Amyloid and Related Disorders Surgical Pathology and Clinical Correlations 2nd Edition by Maria Picken, Guillermo Herrera, Ahmet Dogan 3319192930 9783319192932

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ISBN 10: 3319192930

ISBN 13: 9783319192932

Author: Maria M. Picken; Guillermo A. Herrera; Ahmet Dogan

The second edition of this text presents an overview of the most recent developments in this area including clinical presentation, etiology, pathogenesis, and differential diagnosis. The rationale for various therapies, including transplantation, is discussed and tissue diagnosis (its pitfalls and strategies for avoiding them) and laboratory support are included. The involvement of all major organ systems including renal/genitourinary, cardiac, gastrointestinal, pulmonary, peripheral nerve/central nervous system, soft tissue, skin, lymph node/spleen and bone marrow pathology is also covered. Amyloid and Related Disorders, Second Edition will be invaluable to specialized and general pathologists as well as cytopathologists. Other medical professionals may also benefit from this concise update on the systemic amyloidoses.

Amyloid and Related Disorders Surgical Pathology and Clinical Correlations 2nd Table of contents:

Part I: Introduction/General

1: Aspects of the History and Nomenclature of Amyloid and Amyloidosis

A Short History of Amyloid

Biochemical Nature of Amyloid

Diagnosis of Amyloidosis

Nomenclature

What Is Amyloid?

Older Nomenclatures

Modern Amyloid Nomenclature

References

2: Amyloid Diseases at the Molecular Level: General Overview and Focus on AL Amyloidosis

General Overview

What Makes a Protein Amyloidogenic?

Common Constituents of Amyloid Deposits

Amyloid Structure

Amyloid Formation: From Monomers to Fibrils

Kinetics of Fibril Formation

Organ Tropism

Mechanisms of Tissue Damage

Immunoglobulin Light Chain Amyloidosis (AL)

The Amyloidogenic Clone

Genetics of Amyloidogenic Light Chains

Structural Features of Amyloidogenic Light Chains

Mechanisms of Toxicity

Organ Tropism in AL Amyloidosis

Clinical Manifestations

Clinical Approach

References

3: AA Amyloidosis

AA Amyloidosis in Rheumatic Disease

The Hereditary Autoinflammatory Diseases

Monogenic Autoinflammatory Diseases

Familial Mediterranean Fever

Tumor Necrosis Factor Receptor-�Associated Periodic Syndrome

Cryopyrin-Associated Periodic Fever Syndromes

Hyper IgD Syndrome

Other Monogenic Autoinflammatory Diseases

Polygenic and Complex Autoinflammatory Disease

Inflammatory Bowel Disease

Sarcoidosis and Sinus Histiocytosis with Massive Lymphadenopathy

AA Amyloidosis and Obesity

Summary

References

4: Leukocyte Cell-Derived Chemotaxin 2 Amyloidosis (ALECT2)

Introduction

Overview of LECT2 Biology and ALECT2 Pathogenesis

Renal ALECT2 Amyloidosis

Hepatic ALECT2 Amyloidosis

Conclusions

References

5: The Hereditary Amyloidoses

Introduction

Types of Hereditary Amyloidosis

Transthyretin

Apolipoprotein AI

Fibrinogen Aα-Chain

Gelsolin

Lysozyme

Apolipoprotein AII

Cystatin C

Lect2

Conclusion

References

6: Dialysis-Associated Amyloidosis

Introduction

Epidemiology

Pathophysiology

Risk Factors

Clinical Manifestations

Carpal Tunnel Syndrome

Scapulohumeral and Other Arthropathies

Bone Cysts and Pathological Fractures

Destructive Spondyloarthropathy

Visceral Involvement

Clinical Diagnosis

Differential Diagnosis

Clinical Investigations

Radiological Imaging

Plain X-Rays

Scintigraphy

Ultrasonography

X-Ray Computed Tomography

Magnetic Resonance Imaging

Tissue Biopsy

Treatment

Supportive Treatment

Specific Treatment

Prevention

Dialysis Modality

Ultrapure Dialysate

Conclusion

References

7: Localized Amyloidoses and Amyloidoses Associated with Aging Outside the Central Nervous System

Introduction

Localized AL Amyloidosis

Amyloid in Endocrine Organs and Tumors

Islet of Langerhans

Parathyroid Glands

Amyloid in the Cardiac Atria

Pituitary Gland

Amyloid in Endocrine Tumors

Medullary Carcinoma of the Thyroid

Insulinoma of the Pancreas

Pituitary Adenoma

Amyloid at Sites of Peptide Injection

Insulin

Enfuvirtide

Localized Amyloid Deposits in the Skin

Amyloid in Skin Tumors

Calcifying Epithelial Odontogenic Tumor

Wild-type Transthyretin (Senile Systemic) Amyloidosis and Peripheral Vascular Amyloid

