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Research ArticleADULT BRAIN

Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype

V.C. Keil, M. Warmuth-Metz, C. Reh, S.J. Enkirch, C. Reinert, D. Beier, D.T.W. Jones, T. Pietsch, H.H. Schild, E. Hattingen and P. Hau
American Journal of Neuroradiology August 2017, DOI: https://doi.org/10.3174/ajnr.A5313
V.C. Keil
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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M. Warmuth-Metz
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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C. Reh
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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S.J. Enkirch
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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C. Reinert
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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D. Beier
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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D.T.W. Jones
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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T. Pietsch
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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H.H. Schild
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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E. Hattingen
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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P. Hau
From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.
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Abstract

BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.

MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.

RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm3 versus 35.1–47.6 cm3; P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).

CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

Abbreviations

AUC
area under the curve
CE
contrast-enhanced
CMB
classic medulloblastoma
DNMB
desmoplastic/nodular medulloblastoma
SHH
sonic hedgehog
WHO
World Health Organization
WNT
wingless

Footnotes

  • Elke Hattingen and Peter Hau contributed equally to this work.

  • © 2017 American Society of Neuroradiology
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V.C. Keil, M. Warmuth-Metz, C. Reh, S.J. Enkirch, C. Reinert, D. Beier, D.T.W. Jones, T. Pietsch, H.H. Schild, E. Hattingen, P. Hau
Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype
American Journal of Neuroradiology Aug 2017, DOI: 10.3174/ajnr.A5313

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Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype
V.C. Keil, M. Warmuth-Metz, C. Reh, S.J. Enkirch, C. Reinert, D. Beier, D.T.W. Jones, T. Pietsch, H.H. Schild, E. Hattingen, P. Hau
American Journal of Neuroradiology Aug 2017, DOI: 10.3174/ajnr.A5313
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