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| Format: | Artículo Open Access |
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Wiley
2025
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| Online Access: | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6476 |
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| author | Maria‐Myrsini Tzioni Francesco Cucco Lívia Rásó‐Barnett Zi Chen Andrew Wotherspoon Katrin S Kurz Ewelina Madej Jasmine Makker Anna E Strazda Fang Guo Caoimhe Egan Elizabeth Soilleux Liz Hook Laszlo Krenacs Julia T Geyer Camille Laurent Luc Xerri Lenaïg Mescam Lukas Plank Lise Mette Rahbek Gjerdrum Nicolas Lopez‐Hisijos Timothy Greiner Joseph Khoury Wolfram Klapper Ilske Oschlies Andreas Rosenwald German Ott Ming‐Qing Du |
| author_facet | Maria‐Myrsini Tzioni Francesco Cucco Lívia Rásó‐Barnett Zi Chen Andrew Wotherspoon Katrin S Kurz Ewelina Madej Jasmine Makker Anna E Strazda Fang Guo Caoimhe Egan Elizabeth Soilleux Liz Hook Laszlo Krenacs Julia T Geyer Camille Laurent Luc Xerri Lenaïg Mescam Lukas Plank Lise Mette Rahbek Gjerdrum Nicolas Lopez‐Hisijos Timothy Greiner Joseph Khoury Wolfram Klapper Ilske Oschlies Andreas Rosenwald German Ott Ming‐Qing Du Maria‐Myrsini Tzioni Francesco Cucco Lívia Rásó‐Barnett Zi Chen Andrew Wotherspoon Katrin S Kurz Ewelina Madej Jasmine Makker Anna E Strazda Fang Guo Caoimhe Egan Elizabeth Soilleux Liz Hook Laszlo Krenacs Julia T Geyer Camille Laurent Luc Xerri Lenaïg Mescam Lukas Plank Lise Mette Rahbek Gjerdrum Nicolas Lopez‐Hisijos Timothy Greiner Joseph Khoury Wolfram Klapper Ilske Oschlies Andreas Rosenwald German Ott Ming‐Qing Du |
| collection | Wiley Open Access |
| contents | Mutation profiling in differential diagnosis between TdT ‐positive high‐grade/large B‐cell lymphoma and B‐lymphoblastic leukaemia/lymphoma Maria‐Myrsini Tzioni Francesco Cucco Lívia Rásó‐Barnett Zi Chen Andrew Wotherspoon Katrin S Kurz Ewelina Madej Jasmine Makker Anna E Strazda Fang Guo Caoimhe Egan Elizabeth Soilleux Liz Hook Laszlo Krenacs Julia T Geyer Camille Laurent Luc Xerri Lenaïg Mescam Lukas Plank Lise Mette Rahbek Gjerdrum Nicolas Lopez‐Hisijos Timothy Greiner Joseph Khoury Wolfram Klapper Ilske Oschlies Andreas Rosenwald German Ott Ming‐Qing Du The Journal of Pathology Abstract Terminal deoxynucleotidyl transferase (TdT) is occasionally expressed in large B‐cell lymphoma (LBCL), and this causes difficulty in differential diagnosis from B‐lymphoblastic leukaemia/lymphoma (B‐ALL/LBL). We reviewed 31 cases of TdT‐positive LBCL and B‐ALL/LBL, and their final diagnosis included 19 diffuse large/high‐grade BCLs with MYC and BCL2 rearrangements (five DLBCL‐ MYC / BCL2 , 14 HGBCL‐ MYC/BCL2 ), three DLBCL not otherwise specified (NOS), three HGBCL‐NOS, four B‐ALL/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‐ MYC / BCL2 , 2/3 HGBCL‐NOS, and 2/2 unclassified, albeit not in DLBCL‐NOS. Expression of BCL6 and/or MUM1 was seen in 3/4 B‐ALL/LBLs and 2/2 unclassified. Next‐generation sequencing revealed characteristic mutations associated with follicular lymphoma and its high‐grade transformation in each DLBCL/HGBCL‐ MYC / BCL2 , and also frequent variants in genes targeted by somatic hypermutation (SHM) in almost all DLBCL/HGBCL‐ MYC / BCL2 , DLBCL‐NOS, and HGBCL‐NOS but one case. In contrast, such mutations were absent in B‐ALL/LBL. There were no pathognomonic mutations in the two unclassifiable cases, although one showed a moderate level of somatic mutations in its rearranged IGHV . Furthermore, in three cases of TdT‐positive HGBCL‐ MYC / BCL2 , studies of previous or concurrent follicular lymphoma demonstrated their divergent evolution from an IGH :: BCL2 ‐positive cell population following acquisition of MYC translocation. In conclusion, mutation profiling analysis including the SHM target genes is highly valuable in the differential diagnosis between TdT‐positive LBCL and B‐ALL/LBL. