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Book Details
Abstract
This issue of Immunology and Allergy Clinics, edited by Dr. Cem Akin, is devoted to Mastocytosis. Articles in this issue include Human Mast Cell Signal Transduction; Mast cell tryptase role in homeostasis and coagulation; Mastocytosis: Current Classification and Diagnostic criteria; Epidemiology, risk factors and prognosis of mastocytosis; Mast cell sarcoma: Clinical management; Molecular defects in mastocytosis: c-kit mutations and beyond; Flow cytometry in mastocytosis: Utility as a diagnostic and prognostic tool; Morphology of mastocytosis with special reference to immunophenotypical aberrancies; CD30 expression in mastocytosis; Extramedullary mastocytosis: Pathologic aspects; Bone involvement and osteoporosis in mastocytosis; Drug allergy in mastocytosis; Eosinophilia in mastocytosis; Venom allergy and mastocytosis; Skin disease in mastocytosis; Treatment of advanced mastocytosis; Treatment strategies of mediator related symptoms in mastocytosis; and Neuro and psychological involvement in Mastocytosis.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Mastocytosis | i | ||
| copyright\r | ii | ||
| Contributors | iii | ||
| Contents | ix | ||
| Immunology\rand Allergy Clinics Of North America | xiv | ||
| Foreword\r | xv | ||
| References | xvi | ||
| Preface\r | xvii | ||
| Erratum | xix | ||
| Diagnostic Criteria and Classification of Mastocytosis in 2014 | 207 | ||
| Key points | 207 | ||
| Definition and overview of categories | 207 | ||
| Diagnosis | 208 | ||
| Major Criterion | 210 | ||
| Minor Criteria | 210 | ||
| Classification | 212 | ||
| Summary | 214 | ||
| References | 214 | ||
| Functional Deregulation of KIT | 219 | ||
| Key points | 219 | ||
| Introduction | 219 | ||
| c-Kit mutations and link to malignancies | 220 | ||
| c-Kit and Neoplastic Growth of Mast Cells | 221 | ||
| Mechanisms of KIT activation | 223 | ||
| Structure of KIT | 223 | ||
| Signaling Pathways of KIT in Mast Cells | 223 | ||
| Gain-of-Function c-Kit Mutations and Mechanisms for Constitutive Activation | 225 | ||
| Trafficking of KIT and Its Impact on Signaling | 227 | ||
| KIT inhibitors and treatment of mutated KIT-driven proliferative diseases | 229 | ||
| Concluding remarks and future directions | 230 | ||
| References | 231 | ||
| Molecular Defects in Mastocytosis | 239 | ||
| Key points | 239 | ||
| Introduction | 240 | ||
| Critical roles of SCF and KIT in the development and biology of MCs | 240 | ||
| Structure of SCF | 240 | ||
| Normal Structure of KIT | 241 | ||
| Physiologic Signaling by Normal KIT in MCs | 242 | ||
| Classification of mastocytosis | 242 | ||
| Involvement of KIT defects in mastocytosis | 243 | ||
| Pediatric CM | 244 | ||
| ISM | 245 | ||
| ASM | 246 | ||
| SM-AHNMD | 246 | ||
| MCL | 246 | ||
| MCS | 246 | ||
| Familial Forms of Mastocytosis | 247 | ||
| Abnormal signaling evoked by the KIT D816V oncogenic mutant | 247 | ||
| Changes in Intracellular Localization | 247 | ||
| Altered Substrate Specificity | 249 | ||
| Consequences of the various defects in KIT for targeted therapy | 250 | ||
| PTD Mutants | 250 | ||
| JMD, Transmembrane Domain, and Extracellular Membrane Domain Mutants | 250 | ||
