Tata Memorial Centre Textbook of Oncology (Sep 20, 2024)

Preface Acknowledgements Contents Editors and Contributors About the Editors Contributors Part I: Basic Principles Basic and Translational Science in Oncology 1 Introduction 2 Hallmarks of Cancer 3 Biological Underpinnings of the Cancer Hallmarks 3.1 Oncogenes and Tumor Suppressor Genes 3.1.1 Oncogene Addiction/Aberrant Cell Signaling 3.1.2 Tumor Suppressors Retinoblastoma (Rb) Suppressors The p53 Gene Breast Cancer Susceptibility Genes: BRCA1 and BRCA2 Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) 3.2 Regulation of Gene Expression 3.3 Dysregulation of Cell Cycle Checkpoints 3.3.1 The Cyclin–CDK–Rb Axis 3.3.2 DNA Damage Response Checkpoints 3.4 Avoiding Immune Destruction 3.5 Cancer Invasion and Metastasis 4 Conclusions References Surgical Oncology 1 Introduction 2 Historical Perspective 3 Operative Risk Assessment 3.1 Preoperative Fitness Assessment and Operative Risk Prediction 4 Diagnostic Biopsy in Solid Cancers 4.1 Types of Biopsies Performed 4.2 Principles of Performing Biopsies in Solid Tumors 5 The Role of Surgery 5.1 Preventive/Prophylactic Surgery 5.2 Criteria for Prophylactic Surgery 5.3 Examples of Prophylactic Surgery 6 Curative Surgery 6.1 Principles of Resection of the Primary Cancer 6.2 Minimally Invasive Surgery in Oncology 6.3 Resection of Metastatic Disease 7 Reconstructive Surgery in Oncology 7.1 Principles of Reconstructive Surgery [32] 8 Palliative Surgery References Radiation Oncology 1 The Discipline of Radiation Oncology 2 The Historical Aspects of Radiation Oncology 3 The Biological Basis of Radiotherapy 3.1 Direct and Indirect Effects of Radiation 3.2 Cellular Targets of Radiation 3.3 Factors Influencing the Radiation Effect on Cells 3.4 The Acute and Late Effects of Radiation 3.5 Fractionation 4 QUANTEC and Dose Constraints 5 Radiobiology of Brachytherapy 6 Radiation Modifiers 7 The Physics of Radiotherapy 7.1 The Basic Physics of Radiotherapy 8 External Beam Radiography 9 Brachytherapy 10 Special Techniques and Technologies in Radiation Oncology 10.1 Total Skin Electron Therapy (TSET) 10.2 Stereotactic Radiosurgery (SRS)/Stereotactic Radiotherapy (SRT) 10.3 Stereotactic Body Radiotherapy (SBRT) 10.4 Total Body Irradiation (TBI) References Systemic Treatment of Cancer 1 Introduction 2 The History of Systemic Treatment 3 Types of Cancer Systemic Therapies 4 Settings for Cancer Systemic Treatment 5 The Principles of Chemotherapy 5.1 Cancer Cellular Kinetics 5.2 Rationale for Chemotherapeutic Combinations 5.3 The Concept of Dose Intensity 5.4 Cell Cycle and Chemotherapeutic Agents 6 The Principles of Hormonal Therapy for Cancer 6.1 The Concept of Hormone Dependence 6.2 The Effects of Hormonal Therapies on the Cell Cycle 6.3 Breast Cancer and the Estrogen Receptor 6.4 Prostate Cancer and the Androgen Receptor 6.5 Hormones and Other Tumors 7 The Principles of Targeted Therapy for Cancer 7.1 Druggability of Molecular Targets 8 The Principles of Cancer Immunotherapy 8.1 The Immune System 8.2 Antigen Presentation and Recognition 8.3 Immunoevasion 8.4 Cancer Immunotherapy References Pediatric Oncology 1 Introduction 2 Epidemiology of Childhood Cancers in the World 2.1 Published Estimates of Global Cancer Burden 2.2 Surveillance, Epidemiology, and End Results (SEER) Data 2.3 Estimates of Global Childhood Cancer Survival 3 Epidemiology of Childhood Cancers in India 3.1 Estimates of Incidence and Patterns 3.2 Estimates of Cancer-related Mortality and Survival in India 4 Challenges in the Management of Childhood Cancers in LMICs References Oncopathology 1 Principles 2 Grossing 2.1 Basic Requirements of Dissection/Grossing