Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: Comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types

Yuka Gion, Noriko Iwaki, Katsuyoshi Takata, Mai Takeuchi, Keiichiro Nishida, Yorihisa Orita, Tomoyasu Tachibana, Tadashi Yoshino, Yasuharu Sato

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Patients with rheumatoid arthritis often develop methotrexate-associated lymphoproliferative disorders (MTX-LPD) during MTX treatment. MTX-LPD occasionally regresses spontaneously after simply discontinuing MTX treatment. In patients without spontaneous regression, additional chemotherapy is required to avoid disease progression. However, the differences between spontaneous and non-spontaneous regression have yet to be elucidated. To clarify the factors important for spontaneous regression, we analyzed the clinicopathological features of 51 patients with rheumatoid arthritis who developed MTX-LPD (diffuse large B-cell lymphoma [DLBCL]-type [n = 34] and classical Hodgkin lymphoma [CHL]-type [n = 17]). We examined the interval from MTX discontinuation to the administration of additional chemotherapy. The majority of DLBCL-type MTX-LPD patients (81%) exhibited remission with MTX discontinuation alone. In contrast, the majority of CHL-type MTX-LPD patients (76%) required additional chemotherapy. This difference was statistically significant (P = 0.001). However, overall survival was not significantly different between DLBCL-type and CHL-type (91% vs 94%, respectively; P > 0.05). Thus, the morphological differences in the pathological findings of MTX-LPD may be a factor for spontaneous or non-spontaneous regression after discontinuation of MTX.

Original languageEnglish
Pages (from-to)1271-1280
Number of pages10
JournalCancer Science
Issue number6
Publication statusPublished - Jun 1 2017



  • Epstein-Barr virus
  • histological findings
  • methotrexate-associated lymphoproliferative disorders
  • rheumatoid arthritis
  • spontaneous remission

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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