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Lymphoproliferative Disorders in Rheumatoid Arthritis: Clinicopathological Analysis of 76 Cases in Relation to Methotrexate Medication YOSHIHIKO HOSHIDA, JING-XIAN XU, SHIGEKI FUJITA, ITSUKO NAKAMICHI, JUN-ICHIRO IKEDA, YASUHIKO TOMITA, SHIN-ICHI NAKATSUKA, JUN-ICHI TAMARU, ATSUSHI IIZUKA, TSUTOMU TAKEUCHI, and KATSUYUKI AOZASA ABSTRACT. Objective. Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. Methods. We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. Results. Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). Conclusion. The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD. (First Release Nov 15 2006; J Rheumatol 2007;34:322–31) Key Indexing Terms:
RHEUMATOID ARTHRITIS From the Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka; and the Department of Pathology and Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan. Supported in part by grants from the Ministry of Education, Science, Culture and Sports of Japan (15026209, 15406013, 15639004, 16390105, 16590276, 16590277). Y. Hoshida, MD; J-X. Xu, MD; S. Fujita, MD; I. Nakamichi, MD; J-I. Ikeda, MD; Y. Tomita, MD; S-I. Nakatsuka, MD, Department of Pathology, Osaka University Graduate School of Medicine; J-I. Tamaru, MD, Department of Pathology, Saitama Medical Center; A. Iizuka, MD; T. Takeuchi, MD, Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School; K. Aozasa, MD, Department of Pathology, Osaka University Graduate School of Medicine. Address reprint requests to Dr. Y. Hoshida, Department of Pathology (C3), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. E-mail: hoshida@molpath.med.osaka-u.ac.jp Accepted for publication August 30, 2006.
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