title: Clinical, Imaging, Histopathological and Molecular Characterization of Anaplastic Ganglioglioma.
abstract: Anaplastic ganglioglioma (AGG) is a rare and malignant variant of ganglioglioma. According to the World Health Organization classification version 2016, their histopathological grading criteria are still ill-defined. The aim of the present study was to assess the clinical, imaging, histopathological, and molecular characteristics and outcomes of AGGs in a large consecutive and retrospective adult and pediatric case series. Eighteen patients with AGGs (13 adults and 5 children) were identified (14 de novo and 4 secondary) from a cohort of 222 gangliogliomas (GG) (8%) treated at our institution between 2000 and 2015. AGGs represented a very aggressive disease with poor outcome (median progression-free survival, 10 months; median overall survival, 27 months). They were located in the temporal lobe only in 22% and presented with seizures (44%) or increased intracranial pressure (44%) at diagnosis. Concerning histopathological and molecular data, they shared morphological characteristics and BRAF V600E mutation (39%) with their benign counterparts but also showed hTERT promoter mutation (61%), p53 accumulation (39%), ATRX loss (17%), or p.K27M H3F3A mutation (17%). AGGs are malignant neoplasms requiring aggressive oncological treatment. In the perspective of targeted therapies, AGGs should be screened for BRAF V600E, hTERT, ATRX, and mutations of histone genes.
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Marc
authors.initials: M
authors.lastname: Zanello
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Mélanie
authors.initials: M
authors.lastname: Pages
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Arnault
authors.initials: A
authors.lastname: Tauziède-Espariat
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Raphael
authors.initials: R
authors.lastname: Saffroy
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Puget
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Edouard
authors.initials: E
authors.lastname: Dezamis
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Bertrand
authors.initials: B
authors.lastname: Devaux
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Felipe
authors.initials: F
authors.lastname: Andreiuolo
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Christian
authors.initials: C
authors.lastname: Sainte-Rose
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Michel
authors.initials: M
authors.lastname: Zerah
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dhermain
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Sarah
authors.initials: S
authors.lastname: Dumont
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Guillaume
authors.initials: G
authors.lastname: Louvel
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Meder
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Christelle
authors.initials: C
authors.lastname: Dufour
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD) johanpallud@hotmail.com.
authors.forename: Johan
authors.initials: J
authors.lastname: Pallud
authors.affiliation: From the Department of Neurosurgery(MZ, ED, BD, JP), Department of Neuropathology, Sainte-Anne Hospital, Paris, France(MP, AT-E, FC, FA, PV), Department of Biochemistry, Paul Brousse Hospital, Paris, France(RS) Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France(SP, CS-R, MZ), Paris Descartes University, Paris, France(MZ, MP, AT-E, SP, ED, BD, FC, FA, CS-R, MZ, J-FM, JP, PV), Department of Medical Biology and Pathology(LL), Department of Neurooncology, Gustave Roussy Institute, Villejuif, France(FD, SD, GL), Department of Neuroradiology, Sainte-Anne Hospital, Paris, France(J-FM) and Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France(JG, CD).
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
keywords: ATRX; Anaplasia; BRAF; Ganglioglioma; H3K27M; Molecular genetics; Neoplasm; Prognosis.