Clinicopathologic features of methotrexate-associated lymphoproliferative disorders

2019 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

病理学、血液内科学

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。