Room 2.2 Receiving Specimens 2.3 Specimen Fixation 2.4 Grossing/Surgical Cutup 2.4.1 Orientation of Specimens 2.4.2 The General Principles of Grossing 2.4.3 Gross Description 2.4.4 Margin Evaluation 2.5 Blocking Principles 2.5.1 Primary Lesion/Tumor 2.5.2 Margins 2.5.3 Adjacent Tissues 2.5.4 Lymph Nodes (LNs) 2.5.5 Bone 3 Safety Precautions 4 Staining 4.1 Hematoxylin and Eosin (H&E) Staining 4.2 Special Stains 5 Frozen Section (FS) 5.1 Basic Frozen Section (FS) Workflow 5.2 Indications 5.3 Diagnostic 5.4 Margin Status 5.5 Lymph Node (LN) Status 5.6 Frozen Artifacts and Limitations 5.6.1 Sampling Errors 5.6.2 Technical Errors 5.6.3 Interpretative Errors 6 Microscopic Techniques 7 Cytology 7.1 Types of Cytological Specimens 7.1.1 Exfoliative Cytology 7.1.2 From a Lesion/Mass 7.1.3 Selection of Stains and Fixatives 7.2 Key Points in the Evaluation of Cytological Specimens 7.3 Approach to Evaluation of Cytological Specimens 7.4 Cytology in Oncopathology: Interpretative Issues 8 Immunohistochemistry 8.1 Applications 8.2 Diagnostic 8.3 Prognostic 8.4 Predictive/Theranostic 8.5 Genogenic 9 Molecular Pathology 9.1 Diagnostic 9.2 Predictive 9.3 Prognostic 10 Biorepository 11 Digital Pathology 11.1 Digital Pathology and Artificial Intelligence Further Reading Oncological Hematopathology 1 Introduction 2 Organization and Elements of a Hematopathology Laboratory 2.1 Sample Processing 2.2 Analysis 3 Collection, Transport, and Processing of Samples 3.1 Flow Cytometry 3.2 Molecular Techniques 4 General Techniques 4.1 Cell Counts, Morphology, and Cytochemistry 4.2 Red Cell Lysis 5 Flow Cytometry 5.1 Principle 5.2 What Happens Inside a Flow Cytometer? 5.3 Indications 5.4 Additional Indications 5.5 An Overview of Immunophenotypic Analysis of Hematolymphoid Malignancies 5.5.1 Acute Leukemia 5.5.2 Acute Lymphoblastic Leukemia (ALL) 5.5.3 Precursor B-Cell Acute Lymphocytic Leukemia (B-ALL) 5.5.4 Precursor T-cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL) 5.5.5 Acute Myeloid Leukemia (AML) 5.5.6 Recently Described Immunophenotypic Subgroup in AML 5.5.7 Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCNs) 5.5.8 Acute Leukemia of Ambiguous Lineage 5.5.9 Flow Cytometric Analysis of Mature Lymphoid Neoplasms Mature B-Cell Neoplasms Classification Mature T- and Natural Killer (NK)-Cell Neoplasms 5.5.10 Flow Cytometric Analysis in Plasma Cell Neoplasms (PCNs) 5.5.11 Flow Cytometric Analysis in Myelodysplastic Syndromes (MDS) 5.5.12 Minimal Residual Disease (MRD) Monitoring by FC 5.6 The Role of FCI in the Prognosis of Hematolymphoid Neoplasms 6 Molecular Hemato-Oncology 6.1 An Overview of Molecular Diagnostic Techniques 6.2 Molecular Diagnosis of Hematolymphoid Neoplasms 6.2.1 Myeloproliferative Neoplasms Chronic Myeloid Leukemia (CML) Philadelphia-Negative Myeloproliferative Neoplasms Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNs) 6.2.2 Myelodysplastic Syndromes 6.2.3 Myeloid Neoplasms with Eosinophilia and Gene Rearrangements 6.2.4 Myeloid Neoplasms with Germline Predisposition 6.2.5 Acute Myeloid Leukemia 6.2.6 Clonality Assays in Lymphoproliferative Disorders 6.2.7 Precursor B-Cell Acute Lymphoblastic Leukemia/Lymphoma (BCP-ALL) 6.2.8 Precursor T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL) 6.2.9 B-Cell Lymphoproliferative Disorders Chronic Lymphocytic Leukemia Hairy Cell Leukemia Lymphoplasmacytic Lymphoma 6.2.10 T-Cell Lymphoproliferative Disorders 6.2.11 Plasma Cell Neoplasms References Microbiology in Oncology 1 Introduction 2 Specimen Selection, Collection, and Processing 2.1 Direct Examination 2.2 Molecular Diagnostics 2.3 General Guidelines for Specimen Processing for