Human Brain and Spinal Cord Tumors: From Bench to Bedside. Volume 2: The Path to Bedside Management (Advances in Experimental Medicine and Biology, 1405)

This book aims to gather the current knowledge regarding different aspects of brain and spinal cord tumors in order to more efficiently help the patients. Brain tumors comprise about 5–9% of all human neoplasms; and the central nervous system (CNS) neoplasms are ranked among the most prevalent neoplasms of childhood as well. The more we know about the nature and characteristic of brain and spinal cord tumors, the more precise decision could be made for each patient, in order to reach the best outcome. While surgical resection, chemotherapy, and radiotherapy have been considered as the standards of care for benign and/or malignant CNS tumors since a long time ago, new therapeutic approaches such as immunotherapy have been recently proposed to be considered for treatment of CNS tumors, especially as in some cases, the tumors might be inoperable or the patient may not benefit from other treatment modalities after several recurrences. The second volume of the book focuses on clinical aspects of these tumors. Accordingly, the most important brain and spinal cord tumors are specifically discussed in each chapter based on a rational outlining for all chapter in this volume: Background and epidemiology, genetics, immunology and molecular biology, histopathology and morphology, imaging and radiologic features, clinical manifestations, therapeutic approaches, surgical intervention, chemotherapy and radiotherapy, new therapeutic modalities, follow-up, and prognosis. The chapters of this volume discuss the following pathologies of brain and spinal cord tumors: malignant glioma, benign glioma, meningiomas and other meningeal tumors, ependymomas, medulloblastomas, pineal tumors, choroid plexus and ventricular tumors, neuroectodermal tumors of CNS, neuroepithelial tumors of CNS, pituitary gland tumors, craniopharyngioma, schwannomas and nerve-sheet tumors, hemangioblastomas and other vascular originating tumors, brain and spinal tumors of embryonic origin, germ line cell tumors, malignant bone or cartilage-originating tumors of brain and spine, benign bone or cartilage-originating tumors of brain and spine, brain tumors affecting the orbit globe and orbit tumors affecting the brain, CNS lymphomas, metastatic lesions of the brain and spine, malignant spinal tumors, benign spinal tumors, brain and/or spinal cord tumors accompanied with other diseases or syndromes, psychological and psychiatric aspects of brain and spinal cord tumors, a brief explanation on surgical approaches for treatment of different brain tumors. This volume of book is useful for physicians of different specialties, mainly neurosurgeons, neurologists, neuropathologists, and neuroradiologists. Foreword by Prof. Karl Schaller Foreword by Prof. Charlie Teo Preface Contents Editors and Contributors 1 Malignant Glioma Abstract 1.1 Background and Epidemiology 1.1.1 Astrocytoma 1.1.2 Oligodendroglioma 1.1.3 Diffuse Midline Glioma 1.2 Genetics, Immunology, and Molecular Biology 1.2.1 Anaplastic Astrocytoma 1.2.2 Glioblastoma 1.2.3 Anaplastic Oligodendroglioma 1.2.4 Diffuse Midline Glioma 1.3 Histopathology and Morphology 1.3.1 Glioblastoma 1.3.2 Anaplastic Oligodendroglioma 1.3.3 Diffuse Midline Glioma 1.4 Imaging and Radiologic Features 1.4.1 Astrocytoma 1.4.2 Oligodendroglioma 1.4.3 Diffuse Midline Glioma 1.5 Clinical Manifestations 1.5.1 Increased Intracranial Pressure 1.5.2 Focal Neurologic Deficits 1.5.3 Seizures 1.6 Therapeutic Approaches 1.6.1 Surgical Intervention 1.6.2 Chemotherapy and Radiotherapy 1.6.2.1 Adjuvant Treatment Options Based on Tumor Type 1.6.3 New Therapeutic Modalities 1.6.4 Symptomatic Management 1.7 Follow-Up and Prognosis 1.8 Conclusion References 2 Benign Glioma Abstract 2.1 Background and Epidemiology 2.1.1 Pilocytic Astrocytoma (PA) 2.1.2 Pilomyxoid Astrocytoma (PMA) 2.1.3 Subependymal Giant Cell Astrocytoma (SEGA) 2.1.4 Subependymoma (SE) 2.1.5 Angiocentric Glioma 2.1.6 Ganglioglioma 2.1.7 Chordoid