Wild-type Transthyretin Amyloidosis

Aorta and Other Arteries

Medin (AMed) Amyloid

Amyloid in Atherosclerotic Plaques and Cardiac Valves

Amyloid in the Seminal Vesicles

Corneal Amyloid

Amyloid in Joints, Ligaments, and Tendons

Additional Localized Aggregates with Amyloid Properties

References

8: Amyloid Deposition in the Central Nervous System

Introduction

Amyloid-Associated Neurodegenerative Diseases

Cerebral Amyloid Angiopathy

Tumefactive and Neoplasia-­Associated CNS Amyloidosis

Systemic Amyloidosis and CNS Involvement

Pituitary Amyloid

References

Part II: Non-amyloid Protein Deposits

9: Differential Diagnosis of Amyloid in Surgical Pathology: Organized Deposits and Other Material

Introduction

The Diagnosis of Amyloidosis: A Historical Account with Emphasis on Differentiating It from Oth

The Different Entities in the Kidney and Extrarenal Manifestations Associated with Organized De

The Nature of the Problem: What Is in the Differential Diagnosis of Amyloidosis in the Kidne

Fibrillary Glomerulonephritis (Nephropathy)

Renal

Extrarenal

Pathogenesis

Cryoglobulinemic Nephropathy

Extrarenal

Pathogenesis

Immunotactoid Glomerulopathy

Extrarenal Manifestations

Pathogenesis

Hyalinosis

Pathogenesis

Hyalinized Collagen

Pathogenesis

Other Nonspecific Fibrils that Are Confused with Amyloid

A Logical Approach to the Differential Diagnosis with Emphasis on Type of Specimens Required

Conclusions

References

10: Light/Heavy Chain Deposition Disease as a Systemic Disorder

Introduction

Historical Perspective

Kidneys

Extrarenal Manifestations of Light/Heavy Chain Deposition Disease

Liver

Heart

Peripheral and Central Nervous System Involvement

Lungs

Gastrointestinal

Pancreas

Skin

Muscle

Other Organs

Diagnostic Criteria/Pitfalls

Mechanisms Associated with Organ Pathology

Physicochemical Characteristics of Pathologic Light/Heavy Chains Associated with LHCDD

Conclusions

References

11: Non-Randall Glomerulonephritis with Non-Organized Monoclonal Ig Deposits

Proliferative GN with Non-­Organized Monoclonal Ig Deposits

Nonproliferative GN with Non-­Organized Monoclonal Ig Deposits

Revisiting the Disease Spectrum of GN with Monoclonal Ig Deposits

Pathophysiological Considerations

Diagnostic Considerations

Therapeutic Considerations

References

12: Pathologies of Renal and Systemic Intracellular Paraprotein Storage: Crystalopathies and Beyo

Kidney Pathology Associated with Intracellular Paraprotein Storage: Light Chain Proximal Tubulopath

Pathology

Extrarenal Pathology Associated with Intracellular Paraprotein Storage: Crystal-Storing Histiocyto

Pathology

References

Part III: Diagnosis

13: Diagnosis of Amyloid Using Congo Red

Amyloid and Congo Red: Historical and Technical Notes

Stokes’ Method for Congo Red Staining of Amyloid

Analysis of Congo Red Staining

Polarisation Microscopy of Amyloid Stained by Congo Red

Principles of Polarisation Microscopy and Explanation of the Optical Properties of Amyloid Sta

Birefringence

Absorption

Anomalous Dispersion of the Refractive Index

Compensation

Effect of Uncrossing of Polariser and Analyser

Description of the Effects Seen

Summary of the Procedure to Diagnose Amyloid Using Congo Red

References

14: Diagnosis of Minimal Amyloid Deposits by Congo Red Fluorescence and Amyloid Type-­Specific Im

Introduction and Overview

Tissues and Congo Red Staining for the Diagnosis of Amyloid

Evaluation of Congo Red-Stained Sections and Pitfalls

Sampling Error as a Major Pitfall

The Low Sensitivity of the Classical Congo Red Method and Possibilities for Improvements

Minute Amounts of Missed Amyloids: Identified and Classified

High-Sensitivity Diagnosis of Minute Amyloid Deposits with Congo Red Fluorescence

Report for the Clinician

Take-Home Lessons

References

15: Thioflavin T Stain: An Easier and More Sensitive Method for Amyloid Detection

