Azadeh Ebrahimi1,2,3,4, Marco Skardelly5,6,7,8, Martin U Schuhmann5, Martin Ebinger9, David Reuss10,11, Manuela Neumann12,8, Ghazaleh Tabatabai6,7,13,14,8, Patricia Kohlhof-Meinecke15, Jens Schittenhelm16,17. 1. Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany. azadeh.ebrahimi@med.uni-heidelberg.de. 2. Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. azadeh.ebrahimi@med.uni-heidelberg.de. 3. Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany. azadeh.ebrahimi@med.uni-heidelberg.de. 4. Department of Neuropathology, Institute of Pathology, University Hospital of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. azadeh.ebrahimi@med.uni-heidelberg.de. 5. Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany. 6. Interdisciplinary Division of Neurooncology, Departments of Vascular Neurology and Neurosurgery, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany. 7. Laboratory for Clinical and Experimental Neurooncology, Hertie-Institute for Clinical Brain Research, Tuebingen, Germany. 8. Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany. 9. Department of General Pediatrics, Hematology/Oncology, University Children's Hospital, 72076, Tuebingen, Germany. 10. Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. 11. Department of Neuropathology, Institute of Pathology, University Hospital of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. 12. Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany. 13. Center for Personalized Medicine, Eberhard Karls University of Tuebingen, Tuebingen, Germany. 14. German Consortium for Translational Cancer Research (DKTK), DKFZ Partner Site Tuebingen, Tuebingen, Germany. 15. Department of Pathology, Katharinenhospital Stuttgart, Stuttgart, Germany. 16. Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany. jens.schittenhelm@med.uni-tuebingen.de. 17. Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany. jens.schittenhelm@med.uni-tuebingen.de.
Abstract
PURPOSE: Diffuse midline gliomas, H3 K27M-mutant were introduced as a new grade IV entity in WHO classification of tumors 2016. These tumors occur often in pediatric patients and show an adverse prognosis with a median survival less than a year. Most of the studies on these tumors, previously known as pediatric diffuse intrinsic pontine glioma, are on pediatric patients and its significance in adult patients is likely underestimated. METHODS: We studied 165 cases of brain tumors of midline localization initially diagnosed as diffuse astrocytomas, oligodendrogliomas, pilocytic astrocytomas, supependymomas, ependymomas and medulloblastomas in patients with an age range of 2-85. RESULTS: We identified 41 diffuse midline gliomas according WHO 2016, including 12 pediatric and 29 adult cases, among them two cases with histological features of low grade tumors: pilocytic astrocytoma and subependymoma. 49% (20/41) of the patients were above 30 years old by the first tumor manifestation including 29% (11/41) above 54 that signifies a broader age spectrum as previously reported. Our study confirms that H3 K27M mutations are associated with a poorer prognosis in pediatric patients compared to wild-type tumors, while in adult patients these mutations do not influence the survival significantly. The pattern of tumor growth was different in pediatric compared to adult patients; a diffuse growth along the brain axis was more evident in adult compared to pediatric patients (24% vs. 15%). CONCLUSION: H3 K27M mutations are frequent in adult midline gliomas and have a prognostic role similar to H3 K27M wild-type high-grade tumors.
PURPOSE: Diffuse midline gliomas, H3 K27M-mutant were introduced as a new grade IV entity in WHO classification of tumors 2016. These tumors occur often in pediatric patients and show an adverse prognosis with a median survival less than a year. Most of the studies on these tumors, previously known as pediatric diffuse intrinsic pontine glioma, are on pediatric patients and its significance in adult patients is likely underestimated. METHODS: We studied 165 cases of brain tumors of midline localization initially diagnosed as diffuse astrocytomas, oligodendrogliomas, pilocytic astrocytomas, supependymomas, ependymomas and medulloblastomas in patients with an age range of 2-85. RESULTS: We identified 41 diffuse midline gliomas according WHO 2016, including 12 pediatric and 29 adult cases, among them two cases with histological features of low grade tumors: pilocytic astrocytoma and subependymoma. 49% (20/41) of the patients were above 30 years old by the first tumor manifestation including 29% (11/41) above 54 that signifies a broader age spectrum as previously reported. Our study confirms that H3 K27M mutations are associated with a poorer prognosis in pediatric patients compared to wild-type tumors, while in adult patients these mutations do not influence the survival significantly. The pattern of tumor growth was different in pediatric compared to adult patients; a diffuse growth along the brain axis was more evident in adult compared to pediatric patients (24% vs. 15%). CONCLUSION: H3 K27M mutations are frequent in adult midline gliomas and have a prognostic role similar to H3 K27M wild-type high-grade tumors.
Authors: Débora Cabral de Carvalho Corrêa; Francine Tesser-Gamba; Indhira Dias Oliveira; Nasjla Saba da Silva; Andrea Maria Capellano; Maria Teresa de Seixas Alves; Patrícia Alessandra Dastoli; Sergio Cavalheiro; Silvia Regina Caminada de Toledo Journal: J Cancer Res Clin Oncol Date: 2021-10-09 Impact factor: 4.553
Authors: John Lynes; Alvina A Acquaye; Hannah Sur; Anthony Nwankwo; Victoria Sanchez; Elizabeth Vera; Tianxia Wu; Brett Theeler; Terri S Armstrong; Mark R Gilbert; Edjah K Nduom Journal: J Neurooncol Date: 2020-07-23 Impact factor: 4.130