{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:14:06Z","timestamp":1747185246311,"version":"3.40.5"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>T cell large granular lymphocytic leukaemia (T\u2010LGLL) is a rare disorder that may underlie otherwise unexplained cytopenias. The identification of T\u2010LGLL cells in bone marrow biopsies can be a challenge, because a robust immunohistochemistry marker is lacking. The markers currently in use (granzyme B, TIA\u20101 and CD8) are difficult to interpret or lack specificity. Therefore, we investigated whether immunohistochemistry for thymocyte selection\u2010associated high\u2010mobility group box (TOX), a transcription factor that associates with chronic T cell stimulation, could be a reliable tool for the identification of T\u2010LGLL cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>In this retrospective study, expression of TOX in CD8<jats:sup>+<\/jats:sup> cells in bone marrow biopsies of T\u2010LGLL patients (<jats:italic>n<\/jats:italic>\u2009=\u200938) was investigated and compared to bone marrow of controls with reactive T cell lymphocytosis (<jats:italic>n<\/jats:italic>\u2009=\u200910). All biopsies were evaluated for TOX staining within the CD8\u2010positive T cell population. The controls were essentially negative for TOX, whereas all T\u2010LGLL cases were positive (median\u2009=\u200980%, range\u2009=\u200910\u2013100%), even when bone marrow involvement was subtle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TOX is a highly sensitive marker for the neoplastic cells of T\u2010LGLL and we recommend its use, especially in the diagnostic work\u2010up of patients with unexplained cytopenias.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15114","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T05:59:05Z","timestamp":1702447145000},"page":"697-701","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TOX<\/scp> as a new diagnostic marker for T cell large granular lymphocytic leukaemia"],"prefix":"10.1111","volume":"84","author":[{"given":"Manske M L","family":"Burg","sequence":"first","affiliation":[{"name":"Department of Pathology and Medical Biology University of Groningen, University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology University of Groningen, University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9239-1050","authenticated-orcid":false,"given":"Arjan","family":"Diepstra","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology University of Groningen, University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.56.8881"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102800"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2017.1.181"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2005.07.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-692590"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0644-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18711"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-724856"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-435297"},{"volume-title":"WHO classification of tumours series","year":"2022","author":"WHO Classification of Tumours Editorial Board","key":"e_1_2_7_11_1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxac037"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00568-0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2033433"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1324-y"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.888.888"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229743"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29173-z"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T09:02:36Z","timestamp":1707296556000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,12]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/his.15114"],"URL":"https:\/\/doi.org\/10.1111\/his.15114","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"type":"print","value":"0309-0167"},{"type":"electronic","value":"1365-2559"}],"subject":[],"published":{"date-parts":[[2023,12,12]]},"assertion":[{"value":"2023-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}