Thioflavin T Stain for Amyloid

References

16: Fat Tissue Analysis in the Management of Patients with Systemic Amyloidosis

Introduction

Aspiration Versus Biopsy

Detection of Amyloid Using Congo Red-Stained Fat Tissue Specimens

Typing of Amyloid

Antibody-Based Detection

Antibody-Based Quantification of Amyloid Proteins

Advantages and Disadvantages of Antibody-Based Typing

Proteomics-Based Detection

Semiquantitative Assessment of Amyloid in Fat Tissue

Quantification of Amyloid in Fat Tissue for Diagnosing and Typing Amyloid

Amyloid Quantity in Fat Tissue and Clinical Characteristics

Amyloid Quantity in Fat Tissue and Follow-Up

Future Perspectives

Appendix: Fat Aspiration Technique and Tissue Analysis Currently Practiced in Groningen

Fat Aspiration Technique

Stepwise Description of the Procedure

Frequently Encountered Problems During the Procedure

Congo Red Stain and Grading of Amyloid in Fat Tissue

Preparing Slides for Microscopy

Congo Red Stain, Microscopy, and Amyloid Grading

Immunochemical Quantification of Amyloid Proteins in Fat Tissue Extracts

References

17: Generic Diagnosis of Amyloid: A Summary of Current Recommendations and the Editor’s Comme

Clinical Diagnosis: The “Gold Standard”

Thickness of Paraffin Sections for Congo Red Stain

Sampling Error

Other Stains and/or Modifications of the Congo Red Stain that Are Worth Considering and Strongly

Other Stains that Are Less Useful and/or Obsolete

The Diagnosis of Amyloid: Summary of Options for Clinical Diagnosis

Electron Microscopy

The Choice of Tissue Specimen: Fat as an Underutilized Source of Tissue for Amyloid Detection,

Clinical Diagnosis: Current Challenges and Possible Solutions

Amyloid Diagnosis in the Future?

Summary and Conclusions

Conclusions

References

18: Typing of Amyloid for Routine Use on Formalin-Fixed Paraffin Sections of 626 Patients by Ap

Introduction and Overview

Tissues, Amyloid type-specific Antibodies, Immunohistochemistry, and Execution

Evaluation of Immunohistochemical Reactivities

Comparative Amyloid type-Specific Immunohistochemistry as a Routine Method for Amyloid Typing

High-Sensitivity Classification of Single Minute Amyloid Deposits

Performance and Prevalence

Pitfalls and Remedies

Take Home Message

Report for Clinicians

References

19: Amyloid Typing: Experience from a Large Referral Centre

Introduction

Biopsies

Congo Red

Immunohistochemistry for Amyloid at the NAC

Laser Capture Microdissection and Mass Spectrometry Dissection Mass Spectrometry

Anomalies

Summary

References

20: Options for Amyloid Typing in Renal Pathology: The Advantages of Frozen Section Immunofluores

Frozen Section Immunofluorescence Amyloid Typing

Amyloid Immunohistochemistry Versus General Immunohistochemistry

Antibody Reactivity

Other Factors

Paraffin Versus Frozen Sections

General Comments Regarding Antibody Typing by Frozen Section Immunofluorescence

Summary Comments Regarding Amyloid Typing

Recommendations

References

21: Amyloid Typing in Plastic-­Embedded Tissue by Immune-Gold-­Silver Method

Introduction

Development of the immune-gold-silver labeling method in plastic-embedded tissue

Immune-Gold-Silver Method for Amyloid Typing in Plastic-­Embedded Tissue

Conclusions

References

22: The Role of Immuno-Electron Microscopy in Amyloid Typing: The Experience of the Pavia Refer

Introduction: The Role of Electron Microscopy in the Diagnosis of Amyloidosis

Electron and Immuno-Electron Microscopy

Techniques of Electron Microscopy

Principles of Immuno-Electron Microscopy

Techniques of Immuno-Electron Microscopy

Abdominal Fat

Salivary Gland Biopsy

Clinically Affected Organ Biopsy

Conclusions

References

23: Classification of Amyloidosis by Mass Spectrometry-Based Proteomics

Laser Microdissection

High-Performance Liquid Chromatography (LC) Tandem Mass Spectrometry (MS/MS)-Based Proteomics

Classification of Amyloidosis by LC–MS/MS-Based Proteomics

Conclusions

References

24: The Role of Differential Proteomics in Amyloid Typing: The Experience of the Pavia Referral

Introduction: Proteomics in the Diagnosis of Amyloidosis

Differential Proteomics for Amyloid Characterization

Principles of Differential Proteomics

Differential Proteomic Techniques Used in Amyloid Typing

Subcutaneous Abdominal Fat

Formalin-Fixed Paraffin-Embedded Biopsies

The “Amyloid Signature” Proteome in Diagnosis; Novel Proteomic Biomarkers of Tissue Dysfuncti

Conclusions

References

Part IV: Ancillary Studies of Amyloidosis

25: Laboratory Support for Diagnosis of Amyloidosis

Introduction

Free Light Chain Quantitation

Diagnostic Sensitivity for Identification of Monoclonal FLC

Monitoring Disease Activity

Future Directions

References

26: Bone Marrow Biopsy and Its Utility in the Diagnosis of AL Amyloidosis

Bone Marrow Biopsy Procedure and General Findings

Detecting Amyloid Deposits

Establishing a Diagnosis of a Plasma Cell Neoplasm

Comparison of Bone Marrow Biopsy with Serum/Urine Immunofixation Electrophoresis and Serum-Free

