{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:36:37Z","timestamp":1788791797859,"version":"build-2803163510"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Infratentorial oligodendrogliomas, a rare pathological entity, are generally considered metastatic lesions from supratentorial primary tumors. Here, we report the case of a 23-year-old man presenting with a histopathologically confirmed right precentral gyrus grade 2 oligodendroglioma and a concurrent pontine grade 3 oligodendroglioma. The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease. Histology and genetic analysis of the pontine biopsy were consistent with grade 3 oligodendroglioma, and comparison of the two lesions demonstrated common 1p\/19q co-deletions and <jats:italic>TERT<\/jats:italic> promoter mutations but distinct <jats:italic>IDH1<\/jats:italic> mutations, with a non-canonical <jats:italic>IDH1<\/jats:italic> R132G mutation identified in the infratentorial lesion and a R132H mutation identified in the cortical lesion. Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54\u00a0Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different <jats:italic>IDH1<\/jats:italic> mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas.<\/jats:p>","DOI":"10.1186\/s40478-021-01265-9","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T13:06:00Z","timestamp":1632920760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synchronous supratentorial and infratentorial oligodendrogliomas with incongruous IDH1 mutations, a case report"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1914-7857","authenticated-orcid":false,"given":"Alexander H. C. W.","family":"Agopyan-Miu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matei A.","family":"Banu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Troy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Hargus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Canoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony J. C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Feldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Haggiagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Guy M.","family":"McKhann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"1265_CR1","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1093\/neuonc\/now231","volume":"19","author":"K Abou-El-Ardat","year":"2017","unstructured":"Abou-El-Ardat K, Seifert M, Becker K, Eisenreich S, Lehmann M, Hackmann K, Rump A, Meijer G, Carvalho B, Temme A et al (2017) Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas. Neuro Oncol 19:546\u2013557. https:\/\/doi.org\/10.1093\/neuonc\/now231","journal-title":"Neuro Oncol"},{"key":"1265_CR2","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s10014-013-0157-x","volume":"31","author":"J Akimoto","year":"2014","unstructured":"Akimoto J, Sasaki H, Haraoka R, Nakajima N, Fukami S, Kohno M (2014) Case of radiologically multicentric but genetically identical multiple glioblastomas. Brain Tumor Pathol 31:113\u2013117. https:\/\/doi.org\/10.1007\/s10014-013-0157-x","journal-title":"Brain Tumor Pathol"},{"key":"1265_CR3","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s00401-020-02194-y","volume":"140","author":"R Banan","year":"2020","unstructured":"Banan R, Stichel D, Bleck A, Hong B, Lehmann U, Suwala A, Reinhardt A, Schrimpf D, Buslei R, Stadelmann C et al (2020) Infratentorial IDH-mutant astrocytoma is a distinct subtype. Acta Neuropathol 140:569\u2013581. https:\/\/doi.org\/10.1007\/s00401-020-02194-y","journal-title":"Acta Neuropathol"},{"key":"1265_CR4","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1056\/NEJMoa1500925","volume":"374","author":"JC Buckner","year":"2016","unstructured":"Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, Coons S, Ricci P, Bullard D, Brown PD et al (2016) Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374:1344\u20131355. https:\/\/doi.org\/10.1056\/NEJMoa1500925","journal-title":"N Engl J Med"},{"key":"1265_CR5","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s00401-012-1011-7","volume":"124","author":"B Ellezam","year":"2012","unstructured":"Ellezam B, Theeler BJ, Walbert T, Mammoser AG, Horbinski C, Kleinschmidt-DeMasters BK, Perry A, Puduvalli V, Fuller GN, Bruner JM et al (2012) Low rate of R132H IDH1 mutation in infratentorial and spinal cord grade II and III diffuse gliomas. Acta Neuropathol 124:449\u2013451. https:\/\/doi.org\/10.1007\/s00401-012-1011-7","journal-title":"Acta Neuropathol"},{"key":"1265_CR6","doi-asserted-by":"publisher","DOI":"10.1080\/02688697.2019.1594692","author":"O Erdogan","year":"2019","unstructured":"Erdogan O, Sakar M, Bozkurt S, Bayrakli F (2019) Low grade