Bacterial and Fungal Culture 3 Detection and Identification Methods 4 Antimicrobial Susceptibility Testing 5 Specific Recommendations for Major Infections 5.1 The Respiratory Tract 5.2 Tissue Diagnosis 5.3 Fungal Infections 5.4 Blood Stream Infections 5.5 The Central Nervous System 5.6 The Urinary Tract 5.7 Gastrointestinal Specimens 6 Conclusions Further Reading Imaging in Oncology 1 Introduction 2 Indications for Conventional Radiography in Oncology 3 Fluoroscopy and Contrast Studies 4 Mammography 5 Ultrasonography (USG) in Oncology 6 Computed Tomography in Oncology 7 Magnetic Resonance Imaging in Oncology 8 Response Evaluation in Oncology 9 Molecular and Functional Imaging in Oncology 10 Conclusions References Nuclear Medicine in Oncology 1 History 2 Radiopharmaceuticals 3 Positron Emission Tomography (PET) 4 Radiommunodiagnostics 5 Hybrid Imaging 6 Indications of F18-Labeled Radiopharmaceuticals in Clinical Oncology 6.1 18F-FDG 6.1.1 The Role of FDG PET/CT in Specific Tumors Lymphomas Lung Cancers Esophageal Carcinoma Bone and Soft Tissue Tumors Head and Neck Malignancies Breast Carcinomas Melanomas Cancer of Unknown Primary Colorectal Carcinomas 6.2 F18 NaF 6.3 18F FLT (3′-Deoxy-3′-18F Fluorothymidine) 6.4 F18 FMISO (F18 Fluoromisonidazole) 6.5 18F FET (18F-Fluoro-ethyl-tyrosine) 7 Radioguided Surgery and Radioguided Biopsy 7.1 PET/MRI Hybrid Imaging 7.1.1 Specific Indications of PET/MRI in Clinical Oncology Head and Neck Cancers Liver Metastasis Brain Tumors Prostate Cancer Lung Cancer Breast Cancer Bone and Soft Tissue Malignancies Pediatric Malignancies and Lymphomas 8 Therapeutic Nuclear Medicine in Oncology Practice 8.1 The Fundamental Principles of Radionuclide Therapy Using Unsealed Sources 9 Specific Indications in Clinical Oncology 9.1 Thyroid Cancer 9.1.1 Remnant Ablation 9.1.2 Adjuvant Therapy 9.1.3 Treatment of Metastatic Diseases 9.1.4 Treatment for Iodine Refractory Thyroid Cancer 9.2 Polycythemia Rubra Vera 9.3 Bone Pain Palliation 9.4 Neuroblastomas 10 Theranostics 10.1 Receptor-Targeted Therapy in Theranostics 10.1.1 Peptide Receptor Radionuclide Therapy (PRRT) in Metastatic Neuroendocrine Tumors (NETs) 10.1.2 177Lu-PSMA Therapy (Peptide Receptor Radioligand Therapy: PRRLT) in Metastatic Castrate-Resistant Prostate Carcinoma 11 Alpha Therapy 11.1 Applications 12 Radioimmunotherapy References Interventional Radiology in Oncology 1 Introduction 2 Image Guidance for Procedures 3 Patient Evaluation and Peri-procedural Care 3.1 Laboratory Tests 4 Non-vascular Interventions 4.1 Percutaneous Image-Guided Biopsy (Fig. 3) 4.1.1 Indications 4.1.2 Procedure Contraindications 4.1.3 Complications 4.2 Image-Guided Drainages (Fig. 4) 4.2.1 Pre-procedure 4.2.2 Post-procedure 4.3 Tumor Ablation 4.3.1 Thermal Ablation Modalities Radiofrequency Microwave Cryoablation Irreversible Electroporation 5 Vascular Interventions 5.1 Trans-arterial Embolization (Angioembolization) 5.2 Transarterial Chemoembolization 5.3 Transarterial Chemoinfusion 5.4 Transarterial Radioembolization (TARE) 6 Pulmonary Interventions 6.1 Endobronchial Ultrasound-Transbronchial Needle Aspiration (EBUS-TBNA) 6.1.1 Indications 6.1.2 Advantages 6.1.3 Complications 6.1.4 Disadvantages 6.2 Ablation of Lung Tumors 6.2.1 Indications 6.2.2 Ablation Techniques 6.2.3 Technique 6.2.4 Follow-Up 6.2.5 Complications (Table 3) Outcome 6.3 Tracheal Stenting 6.3.1 Indications 6.3.2 Image Guidance and Procedure 6.3.3 Complications 6.4 Superior Vena Cava Obstruction 6.4.1 Complications 7 Hepato-Biliary Interventions 7.1 Transjugular Liver Biopsy (TJLB) 7.1.1 Indications 7.2 Percutaneous Transhepatic Biliary Drainage and Biliary Stenting 7.2.1 