| Other (additional) molecular defects found in various forms of mastocytosis: beyond KIT | 251 | ||
| TET2 Mutations | 251 | ||
| TET2 functions and impact in hematologic malignancies | 251 | ||
| TET2 and mastocytosis | 251 | ||
| Mutations in the Spliceosome Machinery | 252 | ||
| ASXL1 Mutations | 253 | ||
| RAS Mutations | 254 | ||
| CBL, DNMT3A, ETV6, EZH2, RUNX1, and SETBP1 Mutations | 254 | ||
| Summary and future considerations | 255 | ||
| References | 256 | ||
| Mast Cell–Restricted Tetramer-Forming Tryptases and Their Beneficial Roles in Hemostasis and Blood Coagulation | 263 | ||
| Key points | 263 | ||
| Introduction | 264 | ||
| Human MC tryptases | 265 | ||
| Mouse MC tryptases | 266 | ||
| Serglycin proteoglycans | 267 | ||
| Structural analysis of MC tryptases | 267 | ||
| Bioactivity of MC tryptases | 268 | ||
| Substrate preferences of MC tryptases | 268 | ||
| Thrombin-dependent conversion of fibrinogen to fibrin | 270 | ||
| Heparin-dependent anticoagulation | 270 | ||
| Anticoagulant activity of MC tryptases | 271 | ||
| Selective proteolysis of the C-terminus of the α chain of human fibrinogen by hTryptase-β–heparin complexes | 271 | ||
| Preferential proteolysis of mouse fibrinogen’s α chain by hTryptase-β–heparin, mMCP-6–heparin, and mMCP-6–SGPG complexes | 272 | ||
| In vitro anticoagulant activity of mMCP-6–heparin and hTryptase-β–heparin complexes | 273 | ||
| In vivo anticoagulant activity of mMCP-6–heparin SGPG complexes | 273 | ||
| Clinical implications | 273 | ||
| Future considerations | 274 | ||
| References | 275 | ||
| Epidemiology, Prognosis, and Risk Factors in Mastocytosis | 283 | ||
| Key points | 283 | ||
| Epidemiology of mastocytosis and mast cell activation syndromes | 283 | ||
| Prevalence of Mastocytosis | 283 | ||
| Mastocytosis in Different Age and Gender Groups | 284 | ||
| Systemic Mastocytosis Without Skin Lesions | 284 | ||
| Incidence of Monoclonal Mast Cell Activation Syndrome | 285 | ||
| Incidence of Idiopathic Mast Cell Activation Syndrome | 285 | ||
| Epidemiology of different forms of mastocytosis | 285 | ||
| Prevalence of Systemic Disease in Patients with Mastocytosis | 285 | ||
| Prevalence of Different Forms of SM | 286 | ||
| Prevalence of Different Forms of MIS | 287 | ||
| Prognosis for regression or progression of disease | 287 | ||
| Prognosis for Resolution of CM in Children | 287 | ||
| Prognosis for Resolution of CM in Adults | 288 | ||
| Prognosis for Progression of Disease and Survival | 288 | ||
| Risk factors for major complications of mastocytosis | 290 | ||
| Risk Factors for More Severe Clinical Disease | 290 | ||
| Risk Factors for Anaphylaxis in Patients with Mastocytosis | 291 | ||
| Risk Factors for Osteoporosis in Patients with Mastocytosis | 291 | ||
| References | 291 | ||
| Flow Cytometry in Mastocytosis | 297 | ||
| Key points | 297 | ||
| Introduction | 297 | ||
| Methodological approach for the identification, enumeration, and characterization of bone marrow mast cells | 298 | ||
| Immunophenotypic features of normal bone marrow mast cells | 300 | ||
| The MC-Committed Progenitor Cell | 300 | ||
| Immunophenotypic Characteristics of Normal/Reactive Mature BM MCs | 302 | ||
| Utility of flow cytometry for the diagnosis of systemic mastocytosis | 302 | ||