Glioma (CG) 2.1.8 Pleomorphic Xanthoastrocytoma (PXA) 2.1.9 Diffuse Low-Grade Glioma 2.2 Genetics, Immunology, Molecular Biology 2.3 Histopathology and Morphology 2.3.1 Pilocytic Astrocytoma (PA) 2.3.2 Pilomyxoid Astrocytoma (PMA) 2.3.3 Subependymal Giant Cell Astrocytoma (SEGA) 2.3.4 Subependymoma (SE) 2.3.5 Angiocentric Glioma 2.3.6 Ganglioglioma 2.3.7 Chordoid Glioma (CG) 2.3.8 Pleomorphic Xanthoastrocytoma (PXA) 2.3.9 Diffuse Low-Grade Glioma 2.4 Imaging and Radiologic Features 2.4.1 Pilocytic Astrocytoma (PA) 2.4.2 Pilomyxoid Astrocytoma (PMA) 2.4.3 Subependymal Giant Cell Astrocytoma (SEGA) 2.4.4 Subependymoma (SE) 2.4.5 Angiocentric Glioma 2.4.6 Ganglioglioma 2.4.7 Pleomorphic Xanthoastrocytoma (PXA) 2.4.8 Diffuse Low-Grade Glioma 2.5 Clinical Manifestations 2.5.1 Pilomyxoid Astrocytoma (PMA) 2.5.2 Subependymal Giant Cell Astrocytoma (SEGA) 2.5.3 Chordoid Glioma (CG) 2.6 Therapeutic Approaches 2.6.1 Observation 2.6.2 Surgical Intervention 2.6.2.1 Biopsy 2.6.2.2 Surgical Resection Surgical Resection for Pilocytic Astrocytoma Surgical Resection for Pilomyxoid Astrocytoma (PMA) Surgical Resection for Subependymal Giant Cell Astrocytoma (SEGA) Surgical Resection for Subependymoma (SE) Surgical Resection for Angiocentric Glioma Surgical Resection for Ganglioglioma Surgical Resection for Chordoid Glioma (CG) Surgical Resection for Pleomorphic Xanthoastrocytoma (PXA) Surgical Resection for Diffuse Low-Grade Glioma 2.6.3 Chemotherapy and Radiotherapy 2.6.3.1 Radiation 2.6.3.2 Chemotherapy Chemotherapy for Pilocytic Astrocytoma Chemotherapy for Subependymal Giant Cell Astrocytoma (SEGA) Chemotherapy for Diffuse Low-Grade Glioma 2.6.4 New Therapeutic Modalities 2.7 Follow-Up and Prognosis 2.7.1 Pilocytic Astrocytoma (PA) 2.7.2 Pilomyxoid Astrocytoma (PMA) 2.7.3 Subependymal Giant Cell Astrocytoma (SEGA) 2.7.4 Subependymoma (SE) 2.7.5 Ganglioglioma 2.7.6 Pleomorphic Xanthoastrocytoma (PXA) 2.7.7 Diffuse Low-Grade Glioma 2.8 Conclusion References 3 Meningioma and Other Meningeal Tumors Abstract 3.1 Background and Epidemiology 3.1.1 Epidemiology 3.1.2 Risk Factors 3.2 Genetics, Immunology, and Molecular Biology 3.3 Histopathology and Morphology 3.4 Imaging and Radiologic Features 3.5 Clinical Manifestations 3.6 Therapeutic Approaches 3.6.1 Observation 3.6.2 Surgical Intervention 3.6.2.1 Intracranial Meningiomas 3.6.2.2 Spinal Meningiomas 3.6.2.3 Advancements in Surgical Techniques 3.6.3 Radiation Therapy 3.6.3.1 Radiation Therapy as Primary Treatment 3.6.3.2 Radiation Therapy as Adjuvant/Salvage Treatment 3.6.4 Chemotherapy and New Therapeutic Modalities 3.7 Prognosis and Follow-Up 3.8 Other Meningeal Tumors 3.8.1 Hemangiopericytoma/Solitary Fibrous Tumor 3.8.2 Melanocytic Tumors 3.8.3 Sarcomas 3.8.4 Lymphomas 3.8.5 Fibrous Histiocytoma 3.8.6 Metastases 3.9 Conclusion References 4 Ependymomas in Children and Adults Abstract 4.1 Background and Epidemiology 4.1.1 Epidemiology Across All Age Groups 4.1.2 Epidemiology of Ependymomas in Adults 4.1.3 Epidemiology of Ependymomas in Children and Adolescents 4.2 Genetics, Immunology, and Molecular Biology 4.3 Histopathology and Morphology 4.3.1 WHO Classification 4.3.2 Molecular Classification 4.4 Imaging and Radiological Features 4.4.1 Infratentorial Ependymomas 4.4.2 Supratentorial Ependymomas 4.4.3 Spinal Ependymomas 4.4.4 Subependymomas 4.5 Clinical Manifestations 4.6 Therapeutic Approaches 4.6.1 Surgical Intervention 4.6.2 Chemotherapy and Radiotherapy 4.6.2.1 Radiotherapy 4.6.2.2 Chemotherapy 4.6.3 New Therapeutic Modalities 4.6.4 Management of Subependymomas 4.7 Follow-Up and Prognosis 4.8 Conclusion References 5 Medulloblastomas in Pediatric and Adults Abstract 5.1 Background and Epidemiology 5.1.1 Historical Background 5.1.2 Epidemiology and Syndromology 5.2 Genetics, Immunology, and Molecular Biology 5.2.1 The WNT Group 5.2.2 The SHH Group 5.2.3 Group 3 5.2.4 Group 4 5.3 Histopathology and Morphology 5.4 Imaging and Radiologic Features 5.4.1 Topography 5.5 Clinical Manifestations 5.6 Therapeutic Approaches 5.6.1 Surgical Intervention 5.6.1.1 Morbidity 5.6.1.2 Hydrocephalus 5.6.2 Chemotherapy