Increased MYC expression without MYC gene translocation in patients with the diffuse large B-cell-lymphoma subtype of iatrogenic immunodeficiency-associated lymphoproliferative disorders

• Kabasawa Nobuyuki

  Department of Pathology, Showa University School of Medicine, Tokyo, Japan, Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Shiozawa Eisuke

  Department of Pathology, Showa University School of Medicine, Tokyo, Japan,

• Murai So

  Department of Pathology, Showa University School of Medicine, Tokyo, Japan,

• Homma Mayumi

  Department of Pathology, Showa University School of Medicine, Tokyo, Japan,

• Uesugi Yuka

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Matsui Tomoharu

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Nakata Ayaka

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Shimada Shotaro

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Sasaki Yohei

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Baba Yuta

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Watanuki Megumi

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Arai Nana

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Fujiwara Shun

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Kawaguchi Yukiko

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Tsukamoto Hiroyuki

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Uto Yui

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Yanagisawa Kouji

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Hattori Norimichi

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Sakai Hirotaka

  Division of Hematology, Department of Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan

• Harada Hiroshi

  Division of Hematology, Department of Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan

• Nakamaki Tsuyoshi

  Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,

• Takimoto Masafumi

  Department of Pathology, Showa University School of Medicine, Tokyo, Japan,

• Yamochi-Onizuka Toshiko

  Department of Pathology, Showa University School of Medicine, Tokyo, Japan,

Abstract

Post-transplant lymphoproliferative disorder (PTLD) and other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are iatrogenic lymphoproliferative disorders (LPD) that develop in association with immunosuppressive treatment in the setting of organ transplantation and autoimmune disease, respectively. Each has a spectrum of pathologies ranging from lymphoid hyperplasia to lymphoma. To clarify the characteristics of the diffuse large B-cell lymphoma (DLBCL) subtype in a cohort of 25 patients with PTLD or OIIA-LPD from our institute, we selected 13 with a histological subtype of DLBCL, including 2 cases of PTLD and 11 of OIIA-LPD. The median patient age at diagnosis was 70 years, with a female predominance. Both PTLD cases developed after kidney transplant. Of the patients with OIIA-LPD, 10 had rheumatoid arthritis, 1 had mixed connective tissue disease, and 8 were treated using methotrexate. Both of the PTLD patients and 6 of the OIIA-LPD patients had extranodal manifestations. All patients except for one were classified as having the non-germinal center B-cell (non-GCB) subtype according to the Hans algorithm. Tissue samples from 8 patients were positive for CD30 and 8 were positive for Epstein–Barr virus (EBV)-encoded small RNA. Seven patients had MYC-positive tissue samples, but none had MYC translocation. Our study suggests that extranodal manifestations and the non-GCB subtype are common, that EBV is associated with the DLBCL subtype of PTLD and OIIA-LPD, and that anti-CD30 therapy is applicable. In addition, our patients with the DLBCL subtype of PTLD and OIIA-LPD exhibited MYC overexpression without MYC translocation, suggesting an alternative mechanism of MYC upregulation.

Journal

• Journal of Clinical and Experimental Hematopathology

  Journal of Clinical and Experimental Hematopathology 61 (3), 120-125, 2021

  The Japanese Society for Lymphoreticular Tissue Research

Keywords

• Immunocompromised
• Organ transplantation
• Autoimmune disease
• Germinal center
• Epstein–Barr virus

Details

• CRID: 1390007857410596480
• NII Article ID: 130008087384
• DOI: 10.3960/jslrt.20025
• ISSN: 18809952
• ISSN: 13464280
• Web Site: https://www.jstage.jst.go.jp/article/jslrt/61/3/61_20025/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2022197351
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed