A methotrexate-associated lymphoproliferative disorder expressing CD10 and BCL6 with the IGH/CCND1 translocation
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LETTER TO THE EDITOR
A methotrexate-associated lymphoproliferative disorder expressing CD10 and BCL6 with the IGH/CCND1 translocation Hiroo Katsuya 1 & Haruna Kizuka-Sano 1 & Masako Yokoo 2 & Keisuke Kidoguchi 1 & Kyosuke Yamaguchi 1 & Atsujiro Nishioka 1 & Hiroshi Ureshino 1 & Yasushi Kubota 1 & Toshihiko Ando 1 & Shinji Naito 3 & Koichi Ohshima 4 & Shinya Kimura 1 Received: 7 July 2020 / Accepted: 10 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Dear Editor, Methotrexate (MTX) is well known to be an immunosuppressive drug related with immunodeficiency-associated lymphoproliferative disorders (MTX-LPD) [1, 2]. Although a direct effect of immunosuppressive drugs on an increased lymphoma risk remains controversial, spontaneous regression of LPD after MTX-withdrawal was observed in 86.2% of patients treated with MTX, pointing to its pathogenic role in MTX-LPD [3]. The common histological subtype of MTX-LPD is diffuse large B-cell lymphoma (DLBCL), followed by Hodgkin lymphoma, lymphoplasmacytic lymphoma, and follicular lymphoma [1]. Mantle cell lymphoma (MCL) is defined by the expression of cyclin D1 as a result of CCND1 rearrangement. The immunohistochemical staining is typically positive for pan B cell antigens, CD5, BCL-2, and SOX11 along with cyclin D1. Here, we report an extremely rare case of MCL expressing CD10 and BCL6 in a patient treated with MTX. A 75-year-old woman, who was diagnosed with rheumatoid arthritis at age 28, initiated treatment with MTX 14 years ago. At the time of presentation, the patient showed left cervical and axillary lymphadenopathies without systemic * Hiroo Katsuya [email protected] 1
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga 849-8501, Japan
2
Department of Hematology, Saga-Ken Medical Center Koseikan, Saga, Japan
3
Department of Diagnostic Pathology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
4
Department of Pathology, Kurume University School of Medicine, Kurume, Japan
symptoms. Laboratory testing identifies extremely high serum lactate dehydrogenase (LDH) level of 1549 U/L and soluble IL-2 receptor level (sIL-2R) of 18,566 U/mL (Fig. 1a). The imaging tests reveal systemic lymphadenopathy (Fig. 1b,c). Biopsy of a left cervical lymph node shows the proliferation of large atypical centroblasts, which expressed CD20, CD10, BCL2, BCL6, and MIB1, but not CD5 and Epstein-Barr virus (Fig. 1d–i). Thus, she was first diagnosed with DLBCL. After ceasing MTX treatment, the values of LDH and sIL-2R decrease, and lymphadenopathy spontaneously regresses within a month (Fig. 1a,c). Cytogenetic analysis showed a complex karyotype with t(11;14)(q13;q32) among other changes {70, XXX, + X, + 1, add(1)(p11)×2, − 2, add(3)(q21), add(3)(q27), − -4, del(4)(q?), − 5, − 6, − 8, − 13, − 14, − 15, − 22, + 8mar}. The translocation of IGH/CCND1 is subsequently confirmed by fluorescent in situ hybridization (Fig. 1l). Additional im
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