| Utility of flow cytometry for the subclassification of systemic mastocytosis | 304 | ||
| Immunophenotypic Profiles of BM MCs in SM | 304 | ||
| Expression of Novel Antigens: CD30 | 306 | ||
| Coexistence of Normal and Pathologic BM MCs | 307 | ||
| Identification of MCs in Peripheral Blood, Organic Fluids, or Tissues | 307 | ||
| Identification of circulating MCs in peripheral blood | 307 | ||
| Identification of MCs in organic fluids or tissues | 307 | ||
| Utility of flow cytometry for the prognostic stratification of systemic mastocytosis patients | 308 | ||
| Analysis of KIT Mutation on BM Purified Cells | 308 | ||
| Summary | 309 | ||
| References | 310 | ||
| Mastocytosis | 315 | ||
| Key points | 315 | ||
| Introduction | 315 | ||
| Classification and diagnosis of systemic mastocytosis | 316 | ||
| Immunohistochemistry | 316 | ||
| CD30+ SM | 319 | ||
| Summary | 320 | ||
| References | 321 | ||
| Pathology of Extramedullary Mastocytosis | 323 | ||
| Key points | 323 | ||
| Ancillary markers in surgical pathology for the evaluation of mastocytosis | 323 | ||
| KIT | 324 | ||
| Mast Cell Tryptase | 325 | ||
| CD25 | 325 | ||
| CD2 | 325 | ||
| CD30 | 325 | ||
| Cutaneous mastocytosis | 326 | ||
| Urticaria Pigmentosa | 326 | ||
| Telangiectasia Macularis Eruptiva Perstans | 327 | ||
| Solitary Mastocytoma of Skin | 328 | ||
| Diffuse Cutaneous Mastocytosis | 328 | ||
| Mastocytosis involving the gastrointestinal tract | 328 | ||
| Mastocytosis involving the liver | 330 | ||
| Mastocytosis involving the spleen and lymph nodes | 332 | ||
| Mast cell sarcoma | 333 | ||
| Summary | 335 | ||
| References | 335 | ||
| CD30 in Systemic Mastocytosis | 341 | ||
| Key points | 341 | ||
| Introduction | 341 | ||
| The CD30 receptor and its ligand CD30L | 342 | ||
| Soluble CD30 and sCD30L | 342 | ||
| Expression of CD30 and CD30L in physiology | 342 | ||
| Expression of CD30 and sCD30 in allergic and immunologic diseases | 344 | ||
| Expression of CD30 and sCD30 in malignancy | 345 | ||
| Functional role of CD30 in proliferation and apoptosis | 346 | ||
| Function of CD30 in the adaptive immune system | 346 | ||
| Functional role for CD30L signaling in mastocytosis | 346 | ||
| Effects of mastocytosis-expressed CD30 on immune homeostasis | 347 | ||
| The diagnostic applicability of CD30 in mastocytosis | 347 | ||
| CD30 as a marker of advanced systemic mastocytosis | 347 | ||
| Soluble CD30 and mastocytosis | 348 | ||
| CD30 as a target for cytoreductive therapy | 348 | ||
| Summary | 350 | ||
| References | 350 | ||
| Eosinophilia in Mast Cell Disease | 357 | ||
| Key points | 357 | ||
| Introduction | 357 | ||
| Mast cell and eosinophil biology | 357 | ||
| Mast Cells | 357 | ||
| Eosinophils | 358 | ||
| The Mast Cell-Eosinophil Pair | 358 | ||
| Nonclonal disorders in which both cells are present and likely drive disease pathogenesis | 358 | ||
| Asthma and Allergic Rhinitis | 358 | ||
| EoE | 359 | ||
| Idiopathic Hypereosinophilic Syndrome | 359 | ||
| Clonal disorders affecting mast cells and eosinophils | 360 | ||
| Chronic Eosinophilic Leukemia | 360 | ||
| Mastocytosis | 361 | ||
| Future directions | 362 | ||
| Therapies | 362 | ||
| References | 363 | ||