and Radiotherapy 5.6.3 New Therapeutic Modalities 5.7 Follow-Up and Prognosis 5.7.1 Stratification and Risk Factors 5.7.2 Long-Term Follow-Up 5.7.2.1 Endocrine Disorders 5.7.2.2 Cognitive Impairment 5.7.2.3 Ototoxicity 5.8 Conclusion References 6 Benign and Malignant Tumors of the Pineal Region Abstract 6.1 Background and Epidemiology 6.2 Genetics, Immunology, and Molecular Biology 6.3 Histopathology and Morphology 6.3.1 Benign Pineal Region Tumors 6.3.2 Glial Pineal Tumors 6.3.3 Papillary Tumors of the Pineal Region 6.3.4 Primary Pineal Parenchymal Tumors 6.3.5 Germ Cell Tumors (GCT) 6.4 Imaging and Radiologic Features 6.4.1 Diffusion-Weighted Imaging and MR Spectroscopy 6.5 Clinical Manifestations 6.5.1 Diagnosis of Pineal Region Tumors 6.6 Therapeutic Approaches 6.6.1 Surgical Intervention 6.6.1.1 Stereotactic or Neuroendoscopic Biopsy 6.6.1.2 Open Surgical Planning—Overview 6.6.1.3 Supracerebellar Infratentorial (SCIT) 6.6.1.4 Lateral SCIT 6.6.1.5 Occipital Transtentorial and Interhemispheric Transcallosal Approaches 6.6.1.6 Transcortical Transventricular Approach 6.6.1.7 Post-operative Care and Complications 6.6.2 Chemotherapy and Radiotherapy 6.6.3 New Therapeutic Modalities 6.7 Follow-Up and Prognosis 6.8 Conclusion References 7 Tumors of Choroid Plexus and Other Ventricular Tumors Abstract 7.1 Background and Epidemiology 7.2 Genetics, Immunology, and Molecular Biology 7.2.1 Genetic of Choroid Plexus Tumors 7.2.2 Epigenetic Profile of Choroid Plexus Tumors 7.2.3 Environmental Exposure 7.2.4 Preclinical Studies 7.3 Histopathology and Morphology 7.3.1 Gross Pathology 7.3.2 Histology 7.3.2.1 Choroid Plexus Papilloma 7.3.2.2 Atypical Papilloma 7.3.2.3 Choroid Plexus Carcinoma 7.3.3 Immunohistochemistry 7.3.4 Differential Diagnosis 7.3.4.1 Choroid Plexus with Villous Hypertrophy 7.3.4.2 Ependymoma 7.3.4.3 Germ Cell Tumors 7.3.4.4 AT/TR 7.3.4.5 Intraventricular Meningioma 7.3.4.6 Metastases 7.4 Imaging and Radiologic Features 7.4.1 Computed Tomography Findings 7.4.2 Magnetic Resonance Imaging Findings 7.4.2.1 Morphological and Functional MRI Findings 7.4.2.2 MRI Staging, Differential Diagnosis, and Follow-Up 7.5 Clinical Manifestations 7.6 Therapeutic Approaches 7.6.1 Management of Hydrocephalus 7.6.2 Surgical Intervention 7.6.2.1 Preparing and Positioning 7.6.2.2 Surgical Approaches to the Lateral and Third Ventricles 7.6.2.3 Anterior Approach: Transcortical and Transcallosal 7.6.2.4 Lateral Approaches: Transtemporal and Transparietal 7.6.2.5 Microsurgical Tumor Dissection and Removal 7.6.2.6 Surgical Approaches to the Fourth Ventricle 7.6.2.7 Early Postoperative Period 7.6.2.8 Endoscopic Adjuncts to Intraventricular Surgery 7.6.3 Chemotherapy and Radiotherapy 7.6.3.1 Chemotherapy 7.6.3.2 Marrow-Ablative High-Dose Chemotherapy with Autologous Hematopoietic Cell Rescue 7.6.3.3 Radiation Therapy 7.6.4 New Therapeutic Modalities 7.7 Follow-Up and Prognosis 7.8 Other Intraventricular Tumors 7.8.1 Subependymoma 7.8.2 Central Neurocytoma 7.8.3 Subependymal Giant Cell Astrocytoma (SEGA) 7.8.4 Rarer Histotypes 7.9 Conclusion References 8 Embryonal Tumors of the Central Nervous System with Multilayered Rosettes and Atypical Teratoid/Rhabdoid Tumors Abstract 8.1 Background and Epidemiology 8.1.1 Introduction 8.1.2 Historical Notes 8.1.3 Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC—Altered 8.1.4 Atypical Teratoid/Rhabdoid Tumor (ATRT) (ICD-O 9508/3) 8.1.5 Other Embryonal Tumors of the CNS 8.2 Genetics, Immunology, and Molecular Biology 8.2.1 Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC—Altered 8.2.1.1 Cell of Origin 8.2.1.2 Genetic Changes 8.2.2 Other Embryonal Tumors of the CNS 8.2.2.1 Cell of Origin 8.2.3 Atypical Teratoid/Rhabdoid Tumor (ATRT) (ICD-O 9508/3) 8.2.4 New Emerging Molecular Subtypes 8.2.4.1 CNS HGNET-BCOR 8.2.4.2 DICER1-Associated Tumors 8.3 Histopathology and Morphology 8.3.1 Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC—Altered 8.3.1.1 Macroscopy 8.3.1.2 Microscopy 8.3.1.3 Immunohistochemical Profile 8.3.1.4 Electron Microscopy 8.3.2 Other Embryonal Tumors of the CNS 8.3.2.1 Medulloepithelioma (ICD-O 9501/3) 8.3.2.2 Neuroblastoma (ICD-O Code 9500/3) and Ganglioneuroblastoma (ICD-O Code 9490/3) 8.3.2.3 Embryonal Tumors of the CNS, NOS (ICD-O Code 9473/3) 8.3.3 Atypical Teratoid/Rhabdoid Tumor (ATRT) (ICD-O 9508/3) 8.3.3.1 Macroscopy 8.3.3.2 Microscopy 8.3.3.3 Immunohistochemical Profile 8.4 Imaging and Radiologic Features 8.4.1 Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC—Altered 8.4.1.1 Localization 8.4.1.2 MRI Findings 8.4.2 Atypical Teratoid/Rhabdoid Tumor (ATRT) (ICD-O 9508/3) 8.4.2.1 Localization 8.4.2.2 MRI Findings 8.5 Clinical Manifestations 8.6 Therapeutic Approaches 8.6.1 Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC—Altered 8.6.1.1 Surgical Intervention 8.6.1.2 Chemotherapy and Radiotherapy 8.6.2 Atypical Teratoid/Rhabdoid Tumor (ATRT) (ICD-O 9508/3) 8.6.2.1 Surgical Intervention 8.6.2.2 Chemotherapy and Radiotherapy 8.7 Follow-Up and Prognosis 8.7.1 Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC—Altered 8.7.2 Atypical Teratoid/Rhabdoid Tumor (ATRT) (ICD-O 9508/3) 8.7.3 Other Embryonal Tumors of the CNS 8.8 Conclusion References 9 Glioneuronal and Neuronal Tumors of the Central Nervous System Abstract 9.1 Background and Epidemiology 9.2 Genetics, Immunology, and Molecular Biology 9.2.1 Immunohistochemistry 9.2.1.1 Markers of Neuronal Differentiation 9.2.1.2 Markers of Glial Differentiation 9.2.1.3 Prognostic Markers 9.2.1.4 Other Markers 9.2.2 Molecular Features 9.3 Histopathology and Morphology 9.3.1 WHO Entities 9.3.1.1 Central Neurocytoma (CN) and Extraventricular Neurocytoma (EVN) 9.3.1.2 Cerebellar Liponeurocytoma 9.3.1.3 Desmoplastic Infantile Astrocytoma (DIA) and Desmoplastic Infantile Ganglioglioma (DIG) 9.3.1.4 Dysembryoplastic Neuroepithelial Tumor (DNET) 9.3.1.5 Gangliocytoma (GC) and Ganglioglioma (GG) 9.3.1.6 Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) 9.3.1.7 Papillary Glioneuronal Tumor (PGNT) 9.3.1.8 Rosette-Forming Glioneuronal Tumor (RGNT) 9.3.1.9 Paraganglioma of CNS 9.3.2 Emerging Entities 9.3.2.1 Polymorphous Low-Grade Neuroepithelial Tumor of the Young (PLNTY) 9.3.2.2 Multinodular and Vacuolating Neuronal Tumor (MVNT) 9.3.2.3 Myxoid Glioneuronal Tumor-PDGFRA p.K385-Mutant 9.4 Imaging and Radiologic Features 9.4.1 Central Neurocytoma and Extraventricular Neurocytoma 9.4.2 Cerebellar Liponeurocytoma 9.4.3 Desmoplastic Infantile Astrocytoma, Desmoplastic Infantile Ganglioglioma 9.4.4 Dysembryoplastic Neuroepithelial Tumor (DNET) 9.4.5 Ganglioglioma and Gangliocytoma (GG & GC) 9.4.6 Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) 9.4.7 Papillary Glioneuronal Tumor (PGNT) 9.4.8 Rosette-Forming Glioneuronal Tumor (RGNT) 9.4.9 Paraganglioma 9.4.10 Polymorphous Neuroepithelial Tumor of the Young (PLNTY) 9.4.11 Intraoperative Ultrasound (IUS) 9.5 Clinical Manifestations 9.6 Therapeutic Approaches 9.6.1 Surgical Intervention 9.6.2 Chemotherapy and Radiotherapy 9.6.3 New Therapeutic Modalities 9.7 Follow-Up and Prognosis 9.8 Conclusion References 10 Benign and Malignant Tumors of the Pituitary Gland Abstract 10.1 Background and Epidemiology 10.2 Genetics, Immunology, and Molecular Biology 10.3 Histopathology and Morphology 10.4 Imaging and Radiologic Features 10.5 Clinical Manifestations 10.6 Therapeutic Approaches 10.6.1 Surgical Intervention 10.6.2 Chemotherapy and Radiotherapy 10.6.3 New Therapeutic Modalities 10.7 Follow-Up and Prognosis 10.8 Conclusion References 11 Craniopharyngioma in Pediatrics and Adults Abstract 11.1 Background and Epidemiology 11.2 Genetics, Immunology, and Molecular Biology 11.3 Histopathology and Morphology 11.4 Imaging and Radiologic Features 11.5 Clinical Manifestations 11.6 Therapeutic Approaches 11.6.1 Surgical Intervention 11.6.1.1 Surgical General Considerations 11.6.1.2 Topographic and Surgical Anatomy Classification 11.6.1.3 Surgical Approaches 11.6.1.4 Extent of Resection 11.6.1.5 Postoperative Complications 11.6.1.6 Cyst Drainage 11.6.2 Chemotherapy and Radiotherapy 11.6.2.1 Systemic Chemotherapy 11.6.2.2 Intracystic Chemotherapy 11.6.2.3 External Beam Radiation Therapy (RT) 11.6.2.4 Stereotactic Radiosurgery (SRS) 11.6.2.5 Intracavitary Brachytherapy 11.6.3 New Therapeutic Modalities 11.6.3.1 Proton Beam Therapy (PBT) 11.6.3.2 BRAF Inhibitors 11.7 Follow-Up and Prognosis 11.8 Conclusion References 12 Schwannomas of Brain and Spinal Cord Abstract 12.1 Background and Epidemiology 12.2 Genetics, Immunology, and Molecular Biology 12.3 Histopathology and Morphology 12.4 Imaging and Radiologic Features 12.5 Clinical Manifestations 12.6 Therapeutic Approaches 12.6.1 Surgical Intervention 12.6.1.1 The Retrosigmoid Suboccipital Approach 12.6.1.2 The Translabyrinthine Approach 12.6.1.3 The Middle Fossa Approach 12.6.1.4 The Retrosigmoid Suprameatal (Samii) Approach 12.6.2 Radiotherapy 12.6.3 New Therapeutic Modalities 12.7 Follow-Up and Prognosis 12.8 Conclusion References 13 Other Nerve Sheath Tumors of Brain and Spinal Cord Abstract 13.1 Background and Epidemiology 13.2 Genetics, Immunology and Molecular Biology 13.3 Histopathology and Morphology 13.4 Imaging and Radiologic Features 13.5 Clinical Manifestations 13.6 Therapeutic Approaches 13.6.1 Surgical Intervention 13.6.2 Chemotherapy and Radiotherapy 13.6.3 New Therapeutic Modalities 13.7 Follow-Up and Prognosis 13.8 Conclusion References 14 Hemangioblastomas and Other Vascular Originating Tumors of Brain or Spinal Cord Abstract 14.1 Background and Epidemiology 14.2 Genetics, Immunology, and Molecular Biology 14.3 Histopathology and Morphology 14.4 Imaging and Radiologic Features 14.4.1 Cerebral Hemangioblastomas 14.4.1.1 MR Findings 14.4.1.2 Angiography Findings 14.4.2 Spinal Hemangioblastomas 14.4.2.1 MR Findings 14.4.2.2 Angiography Findings 14.5 Clinical Manifestations 14.6 Therapeutic Approaches 14.6.1 Surgical Intervention 14.6.1.1 Surgery for Intracranial Hemangioblastomas 14.6.1.2 Surgery for Spinal Hemangioblastomas 14.6.1.3 Preoperative Embolization 14.6.2 Radiotherapy and Chemotherapy 14.6.2.1 Radiotherapy 14.6.2.2 Radiotherapy for Intracranial Hemangioblastomas 14.6.2.3 Radiotherapy for Spinal Hemangioblastomas 14.6.2.4 Chemotherapy 14.6.3 New Therapeutic Modalities 14.7 Follow-Up and Prognosis 14.8 Other Vascular Originating Tumors 14.8.1 Hemangioma 14.8.2 Hemangioendothelioma 14.8.3 Solitary Fibrous Tumor 14.8.4 Angiosarcoma 14.9 Conclusion References 15 Brain and Spinal Cord Tumors of Embryonic Origin Abstract 15.1 Background and Epidemiology 15.2 Genetics, Immunology, and Molecular Biology 15.2.1 Medulloblastoma 15.2.2 Atypical Teratoid/Rhabdoid Tumors and CNS Embryonal Tumors with Rhabdoid Features 15.2.3 Embryonal Tumors with Multilayered Rosettes 15.2.4 Other Embryonal Tumors 15.3 Histopathology and Morphology 15.3.1 Medulloblastoma 15.3.1.1 Histologic Classification of Medulloblastoma 15.3.1.2 Genetic Classification of Medulloblastoma 15.3.2 Atypical Teratoid/Rhabdoid Tumors and CNS Embryonal Tumors with Rhabdoid Features 15.3.3 Embryonal Tumors with Multilayered Rosettes (ETMR) 15.3.4 Medulloepithelioma 15.3.5 CNS-Neuroblastoma (NB) and CNS-Ganglioneuroblastoma (GNB) 15.4 Imaging and Radiologic Features 15.4.1 Medulloblastoma 15.4.2 Atypical Teratoid/Rhabdoid Tumors and CNS Embryonal Tumors with Rhabdoid Features 15.4.3 Embryonal Tumors with Multilayered Rosettes (ETMR) 15.4.4 Medulloepithelioma 15.4.5 CNS-Neuroblastoma (NB) and CNS-Ganglioneuroblastoma (GNB) 15.5 Clinical Manifestation 15.5.1 Medulloblastoma 15.5.2 Atypical Teratoid/Rhabdoid Tumors and CNS Embryonal Tumors with Rhabdoid Features 15.5.3 Embryonal Tumors with Multilayered Rosettes (ETMR) 15.5.4 Medulloepithelioma 15.5.5 CNS-Neuroblastoma (NB) and CNS-Ganglioneuroblastoma (GNB) 15.6 Therapeutic Approaches 15.6.1 Surgical Intervention 15.6.2 Chemotherapy and Radiotherapy 15.6.3 New Therapeutic Modalities 15.6.3.1 Medulloblastoma 15.6.3.2 Other Embryonal Tumors 15.7 Follow-Up and Prognosis 15.8 Conclusion References 16 Brain and Spinal Tumors Originating from the Germ Line Cells Abstract 16.1 Background and Epidemiology 16.1.1 Background 16.1.2 Epidemiology 16.2 Genetics, Immunology, and Molecular Biology 16.2.1 KIT-RAS-MAPK and AKT-MTOR Pathways 16.2.2 The Distinction of Genetic Mutation Between Pure