1;Preface;5 2;Contents;6 3;Contributors;12 4;Epidemiology;15 4.1;1.1 Descriptive Epidemiology;15 4.2;1.2 Risk Factors;16 4.3;1.3 Conclusions;18 4.4;References;19 5;Screening for Neuroblastoma;20 5.1;2.1 Introduction;20 5.2;2.2 The Rationale for Neuroblastoma Screening;20 5.3;2.3 Early Pioneering Studies Investigating Neuroblastoma Screening in Japan;21 5.4;2.4 Initial North American and European Neuroblastoma Screening Trials;22 5.5;2.5 Follow-up Studies from Japan and Europe;24 5.6;2.6 Definitive Controlled Trials from Quebec and Germany;24 5.7;2.7 Biologic, Psychologic, Economic, and Clinical Aspects of Neuroblastoma Screening ;30 5.8;2.8 Conclusions;31 5.9;References;31 6;Genetics;34 6.1;3.1 Introduction;34 6.2;3.2 Associated Genetic Conditions;34 6.3;3.3 Constitutional Chromosomal Abnormalities;35 6.4;3.4 Hereditary Neuroblastoma;36 6.5;3.5 Genetic Studies of Familial Neuroblastoma;38 6.6;3.6 Conclusions;38 6.7;References;39 7;Molecular Cytogenetics;40 7.1;4.1 Introduction;40 7.2;4.2 Classical Cytogenetics;40 7.3;4.3 Oncogene Expression Profiling;41 7.4;4.4 "Neuroblastoma Suppressor Genes" and Loss of Heterozygosity;42 7.5;4.5 Comparative Genomic Hybridization;47 7.6;4.6 Tumor Cell Ploidy;47 7.7;4.7 Conclusion;48 7.8;References;48 8;Molecular and Developmental Biology of Neuroblastoma;54 8.1;5.1 Neural Crest Development and Neuroblastoma;54 8.2;5.2 Molecular Bases of Differentiation and Programmed Cell Death ;58 8.3;5.3 Conclusions;63 8.4;References;64 9;Cellular Heterogeneity;67 9.1;6.1 Introduction;67 9.2;6.2 Neural Crest Differentiation;67 9.3;6.3 Neuroblastoma Cellular Heterogeneity;68 9.4;6.4 N-type Neuroblastic Cells;68 9.5;6.5 S-type Non-Neural Cells;69 9.6;6.6 I-type Stem Cells;70 9.7;6.7 Transdifferentiation;71 9.8;6.8 Conclusions;72 9.9;References;72 10;Clinical Presentation;74 10.1;7.1 Introduction;74 10.2;7.2 Diagnosis;75 10.3;7.3 Clinical Presentation ;76 10.4;7.4 Differential Diagnosis ;83 10.5;7.5 Clinical and Laboratory Evaluation ;84 10.6;7.6 Conclusions;93 10.7;References;94 11;Pathology of Peripheral Neuroblastic Tumors;97 11.1;8.1 Introduction;97 11.2;8.2 Historical Overview;98 11.3;8.3 Basic Morphology;98 11.4;8.4 Prognostic Classification;102 11.5;8.5 Biological Relevance;102 11.6;8.6 Conclusion;104 11.7;References;104 12;Molecular Pathology of Neuroblastic Tumors Based on Genome- wide Expression Analysis;106 12.1;9.1 Introduction;106 12.2;9.2 Clinical Issues;107 12.3;9.3 Technical Aspects of Gene Expression Analysis;107 12.4;9.4 Gene Expression Analysis of NB ;109 12.5;9.5 Conclusion;115 12.6;References;115 13;Anatomic and Functional Imaging;117 13.1;10.1 Introduction;117 13.2;10.2 Imaging Modalities ;117 13.3;10.3 Disease Evaluation ;124 13.4;10.4 Prenatally Diagnosed Neuroblastoma;126 13.5;10.5 Stage-4S Neuroblastoma;126 13.6;10.6 Evaluation of Disease Response;128 13.7;10.7 Conclusion;128 13.8;References;128 14;Treatment of Neuroblastoma;131 14.1;11.1 Low-Risk Neuroblastoma;132 14.2;11.2 Intermediate-Risk Neuroblastoma;139 14.3;11.3 High-Risk Neuroblastoma;146 14.4;11.4 The Role of Surgery in the Treatment of Neuroblastoma;157 14.5;11.5 Radiation Therapy;172 14.6;11.6 Stem Cell Transplantation;181 14.7;11.7 Minimal Residual Disease Measurement;193 14.8;References;199 15;Treatment of Relapsed and Refractory Neuroblastoma;201 15.1;12.1 Introduction;201 15.2;12.2 Treatment Strategies for Resistant Disease;203 15.3;12.3 Cytotoxic Chemotherapeutic Agents;204 15.4;12.4 Tumor-Targeted Biologic Agents ;209 15.5;12.5 Immunologic Therapy ;211 15.6;12.6 131I-Metaiodobenzylguanidine;212 15.7;12.7 Conclusion;212 15.8;References;213 16;Management of Neurologic Complications;220 16.1;13.1 Introduction;220 16.2;13.2 Epidural Neuroblastoma;220 16.3;13.3 Metastatic Disease to the Central Nervous System;223 16.4;13.4 Opsoclonus-Myoclonus;224 16.5;13.5 Treatment-Related Neurologic Complications;227 16.6;13.6 Conclusions;227 16.7;References;228 17;Immunology and Immunotherapy;230 17.1;14.1 Introduction: The Case for I