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6476 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/path.6476 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6476 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Mutation profiling in differential diagnosis between TdT ‐positive high‐grade/large B‐cell lymphoma and B‐lymphoblastic leukaemia/lymphoma Maria‐Myrsini Tzioni Francesco Cucco Lívia Rásó‐Barnett Zi Chen Andrew Wotherspoon Katrin S Kurz Ewelina Madej Jasmine Makker Anna E Strazda Fang Guo Caoimhe Egan Elizabeth Soilleux Liz Hook Laszlo Krenacs Julia T Geyer Camille Laurent Luc Xerri Lenaïg Mescam Lukas Plank Lise Mette Rahbek Gjerdrum Nicolas Lopez‐Hisijos Timothy Greiner Joseph Khoury Wolfram Klapper Ilske Oschlies Andreas Rosenwald German Ott Ming‐Qing Du The Journal of Pathology Mutation profiling in differential diagnosis between TdT ‐positive high‐grade/large B‐cell lymphoma and B‐lymphoblastic leukaemia/lymphoma Maria‐Myrsini Tzioni Francesco Cucco Lívia Rásó‐Barnett Zi Chen Andrew Wotherspoon Katrin S Kurz Ewelina Madej Jasmine Makker Anna E Strazda Fang Guo Caoimhe Egan Elizabeth Soilleux Liz Hook Laszlo Krenacs Julia T Geyer Camille Laurent Luc Xerri Lenaïg Mescam Lukas Plank Lise Mette Rahbek Gjerdrum Nicolas Lopez‐Hisijos Timothy Greiner Joseph Khoury Wolfram Klapper Ilske Oschlies Andreas Rosenwald German Ott Ming‐Qing Du The Journal of Pathology Abstract Terminal deoxynucleotidyl transferase (TdT) is occasionally expressed in large B‐cell lymphoma (LBCL), and this causes difficulty in differential diagnosis from B‐lymphoblastic leukaemia/lymphoma (B‐ALL/LBL). We reviewed 31 cases of TdT‐positive LBCL and B‐ALL/LBL, and their final diagnosis included 19 diffuse large/high‐grade BCLs with MYC and BCL2 rearrangements (five DLBCL‐ MYC / BCL2 , 14 HGBCL‐ MYC/BCL2 ), three DLBCL not otherwise specified (NOS), three HGBCL‐NOS, four B‐ALL/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‐ MYC / BCL2 , 2/3 HGBCL‐NOS, and 2/2 unclassified, albeit not in DLBCL‐NOS. Expression of BCL6 and/or MUM1 was seen in 3/4 B‐ALL/LBLs and 2/2 unclassified. Next‐generation sequencing revealed characteristic mutations associated with follicular lymphoma and its high‐grade transformation in each DLBCL/HGBCL‐ MYC / BCL2 , and also frequent variants in genes targeted by somatic hypermutation (SHM) in almost all DLBCL/HGBCL‐ MYC / BCL2 , DLBCL‐NOS, and HGBCL‐NOS but one case. In contrast, such mutations were absent in B‐ALL/LBL. There were no pathognomonic mutations in the two unclassifiable cases, although one showed a moderate level of somatic mutations in its rearranged IGHV . Furthermore, in three cases of TdT‐positive HGBCL‐ MYC / BCL2 , studies of previous or concurrent follicular lymphoma demonstrated their divergent evolution from an IGH :: BCL2 ‐positive cell population following acquisition of MYC translocation. In conclusion, mutation profiling analysis including the SHM target genes is highly valuable in the differential diagnosis between TdT‐positive LBCL and B‐ALL/LBL. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6476 http://creativecommons.org/licenses/by/4.0/ |
| title | Mutation profiling in differential diagnosis between TdT ‐positive high‐grade/large B‐cell lymphoma and B‐lymphoblastic leukaemia/lymphoma |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6476 |