title: Distinct Histomorphology in Molecular Subgroups of Glioblastomas in Young Patients.
abstract: Glioblastomas (GBMs) are malignant brain tumors that can be divided into different molecular subtypes based on genetics, global gene expression, and methylation patterns. Among these subgroups, "IDH" GBMs carry mutations within IDH1 or IDH2 The "K27" and "G34" subgroups are characterized by distinct mutations within Histone 3 (H3). These subtypes can be identified by sequencing methods and are particularly found in younger patients. To determine whether the molecular subtypes correlate with distinct histological features among the diverse histologic patterns of GBM, we performed a blinded assessment of the histology of GBMs of 77 patients ≤30 years old at the time of biopsy. The tumors were of the following molecular subtypes: IDH (n = 12), H3 K27M (n = 25), H3 G34R (n = 12), or no IDH/H3 mutations (n = 28). Of IDH-mutated cases, 75% had microcystic features or gemistocytic tumor cells. K27 GBMs had higher cell densities and pronounced nuclear pleomorphism, with 28% harboring tumor giant cells. All G34 GBMs had variable extents of a poorly differentiated/primitive neuroectodermal tumor-like morphology. GBMs without IDH/H3 mutations had foci of epitheliod-appearing cells. Thus, molecular GBM subgroups are associated with distinct histological patterns, suggesting that morphological features reflect the specific underlying molecular genetic abnormalities.
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc).
authors.forename: Julia E
authors.initials: JE
authors.lastname: Neumann
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc).
authors.forename: Mario M
authors.initials: MM
authors.lastname: Dorostkar
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc).
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc).
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc).
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc).
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.affiliation: From the Center for Neuropathology (JEN, AG, US) and German Center for Neurodegenerative Diseases (MMD), Ludwig-Maximilians-University, Munich, Germany; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany (AKor); Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany (AKor); Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany (CM); and Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany (AKoc). ulrich.schueller@lmu.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schüller
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006657:Histones / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: G34R; Glioblastoma; H3; Histology; IDH1; K27M; Molecular subgroups.