{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:55:20Z","timestamp":1790841320810,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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":["Brain Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    DNA methylation profiling of CNS tumors led to the identification of HPAP (high\u2010grade glioma with pleomorphic and pseudopapillary features), a recently proposed entity with variable morphology, recurrent MAP\u2010kinase pathway activating events, and longer survival compared to glioblastoma. We aimed to independently validate and further characterize this entity. We retrieved a multicentric cohort of gliomas compatible with HPAP and performed t\u2010SNE dimensionality reduction on their DNA methylation profile. Clinical, radiological, histological, and molecular data were reviewed. Twenty tumors clustering with previously reported HPAP cases were identified. Median age at diagnosis was 37\u2009years. Radiologically, the tumors appeared as expansive lesions with heterogeneous enhancement and frequent cysts. Histologically, they were well\u2010circumscribed, with papillary and pleomorphic features variably present. Marked histological signs of aggressivity were present in seven. Immunostainings showed expression of GFAP, OLIG2, and CD34. All cases were\n                    <jats:italic>IDH1\/2<\/jats:italic>\n                    wildtype and pMGMT unmethylated. Recurrently mutated genes included\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>ATRX<\/jats:italic>\n                    ,\n                    <jats:italic>RB1,<\/jats:italic>\n                    and\n                    <jats:italic>BRAF<\/jats:italic>\n                    . Five patients had germline pathogenic variants in genes associated with hereditary tumor predisposition syndromes (\n                    <jats:italic>MLH1<\/jats:italic>\n                    ,\n                    <jats:italic>BRCA2<\/jats:italic>\n                    ,\n                    <jats:italic>CHEK2<\/jats:italic>\n                    ,\n                    <jats:italic>NF2<\/jats:italic>\n                    ,\n                    <jats:italic>RB1<\/jats:italic>\n                    ). All patients underwent surgical resection, but subsequent management was heterogeneous. Ten\u2010year estimated survival was 85%.\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    homozygous deletion seemed to identify more aggressive tumors. In conclusion, our data suggest the existence of a novel entity of circumscribed gliomas with long\u2010term survival despite possible high\u2010grade histological presentation, for which we propose the nomenclature \u201cGliomas with pleomorphic and pseudopapillary features\u201d with a spectrum encompassing provisory grade 2 and 3. A proper identification could guide treatment choices.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70153","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:24:33Z","timestamp":1790749473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gliomas with pleomorphic and pseudopapillary features (\n                    <scp>GPAP<\/scp>\n                    ) are circumscribed tumors with targetable mutations, prolonged survival, and frequent tumor predisposition"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-5393","authenticated-orcid":false,"given":"Alberto","family":"Picca","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM), Equipe labellis\u00e9e Ligue Nationale contre le Cancer  Paris France"},{"name":"Service de Neuro\u2010Oncologie, Institut de Neurologie, DMU Neurosciences, AP\u2010HP H\u00f4pital Universitaire Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7086-1920","authenticated-orcid":false,"given":"Valeria","family":"Barresi","sequence":"additional","affiliation":[{"name":"Neuropathology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8372-8069","authenticated-orcid":false,"given":"Aude","family":"Trinquet","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie Pathologiques, CHU de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-7668","authenticated-orcid":false,"given":"Luca","family":"Bertero","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0934-5365","authenticated-orcid":false,"given":"Lucia","family":"Nichelli","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM), Equipe labellis\u00e9e Ligue Nationale contre le Cancer  Paris France"},{"name":"Service de Neuroradiologie, AP\u2010HP H\u00f4pital Universitaire Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0992-1597","authenticated-orcid":false,"given":"Guillaume","family":"Chotard","sequence":"additional","affiliation":[{"name":"Service de Pathologie, Groupe Hospitalier Pellegrin, CHU de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Bernier","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie 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