oligodendroglioma seeding around the 4th ventricle. Br J Neurosurg. https:\/\/doi.org\/10.1080\/02688697.2019.1594692","journal-title":"Br J Neurosurg"},{"key":"1265_CR7","doi-asserted-by":"publisher","first-page":"33623","DOI":"10.18632\/oncotarget.25890","volume":"9","author":"K Hafazalla","year":"2018","unstructured":"Hafazalla K, Sahgal A, Jaja B, Perry JR, Das S (2018) Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review. Oncotarget 9:33623\u201333633. https:\/\/doi.org\/10.18632\/oncotarget.25890","journal-title":"Oncotarget"},{"key":"1265_CR8","doi-asserted-by":"publisher","first-page":"576","DOI":"10.3171\/2010.6.JNS091326","volume":"114","author":"W Hassaneen","year":"2011","unstructured":"Hassaneen W, Levine NB, Suki D, Salaskar AL, de Moura LA, McCutcheon IE, Prabhu SS, Lang FF, DeMonte F, Rao G et al (2011) Multiple craniotomies in the management of multifocal and multicentric glioblastoma. Clinical article. J Neurosurg 114:576\u2013584. https:\/\/doi.org\/10.3171\/2010.6.JNS091326","journal-title":"J Neurosurg"},{"key":"1265_CR9","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1093\/neuonc\/nox205","volume":"20","author":"J Hayes","year":"2018","unstructured":"Hayes J, Yu Y, Jalbert LE, Mazor T, Jones LE, Wood MD, Walsh KM, Bengtsson H, Hong C, Oberndorfer S et al (2018) Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas. Neuro Oncol 20:632\u2013641. https:\/\/doi.org\/10.1093\/neuonc\/nox205","journal-title":"Neuro Oncol"},{"key":"1265_CR10","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/neup.12043","volume":"34","author":"E Hewer","year":"2014","unstructured":"Hewer E, Beck J, Vassella E, Vajtai I (2014) Anaplastic oligodendroglioma arising from the brain stem and featuring 1p\/19q co-deletion. Neuropathology 34:32\u201338. https:\/\/doi.org\/10.1111\/neup.12043","journal-title":"Neuropathology"},{"key":"1265_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041298","volume":"7","author":"U Lass","year":"2012","unstructured":"Lass U, Numann A, von Eckardstein K, Kiwit J, Stockhammer F, Horaczek JA, Veelken J, Herold-Mende C, Jeuken J, von Deimling A et al (2012) Clonal analysis in recurrent astrocytic, oligoastrocytic and oligodendroglial tumors implicates IDH1-mutation as common tumor initiating event. PLoS ONE 7:e41298. https:\/\/doi.org\/10.1371\/journal.pone.0041298","journal-title":"PLoS ONE"},{"key":"1265_CR12","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/ng.3806","volume":"49","author":"JK Lee","year":"2017","unstructured":"Lee JK, Wang J, Sa JK, Ladewig E, Lee HO, Lee IH, Kang HJ, Rosenbloom DS, Camara PG, Liu Z et al (2017) Spatiotemporal genomic architecture informs precision oncology in glioblastoma. Nat Genet 49:594\u2013599. https:\/\/doi.org\/10.1038\/ng.3806","journal-title":"Nat Genet"},{"issue":"Suppl 4","key":"1265_CR13","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/nov189","volume":"17","author":"QT Ostrom","year":"2015","unstructured":"Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008\u20132012. Neuro Oncol 17(Suppl 4):iv1\u2013iv62. https:\/\/doi.org\/10.1093\/neuonc\/nov189","journal-title":"Neuro Oncol"},{"key":"1265_CR14","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.nec.2012.01.012","volume":"23","author":"CG Patil","year":"2012","unstructured":"Patil CG, Eboli P, Hu J (2012) Management of multifocal and multicentric gliomas. Neurosurg Clin N Am 23:343\u2013350. https:\/\/doi.org\/10.1016\/j.nec.2012.01.012","journal-title":"Neurosurg Clin N Am"},{"key":"1265_CR15","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1080\/02688697.2018.1501465","volume":"32","author":"T Picart","year":"2018","unstructured":"Picart T, Le Corre M, Chan-Seng E, Cochereau J, Duffau H (2018) The enigma of multicentric glioblastoma: physiopathogenic hypothesis and discussion about two cases. Br J Neurosurg 32:610\u2013613. https:\/\/doi.org\/10.1080\/02688697.2018.1501465","journal-title":"Br J Neurosurg"},{"key":"1265_CR16","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s11060-020-03662-x","volume":"151","author":"L Poetsch","year":"2021","unstructured":"Poetsch L, Bronnimann C, Loiseau H, Frenel JS, Siegfried A, Seizeur R, Gauchotte G, Cappellen D, Carpentier C, Figarella-Branger D et al (2021) Characteristics of IDH-mutant gliomas with non-canonical IDH mutation. J Neurooncol 151:279\u2013286. https:\/\/doi.org\/10.1007\/s11060-020-03662-x","journal-title":"J Neurooncol"},{"key":"1265_CR17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/2051-5960-2-19","volume":"2","author":"S Pusch","year":"2014","unstructured":"Pusch S, Schweizer L, Beck AC, Lehmler JM, Weissert S, Balss J, Miller AK, von Deimling A (2014) D-2-Hydroxyglutarate