Germinoma and NGGCT 16.2.3 BCORL1 and JMJD1C 16.2.4 Chromosomal Aberrations and Intracranial Germ Cell Tumors (IGCTs) 16.2.5 Epithelial Mesenchymal Transition (EMT) Signatures and Immunology 16.3 Histopathology and Morphology 16.3.1 Germinoma 16.3.2 Teratoma and Growing Teratoma Syndrome 16.3.2.1 Teratoma 16.3.2.2 Growing Teratoma Syndrome (GTS) 16.3.3 Yolk Sac Tumor 16.3.4 Choriocarcinoma 16.3.5 Embryonal Carcinoma 16.3.6 Mixed Germ Cell Tumors 16.3.7 Tumor Markers 16.3.8 Staging 16.3.9 Histogenesis 16.4 Imaging and Radiologic Features 16.4.1 Location 16.4.2 Germinoma (See 16.3.1) 16.4.3 Teratoma and Intracranial Growing Teratoma Syndrome (GTS) (See 16.3.2) 16.4.4 Other Nongerminomatous Malignant GCT (NGMGCT) (See 16.3.3–16.3.5) 16.4.5 Mixed GCT (See 16.3.6) 16.5 Clinical Manifestations 16.6 Therapeutic Approaches 16.6.1 Surgical Intervention 16.6.2 Chemotherapy and Radiotherapy 16.6.2.1 Primary Chemotherapy 16.6.2.2 Treatment Strategies for Localized Tumors 16.6.3 Metastasis (at Diagnosis), Relapsed, or Refractory Tumors 16.6.4 New Therapeutic Modalities 16.6.4.1 Targeted Biologic Therapy 16.6.4.2 Immunotherapy (See 16.2.5) 16.7 Follow-Up and Prognosis 16.7.1 Follow-Up 16.7.1.1 Cognitive Dysfunction 16.7.1.2 Other Late CNS Complications After Cranial Radiotherapy 16.7.1.3 Physical Disability and Pituitary Hormone Deficiency 16.7.2 Prognosis 16.8 Conclusion Acknowledgements References 17 Benign Brain and Spinal Tumors Originating from Bone or Cartilage Abstract 17.1 Background and Epidemiology 17.2 Genetics, Immunology, and Molecular Biology 17.2.1 Osteoid Osteoma 17.2.2 Osteochondromas 17.2.3 Chondromas 17.2.4 Aneurysmal Bone Cysts (ABCs) 17.2.5 Giant Cell Tumor (GCT) 17.2.6 Fibrous Dysplasia 17.2.7 Langerhans Cell Histiocytosis 17.3 Histopathology and Morphology 17.3.1 Osteoid Osteoma 17.3.2 Osteochondroma 17.3.3 Chondromas 17.3.4 Aneurysmal Bone Cysts (ABCs) 17.3.5 Giant Cell Tumor (GCT) 17.3.6 Fibrous Dysplasia 17.3.7 Hemangioma 17.3.8 Langerhans Cell Histiocytosis 17.4 Imaging and Radiologic Features 17.5 Clinical Manifestations 17.6 Therapeutic Approaches 17.6.1 Surgical Intervention 17.6.2 Chemotherapy and Radiotherapy 17.6.3 New Therapeutic Modalities 17.7 Follow-Up and Prognosis 17.8 Conclusion References 18 Malignant Brain and Spinal Tumors Originating from Bone or Cartilage Abstract 18.1 Background and Epidemiology 18.1.1 Chordoma 18.1.2 Chondrosarcoma 18.1.3 Giant-Cell Tumor 18.1.4 Osteosarcoma 18.1.5 Miscellaneous 18.1.5.1 Multiple Myeloma and Plasmacytoma 18.1.5.2 Fibrous Dysplasia 18.1.5.3 Metastasis 18.1.5.4 Cholesterol Granuloma 18.2 Genetics, Immunology, and Molecular Biology 18.2.1 Chordomas 18.2.2 Chondrosarcoma 18.2.3 Giant-Cell Tumor 18.2.4 Osteosarcomas 18.2.5 Miscellaneous 18.2.5.1 Multiple Myeloma and Plasmacytoma 18.2.5.2 Fibrous Dysplasia 18.2.5.3 Metastasis 18.2.5.4 Cholesterol Granuloma 18.3 Morphology and Histopathology 18.3.1 Chordoma 18.3.2 Chondrosarcoma 18.3.3 Giant-Cell Tumor 18.3.4 Osteosarcoma 18.3.5 Miscellaneous 18.3.5.1 Multiple Myeloma and Plasmacytoma 18.3.5.2 Fibrous Dysplasia 18.3.5.3 Metastasis 18.3.5.4 Cholesterol Granuloma 18.4 Imaging and Radiologic Features 18.4.1 Chordoma 18.4.2 Chondrosarcoma 18.4.3 Giant-Cell Tumor 18.4.4 Osteosarcoma 18.4.5 Miscellaneous 18.4.5.1 Multiple Myeloma and Plasmacytoma 18.4.5.2 Fibrous Dysplasia 18.4.5.3 Metastasis 18.4.5.4 Cholesterol Granuloma 18.5 Clinical Manifestations 18.5.1 Chordoma 18.5.2 Chondrosarcoma 18.5.3 Giant-Cell Tumor 18.5.4 Osteosarcomas 18.5.5 Miscellaneous 18.5.5.1 Multiple Myeloma and Plasmacytoma 18.5.5.2 Fibrous Dysplasia 18.5.5.3 Metastasis 18.5.5.4 Cholesterol Granuloma 18.6 Therapeutic Approaches 18.6.1 Chordoma 18.6.1.1 Surgical Intervention 18.6.1.2 Chemotherapy and Radiotherapy 18.6.1.3 New Therapeutic Modalities 18.6.2 Chondrosarcoma 18.6.2.1 Surgical Intervention 18.6.2.2 Chemotherapy and Radiotherapy 18.6.2.3 New Therapeutic Modalities 18.6.3 Giant-Cell Tumor 18.6.3.1 Surgical Intervention 18.6.3.2 Chemotherapy and Radiotherapy 18.6.3.3 New Therapeutic Modalities 18.6.4 Osteosarcoma 18.6.4.1 Surgical Intervention 18.6.4.2 