Indications 7.2.2 Contraindications 8 Hepatocellular Carcinoma 8.1 Ablation 8.1.1 Indications 8.1.2 Ablation Modalities 8.2 Transcatheter Arterial Chemoembolization 8.2.1 Complications 8.3 Follow-Up 8.4 Selective Internal Radiation Therapy (SIRT) or Transarterial Radioembolization (TARE) 8.4.1 Follow-Up 8.4.2 Complications 9 Genitourinary Interventions 9.1 Transjugular Renal Biopsy 9.1.1 Indications 9.2 Percutaneous Nephrostomy and Antegrade Ureteric Stenting 9.2.1 Indications 9.2.2 Procedure 9.2.3 Medications 9.2.4 Technique 9.2.5 Complications 9.3 Renal RFA 9.3.1 Indications 9.3.2 Ablation Techniques Thermal Procedure Adjuvant Techniques in Renal Tumor Ablation Complications Outcomes 9.4 Renal Angioembolization 9.4.1 Indications 10 Other Interventions 10.1 Central Venous Access 10.1.1 Complications 10.2 Bone and Soft Tissue Interventions 10.2.1 Indications 10.2.2 Ablation Modalities 10.3 Percutaneous Vertebroplasty 10.3.1 Indications 10.3.2 Absolute Contraindications 10.3.3 Relative Contraindications 10.3.4 Procedure 10.3.5 Complications 10.4 Angioembolization of Bone Tumors 10.4.1 Indications 10.5 Ophthalmic Artery Chemoinfusion for Retinoblastoma 10.6 Lymphangiography and Thoracic Duct Embolization 10.6.1 Indications 10.6.2 Procedure 11 Emergencies 11.1 Vascular Intervention 11.2 Gastrointestinal Bleeding 11.2.1 Causes of Upper GI Bleeding 11.2.2 Causes of Lower GI Bleeding 11.2.3 Evaluation of the Patient with Bleed (Fig. 19) Angioembolization Positive Findings 11.2.4 Complications 11.3 Hemoptysis and Bronchial Artery Embolization 11.3.1 Pre-procedural Imaging and Endovascular Treatment 11.3.2 Outcomes 11.3.3 Complications 11.3.4 Management of Hematuria and Bleeding per Vaginum 11.3.5 Management of Postoperative Hemorrhage 11.3.6 Management of Deep Venous Thrombosis and Pulmonary Thromboembolism 11.3.7 Procedure References Anaesthesia in Oncology 1 Introduction 2 Preoperative Chemotherapy 3 Preoperative Radiotherapy 4 Perioperative Care 5 Cardiovascular Evaluation in Patients Undergoing Oncologic Surgery 6 Frailty and Anaesthesia 7 Prehabilitation 8 Anaesthesia and Enhanced Recovery After Surgery (ERAS) 9 Patient Blood Management 10 Intraoperative Techniques that Affect Postoperative Outcome 11 Anaesthesia for Head and Neck Surgery 12 Laser Resections for Airway Tumours 13 Anaesthesia and Thoracic Surgery 14 Unique Onco-Surgical Procedures 14.1 Cytoreductive Surgery with Intraoperative Chemotherapy (Hyperthermic Intraperitoneal Chemotherapy [HIPEC] and Hyperthermic Intra-thoracic Chemotherapy [HITHOC]) 14.2 Robotic Surgery 14.3 Proton Radiation Therapy 15 Acute Pain Management After Cancer Surgery 16 Adjuvants 17 Anaesthesia and Cancer Recurrence 18 Conclusion References Transfusion Medicine in Oncology 1 Introduction 2 History of Transfusion Medicine in India 3 History of Transfusion Medicine in Oncology 4 Physiological Aspects of Blood 4.1 Red Cell Kinetics 4.2 WBC Kinetics 4.3 Platelet Kinetics 4.4 Normal Hemostasis 5 Blood Group Antigens and Antibodies 6 Blood and Blood Components 6.1 Whole Blood 6.2 Packed Red Blood Cell (pRBC) 6.3 Platelet Concentrates 6.4 Fresh Frozen Plasma (FFP) 6.5 Cryoprecipitate 6.6 Granulocyte Concentrate 6.7 Components Collected by Apheresis Technology 7 Modifications of Blood Components 7.1 Leukoreduction 7.2 Irradiation 7.3 Washing 7.4 Pathogen Reduction 8 Special Considerations in Oncology Patients 8.1 Pretransfusion Testing Issues in Oncology Patients 9 Transfusion in Oncology Patients 10 Transfusion Reactions 11 Conclusion References Palliative Care in Oncology 1 History of Palliative Care in India 2 Palliative Care Need in India 3 Principles of Palliative Care 4 Symptom Management 4.1 Guidelines for Cancer Pain Management in Ambulatory Palliative Care Setting 4.2 Guidelines for Cancer Pain Management in Acute Inpatient Palliative Care Setting 4.3 Guidelines for Cancer Pain Management in Home-Based Palliative Care Setting 4.4 Guidelines for Cancer Pain Management in Hospice and End-of-Life Care Patients 5 Psychosocial Aspects of Palliative Care 6 Ethics of Palliative Care 7 End-of-Life Care and Bereavement Support 8 Paediatric Palliative Care 8.1 End-of-Life Care 8.2 Spiritual Care 8.3 Symptom Management 8.4 Bereavement Support 9 Challenges in Delivering Palliative Care in India References Clinical Pharmacology in Oncology 1 Introduction to Clinical Pharmacology 2 Pharmacokinetics 2.1 Absorption 2.2 Distribution 2.3 Metabolism 2.4 Elimination 2.5 Concentration–Time Relationship 2.6 Repeated Drug Administration 2.6.1 Steady State 3 Pharmacodynamics 4 Interindividual Variability 4.1 Pharmacodynamics 4.2 Pharmacokinetics 4.3 Therapeutic Drug Monitoring (TDM) 5 Risk Versus Benefit 6 Pharmacovigilance 7 Drug Interactions 8 Special Population 8.1 Dosing Recommendations in Kidney Disease 8.2 Dosing Recommendations in Hepatic Impairment 8.3 Dose Modifications in Obesity 9 Clinical Pharmacology in Drug Development 9.1 Biomarkers 9.1.1 Pharmacodynamic Biomarker 9.1.2 Predictive Biomarker Enrichments Designs 9.1.3 Prognostic Biomarkers 9.1.4 PK/PD Modelling (Fig. 5) 10 Pharmacoeconomics 10.1 Assessment of Costs and Outcomes 10.1.1 Outcomes 10.2 Pharmacoeconomic Evaluation Methods (Fig. 6) 10.2.1 Economic Evaluation Methods 10.2.2 Humanistic Evaluation Methods 10.3 Pharmacoeconomics in Oncology 11 Personalized Medicine 11.1 Pharmacogenetics and Pharmacogenomics References Cancer Staging 1 Introduction 2 Principles and Need of Cancer Staging 2.1 The TNM Oncotaxonomy [2, 3] 2.2 Groome’s Criteria and the Staging System [4–6] 2.2.1 Stage Migration 2.3 General Rules of the TNM System [8, 9] 2.3.1 Staging Groups 2.3.2 The TNM Clinical Classification 2.3.3 The TNM Pathological Classification 2.3.4 Additional Descriptions 2.3.5 Stage Grouping [8–10] Staging Rules 2.4 Cancer Staging Systems in Clinical Practice [8, 9, 11] 2.4.1 Supplementary/Alternate Staging/Grading System to TNM System: Few Examples 2.4.2 Publications and Organisations Associated with TNM System [1, 8] 2.4.3 The AJCC-UICC Lexicon Project [8] 2.5 Evolution of Staging System and Their Implications 2.5.1 Concerns Associated with the Revisions in Staging System 2.5.2 Types of Changes in the TNM System [10] 2.6 Prognostic Factors and ‘Grid’ [9, 12, 13] 2.6.1 Grids of Prognostic Factors 2.7 Changes Observed in the TNM System 2.7.1 C-Factor [8, 9] 2.8 Future of Cancer Staging [3, 14] References Part II: Public Health Cancer Registration in India 1 Establishing Cancer Registries 2 Cancer Burden in India 3 Regional Diversity in Cancer Burden and Type 4 Utility of Cancer Registry Data References Cancer Screening in India 1 Principles of Screening 1.1 Disease Condition 1.2 Suitable Screening Test 1.3 Health System Requirements 1.4 Practical Concerns, Harms and Benefits from Screening 2 Cervical Cancer Screening 2.1 Cervical Cancer Screening Tests 2.1.1 Cervical Cytology 2.1.2 Visual Inspection with Acetic Acid (VIA) 2.1.3 Human Papilloma Virus (HPV) Testing 2.1.4 Self-Collected Vaginal Samples 2.2 Conclusion 3 Breast Cancer Screening 3.1 Mammography 3.2 Clinical Breast Examination (CBE) 3.3 Breast Self-Examination (BSE) 3.4 Ultrasonography 3.5 Conclusion 4 Oral Cancer Screening 4.1 Oral Cancer Screening Tests 4.1.1 Oral Visual Inspection (OVI) 4.1.2 Mouth Self-Examination and Other Screening Methods 5 Other