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Although Y chromosome alterations have been studied in various male\u2010predominant tumors, a limited number of studies have evaluated their role in meningiomas. To evaluate the clinicopathological significance of Y chromosome loss in male meningiomas, we assessed the frequency of loss of the Y chromosome (LOY) using droplet digital polymerase chain reaction in combination with multiplex ligation\u2010dependent probe amplification on tumor DNA from 93 male meningioma samples. LOY, detected in nine cases (9.7%), was significantly associated with a higher World Health Organization tumor grade (grade 2: 55.6% versus 14.3%; grade 1: 44.4% versus 85.7%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009) and loss of the NF2 gene\u2010encoded protein, moesin\u2010ezrin\u2010radixin\u2010like protein (merlin) (loss: 88.9% versus 50.0%; retained: 11.1% versus 50.0%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.035). RNA\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization targeting\n                    <jats:italic>KDM5D<\/jats:italic>\n                    on formalin\u2010fixed paraffin\u2010embedded tissue sections demonstrated a sensitivity of 100% (9\/9) and a specificity of 76.2% (64\/84) for LOY detection, supporting its utility as a screening modality. Moreover, spatial transcriptomic analysis revealed significant differences in the expression of genes associated with epithelial\u2013mesenchymal transition and extracellular matrix organization between LOY and non\u2010LOY meningioma tumor cells. Our findings emphasize the presence of atypical pathological features and distinct transcriptional profiles in LOY\u2010associated meningiomas. \u00a9 2026 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.70040","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:20:52Z","timestamp":1771568452000},"page":"125-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinicopathological significance of loss of Y chromosome in male meningiomas"],"prefix":"10.1002","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0321-3094","authenticated-orcid":false,"given":"Maki","family":"Sakaguchi","sequence":"first","affiliation":[{"name":"Department of Molecular 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Neurosurgery, Graduate School of Medical Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kanazawa University Hospital  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-6101","authenticated-orcid":false,"given":"Mitsutoshi","family":"Nakada","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Medical Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Nara Medical University  Kashihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daichi","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of 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