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

Nobuyuki Kabasawa; Eisuke Shiozawa; So Murai; Mayumi Homma; Yuka Uesugi; Tomoharu Matsui; Ayaka Nakata; Shotaro Shimada; Yohei Sasaki; Yuta Baba; Megumi Watanuki; Nana Arai; Shun Fujiwara; Yukiko Kawaguchi; Hiroyuki Tsukamoto; Yui Uto; Kouji Yanagisawa; Norimichi Hattori; Hirotaka Sakai; Hiroshi Harada; Tsuyoshi Nakamaki; Masafumi Takimoto; Toshiko Yamochi-Onizuka

doi:10.3960/jslrt.20025

Original Article

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

Nobuyuki Kabasawa , Eisuke Shiozawa, So Murai, Mayumi Homma, Yuka Uesugi, Tomoharu Matsui, Ayaka Nakata, Shotaro Shimada, Yohei Sasaki, Yuta Baba, Megumi Watanuki, Nana Arai, Shun Fujiwara, Yukiko Kawaguchi, Hiroyuki Tsukamoto, Yui Uto, Kouji Yanagisawa, Norimichi Hattori, Hirotaka Sakai, Hiroshi Harada, Tsuyoshi Nakamaki, Masafumi Takimoto, Toshiko Yamochi-Onizuka

Author information

Nobuyuki Kabasawa Corresponding author
Department of Pathology, Showa University School of Medicine, Tokyo, Japan,
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Eisuke Shiozawa
Department of Pathology, Showa University School of Medicine, Tokyo, Japan,
So Murai
Department of Pathology, Showa University School of Medicine, Tokyo, Japan,
Mayumi Homma
Department of Pathology, Showa University School of Medicine, Tokyo, Japan,
Yuka Uesugi
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Tomoharu Matsui
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Ayaka Nakata
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Shotaro Shimada
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Yohei Sasaki
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Yuta Baba
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Megumi Watanuki
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Nana Arai
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Shun Fujiwara
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Yukiko Kawaguchi
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Hiroyuki Tsukamoto
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Yui Uto
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Kouji Yanagisawa
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Norimichi Hattori
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Hirotaka Sakai
Division of Hematology, Department of Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
Hiroshi Harada
Division of Hematology, Department of Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
Tsuyoshi Nakamaki
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Masafumi Takimoto
Department of Pathology, Showa University School of Medicine, Tokyo, Japan,
Toshiko Yamochi-Onizuka
Department of Pathology, Showa University School of Medicine, Tokyo, Japan,

Keywords: Immunocompromised, Organ transplantation, Autoimmune disease, Germinal center, Epstein–Barr virus

JOURNAL OPEN ACCESS

2021 Volume 61 Issue 3 Pages 120-125

DOI https://doi.org/10.3960/jslrt.20025

Details

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.

Corresponding author

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