Cancers 5.1 Prostate Cancer Screening 5.2 Lung Cancer Screening 5.3 Colorectal Cancer Screening References Part III: Hematological Malignancies Adult Lymphoblastic Leukemias 1 Acute Myeloid Leukemia 1.1 Incidence and Epidemiology 1.2 Clinical Presentation 1.3 Diagnosis and Classification 1.4 Investigations 1.5 Evaluation and Risk Stratification 1.6 Management of AML 1.6.1 Supportive Care for AML 1.7 Treatment of AML 1.7.1 Treatment of AML in Elderly Patients 1.8 Response Assessment and Monitoring 1.9 Prognosis and Outcomes 1.10 Summary and Practice at TMH (See Table 3) 2 Acute Promyelocytic Leukemia 2.1 Incidence and Epidemiology in India and Global 2.2 Clinical Presentation in India and Global 2.3 Evaluation and Work-up 2.3.1 Immunophenotyping 2.3.2 Cytogenetics Fluorescence In Situ Hybridization Conventional Karyotype 2.3.3 RT-PCR for PML-RARA RNA 2.4 Risk Stratification (Table 4) 2.4.1 Principles of Management 2.4.2 Medical Management and Monitoring Induction-Low- or Intermediate-Risk APL Induction-High-Risk APML Monitoring During Induction Other Issues During Induction Differentiation Syndrome Idiopathic Intracranial Hypertension or Pseudotumor Cerebri Response Assessment After Induction Consolidation Non-High-Risk APML Consolidation High-Risk APML Maintenance 2.5 Prognosis 2.6 Management of Resistant/Refractory Disease 2.7 Management for APML (Fig. 3) 2.8 How We Do It at TMC 3 Acute Lymphoblastic Leukemia 3.1 Incidence and Epidemiology 3.2 Clinical Presentation 3.3 Evaluation and Work-Up 3.4 Risk Stratification 3.5 Principles of Management 3.6 Supportive Care 3.7 Management of Recurrent Disease 3.8 How We Do It at TMC 4 Chronic Myeloid Leukemia 4.1 Incidence and Epidemiology of CML in India and Global 4.2 Clinical Features 4.3 Signs 4.4 Evaluation and Risk Stratification 4.4.1 Blood and Bone Marrow Examination 4.4.2 Molecular Tests 4.4.3 Prognostic Factors 4.5 Treatment at TMH 4.6 Practical Management Algorithmwfor CML 4.7 Monitoring of CML 4.8 Treatment-Free Remission 5 Chronic Lymphocytic Leukemia 5.1 Incidence and Epidemiology in India and Global 5.2 Clinical Presentation in India and Global 5.3 Evaluation and Work-Up 5.4 Work-Up for Confirmation of Diagnosis 5.5 Principles of Management 5.6 Medical Management and Monitoring 5.7 Management Algorithm According to Risk Stratification (Fig. 6) 5.8 Management of Recurrent Disease Including Specific Palliative Measures 5.9 How We Do It at TMC 6 Hairy Cell Leukemia 6.1 Incidence and Epidemiology in India and Global 6.2 Clinical Presentation in India and Globally 6.3 Evaluation and Work-Up Including Risk Stratification 6.4 Principles of Management (an Integrated Brief Overview of Rx Philosophy) 6.5 Medical Management and Monitoring 6.6 Prognosis with Current Rx 6.7 Management of Recurrent Disease Including Specific Palliative Measures 6.8 How We Do It at TMC References Adult Lymphomas 1 Introduction 2 Incidence and Epidemiology 3 Clinical Features and Staging of Lymphomas 4 Evaluation and Work-Up of Lymphomas 4.1 Lymphoma Diagnosis: Lab Approach 4.1.1 Morphological/Histopathological Approach to Lymphoma Diagnosis 4.1.2 Immunophenotyping 4.1.3 Cytogenetics 4.1.4 Molecular Tests 5 Principles of Management of Lymphomas 6 Management of Non-Hodgkin Lymphomas 6.1 Precursor B- and T-Cell Lymphomas 6.2 Mature B-Cell Lymphomas 6.2.1 Diffuse Large B-Cell Lymphoma (DLBCL) 6.2.2 Burkitt Lymphoma 6.2.3 Mantle Cell Lymphoma 6.2.4 Marginal Zone Lymphomas 6.2.5 Small Lymphocytic Lymphomas/Chronic Lymphoid Leukemia 6.2.6 Follicular Lymphoma 6.2.7 Peripheral T-Cell Lymphomas 7 Management of Hodgkin Lymphoma 7.1 Early Stage Favorable 7.2 Early Unfavorable 7.3 