Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases.
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.
Kojima
Masaru
M
Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, Ohta, Japan. mkojima@gunma-cc.jp
Itoh
Hideaki
H
Hirabayashi
Kaoru
K
Igarashi
Seiji
S
Tamaki
Yoshio
Y
Murayama
Kayoko
K
Ogura
Hidemi
H
Saitoh
Ryuta
R
Kashiwabara
Kenji
K
Takimoto
Jyuro
J
Masawa
Nobuhide
N
Nakamura
Shigeo
S
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
D000964:Antimetabolites, Antineoplastic; D012367:RNA, Viral; D008727:Methotrexate