Clinicopathologic features of methotrexate-associated lymphoproliferative disorders

• Project/Area Number: 17K15658
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kyoto University
• Principal Investigator: Kurita Daisuke 京都大学, ウイルス・再生医科学研究所, 特定研究員 (70790294)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: リンパ増殖性疾患 / 悪性リンパ腫 / 臨床病理学的解 / EBウイルス / 臨床病理学的解析 / 病理学

Outline of Final Research Achievements

Methotrexate-associated lymphoproliferative disorders (MTX-LPDs) are disease, which exhibit various types of histology, and the definitive diagnostic criteria and histologic categories for MTX-LPDs are yet to be established. In this study, MTX-LPD lesions were classified into 4 diagnostic categories, and clinicopathologic features of reactive lymphoid hyperplasias (RHs), polymorphic LPDs (Poly-LPDs), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphomas (CHLs) were analyzed. Many features were significantly different among these histologic categories. After MTX withdrawal, progression-free survival (PFS) was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL. Furthermore, predictive factors for PFS were identified in each histologic category.
Current results indicate that histologic categorization and histology-specific factors could be useful for predicting MTXLPD progression after MTX withdrawal.

Academic Significance and Societal Importance of the Research Achievements

本研究ではこれまでにない多数のMTX-LPD症例を対象として組織分類を定義し、各組織分類に対応した特徴的な臨床所見および臨床経過予測因子見出した。これによりMTX-LPD診断の均てん化を推進するとともに、組織診断に基づくMTX-LPDの治療法の確立へと繋げる。また本研究で確立したMTX-LPDの組織分類を元に遺伝子発現解析を進める事で、発症に関与する遺伝子異常を同定し、MTX-LPDを発症するリスク因子を特定される事が期待される。これはMTXを用いた治療に対しての新しいガイドライン、つまり自己免疫性疾患治療における新たな指針となる可能性がある。

Research Products

• [Journal Article] Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis (2019)
  • Author(s): 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
  • Journal Title: The American Journal of Surgical Pathology Volume: 43 Issue: 7 Pages: 869-884
  • DOI: 10.1097/pas.0000000000001271
  • Peer Reviewed
• [Presentation] 慢性関節リウマチに発症するメトトレキサート関連リンパ増殖性疾患の臨床病理学的解析：組織学的分類および予後予測因子の提唱 (2018)
  • Author(s): 栗田大輔，三好寛明，市川理子，山田恭平，武藤礼治，佐々木裕哉，河本啓介，田丸淳一，得平道英，大島孝一
  • Organizer: 第58回日本リンパ網内系学会総会
• [Presentation] Clinicopathological Study of Methotrexate-Associated Lymphoproliferative Disorders in Rheumatoid Arthritis Patients: Histological Classification and Predictive Factors for Disease Progression (2017)
  • Author(s): Daisuke Kurita, Hiroaki Miyoshi, Ayako Ichikawa, Yuya Sasaki, Keisuke Kawamoto, Joji Shimono, Masao Matsuoka, Masahiro Kizaki, Masao Seto, Jun-ichi Tamaru, Michihide Tokuhira and Koichi Ohshima
  • Organizer: The 59th ASH Annual Meeting & Exposition
  • Int'l Joint Research