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We reviewed 31 cases of TdT\u2010positive LBCL and B\u2010ALL\/LBL, and their final diagnosis included 19 diffuse large\/high\u2010grade BCLs with\n                    <jats:italic>MYC<\/jats:italic>\n                    and\n                    <jats:italic>BCL2<\/jats:italic>\n                    rearrangements (five DLBCL\u2010\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    , 14 HGBCL\u2010\n                    <jats:italic>MYC\/BCL2<\/jats:italic>\n                    ), three DLBCL not otherwise specified (NOS), three HGBCL\u2010NOS, four B\u2010ALL\/LBL, and two unclassifiable cases. TdT was variably expressed in all these cases, without any clear demarcation among different groups. Loss or partial loss of CD20 expression was seen in 13\/17 DLBCL\/HGBCL\u2010\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    , 2\/3 HGBCL\u2010NOS, and 2\/2 unclassified, albeit not in DLBCL\u2010NOS. Expression of BCL6 and\/or MUM1 was seen in 3\/4 B\u2010ALL\/LBLs and 2\/2 unclassified. Next\u2010generation sequencing revealed characteristic mutations associated with follicular lymphoma and its high\u2010grade transformation in each DLBCL\/HGBCL\u2010\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    , and also frequent variants in genes targeted by somatic hypermutation (SHM) in almost all DLBCL\/HGBCL\u2010\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    , DLBCL\u2010NOS, and HGBCL\u2010NOS but one case. In contrast, such mutations were absent in B\u2010ALL\/LBL. There were no pathognomonic mutations in the two unclassifiable cases, although one showed a moderate level of somatic mutations in its rearranged\n                    <jats:italic>IGHV<\/jats:italic>\n                    . Furthermore, in three cases of TdT\u2010positive HGBCL\u2010\n                    <jats:italic>MYC<\/jats:italic>\n                    \/\n                    <jats:italic>BCL2<\/jats:italic>\n                    , studies of previous or concurrent follicular lymphoma demonstrated their divergent evolution from an\n                    <jats:italic>IGH<\/jats:italic>\n                    ::\n                    <jats:italic>BCL2<\/jats:italic>\n                    \u2010positive cell population following acquisition of\n                    <jats:italic>MYC<\/jats:italic>\n                    translocation. In conclusion, mutation profiling analysis including the SHM target genes is highly valuable in the differential diagnosis between TdT\u2010positive LBCL and B\u2010ALL\/LBL. \u00a9 2025 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6476","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T07:26:08Z","timestamp":1759735568000},"page":"410-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutation profiling in differential diagnosis between\n                    <scp>TdT<\/scp>\n                    \u2010positive high\u2010grade\/large B\u2010cell lymphoma and B\u2010lymphoblastic leukaemia\/lymphoma"],"prefix":"10.1002","volume":"267","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-2045","authenticated-orcid":false,"given":"Maria\u2010Myrsini","family":"Tzioni","sequence":"first","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cucco","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"},{"name":"Institute of Clinical Physiology, CNR  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"R\u00e1s\u00f3\u2010Barnett","sequence":"additional","affiliation":[{"name":"The Haematopathology and Oncology Diagnostic Service Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wotherspoon","sequence":"additional","affiliation":[{"name":"Department of Histopathology The Royal Marsden Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin S","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology Robert\u2010Bosch\u2010Krankenhaus, and Dr. Margarete Fischer\u2010Bosch Institute for Clinical Pharmacology  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Madej","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-3351","authenticated-orcid":false,"given":"Jasmine","family":"Makker","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E","family":"Strazda","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"},{"name":"Hubei Cancer Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caoimhe","family":"Egan","sequence":"additional","affiliation":[{"name":"The Haematopathology and Oncology Diagnostic Service Cambridge University Hospitals NHS Foundation Trust  Cambridge 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Laurent","sequence":"additional","affiliation":[{"name":"Department of Bio\u2010Pathology Institut Universitaire Cancer\u2010Oncopole, Centre de Recherches en Canc\u00e9rologie de Toulouse INSERM U1037  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Xerri","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institut Paoli\u2010Calmettes, Centre de Recherche en Canc\u00e9rologie de Marseille Aix\u2010Marseille University  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena\u00efg","family":"Mescam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institut Paoli\u2010Calmettes, Centre de Recherche en Canc\u00e9rologie de Marseille Aix\u2010Marseille University  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Plank","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy University Hospital Martin, Jessenius Faculty of Medicine, Comenius University  Martin Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise Mette","family":"Rahbek Gjerdrum","sequence":"additional","affiliation":[{"name":"Department of Pathology Copenhagen University Hospital\u2013Zealand University Hospital  Roskilde Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Lopez\u2010Hisijos","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Greiner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology University 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