{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T08:40:25Z","timestamp":1792744825011,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Large cell\/anaplastic medulloblastoma is a high\u2010risk variant whose histopathological diagnosis can be challenging. We analyzed 12 pediatric cases enriched for LC\/A morphology, with centralized review available for 11. In this deliberately selected, diagnostically challenging series, institutional and central LC\/A versus non\u2010LC\/A assessments were discordant in 36% (4 of 11), illustrating the difficulty of applying the LC\/A designation rather than a general estimate of inter\u2010observer reproducibility. DNA methylation profiling was performed using four classifiers: Heidelberg CNS Tumor Methylation Classifier, Methylscape Analysis, EpiDiP, and the MAGIBU classifier, which applies a UMAP\u2010based distance approach. Tumor classification was largely concordant across platforms, identifying two\n                    <jats:italic>WNT<\/jats:italic>\n                    \u2010activated medulloblastomas, eight non\u2010\n                    <jats:italic>WNT<\/jats:italic>\n                    \/non\u2010\n                    <jats:italic>SHH<\/jats:italic>\n                    medulloblastomas, and one tumor reclassified as an embryonal tumor with multilayered rosettes. One misclassification occurred with EpiDiP, where an\n                    <jats:italic>SHH<\/jats:italic>\n                    \u2010activated medulloblastoma aligned with the normal cerebellar cortex reference profile. Copy number analysis revealed\n                    <jats:italic>MYC<\/jats:italic>\n                    amplification in two non\u2010\n                    <jats:italic>WNT<\/jats:italic>\n                    \/non\u2010\n                    <jats:italic>SHH<\/jats:italic>\n                    tumors, chromosome 6 loss in both\n                    <jats:italic>WNT<\/jats:italic>\n                    \u2010activated cases, and isochromosome 17q in one\n                    <jats:italic>MYC<\/jats:italic>\n                    \u2010amplified non\u2010\n                    <jats:italic>WNT<\/jats:italic>\n                    \/non\u2010\n                    <jats:italic>SHH<\/jats:italic>\n                    tumor. Adjunctive molecular data for a subset of cases were obtained from PedcBioPortal. The reclassified tumor lacked canonical molecular alterations but harbored additional\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    and\n                    <jats:italic>TP53<\/jats:italic>\n                    variants whose contribution to its pathogenesis remains uncertain. One\n                    <jats:italic>WNT<\/jats:italic>\n                    \u2010activated medulloblastoma also carried a\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    variant. The MAGIBU classifier correctly identified the ETMR case, classified all remaining tumors as medulloblastomas, and showed concordant subgroup assignment with the Heidelberg CNS Tumor Methylation Classifier and Methylscape Analysis, including the\n                    <jats:italic>SHH<\/jats:italic>\n                    \u2010activated case misclassified by EpiDiP. On external validation across four independent medulloblastoma cohorts (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091063), MAGIBU achieved 98.5% family\u2010level recall and 96.4% subclass\u2010level recall. In conclusion, our findings indicate that, in these diagnostically challenging, LC\/A\u2010enriched cases, morphology\u2010based diagnostic assessment can be inconsistent. DNA methylation profiling serves to refine tumor reclassification and ensure accurate risk stratification. Interpreting each tumor across complementary classifiers provides a triangulation that enhances diagnostic robustness.\n                  <\/jats:p>","DOI":"10.1111\/neup.70080","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:01:54Z","timestamp":1791860514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pediatric Large Cell\/Anaplastic Medulloblastomas: Diagnostic Concordance and Multi\u2010Classifier DNA Methylation Profiling, Including the In\u2010House MAGIBU Framework"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8081-3039","authenticated-orcid":false,"given":"Laura","family":"Giunti","sequence":"first","affiliation":[{"name":"Neuro\u2010Oncology Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-0663","authenticated-orcid":false,"given":"Gianluca","family":"Mattei","sequence":"additional","affiliation":[{"name":"UOR4 Cellular and Morphofunctional Neurobiology Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0233-5683","authenticated-orcid":false,"given":"Chiara","family":"Caporalini","sequence":"additional","affiliation":[{"name":"Pathology Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8463-8495","authenticated-orcid":false,"given":"Mirko","family":"Scagnet","sequence":"additional","affiliation":[{"name":"Neuro\u2010Surgery Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-2543","authenticated-orcid":false,"given":"Federico","family":"Mussa","sequence":"additional","affiliation":[{"name":"Neuro\u2010Surgery Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9734-5124","authenticated-orcid":false,"given":"Rina","family":"Agushi","sequence":"additional","affiliation":[{"name":"Neuro\u2010Surgery Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Guidi","sequence":"additional","affiliation":[{"name":"Neuro\u2010Oncology Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-2237","authenticated-orcid":false,"given":"Debora","family":"Vergani","sequence":"additional","affiliation":[{"name":"Medical Genetics Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Balasco","sequence":"additional","affiliation":[{"name":"Neuro\u2010Oncology Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Yuto","family":"Civale","sequence":"additional","affiliation":[{"name":"Department of Information Engineering University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Carnevali","sequence":"additional","affiliation":[{"name":"Department of Information Engineering University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Genitori","sequence":"additional","affiliation":[{"name":"Neuro\u2010Surgery Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Magi","sequence":"additional","affiliation":[{"name":"Department of Information Engineering University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Sardi","sequence":"additional","affiliation":[{"name":"Neuro\u2010Oncology Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-0765","authenticated-orcid":false,"given":"Anna Maria","family":"Buccoliero","sequence":"additional","affiliation":[{"name":"Pathology Unit Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy131"},{"key":"e_1_2_13_3_1","volume-title":"WHO Classification of Tumours of the Central Nervous System","author":"WHO Classification of Tumours Editorial Board","year":"2021"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3340\/jkns.2018.0028"},{"key":"e_1_2_13_5_1","volume-title":"Pathology and Genetics of Tumours of the Nervous System. 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