title: Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases.
abstract: We conducted clinicopathological and immunohistochemical analyses to investigate the prevalence of Epstein-Barr virus (EBV) among 13 cases with methotrexate (MTX)-associated lymphoproliferative disorder (LPD). The subjects of this study were four men and nine women ranging in age from 53 to 78 years (mean: 63 years). All 13 patients had received low dose MTX therapy for 1-13 years before the onset of LPD (mean: 5.8 years). LPDs were found at extranodal sites in six cases, and the disease stage was advanced in seven cases. The present study confirmed certain aspects of a previous observation made in the USA, including the following findings (i) the cases commonly showed diffuse large B-cell lymphomas (n=4) and Hodgkin lymphomas (HL) (n=3), (ii) EBV-encoded small RNA (EBER) + cells were identified in seven cases (60%), which is a much higher percentage than would be expected in lymphomas occurring in a general population, and (iii) three cases of polymorphous small lymphocytic or lymphoplasmacytic infiltrate achieved spontaneous remission of LPDs after MTX withdrawal. Of seven cases of EBER + in our series, three cases were PSLLPI, and two were HL. EBER + tumor cells were detected in only two (30%) of the seven cases with non-Hodgkin lymphomas. The present study suggests that EBV- associated non-Hodgkin lymphomas comprise only a portion of all non-Hodgkin lymphomas among MTX-associated LPDs.
authors.affiliation: Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, Ohta, Japan. mkojima@gunma-cc.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Kojima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Igarashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Kayoko
authors.initials: K
authors.lastname: Murayama
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ogura
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saitoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashiwabara
authors.forename: Jyuro
authors.initials: J
authors.lastname: Takimoto
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Masawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008232:Lymphoproliferative Disorders / Q000139:chemically induced* / Q000821:virology*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D015995:Prevalence; D012367:RNA, Viral / Q000302:isolation & purification
chemical_list: D000964:Antimetabolites, Antineoplastic; D012367:RNA, Viral; D008727:Methotrexate