Chemotherapy and Radiotherapy 18.6.4.3 New Therapeutic Modalities 18.6.5 Miscellaneous 18.6.5.1 Multiple Myeloma and Plasmacytoma 18.6.5.2 Fibrous Dysplasia 18.6.5.3 Metastasis 18.6.5.4 Cholesterol Granuloma 18.7 Follow-Up and Prognosis 18.7.1 Chordoma 18.7.2 Chondrosarcoma 18.7.3 Giant-Cell Tumor 18.7.4 Osteosarcoma 18.7.5 Miscellaneous 18.7.5.1 Multiple Myeloma and Plasmacytoma 18.7.5.2 Fibrous Dysplasia 18.7.5.3 Metastasis 18.7.5.4 Cholesterol Granuloma 18.8 Conclusion References 19 Brain Tumors Affecting the Orbit Globe and Orbit Tumors Affecting the Brain Abstract 19.1 Background and Epidemiology 19.2 Genetics, Immunology, and Molecular Biology 19.3 Histopathology and Morphology 19.4 Imaging and Radiologic Features 19.5 Clinical Manifestations 19.6 Therapeutic Approaches 19.6.1 Surgery of Orbital Lesions 19.6.1.1 Lateral Orbitotomy 19.6.1.2 Fronto-Orbito-Zygomatic Approach 19.6.2 Chemotherapy and Radiotherapy 19.6.3 New Therapeutic Modalities 19.7 Follow-Up and Prognosis 19.8 Orbital Lesions 19.8.1 Vascular Lesions 19.8.1.1 Cavernous Malformations 19.8.1.2 Lymphangioma 19.8.1.3 Hemangiopericytomas 19.8.1.4 Capillary Hemangiomas and Orbital Arteriovenous Malformations 19.8.2 Tumors Originating from Bone and Cartilaginous Structures 19.8.2.1 Osteoma 19.8.2.2 Fibrous Dysplasia 19.8.3 Aneurysmal Bone Cyst 19.8.4 Tumors Originating from Nervous Structures and Their Covering 19.8.4.1 Peripheral Nerve Sheath Tumors 19.8.4.2 Optic Nerve Gliomas 19.8.4.3 Meningiomas 19.8.5 Miscellaneous Tumors 19.8.5.1 Dermoid and Epidermoid Cysts 19.8.5.2 Adenoid Cystic Carcinomas 19.9 Conclusion References 20 Lymphomas of Central Nervous System Abstract 20.1 Background and Epidemiology 20.2 Genetics, Immunology, and Molecular Biology 20.2.1 Epigenetic Alterations in PCNSL 20.2.2 Insertions and Deletions of Genetic Material 20.2.3 Activated Pathway in PCNSLs 20.3 Histopathology and Morphology 20.4 Imaging and Radiologic Features 20.4.1 CNS Lymphoma Features on CT Scan 20.4.2 CNS Lymphoma Features on Conventional MR Imaging 20.4.3 CNS Lymphoma Features on Advanced MR Imaging 20.4.4 CNS Lymphoma Features on Nuclear Imaging 20.4.5 Differential Diagnosis of CNS Lymphoma 20.5 Clinical Manifestations 20.6 Therapeutic Approaches 20.6.1 Surgical Intervention 20.6.2 Chemotherapy and Radiotherapy 20.6.2.1 Chemotherapy 20.6.2.2 Steroid Therapy 20.6.2.3 Radiotherapy 20.6.2.4 Management in the Elderly 20.6.2.5 Recurrence 20.6.3 New Therapeutic Modalities 20.7 Follow-Up and Prognosis 20.8 Conclusion References 21 Metastatic Lesions of the Brain and Spine Abstract 21.1 Background and Epidemiology 21.2 Genetics, Immunology, and Molecular Biology 21.2.1 Metastatic Lung Cancer to the CNS 21.2.2 Metastatic Breast Cancer to the CNS 21.2.3 Metastatic Melanoma to the CNS 21.3 Histopathology and Morphology 21.4 Imaging and Radiologic Features 21.4.1 Brain Metastasis 21.4.2 Spinal Metastasis 21.5 Clinical Manifestations 21.5.1 Brain Metastases 21.5.2 Spinal Metastases 21.6 Therapeutic Approaches 21.6.1 Surgical Intervention 21.6.2 Chemotherapy and Radiotherapy 21.6.2.1 Radiotherapy 21.6.2.2 Chemotherapy 21.6.3 New Therapeutic Modalities 21.7 Follow-Up and Prognosis 21.8 Conclusion References 22 Malignant Spinal Tumors Abstract 22.1 Background and Epidemiology 22.2 Genetics, Immunology, and Molecular Biology 22.2.1 Anaplastic Astrocytoma and Glioblastoma 22.2.2 Anaplastic Ependymoma 22.2.3 Embryonal Tumors 22.2.4 Malignant Peripheral Nerve Sheath Tumors 22.3 Histopathology and Morphology 22.3.1 Anaplastic Astrocytoma and Glioblastoma 22.3.2 Anaplastic Ependymoma 22.3.3 Embryonal Tumors 22.3.4 Malignant Peripheral Nerve Sheath Tumors (MPNSTs) 22.4 Imaging and Radiologic Features 22.5 Clinical Manifestations 22.6 Therapeutic Approaches 22.6.1 Surgical Intervention 22.6.2 Chemotherapy and Radiotherapy 22.6.3 New Therapeutic Modalities 22.7 Follow-Up and Prognosis 22.8 Conclusion References 23 Benign Spinal Tumors Abstract 23.1 Background and Epidemiology 23.2 Genetics, Immunology, and Molecular Biology 23.2.1 Intramedullary 23.2.1.1 Low-Grade Astrocytoma 23.2.1.2 Ependymoma 