Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis: Clinicopathologic Features and Prognostic Factors. (July 2019)

• Record Type: Journal Article
• Authors: Kurita, Daisuke; Miyoshi, Hiroaki; Ichikawa, Ayako; Kato, Koji; Imaizumi, Yoshitaka; Seki, Ritsuko; Sato, Kensaku; Sasaki, Yuya; Kawamoto, Keisuke; Shimono, Joji; Yamada, Kyohei; Muto, Reiji; Kizaki, Masahiro; Nagafuji, Koji; Tamaru, Jun-ichi; Tokuhira, Michihide; Ohshima, Koichi
• Is Part Of: American journal of surgical pathology. Volume 43:Number 7(2019)
• Publication Date: 2019-07
• Subjects: lymphoproliferative disorders -- methotrexate -- immunodeficiency -- disease progression -- rheumatoid arthritis; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001271
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30, 33, 106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P <0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal. Abstract : Supplemental Digital Content is available in the text.