{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:52:08Z","timestamp":1792414328152,"version":"4.4.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The 2021 World Health Organization classification of Central Nervous System tumors (CNS5) includes molecular biomarkers in the necessary diagnostic criteria for many tumors. Identifying these markers often requires next-generation sequencing (NGS) and\/or DNA methylation profiling, presenting challenges in diagnosing these tumors in low or middle-income countries (LMICs) and other resource-limited settings. Here, we will illustrate the real-world scope of the problem by presenting a neuropathologist\u2019s experience with implementing the CNS5 criteria in an academic medical center in Karachi, Pakistan.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>CNS tumor biopsies received by a single neuropathologist (AG) in Karachi during a 6-month period (October 2022 to March 2023) were included in the study. Routine histologic processing, H&amp;E and immunohistochemistry were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 443 tumor cases were received, 87 of those (19.64% of total, 36.86% of glial, embryonal, and glioneuronal tumors) could not be assigned a CNS5 diagnosis. Top reasons for failure to reach a CNS5 diagnosis were low-grade gliomas or infiltrative glioma in pediatric\/ adolescent young adults not further classifiable on histology, IDH-mutant tumors requiring 1p\/19q testing to rule out oligodendroglioma, undifferentiated tumors with unclear lineage and adult grade 2 or 3 IDH-wildtype astrocytomas suspicious for glioblastoma, IDH-wildtype. Send-out DNA methylation testing in 22 cases resolved the diagnostic questions in all except one case.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Without access to molecular testing, up to a third of all glial, embryonal, and glioneuronal tumors could not be assigned a CNS5 diagnosis, leading to diagnostic ambiguity and therapeutic confusion. Until affordable molecular assays are available, CNS5 diagnostic criteria have limited applicability in resource-limited settings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/nop\/npae124","type":"journal-article","created":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T04:22:36Z","timestamp":1734841356000},"page":"401-412","source":"Crossref","is-referenced-by-count":7,"title":["Challenges in implementing 2021 WHO CNS tumor classification in a resource-limited setting"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-2892","authenticated-orcid":false,"given":"Ahmed","family":"Gilani","sequence":"first","affiliation":[{"name":"Department of Medicine, Aga Khan University , Karachi ,","place":["Pakistan"]},{"name":"Department of Pathology, University of Colorado Anschutz Medical Campus , Aurora, CO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Altaf","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Aga Khan University Hospital , Karachi ,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Shakir","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Aga Khan University Hospital , Karachi ,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurram","family":"Minhas","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Aga Khan University Hospital , Karachi ,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Ather","family":"Enam","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Aga Khan University Hospital , Karachi 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