producing neo-enzymatic activity inversely correlates with frequency of the type of isocitrate dehydrogenase 1 mutations found in glioma. Acta Neuropathol Commun 2:19. https:\/\/doi.org\/10.1186\/2051-5960-2-19","journal-title":"Acta Neuropathol Commun"},{"key":"1265_CR18","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s11060-013-1312-2","volume":"116","author":"G Reyes-Botero","year":"2014","unstructured":"Reyes-Botero G, Giry M, Mokhtari K, Labussiere M, Idbaih A, Delattre JY, Laigle-Donadey F, Sanson M (2014) Molecular analysis of diffuse intrinsic brainstem gliomas in adults. J Neurooncol 116:405\u2013411. https:\/\/doi.org\/10.1007\/s11060-013-1312-2","journal-title":"J Neurooncol"},{"key":"1265_CR19","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1093\/neuonc\/noaa024","volume":"22","author":"A Roux","year":"2020","unstructured":"Roux A, Pallud J, Saffroy R, Edjlali-Goujon M, Debily MA, Boddaert N, Sanson M, Puget S, Knafo S, Adam C et al (2020) High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts. Neuro Oncol 22:1190\u20131202. https:\/\/doi.org\/10.1093\/neuonc\/noaa024","journal-title":"Neuro Oncol"},{"key":"1265_CR20","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.3171\/2013.2.JNS121747","volume":"118","author":"Y Terakawa","year":"2013","unstructured":"Terakawa Y, Yordanova YN, Tate MC, Duffau H (2013) Surgical management of multicentric diffuse low-grade gliomas: functional and oncological outcomes: clinical article. J Neurosurg 118:1169\u20131175. https:\/\/doi.org\/10.3171\/2013.2.JNS121747","journal-title":"J Neurosurg"},{"key":"1265_CR21","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1200\/JCO.2012.43.2229","volume":"31","author":"MJ van den Bent","year":"2013","unstructured":"van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W et al (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31:344\u2013350. https:\/\/doi.org\/10.1200\/JCO.2012.43.2229","journal-title":"J Clin Oncol"},{"key":"1265_CR22","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1158\/1078-0432.CCR-09-2902","volume":"16","author":"MJ van den Bent","year":"2010","unstructured":"van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A et al (2010) IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 16:1597\u20131604. https:\/\/doi.org\/10.1158\/1078-0432.CCR-09-2902","journal-title":"Clin Cancer Res"},{"key":"1265_CR23","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s11060-017-2571-0","volume":"135","author":"M Visani","year":"2017","unstructured":"Visani M, Acquaviva G, Marucci G, Paccapelo A, Mura A, Franceschi E, Grifoni D, Pession A, Tallini G, Brandes AA et al (2017) Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria. J Neurooncol 135:245\u2013254. https:\/\/doi.org\/10.1007\/s11060-017-2571-0","journal-title":"J Neurooncol"},{"key":"1265_CR24","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.2353\/ajpath.2009.080958","volume":"174","author":"T Watanabe","year":"2009","unstructured":"Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149\u20131153. https:\/\/doi.org\/10.2353\/ajpath.2009.080958","journal-title":"Am J Pathol"},{"key":"1265_CR25","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s00401-015-1424-1","volume":"129","author":"P Wesseling","year":"2015","unstructured":"Wesseling P, van den Bent M, Perry A (2015) Oligodendroglioma: pathology, molecular mechanisms and markers. Acta Neuropathol 129:809\u2013827. https:\/\/doi.org\/10.1007\/s00401-015-1424-1","journal-title":"Acta Neuropathol"},{"key":"1265_CR26","doi-asserted-by":"publisher","first-page":"5874","DOI":"10.1200\/JCO.2009.23.6497","volume":"27","author":"W Wick","year":"2009","unstructured":"Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R et al (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874\u20135880. https:\/\/doi.org\/10.1200\/JCO.2009.23.6497","journal-title":"J Clin Oncol"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01265-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-021-01265-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01265-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T13:17:33Z","timestamp":1632921453000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-021-01265-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1265"],"URL":"https:\/\/doi.org\/10.1186\/s40478-021-01265-9","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]},"assertion":[{"value":"17 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The patient has consented to the use of their information for the purposes of this case report. A signed consent form is available for review upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"160"}}