Early-Stage Risk/Response-Adapted Frontline Therapy 8 Advanced Hodgkin Lymphoma 8.1 Response-Adapted Therapy in Advanced Hodgkin Lymphoma 8.2 Role of Radiotherapy in Hodgkin Lymphoma 8.3 Long-Term Complications References Adult Myeloproliferative Disorders/Myelodysplastic Syndromes/Overlap Syndromes 1 Introduction 2 Epidemiology 3 Clinical Presentation 4 Evaluation, Work-Up and Risk Stratification 5 Principles and Guidelines for Management 6 Medical Management Options for MDS 7 Medical Management Options for MPN 8 Medical Management Options for Overlap Syndromes 9 Prognosis with Current Therapy 10 Treatment of Relapsed Refractory Disease and Palliative Care Measures 11 How We Do It at TMC References Plasma Cell Dyscrasias 1 Introduction 2 Incidence and Epidemiology in India and Global 2.1 Monoclonal Gammopathy of Unknown Significance and Smoldering Myeloma 2.2 Multiple Myeloma 2.3 Solitary Plasmacytoma 2.4 Systemic (AL) Amyloidosis 3 Etiology and Pathogenesis 4 Clinical Presentation 5 Evaluation and Work-Up Including Risk Stratification 5.1 Initial Work-Up 5.2 Additional Work-Up 6 Minimal Residual Disease (MRD) Monitoring 7 Principles of Management 8 Medical Management and Monitoring 8.1 Indications for Systemic Therapy 8.2 Therapy for Newly Diagnosed Myeloma 8.3 Initial Therapy 8.4 Autologous Stem Cell Transplant (ASCT) 8.5 Post ASCT Consolidation/Maintenance 8.6 Maintenance Therapy 8.7 Prognosis with Current Rx 8.8 Management of Recurrent Disease Including Specific Palliative Measures 9 Role of Definitive Radiation Therapy (RT) for Solitary Plasmacytoma 9.1 RT Dose Consideration for Solitary Plasmacytoma (SP) 10 Surgery for Multiple Myeloma 11 Multiple Myeloma Palliation with Radiation Therapy 11.1 Management Algorithm for Multiple Myeloma at TMC (Fig. 4) References Immunodeficiency-Associated Lymphoproliferative Disorders 1 Lymphomas Associated with HIV Infection 1.1 Prevalence 1.2 General Features of HIV-Associated Lymphomas 1.3 Pathogenesis 1.4 Histologic Classification of Lymphomas Associated with HIV Infection 1.4.1 Primary CNS Lymphoma (PCNSL) in HIV Patients 1.4.2 Diffuse Large B Cell Lymphoma (DLBCL) in HIV Patients 1.4.3 Burkitt Lymphoma 1.4.4 Polymorphic B Cell Lymphomas 1.4.5 Plasmablastic Lymphoma (PBL) 1.4.6 Primary Effusion Lymphomas (PEL) 1.4.7 Large B Cell Lymphoma Arising in Multicentric Castleman’s Disease (MCD) in HIV Patients 1.4.8 Peripheral T Cell Lymphoma 1.4.9 Hodgkin Lymphoma (HL) in HIV Patients 1.5 Clinical Features and Approach to Patients with HIV-Associated Lymphomas 1.6 Treatment 1.6.1 Concurrent cART 1.6.2 Combination Chemotherapy 1.7 Treatment of DLBCL 1.8 Treatment of Burkitt Lymphoma 1.9 Treatment of Hodgkin Lymphoma 1.10 Treatment of Other Lymphomas 1.11 Supportive Care in HIV-Associated Lymphomas 1.12 CNS Prophylaxis 2 LPDS Associated with Primary Immune Disorders 2.1 Prevalence 2.2 Pathogenesis 2.3 Clinical Features and Management 3 Post-transplant Lymphoproliferative Disorders (PTLD) 3.1 Classification 3.2 Etiology 3.3 Incidence 3.4 Clinical Features 3.5 Prognostic Factors 3.6 Management References Histiocytic and Dendritic Cell Neoplasms 1 Introduction 2 Histiocytes/Macrophages 3 Dendritic Cells 3.1 Myeloid-Derived DCs 3.2 Stromal-Derived DCs 4 Spectrum of Histiocytoses 5 Histiocytic and Dendritic Cell Neoplasms 6 Histiocytic Sarcoma (HS) 7 Tumors Derived from Langerhans Cells 7.1 Langerhans Cell Histiocytosis (LCH) 7.2 Langerhans Cell Sarcoma (LCS) 8 Indeterminate Dendritic Cell Tumor 9 Interdigitating Dendritic Cell Sarcoma (IDCS) 10 Follicular Dendritic Cell Sarcoma (FDCS) and Fibroblastic Reticular Cell Tumor (FRCT) 11 Xanthogranulomatous Group of