{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:33:55Z","timestamp":1790393635379,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,1]]},"abstract":"Abstract<\/jats:title>\n \n Large B\u2010cell lymphoma (LBCL) with\n IRF4<\/jats:italic>\n rearrangement (LBCL\u2010\n IRF4<\/jats:italic>\n \u2010R) is a rare subtype predominantly diagnosed in children and young adults. Whether adult LBCL cases with\n IRF4<\/jats:italic>\n rearrangement (\n IRF4<\/jats:italic>\n \u2010R) should be classified as LBCL\u2010\n IRF4<\/jats:italic>\n \u2010R remains unclear. Clinicopathological and molecular features of 61 adult LBCL cases with\n IRF4<\/jats:italic>\n \u2010R were analyzed and compared to diffuse large B\u2010cell lymphoma, not otherwise specified (DLBCL, NOS), to assess biological heterogeneity. The 61 cases grouped by patient age and site were classified as follows: Group 1 included 13 patients aged \u226440 years, whose features supported LBCL\u2010\n IRF4<\/jats:italic>\n \u2010R, showing favorable outcomes with high frequencies of\n IGH::IRF4<\/jats:italic>\n fusion and\n IRF4<\/jats:italic>\n mutations. Group 2 comprised 37 patients aged >40 years with tumors at usual sites; 17 early\u2010stage cases largely retained LBCL\u2010\n IRF4<\/jats:italic>\n \u2010R characteristics, whereas three other early\u2010stage cases showed molecular or clinical features more consistent with DLBCL, NOS with\n IRF4<\/jats:italic>\n \u2010R. Twelve advanced\u2010stage cases showed aggressive behavior with adverse DLBCL, NOS\u2010associated mutations (e.g.,\n TP53<\/jats:italic>\n ), suggesting classification as follicular lymphoma grade 3A (FL\u20103A) and DLBCL with\n IRF4<\/jats:italic>\n \u2010R or DLBCL, NOS with\n IRF4<\/jats:italic>\n \u2010R. Five cases lacked sufficient data for definitive classification. Group 3 included 11 patients aged >40 years with tumors at unusual extranodal sites; except for one case classified as LBCL\u2010\n IRF4<\/jats:italic>\n \u2010R, the remaining 10 cases showed aggressive clinical behavior with frequent\n MYD88<\/jats:italic>\n mutations, favoring classification as FL\u20103A and DLBCL with\n IRF4<\/jats:italic>\n \u2010R or DLBCL, NOS with\n IRF4<\/jats:italic>\n \u2010R. These findings support a multidimensional approach that integrates age, tumor site, and clinicomolecular features to refine classification, enhance risk stratification, and guide personalized management in adult LBCL cases with\n IRF4<\/jats:italic>\n \u2010R.\n <\/jats:p>","DOI":"10.1002\/hem3.70295","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:39:02Z","timestamp":1768822742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Biological heterogeneity in adult\n IRF4<\/i>\n \u2010rearranged large B\u2010cell lymphoma: Stratification by age and anatomical site"],"prefix":"10.1002","volume":"10","author":[{"given":"Yuxiu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 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Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics; National Research Center for Translational Medicine at Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics; National Research Center for Translational Medicine at Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 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Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-6401","authenticated-orcid":false,"given":"Hongmei","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pathology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"280","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Pittaluga 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