| Epidemiology, Diagnosis, and Treatment of Hymenoptera Venom Allergy in Mastocytosis Patients | 365 | ||
| Key points | 366 | ||
| Introduction | 366 | ||
| Epidemiology | 367 | ||
| Diagnosis | 368 | ||
| Treatment | 371 | ||
| Side Effects of VIT in Mastocytosis | 373 | ||
| The United States Perspective | 375 | ||
| Summary | 377 | ||
| References | 378 | ||
| Bone Involvement and Osteoporosis in Mastocytosis | 383 | ||
| Key points | 383 | ||
| Epidemiology | 383 | ||
| Pathophysiology | 386 | ||
| Clinical features | 391 | ||
| Diagnosis | 391 | ||
| Management | 392 | ||
| References | 393 | ||
| Drug Allergy in Mastocytosis | 397 | ||
| Key points | 397 | ||
| Introduction | 397 | ||
| Drug Anaphylaxis in Patients with Mastocytosis | 398 | ||
| MCD in Patients with Drug Hypersensitivity | 398 | ||
| MCDs and general anesthesia | 398 | ||
| Risk Factors | 399 | ||
| Value of Premedication | 399 | ||
| Tryptase | 399 | ||
| Anesthesia in Childhood Mastocytosis | 400 | ||
| Anesthesia in Adult Patients with Mastocytosis | 400 | ||
| Local Anesthesia | 400 | ||
| General recommendations for anesthesia | 401 | ||
| MCD and use of RCM | 402 | ||
| Other drugs | 402 | ||
| Antibiotics | 402 | ||
| NSAIDs | 402 | ||
| Opioids | 403 | ||
| General Considerations | 403 | ||
| Summary | 403 | ||
| References | 404 | ||
| Neuropsychological Features of Adult Mastocytosis | 407 | ||
| Key points | 407 | ||
| Future considerations | 407 | ||
| Introduction | 408 | ||
| Epidemiology | 408 | ||
| Neurologic Features | 408 | ||
| Depression | 409 | ||
| Cognitive Impairment | 409 | ||
| Clinical symptoms | 409 | ||
| Neurologic Symptoms | 409 | ||
| Psychological Symptoms | 410 | ||
| Depression characteristics and assessment | 410 | ||
| Cognitive impairment characteristics and assessment | 411 | ||
| Pathophysiology | 411 | ||
| Mast Cells in the Brain | 411 | ||
| Mast Cells, Stress Response, Cognition, and Emotionality | 412 | ||
| Mast Cell Neuroinflammation and Depression | 412 | ||
| Mast Cells and Headache | 413 | ||
| Mast Cells and Multiple Sclerosis | 413 | ||
| Diagnosis | 413 | ||
| Mastocytosis Was Not Previously Diagnosed | 413 | ||
| Mastocytosis Was Previously Diagnosed | 414 | ||
| Treatment | 414 | ||
| Psychotherapeutic Interventions | 414 | ||
| Psychotropic Drugs | 415 | ||
| Tyrosine Kinase Inhibitor Therapy | 415 | ||
| Summary | 416 | ||
| References | 416 | ||
| Mast Cell Sarcoma | 423 | ||
| Key points | 423 | ||
| Introduction | 423 | ||
| Clinical presentation and prognosis | 423 | ||
| Organs Affected | 424 | ||
| Age Groups Affected | 424 | ||
| Survival | 424 | ||
| Clinical Presentation | 426 | ||
| Therapeutic modalities | 428 | ||
| Summary | 430 | ||
| References | 431 | ||
| Treatment Strategies in Mastocytosis | 433 | ||
| Key points | 433 | ||
| Introduction | 433 | ||
| General considerations | 435 | ||
| CM in children | 435 | ||
| Skin lesions in adults | 436 | ||
| Skin symptoms | 436 | ||
| Gastrointestinal symptoms | 437 | ||
| Other MC mediator–related symptoms | 437 | ||
| Bone disease and osteoporosis | 438 | ||
| Anaphylaxis | 439 | ||
| Kit-targeting therapies | 440 | ||
| Future perspectives | 440 | ||
| Acknowledgments | 441 | ||
| References | 441 | ||
| Index | 449 |