Diseases: Disseminated Juvenile Xanthogranuloma (JXG) and Erdheim Chester Disease 12 Rosai–Dorfman Disease/Rosai–Dorfman–Destombes Disease (RDD)/Sinus Histiocytosis with Massive Lymphadenopathy (SHML) References Pediatric Acute Leukemias 1 Introduction 2 Acute Lymphoblastic Leukemia 2.1 Introduction 2.2 Incidence and Epidemiology in India and Global 2.3 Clinical Presentation in India and Global 2.4 Precursor B-ALL 2.5 T-Cell ALL 2.6 Special Types of ALL 2.6.1 Infant ALL 2.6.2 Philadelphia-Chromosome Positive ALL 2.6.3 Adolescent ALL 2.7 Evaluation and Work-Up Including Risk Stratification 2.8 Principles of Management (an Integrated Brief Overview of Rx Philosophy) 2.8.1 Remission Induction Phase 2.8.2 Intensification/Consolidation Phase 2.8.3 Interim Maintenance 2.8.4 Re-induction/Delayed Intensification Phase 2.8.5 Continuation/Maintenance Phase 2.8.6 Central Nervous System (CNS) Directed Therapy 2.9 Medical Management and Monitoring 2.10 Management Algorithms According to Risk Stratification 2.11 Prognosis with Current Rx 2.12 Management of Recurrent Disease Including Specific Palliative Measures 3 Acute Myeloid Leukemia 3.1 Introduction 3.2 Incidence and Epidemiology in India and Global 3.3 Clinical Presentation in India and Global 3.4 Evaluation and Work-Up Including Risk Stratification 3.5 Principles of Management (an Integrated Brief Overview of Rx Philosophy) 3.6 Risk Stratification 3.7 Treatment at TMH 3.8 Relapsed AML 3.9 Future Directions 4 Acute Promyelocytic Leukemia 4.1 Introduction 4.2 Incidence 4.3 Principles of Management 4.4 Management and Monitoring 4.5 Treatment Algorithm 4.5.1 Induction 4.5.2 Consolidation 4.6 Common Toxicities 4.7 Management of Recurrent Disease 5 How We Do It at TMC References Pediatric Hodgkin Lymphoma 1 Introduction 2 Incidence and Epidemiology in India and Global 3 Clinical Presentation in India and Global 4 Evaluation and Work-Up Including Risk Stratification 4.1 Diagnosis 4.2 Immunohistochemistry 4.3 Assessment of Involved Regions and Staging 4.4 Risk Stratification 5 Principles of Management 6 Medical Management 6.1 Chemotherapy 6.2 Radiotherapy (RT) 7 Monitoring According to Risk Stratification 7.1 Response Assessment 7.1.1 Early Response Assessment (ERA) 8 Nodular Lymphocyte-Predominant HL (NLPHL) 9 Management of Relapsed and Refractory HL 10 Late Effects 10.1 Cardiac Toxicity 10.2 Pulmonary Toxicity 10.3 Thyroid Abnormalities 10.4 Gonadal Toxicity 10.5 Subsequent Neoplasms (SMN) 10.6 Growth and Development 11 Treatment Algorithms Used in Tata Memorial Hospital (TMH) References Pediatric Myeloproliferative Disorders/Myelodysplastic Syndromes/Overlap Syndromes 1 Introduction 2 Incidence and Epidemiology in India and Globally 3 Clinical Presentation 4 Evaluation and Work-Up Including Risk Stratification 4.1 Juvenile Myelomonocytic Leukemia (JMML) and Other Myelodysplastic/Myeloproliferative Disorders 4.2 Myeloid Leukemia of Down Syndrome (ML-DS) 4.3 Transient Abnormal Myelopoiesis (TAM) 4.4 Refractory Cytopenia (RC) 4.5 Advanced Pediatric MDS 4.6 Principles of Management of MDS 4.7 Refractory Cytopenia (RC) 4.8 Advanced Primary MDS (RAEB/RAEB-t) 4.9 Treatment of Secondary MDS 4.10 Principles of Management of JMML 4.11 Treatment of CBL Mutation 4.12 Treatment of Germline Mutation of KRAS/NRAS 4.13 Treatment of Somatic Mutation of KRAS/NRAS/PTPN11 and NF-1 4.14 Principles of Management of TAM in Downs Syndrome 4.15 Prognosis with Current Treatment 4.15.1 MDS 4.15.2 JMML 4.16 Management of Recurrent Disease in Patients with MDS 4.17 Management of Recurrent Disease in Patients with JMML 5 How We Do It at TMC References Hematopoietic Stem Cell Transplantation