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Int J Clin Exp Pathol 2013;6(10):2237-2241

Case Report
Methotrexate-related Epstein-Barr virus-associated lymphoproliferative disorder
occurring in the gingiva of a patient with rheumatoid arthritis

Mitsuaki Ishida, Keiko Hodohara, Miyuki Yoshii, Hiroko Okuno, Akiko Horinouchi, Ryota Nakanishi, Ayumi Harada, Muneo Iwai, Keiko Yoshida,
Akiko Kagotani, Takashi Yoshida, Hidetoshi Okabe

Department of Clinical Laboratory Medicine, Division of Diagnostic Pathology, Department of Hematology, Shiga University of Medical Science,
Shiga, Japan

Received August 12, 2013; Accepted August 28, 2013; Epub September 15, 2013; Published October 1, 2013

Abstract: It is well recognized that patients with immunodeficiency have a high risk of development of lymphoproliferative disorders (LPDs),
and Epstein-Barr virus (EBV) is associated with the occurrence of LPDs. Methotrexate (MTX) is one of the common cause of
iatrogenic-associated LPD, and approximately 40-50% of MTX-related LPD cases occur in extranodal sites. However, the occurrence of
MTX-related LPD in the gingiva is extremely rare. Herein, we report the fourth documented case of MTX-related EBV-associated LPD occurring
in the gingiva of a patient with rheumatoid arthritis (RA). A 76-year-old Japanese female with a 10-year history of RA, who was treated with MTX
and infliximab, presented with a tumorous lesion in the gingiva. Biopsy of the gingiva tumor revealed diffuse proliferation of large-sized
lymphoid cells with cleaved nuclei containing conspicuous nucleoli. These lymphoid cells were CD20- and EBER-positive. Therefore, a
diagnosis of MTX-related EBV-associated LPD showing features of diffuse large B-cell lymphoma (DLBCL) that occurred in the gingiva was
made. Although the occurrence of LPD in the oral region, as seen in the present case, is rare, the prevalence of this disorder may be on the
rise due to the increased number of patients undergoing immunosuppression therapy. Moreover, immunosenescence can also be a cause of
EBV-associated LPD. Therefore, recognition of the occurrence of this disorder in the oral cavity and consideration of the clinical history can
facilitate the correct diagnosis. (IJCEP1308026).

Keywords: Lymphoproliferative disorder, Epstein-Barr virus, methotrexate, gingiva

Address correspondence to: Dr. Mitsuaki Ishida, Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga
University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan. Tel: +81-77-548-2603; Fax: +81-77-548-2407; E-mail:
mitsuaki@belle.shiga-med.ac.jp