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Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features.

Authors
  • Andreiuolo, Felipe1
  • Varlet, Pascale2
  • Tauziède-Espariat, Arnault2
  • Jünger, Stephanie T1
  • Dörner, Evelyn1
  • Dreschmann, Verena1
  • Kuchelmeister, Klaus1
  • Waha, Andreas1
  • Haberler, Christine3
  • Slavc, Irene4
  • Corbacioglu, Selim5
  • Riemenschneider, Markus J6
  • Leipold, Alfred7
  • Rüdiger, Thomas8
  • Körholz, Dieter9
  • Acker, Till10
  • Russo, Alexandra11
  • Faber, Jörg11
  • Sommer, Clemens12
  • Armbrust, Sven13
  • And 21 more
  • 1 Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany. , (Germany)
  • 2 Department of Neuropathology, Sainte-Anne Hospital and Paris Descartes University, Paris, France. , (France)
  • 3 Institute of Neurology, Medical University of Vienna, Vienna, Austria. , (Austria)
  • 4 Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. , (Austria)
  • 5 Department of Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, Regensburg, Regensburg, Germany. , (Germany)
  • 6 Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany. , (Germany)
  • 7 Children's Hospital Karlsruhe, Karlsruhe, Germany. , (Germany)
  • 8 Institute of Pathology, Hospital Karlsruhe, Karlsruhe, Germany. , (Germany)
  • 9 Division of Pediatric Hematology and Oncology, Department of Pediatrics, Justus-Liebig University of Giessen, Giessen, Germany. , (Germany)
  • 10 Institute of Neuropathology, University of Giessen, Giessen, Germany. , (Germany)
  • 11 Section of Pediatric Oncology, Children's Hospital, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. , (Germany)
  • 12 Institute of Neuropathology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. , (Germany)
  • 13 Department of Pediatrics and Adolescent Medicine, Dietrich-Bonhoeffer Hospital, Neubrandenburg, Germany. , (Germany)
  • 14 University Hospital for Children and Adolescents, Johannes Wesling Hospital Minden, Ruhr University Hospital, Bochum, Germany. , (Germany)
  • 15 Department of Neuropathology, Evangelisches Krankenhaus Bielefeld GmbH, Bielefeld, Germany. , (Germany)
  • 16 Clinic of Pediatrics, Klinikum Dortmund, Dortmund, Germany. , (Germany)
  • 17 Department of Pathology, Klinikum Dortmund, Dortmund, Germany. , (Germany)
  • 18 Department of General Pediatrics, Hematology/Oncology, University Children's Hospital, Tuebingen, Germany. , (Germany)
  • 19 Department of Neuropathology, University Hospital of Tuebingen, Tuebingen, Germany. , (Germany)
  • 20 Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. , (Germany)
  • 21 Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany. , (Germany)
  • 22 Department of Pediatrics, Clinical Hospital Center Rijeka, School of Medicine Rijeka, Rijeka, Croatia. , (Croatia)
  • 23 Department of Pathology, University Hospital Center Zagreb, School of Medicine, Zagreb, Croatia. , (Croatia)
  • 24 Department of Pathology, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea. , (North Korea)
  • 25 Pediatric and Adolescent Oncology and Unite Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Gustave Roussy, Paris-Saclay University, Villejuif, France. , (France)
  • 26 Department of Neurosurgery, Necker Enfants-Malades Hospital and Paris Descartes University, Paris, France. , (France)
  • 27 Department of Pediatric Neurosurgery, Children's Hospital St. Augustin, Sankt Augustin, Germany. , (Germany)
  • 28 Department of Pediatric Oncology, Children's Hospital St. Augustin, Sankt Augustin, Germany. , (Germany)
  • 29 Institute of Clinical Neuropathology, Bremen-Mitte Medical Center, Bremen, Germany. , (Germany)
  • 30 Neuroradiology, Department of Radiology, University of Bonn Medical Center, Bonn, Germany. , (Germany)
Type
Published Article
Journal
Brain Pathology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Mar 01, 2019
Volume
29
Issue
2
Pages
205–216
Identifiers
DOI: 10.1111/bpa.12659
PMID: 30246434
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Ependymoma with YAP1-MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1-MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo-rosettes, small to medium-sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot-like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1-MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1-11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow-up, 4.84 years). In this to date, largest series of ependymomas with YAP1-MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings. © 2018 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

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