{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:24:33Z","timestamp":1786123473468,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The fifth edition of the World Health Organization (WHO) classification defines cold agglutinin disease (CAD) as a clonal B\u2010cell lymphoproliferative disorder occurring in the absence of overt lymphoma, whereas cases associated with lymphoma are classified as cold agglutinin syndrome (CAS). However, whether this distinction fully reflects the biological spectrum of cold agglutinin\u2013associated disorders remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a comprehensive pathological review, immunoglobulin gene analysis and whole\u2010exome sequencing in eight patients with clinically well\u2010characterised CAD or CAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five cases showed pathological findings typical of CAD, whereas two cases demonstrated lymphoma\u2010like bone marrow infiltrates resembling lymphoplasmacytic lymphoma (LPL). Nevertheless, no CD5\u2010positive or CD10\u2010positive clonal B\u2010cell population suggestive of a specific lymphoma subtype was identified by flow cytometry. Six patients showed highly restricted\n                      <jats:italic>IGHV4\u201034<\/jats:italic>\n                      usage, and mutations involving\n                      <jats:italic>KMT2D<\/jats:italic>\n                      and\n                      <jats:italic>CARD11<\/jats:italic>\n                      were identified. No pathogenic\n                      <jats:italic>MYD88<\/jats:italic>\n                      L265P or\n                      <jats:italic>CXCR4<\/jats:italic>\n                      mutations were detected in any case. Notably, the two morphologically LPL\u2010like cases lacked the canonical genetic hallmarks of LPL and instead exhibited immunogenetic and mutational features characteristic of CAD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that CAD\u2010like genetic signatures can be present even in cases with lymphoma\u2010like morphology that would currently be classified as CAS under the WHO criteria. Our results highlight a clinically relevant genotype\u2013phenotype discordance and support the integration of molecular hallmarks into diagnostic algorithms to better reflect the biological spectrum of cold agglutinin\u2013associated disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:bold>Trial Registration<\/jats:bold>\n                      : The authors have confirmed clinical trial registration is not needed for this submission\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jha2.70327","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:46:36Z","timestamp":1781696796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cold Agglutinin Disease\u2013Like Genetic Signatures in Lymphoplasmacytic Lymphoma\u2013Like Cases Challenge the WHO Fifth Edition Classification"],"prefix":"10.1002","volume":"7","author":[{"given":"Yuki","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Hematology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Hematology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoki","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hematology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Fukatsu","sequence":"additional","affiliation":[{"name":"Department of Hematology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ikezoe","sequence":"additional","affiliation":[{"name":"Department of Hematology Fukushima Medical University  Fukushima 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