23.2.1.3 Hemangioblastoma 23.2.1.4 Ganglioglioma 23.2.2 Intradural Extramedullary 23.2.2.1 Neurofibroma 23.2.2.2 Schwannoma 23.2.2.3 Meningioma 23.3 Histopathology and Morphology 23.3.1 Intramedullary 23.3.1.1 Low-Grade Astrocytoma 23.3.1.2 Ependymoma 23.3.1.3 Hemangioblastoma 23.3.1.4 Ganglioglioma 23.3.2 Intradural Extramedullary 23.3.2.1 Neurofibroma 23.3.2.2 Schwannoma 23.3.2.3 Meningioma 23.3.2.4 Lipoma 23.3.2.5 Teratoma 23.4 Imaging and Radiologic Features 23.4.1 Intramedullary 23.4.1.1 Low-Grade Astrocytoma 23.4.1.2 Ependymoma 23.4.1.3 Hemangioblastoma 23.4.1.4 Ganglioglioma 23.4.2 Intradural Extramedullary 23.4.2.1 Neurofibroma 23.4.2.2 Schwannoma 23.4.2.3 Meningioma 23.4.2.4 Lipoma 23.4.2.5 Teratoma 23.5 Clinical Manifestations 23.6 Therapeutic Approaches 23.6.1 Surgical Intervention 23.6.2 Chemotherapy and Radiotherapy 23.7 Follow-Up and Prognosis 23.8 Conclusion References 24 Other Less Prevalent Tumors of the Central Nervous System Abstract 24.1 Introduction 24.2 Neurenteric Cyst and Bronchogenic Cyst 24.2.1 Background and Epidemiology 24.2.2 Genetics, Immunology, and Molecular Biology 24.2.3 Histopathology and Morphology 24.2.4 Imaging and Radiologic Features 24.2.5 Clinical Manifestations 24.2.6 Therapeutic Approaches 24.2.7 Follow-Up and Prognosis 24.3 Lhermitte–Duclos Disease (Dysplastic Gangliocytoma—WHO Grade 1) 24.3.1 Background and Epidemiology 24.3.2 Genetics, Immunology, Molecular Biology 24.3.3 Histopathology and Morphology 24.3.4 Imaging and Radiologic Features 24.3.5 Clinical Manifestations 24.3.6 Therapeutic Approaches 24.3.7 Follow-Up and Prognosis 24.4 Gangliocytoma/Ganglioglioma 24.4.1 Background and Epidemiology 24.4.2 Genetics, Immunology, and Molecular Biology 24.4.3 Histopathology and Morphology 24.4.4 Imaging and Radiologic Features 24.4.5 Clinical Manifestations 24.4.6 Therapeutic Approaches 24.4.7 Follow-Up and Prognosis 24.5 Central Neurocytomas 24.5.1 Background and Epidemiology 24.5.2 Genetics, Immunology, and Molecular Biology 24.5.3 Histopathology and Morphology 24.5.4 Imaging and Radiologic Features 24.5.5 Clinical Manifestations 24.5.6 Therapeutic Approaches 24.5.7 Follow-Up and Prognosis 24.6 Rosette-Forming Glioneuronal Tumor (RGNT) of the CNS 24.6.1 Background and Epidemiology 24.6.2 Genetics, Immunology, and Molecular Biology, 24.6.3 Histopathology and Morphology 24.6.4 Imaging and Radiologic Features 24.6.5 Clinical Manifestations 24.6.6 Therapeutic Approaches 24.7 Pheochromocytomas and Paragangliomas (PPGs) 24.7.1 Background and Epidemiology 24.7.2 Genetics, Immunology, and Molecular Biology 24.7.3 Histopathology and Morphology 24.7.4 Imaging and Radiologic Features 24.7.5 Clinical Manifestations 24.7.6 Diagnosis 24.7.7 Therapeutic Approaches 24.7.8 Follow-Up and Prognosis 24.8 Dysembryoplastic Neuroepithelial Tumor (DNET) 24.8.1 Background and Epidemiology 24.8.2 Genetics, Immunology, and Molecular Biology 24.8.3 Histopathology and Morphology 24.8.4 Imaging and Radiologic Features 24.8.5 Clinical Manifestations 24.8.6 Therapeutic Approaches 24.8.7 Follow-Up and Prognosis 24.9 Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (EWS/pPNET) 24.9.1 Background and Epidemiology 24.9.2 Genetics, Immunology, and Molecular Biology 24.9.3 Histopathology and Morphology 24.9.4 Imaging and Radiologic Feature 24.9.5 Clinical Manifestations 24.9.6 Therapeutic Approaches 24.10 Langerhans Cell Histiocytosis (LCH)—Histiocytosis X 24.10.1 Background and Epidemiology 24.10.2 Genetics, Immunology, and Molecular Biology 24.10.3 Histopathology and Morphology 24.10.4 Imaging and Radiologic Features 24.10.5 Clinical Manifestations 24.10.6 Therapeutic Approaches 24.10.7 Follow-Up and Prognosis 24.11 Solitary Fibrous Tumors (Known Before as Hemangiopericytomas) 24.11.1 Background and Epidemiology 24.11.2 Genetics, Immunology, and Molecular Biology 24.11.3 Histopathology and Morphology 24.11.4 Imaging and Radiologic Features 24.11.5 Clinical Manifestations 24.11.6 Therapeutic Approaches 24.11.7 Follow-Up and Prognosis 24.12 Olfactory Neuroblastoma/Esthesioneuroblastoma (ENB) 24.12.1 Background and Epidemi