{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:05:08Z","timestamp":1785405908772,"version":"3.56.0"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>High\u2010grade glioma with pleomorphic and pseudopapillary features (HPAP) is a recently described entity defined by a distinct DNA methylation signature, recurrent monosomy 13, and mutations in TP53, RB1, and NF1. Most cases are supratentorial with a relatively favorable prognosis. We report a 45\u2010year\u2010old woman who presented with a right cerebellar mass exhibiting striking histopathological heterogeneity comprising low\u2010grade and high\u2010grade components. The high\u2010grade component demonstrated a p53 null immunophenotype and complete loss of RB1 expression, contrasting with wild\u2010type staining in the low\u2010grade areas. Molecular analysis confirmed pathogenic variants in TP53 (p.Pro27LeufsTer17), NF1, and NF2, with losses of chromosomes 13 and 17. Despite gross total resection and adjuvant chemoradiotherapy, the patient developed spinal intradural metastasis 26 months postoperatively. The metastatic lesion mirrored the high\u2010grade primary component immunohistochemically and harbored a newly acquired TERT promoter mutation. DNA methylation profiling of the spinal metastasis classified the tumor as HPAP. This case represents the first documented spinal metastasis and the first p53 null phenotype in HPAP, suggesting a potential role for combined RB1 and p53 immunohistochemistry in the diagnostic workup and highlighting the capacity for neuraxis dissemination in this emerging entity.<\/jats:p>","DOI":"10.1111\/pin.70150","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:46:42Z","timestamp":1784699202000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RB1 Loss as a Diagnostic Clue in a High\u2010Grade Glioma With Pleomorphic and Pseudopapillary Features (HPAP): The First Reported Case With Spinal Metastasis and a Review of the Literature"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1514-249X","authenticated-orcid":false,"given":"Furkan","family":"Aknar","sequence":"first","affiliation":[{"name":"Department of Pathology, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-7030","authenticated-orcid":false,"given":"Tuce","family":"Soylemez\u2010Akkurt","sequence":"additional","affiliation":[{"name":"Department of Pathology, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4292-6392","authenticated-orcid":false,"given":"Pinar","family":"Engin Zerk","sequence":"additional","affiliation":[{"name":"Department of Pathology National Institutes of Health, National Cancer Institute Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-3555","authenticated-orcid":false,"given":"Basak","family":"Atalay","sequence":"additional","affiliation":[{"name":"Department of Radiology, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-389X","authenticated-orcid":false,"given":"Mehmet Sabri","family":"G\u00fcrb\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5590-0637","authenticated-orcid":false,"given":"Numan","family":"Karaarslan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Central Nervous System Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2021"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02404-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlad114"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-025-02017-9"},{"key":"e_1_2_11_6_1","first-page":"140","article-title":"High\u2010Grade Glioma With Pleomorphic and Pseudopapillary Features: A Single\u2010Institution Series of Three Cases","volume":"13","author":"Goethe E. A.","year":"2025","journal-title":"Acta Neuropathologica Communications"},{"key":"e_1_2_11_7_1","first-page":"70","article-title":"High\u2010Grade Glioma With Pleomorphic and Pseudopapillary Features (HPAP): Case Reports and Literature Review","volume":"44","author":"Mezmezian M.","year":"2025","journal-title":"Clinical Neuropathology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noae144.016"},{"key":"e_1_2_11_9_1","first-page":"520","article-title":"High\u2010Grade Glioma With Pleomorphic and Pseudopapillary Features (HPAP) in the Setting of Li\u2010Fraumeni Syndrome and With Extracranial Metastasis","volume":"82","author":"Hiatt K.","year":"2023","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"e_1_2_11_10_1","first-page":"506","article-title":"High\u2010Grade Astrocytoma With Pleomorphic and Pseudopapillary Features (HPAP)\u2014Expanding the Clinicopathologic Spectrum of an Emerging Entity","volume":"84","author":"Smith H.","year":"2025","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"e_1_2_11_11_1","first-page":"517","article-title":"An Institutional Experience With the DNA Methylation Class High Grade Glioma With Pleomorphic and Pseudopapillary Features","volume":"84","author":"Alfattal R.","year":"2025","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"e_1_2_11_12_1","first-page":"518","article-title":"High\u2010Grade Glioma With Pleomorphic and Pseudopapillary Features (HPAP): A Case Report on a Rare Entity","volume":"84","author":"Nobee A.","year":"2025","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdag008"},{"key":"e_1_2_11_14_1","first-page":"507","article-title":"DNA Methylation Profiling of Adult High\u2010Grade Gliomas","volume":"84","author":"Gilani A.","year":"2025","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlab109"},{"key":"e_1_2_11_16_1","first-page":"6","article-title":"Searching for a Cut\u2010Off Point for p53 Immunohistochemistry as Evidence of TP53 Mutations","volume":"5","author":"Caliskan I.","year":"2024","journal-title":"Free Neuropathology"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pin.70150","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:47:43Z","timestamp":1785404863000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.70150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/pin.70150"],"URL":"https:\/\/doi.org\/10.1111\/pin.70150","archive":["Portico"],"relation":{},"ISSN":["1320-5463","1440-1827"],"issn-type":[{"value":"1320-5463","type":"print"},{"value":"1440-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70150"}}