reversible lymphoproliferative disorder related to methotrexate therapy. The patient died of complications of a cerebrovascular accident. Viral studies were inconclusive.
3 ReferencesJeffrey B. Shiroky, M.D., F.R.C.P.(C).
Marianna M. Newkirk, Ph.D.
Montreal General Hospital, Montreal, QC H3G 1A4, Canada1
Kamel OW ,van de Rijn M ,Weiss LM , et al. Reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 1993;328:1317-1321
Full Text | Web of Science | Medline2
Shiroky JB ,Frost A ,Skelton JD ,Haegert DG ,Newkirk MM ,Neville C . Complications of immunosuppression associated with weekly low dose methotrexate. J Rheumatol 1991;18:1172-1175
Web of Science | Medline3
Shiroky J ,Newkirk M ,Haegart D ,Skelton J . T cell lymphoproliferation associated with CMV during methotrexate therapy for rheumatoid arthritis. Arthritis Rheum 1990;33:Suppl 9:S60-S60 abstract.
Author/Editor Response
The authors reply:
To the Editor: The viral studies of the reversible lymphoma in a patient with rheumatoid arthritis that Shiroky and colleagues reported previously1,2 are certainly of interest to us. Although the finding of the cytomegalovirus genome with the polymerase chain reaction indicates that the genome is present in the sample, it does not demonstrate localization of the virus to a specific cell population. Therefore, although cytomegalovirus may be present in the tumor cells, it could be present in non-neoplastic lymphocytes or other nonlymphoid cells in the tissue sample; in situ hybridization studies are required to localize the cytomegalovirus genome to a specific cell population. If cytomegalovirus is, in fact, localized to the neoplastic T cells, this would be an interesting finding. The report of another patient with a reversible lymphoproliferative disorder related to methotrexate therapy provides further documentation of the occurrence of immunosuppression-associated lymphoproliferative disorders in patients with rheumatic disease.
Since our report appeared in the Journal,3 we have reviewed the case material from the files of the Laboratory of Surgical Pathology at Stanford and have found several additional reports of patients with rheumatoid arthritis or dermatomyositis in whom lymphoproliferative disorders developed during methotrexate therapy. Approximately one third of these lymphoproliferative disorders involved the Epstein-Barr virus genome according to in situ hybridization studies.
3 ReferencesOnsi W. Kamel, M.D.
Matthijs van de Rijn, M.D., Ph.D.
Roger A. Warnke, M.D.
Ronald F. Dorfman, M.D., F.R.C.Path.
Stanford University Medical Center, Stanford, CA 943051
Shiroky JB ,Frost A ,Skelton JD ,Haegert DG ,Newkirk MM ,Neville C . Complications of immunosuppression associated with weekly low dose methotrexate. J Rheumatol 1991;18:1172-1175
Web of Science | Medline2
Shiroky J ,Newkirk M ,Haegart D ,Skelton J . T cell lymphoproliferation associated with CMV during methotrexate therapy for rheumatoid arthritis. Arthritis Rheum 1990;33:Suppl 9:S60-S60 abstract.3
Kamel OW ,van de Rijn M ,Weiss LM , et al. Reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 1993;328:1317-1321
Full Text | Web of Science | Medline
- Citing Articles (8)
Citing Articles
1
Rita Rizzi, Paola Curci, Mario Delia, Erminia Rinaldi, Antonia Chiefa, Giorgina Specchia, Vincenzo Liso. (2009) Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature. Medical Oncology 26:1, 1-9
CrossRef2
Frederick Wolfe, Kaleb Michaud. (2007) Biologic treatment of rheumatoid arthritis and the risk of malignancy: Analyses from a large US observational study. Arthritis & Rheumatism 56:9, 2886-2895
CrossRef3
Frederick Wolfe, Kaleb Michaud. (2004) Lymphoma in rheumatoid arthritis: The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis & Rheumatism 50:6, 1740-1751
CrossRef4
Masao Ogata, Hiroshi Kikuchi, Keiji Ono, Eiichi Ohtsuka, Ayako Gamachi, Kenji Kashima, Masaru Nasu. (2004) Spontaneous Remission of Epstein-Barr Virus-Negative Non-Hodgkin's Lymphoma after Withdrawal of Cyclosporine in a Patient with Refractory Anemia. International Journal of Hematology 79:2, 161-164
CrossRef5
Tanusin Ploysangam, Debra L. Breneman, Diya F. Mutasim. (1998) Cutaneous pseudolymphomas. Journal of the American Academy of Dermatology 38:6, 877-898
CrossRef6
Gary S. Hoffman. (1997) Treatment of wegener's granulomatosis: Time to change the standard of care?. Arthritis & Rheumatism 40:12, 2099-2104
CrossRef7
Liviu Georgescu, Geoffrey C. Quinn, Sergio Schwartzman, Stephen A. Paget. (1997) Lymphoma in patients with rheumatoid arthritis: Association with the disease state or methotrexate treatment with the disease state or methotrexate treatment. Seminars in Arthritis and Rheumatism 26:6, 794-804
CrossRef8
R. VIRABEN, P. BROUSSE, L. LAMANT. (1996) Reversible cutaneous lymphoma occurring during methotrexate therapy. British Journal of Dermatology 135:1, 116-118
CrossRef
