Clinicopathological anaalysis of angioimmunoblastic T-cell lymphoma

• Project/Area Number: 18K15104
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Satou Akira 愛知医科大学, 医学部, 助教 (40732699)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 血管免疫芽球性T細胞リンパ腫 / Epstein-Barr virus / メトトレキセート関連リンパ増殖性疾患 / メトトレキセート / 若年発生 / メトトレキサート / T-zone dysplasia / TET2 / RHOA

Outline of Final Research Achievements

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive lymphoma derived from follicular helper T cells. Epstein-Barr virus (EBV)-positive B cells have been detected in majority of patients with AITL. We evaluated the impact of EBV on the clinicopathological characteristics of AITL. We revealed that, among the younger group of AITL (<60 years old), EBV-positive status significantly improved prognosis compared to an EBV-negative status.
We also performed clicopathological study of AITL arising in patients treated with methotrecate (MTX-AITL). The study revealed that approximately 70% of patients with MTX-AITL presented with spontaneous regression (SR) after the cessation of MTX. We further compareted the microenvironment features of MTX-AITL and normal AITL by using nCounter sytem, and found that microenvironment of MTX-AITL is rich with plasmacytoid dendritic cells. This result suggests that plasmacytoid dendritic cells might be a key factor of SR after the MTX cessation.

Academic Significance and Societal Importance of the Research Achievements

若年性AITLにおいて微小環境中のEBV陽性細胞の多寡が予後予測に有用であることを明らかにした。これにより予後不良と予測される症例では骨髄移植を考慮に入れて治療計画を立てるといった様に、治療選択の指標となることが期待される。
MTX-AITLではMTX中止による自然退縮が約7割で認めることから、通常のAITLの様に化学療法を治療の第一選択とするのではなく、MTX中止をまず試すべきであることが分かった。このことは必要でない化学療法を避けることにつながり、患者は化学療法による副作用を回避できる。結果として、患者の肉体的、精神的苦痛の軽減に寄与すると考えられる。

Research Products

• [Journal Article] Nodal EBV-positive polymorphic B cell lymphoproliferative disorder with plasma cell differentiation: clinicopathological analysis of five cases (2021)
  • Author(s): Satou Akira、Tabata Tetsuya、Suzuki Yuka、Sato Yasuharu、Tahara Ippei、Mochizuki Kunio、Oishi Naoki、Takahara Taishi、Yoshino Tadashi、Tsuzuki Toyonori、Nakamura Shigeo
  • Journal Title: Virchows Archiv Volume: 478 (5) Issue: 5 Pages: 969-976
  • DOI: 10.1007/s00428-020-02967-6
  • Peer Reviewed
• [Journal Article] The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma (2021)
  • Author(s): K. Morichika, K. Karube, S. Sakihama, R. Watanabe, M. Kawaki, Y. Nishi, S. Nakachi, S. Okamoto, T. Takahara, A. Satou, S. Shimada, K. Shimada, T. Tsuzuki, T. Fukushima, S. Morishima and H. Masuzaki
  • Journal Title: Am J Surg Pathol Volume: - Issue: 6 Pages: 832-840
  • DOI: 10.1097/pas.0000000000001691
  • Peer Reviewed / Open Access
• [Journal Article] PD‐L1 (SP142) expression in neoplastic cells predicts a poor prognosis for patients with intravascular large B‐cell lymphoma treated with rituximab‐based multi‐agent chemotherapy (2020)
  • Author(s): Suzuki Yuka、Kohno Kei、Matsue Kosei、Sakakibara Ayako、Ishikawa Eri、Shimada Satoko、Shimada Kazuyuki、Mabuchi Seiyo、Takahara Taishi、Kato Seiichi、Nakamura Shigeo、Satou Akira
  • Journal Title: Cancer Medicine Volume: 9 Issue: 13 Pages: 4768-4776
  • DOI: 10.1002/cam4.3104
  • Peer Reviewed / Open Access
• [Journal Article] EBV status has prognostic implication among young patients with angioimmunoblastic T‐cell lymphoma (2019)
  • Author(s): Eladl Ahmed E.、Shimada Kazuyuki、Suzuki Yuka、Takahara Taishi、Kato Seiichi、Kohno Kei、Elsayed Ahmed Ali、Wu Chun‐Chieh、Tokunaga Takashi、Kinoshita Tomohiro、Sakata‐Yanagimoto Mamiko、Nakamura Shigeo、Satou Akira
  • Journal Title: Cancer Medicine Volume: 9 Issue: 2 Pages: 678-688
  • DOI: 10.1002/cam4.2742
  • NAID: 120007127703
  • Peer Reviewed / Open Access
• [Journal Article] Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders with a T- or NK-cell phenotype (2019)
  • Author(s): Satou Akira、Tsuzuki Toyonori、Nakamura Shigeo
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 59 Issue: 2 Pages: 56-63
  • DOI: 10.3960/jslrt.19013
  • NAID: 130007668743
  • ISSN: 1346-4280, 1880-9952
• [Journal Article] Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases (2019)
  • Author(s): Satou A, Tabata T, Miyoshi H, Kohno K, Suzuki Y, Yamashita D, Shimada K, Kawasaki T, Sato Y, Yoshino T, Ohshima K, Takahara T, Tsuzuki T, Nakamura S
  • Journal Title: Mod Pathol Volume: in press Issue: 8 Pages: 1135-1146
  • DOI: 10.1038/s41379-019-0264-2
  • Peer Reviewed
• [Journal Article] EBV-positive mucocutaneous ulcer arising in rheumatoid arthritis patients treated with methotrexate: Single center series of nine cases. (2019)
  • Author(s): Satou A, Banno S, Hanamura I, Takahashi E, Takahara T, Nobata H, Katsuno T, Takami A, Ito Y, Ueda R, Nakamura S, Tsuzuki T
  • Journal Title: Pathology International Volume: 69(1) Issue: 1 Pages: 21-28
  • DOI: 10.1111/pin.12745
  • Peer Reviewed
• [Presentation] Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases. (2019)
  • Author(s): Akira Satou, Tetsuya Tabata, Hiroaki Miyoshi, Kei Kohno, Yasuharu Sato, Tadashi Yoshino, Koichi Ohshima, Taishi Takahara, Toyonori Tsuzuki, Shigeo Nakamura
  • Organizer: 2019 Annual meeting of USCAP
  • Int'l Joint Research