{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T16:42:38Z","timestamp":1783183358515,"version":"3.54.6"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Most patients with methotrexate\u2010associated lymphoproliferative disorder (MTX\u2010LPD) show diffuse large B\u2010cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX\u2010LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL\u2010type MTX\u2010LPD. In this study, we examined whether programmed cell death\u2010ligand 1 (PD\u2010L1) expression levels were associated with the prognosis of MTX\u2010LPD after MTX discontinuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 72\u00a0Japanese patients diagnosed with MTX\u2010LPD were clinicopathologically analyzed, and immunohistochemical staining of PD\u2010L1 was performed in 20 DLBCL\u2010type and 24 CHL\u2010type MTX\u2010LPD cases to compare with the clinical course.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD\u2010L1 was expressed in 5.0% (1\/20) of patients with DLBCL\u2010type MTX\u2010LPD, whereas it was expressed in 66.7% (16\/24) of the patients with CHL\u2010type MTX\u2010LPD in more than 51% of tumor cells. Most CHL\u2010type MTX\u2010LPD patients with high PD\u2010L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD\u2010L1\u00a0high\u2010 and low\u2010expression CHL\u2010type MTX\u2010LPD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PD\u2010L1 expression was significantly higher in patients with CHL\u2010type than DLBCL\u2010type MTX\u2010LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL\u2010type MTX\u2010LPD patients to achieve complete remission. No association was observed between PD\u2010L1 expression levels and clinical findings at diagnosis, suggesting that PD\u2010L1 expression in tumor cells influences the pathogenesis of CHL\u2010type MTX\u2010LPD after MTX discontinuation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4462","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T10:49:54Z","timestamp":1638182994000},"page":"417-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PD\u2010L1 expression is associated with the spontaneous regression of patients with methotrexate\u2010associated lymphoproliferative disorders"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-7914","authenticated-orcid":false,"given":"Yuka","family":"Gion","sequence":"first","affiliation":[{"name":"Division of Pathophysiology Okayama University Graduate School of Health Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misato","family":"Doi","sequence":"additional","affiliation":[{"name":"Division of Clinical Laboratory Hiroshima Red Cross Hospital &amp; Atomic\u2010bomb Survivors Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-7501","authenticated-orcid":false,"given":"Yoshito","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of General Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"},{"name":"Department of Medicine John A. 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