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In repeated blood films, about 15% of lymphocytes showed partial nuclear extrusion, a pattern previously documented in this patient. To test whether the abnormal morphology occurred in vivo, a non-anticoagulated bedside film was compared with EDTA and lithium heparin samples. Nuclear extrusion appeared in anticoagulated films but was completely absent in the non-anticoagulated film, indicating an in vitro phenomenon without clinical impact on CLL progression. The report also questions links to intrinsic fragility and emphasizes bedside non-anticoagulated smear review when atypical findings arise.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/partial-nuclear-extrusion-in-chronic-lymphocytic-leukemia-observed-to-be-an-in-vitro-artefact/439057/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/partial-nuclear-extrusion-in-chronic-lymphocytic-leukemia-observed-to-be-an-in-vitro-artefact/439057.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What morphological finding was observed in this CLL patient?","Question",{"text":112,"@type":113},"About 15% of lymphocytes showed partial nuclear extrusion on blood film, alongside typical CLL small lymphocyte and smudge cell features.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the authors determine whether nuclear extrusion occurred in vivo?",{"text":117,"@type":113},"They performed a non-anticoagulated bedside blood film and compared it with films from anticoagulated EDTA and lithium heparin samples collected in parallel.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the clinical significance of nuclear extrusion in this report?",{"text":121,"@type":113},"The findings support that nuclear extrusion is an in vitro phenomenon occurring in anticoagulated blood, with no apparent clinical impact on CLL progression.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},439057,1791002450,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","American Journal of Hematology  \nPartial Nuclear Extrusion in Chronic Lymphocytic Leukemia Observed to Be an In Vitro Artefact  \nRima Chatila1 | Guillaume Beziat2 | Laure Pirovano1 | Clément Bouyssie1 | Jean-Baptiste Rieu3  | Barbara J. Bain4   \n1Medical Biology Laboratory, Albi General Hospital, Albi, France | 2Department of Haematology, Albi General Hospital, Albi, France | 3Haematology Laboratory, University Hospital of Toulouse, Cancer University Institute of Toulouse–Oncopole, Toulouse, France | 4Centre for Haematology, St Mary's Hospital Campus of Imperial College Faculty of Medicine, St Mary's Hospital, London, UK  \nCorrespondence: Barbara J. Bain ([b.bain@imperial.ac.uk](b.bain@imperial.ac.uk))  \nReceived: 14 August 2025 | Accepted: 14 August 2025  \nA 69-year-old man with a 10-year history of untreated chronic lymphocytic leukemia (CLL) was referred for his annual hematology follow-up. He was in good general condition (ECOG 1), with no lymphadenopathy or splenomegaly on  \nphysical examination. His blood count showed: hemoglobin 125 g/L, platelet count 217 × 109/L, and white blood cell count 66.96 × 109/L with amarked lymphocytosis (94%, 62.94 × 109/L) . Blood film examination revealed a monomorphic population  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2025 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.  \nAmerican Journal of Hematology, 2026; 101:337–338 337  \n[https://doi.org/10.1002/ajh.70041](https://doi.org/10.1002/ajh.70041)  \nof small lymphocytes and smudge cells with typical features of CLL. However, 15% of lymphocytes displayed partial nuclear extrusion (upper images, all images May-Grünwald-Giemsa,×63 objective), a finding already observed in this patient's previous blood films.  \nTo assess whether this morphological abnormality occurred in vivo, a blood film was directly performed at the patient's bedside using a non-anticoagulated sample, in parallel with blood samples collected in EDTA and lithium heparin tubes. Strikingly, nuclear extrusion was clearly observed in the blood films from both anticoagulated samples, EDTA (top) and lithium heparin (bottom left), but was completely absent in thenon-anticoagulated blood film (bottom right) . These findings indicate that, in this case, nuclear extrusion is an in vitro phenomenon occurring in anticoagulated blood.  \nA few cases of nuclear extrusion in CLL lymphocytes have been reported in the literature [1–3], but the underlying mechanism remains unclear. Some authors have argued against an in vitro artefact, citing the consistent presence of this morphological feature in repeated samples from the same patient [2] . However, those observations were limited to heparin-anticoagulated samples. Other authors have suggested that nuclear extrusion reflects the intrinsic fragility ofCLL lymphocytes [3] . Our findings challenge this interpretation: in our case, smudge cells (widely recognized as a marker of lymphocyte fragility, resulting from mechanical disruption during film preparation) were present in both anticoagulated and non-anticoagulated blood samples. In contrast, nuclear extrusion was only observed in the anticoagulated samples. This discrepancy calls into question the hypothesis that nuclear extrusion is related to intrinsic cellular fragility.  \nAlthough the number of reported cases remains too limited to draw firm conclusions, our observation supports the hypothesis that this rare phenomenon only occurs in vitro, developing in anticoagulated blood, and does not appear to have any clinical impact on CLL progression. Moreover, it highlights the importance of performing a non-anticoagulated blood film at the patient's bedside when such atypical morphological findings are observed.  \nConflicts of Interest  \nThe authors declare no conflicts of interest.  \nData Availa","cbCaitpIHmfDxflr","https://ap.wps.com/l/cbCaitpIHmfDxflr","pdf",618673,"English","# Case description\n## Comparative assessment with anticoagulants\n# Interpretation and clinical implications","[{\"question\":\"What morphological finding was observed in this CLL patient?\",\"answer\":\"About 15% of lymphocytes showed partial nuclear extrusion on blood film, alongside typical CLL small lymphocyte and smudge cell features.\"},{\"question\":\"How did the authors determine whether nuclear extrusion occurred in vivo?\",\"answer\":\"They performed a non-anticoagulated bedside blood film and compared it with films from anticoagulated EDTA and lithium heparin samples collected in parallel.\"},{\"question\":\"What is the clinical significance of nuclear extrusion in this report?\",\"answer\":\"The findings support that nuclear extrusion is an in vitro phenomenon occurring in anticoagulated blood, with no apparent clinical impact on CLL progression.\"}]","Partial Nuclear Extrusion in Chronic Lymphocytic Leukemia Observed to Be an In Vitro Artefact | PDF",1790687309]