Histopathological and Clinical Features of Methotrexate-Associated Lymphoproliferative Disorders and Post-Transplant Lymphoproliferative Disorders

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Preeyawat Ngamdamrongkiat
Emvalee Arromdee
Attapong Vongwiwatana
Weerapat Owattanapanich
Sanya Sukpanichnant


Objective: To study histopathological and clinical features of methotrexate-associated lymphoproliferative disorders (MTX-LPD) and post-transplant lymphoproliferative disorders (PTLD).
Material and Methods: A retrospective study on 30 cases of MTX-LPD and 2 cases of PTLD from 2006 to 2021.
Results: By histopathology, the MTX-LPD group had 21 cases of lymphoma (MTX-Lymphoma) and 9 cases of reactive changes (MTX-Reactive). The PTLD group included diffuse large B-cell lymphoma and polymorphic PTLD (1 case each). The distinctive findings in MTX-Lymphoma and PTLD were association with Epstein-Barr virus (EBV) (8/12 cases, 66.7%) and CD30 positivity (13/18 cases, 72.2%). The MTX-LPD group had median MTX dosage of 10 mg/week, median MTX cumulative dosage of 2,613.75 mg, and median duration of MTX usage of 2,186 days. The 14 MTX-LPD and PTLD patients has median duration to response after the varied interventions of 47 days and the time to the first complete remission (CR) of 126 days. The MTX-Reactive patients had a significantly higher absolute lymphocyte count, younger median age, fewer B symptoms, higher rate of single site involvement, less extranodal involvement, shorter duration to response, less time to enter CR, and higher CR rate than the MTXLymphoma patients (p < 0.05).
Conclusion: Histopathology in MTX-LPD and PTLD patients can vary from reactive changes to lymphoma. EBV study and CD30 immunostaining help identify MTX-LPD and PTLD. History of MTX usage and other causes of immunodeficiency should be considered before diagnosing lymphoma. MTX discontinuation or reduction of immunosuppressant dosage are recommended before administrating combined chemotherapeutic agents in unresponsive cases.


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Ngamdamrongkiat, P. ., Arromdee, E. ., Vongwiwatana, A. ., Owattanapanich, W. ., & Sukpanichnant, S. . (2022). Histopathological and Clinical Features of Methotrexate-Associated Lymphoproliferative Disorders and Post-Transplant Lymphoproliferative Disorders. Siriraj Medical Journal, 74(9), 575–589. https://doi.org/10.33192/Smj.2022.69
Original Article


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