{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:23:58Z","timestamp":1790029438752,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T00:00:00Z","timestamp":1423094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan","award":["(No. 25460444)"],"award-info":[{"award-number":["(No. 25460444)"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"\n Aims<\/jats:title>\n \n To analyse the clinicopathological characteristics and prognosis of 40 rheumatoid arthritis (\n RA<\/jats:styled-content>\n ) patients with methotrexate (\n MTX<\/jats:styled-content>\n )\u2010associated large B cell lymphoproliferative disorders (\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n Soluble interleukin 2 receptor titres (median 1500\u00a0U\/ml) in 40 patients with\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n were lower than those of 24\n RA<\/jats:styled-content>\n patients with non\u2010\n MTX<\/jats:styled-content>\n \u2010 associated (non\u2010\n MTX<\/jats:styled-content>\n )\n BLPD<\/jats:styled-content>\n (5731\u00a0U\/ml) and 15 with control diffuse large B cell lymphoma (\n DLBCL<\/jats:styled-content>\n , 5918\u00a0U\/ml) (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0.01). Using\n in\u2010situ<\/jats:italic>\n hybridization, Epstein\u2013Barr virus (\n EBV<\/jats:styled-content>\n ) was detected in tumour cells of 25 of 40\n RA<\/jats:styled-content>\n patients with\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n (63%). Immunohistologically,\n BCL<\/jats:styled-content>\n 2 expression was detected in 35% of patients with\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n , which was lower than 93% of control\n DLBCL<\/jats:styled-content>\n patients (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0.01). Eleven patients with\n EBV<\/jats:styled-content>\n +<\/jats:sup>\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n (44%) showed remission after\n MTX<\/jats:styled-content>\n withdrawal. In\n RA<\/jats:styled-content>\n patients with clinical stage\n III<\/jats:styled-content>\n \/\n IV BLPD<\/jats:styled-content>\n , 15 with rituximab (R)+ cytotoxic therapies pursued better prognosis than 10 with R\u2212 cytotoxic therapies (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0.05). Among the 15 patients, seven with\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n showed better overall survival than nine control\n DLBCL<\/jats:styled-content>\n patients (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In\n RA<\/jats:styled-content>\n patients with\n MTX<\/jats:styled-content>\n \u2013\n BLPD<\/jats:styled-content>\n , immunosuppression by\n MTX<\/jats:styled-content>\n ,\n EBV<\/jats:styled-content>\n infection and low\n BCL<\/jats:styled-content>\n 2 expression in tumour cells may play roles in tumorigenesis and tumour regression. R+ cytotoxic therapies as well as\n MTX<\/jats:styled-content>\n withdrawal were highly effective in these patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.12627","type":"journal-article","created":{"date-parts":[[2014,11,28]],"date-time":"2014-11-28T12:03:14Z","timestamp":1417176194000},"page":"70-80","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Clinicopathological characteristics and rituximab addition to cytotoxic therapies in patients with rheumatoid arthritis and methotrexate\u2010associated large B lymphoproliferative disorders"],"prefix":"10.1111","volume":"67","author":[{"given":"Kozue","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Pathology Faculty of Medicine Fukuoka University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Oshiro","sequence":"additional","affiliation":[{"name":"Department of Pathology Matsuyama Red Cross Hospital Matsuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Okamura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Clinical Research Center National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Fujisaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Matsuyama Red Cross Hospital Matsuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Clinical Research Center National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifuku","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Pathology Clinical Research Center National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Suematsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Clinical Research Center National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Tamura","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Hematology and Infectious Disease Department of Internal Medicine Faculty of Medicine Fukuoka University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morishige","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine Fukuoka University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21675"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2404"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1756-185X.2010.01564.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.11.3909"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305063281806"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-008-9069-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-013-1389-1"},{"key":"e_1_2_7_10_1","first-page":"350","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"Gaulard P","year":"2008"},{"key":"e_1_2_7_11_1","first-page":"322","article-title":"Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication","volume":"34","author":"Hoshida Y","year":"2007","journal-title":"J. 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