Flow Cytometry

Genetic Pathogenesis of AL Amyloidosis

Summary

References

27: Laboratory Methods for the Diagnosis of Hereditary Amyloidoses

Introduction

Mass Spectrometry in TTR

Genetic Testing in Amyloidosis

Genetic Evaluation

Genes Involved in Hereditary Amyloidosis

Notes on Nomenclature

Transthyretin

Apolipoprotein A1

Apolipoprotein A2

Gelsolin A

Fibrinogen Alpha

Lysozyme

LECT2: A New Hereditary Amyloidosis Gene?

Beta-2 Microglobulin: A New Hereditary Amyloid Gene!

Summary

References

Part V: Organ Involvement in Amyloidoses

28: Amyloidoses of the Kidney, the Lower Urinary and Genital Tracts (Male and Female), and the

The Kidney

Clinical Presentation

Pathology

Differential Diagnosis of the Renal Amyloidosis Type

AL/AH Amyloidosis

AA Amyloidosis

Non-AL/AA Amyloidoses

Aβ2M

Extrarenal Genitourinary Tract

Extrarenal Genitourinary Tract in Systemic Amyloidoses

Clinical Presentation

Pathology

Urinary Bladder and Prostate

Testis

Female Genital Tract

Ovary

Adrenal Gland

Breast

Localized Amyloidosis

Clinical Presentation

Pathogenesis

Urinary Bladder

Prostate

Testis, Ovaries, and Adrenal Gland

Penis

Female Genital Tract: Uterus, Cervix, Ovaries, Fallopian Tubes, Vulva

Breast

References

29: Cardiac Amyloidosis

Localized Amyloidoses

Isolated Atrial Amyloidosis

Senile Aortic Amyloid

Valvular Amyloidosis

Systemic Amyloidoses

Immunoglobulin Light Chain Amyloidosis

Transthyretin Amyloidosis

Senile Systemic (Transthyretin) Amyloidosis

Transthyretin-Associated Familial Amyloidosis

Other Systemic Amyloidoses Affecting the Heart

Amyloid A Protein

β2-Microglobulin

Apolipoprotein AI

Fibrinogen

Clinical Features of Cardiac Amyloidosis

Clinical Diagnosis

Gross Morphology of Cardiac Amyloidosis

Endomyocardial Biopsy Evaluation

Amyloid Typing

Differential Diagnosis

Diagnostic Pitfalls

Therapy

Prognosis

References

30: Amyloidosis of the Gastrointestinal Tract and Liver

Introduction

GI Tract

Liver

References

31: Peripheral Nerve Amyloidosis

Introduction

Historical Pathologic Observations of Nerve Amyloid

Clinical Overview Important in Nerve Amyloid Pathologic Discovery

Biopsy Sites in Peripheral Nervous System Amyloidosis

Pathogenesis and Histopathologic Findings

Regional or Focal Peripheral Nervous System Amyloidosis (Amyloidomas)

Mass Spectrophotometric Evaluation of Amyloid in Peripheral Nerve Tissues

AL Primary Amyloidosis

Immunoglobulin Nerve Deposition a Pathologic Mimicker of Amyloid

Familial Amyloid Polyneuropathy

Transthyretin

Gelsolin

Apolipoprotein A1

Treatment of Pathologic Peripheral Nerve Amyloidosis

References

32: Amyloidosis of the Lymph Nodes and the Spleen

Introduction

Amyloidosis Involving Lymph Nodes

Histopathology of Lymph Node Amyloidosis

Amyloidosis Involving the Spleen

Histopathology of Splenic Amyloidosis

References

33: Amyloidosis of the Lung

Introduction

Pulmonary Presentation of Systemic Amyloidosis

Clinicopathological Classification of Localized Pulmonary Amyloidosis

Nodular Pulmonary Amyloidosis

Tracheobronchial Amyloidosis

Other “Non-amyloidogenic” Related Conditions Involving the Lung

Light Chain Deposition Disease

Crystal-Storing Histiocytosis

Conclusions

References

34: Cutaneous Amyloidosis

Introduction

Cutaneous Lesions in Systemic Amyloidosis

Localized Cutaneous Amyloidosis

Keratinic Primary Localized Amyloidosis

Clinical Features of kPLCA

Genetic Linkage Studies in Familial PLCA

Amyloidosis Cutis Dyschromica

Histological Findings in kPLCA

Nodular Localized Primary Cutaneous Amyloidosis

Conclusions

References

35: Iatrogenic Pharmaceutical Amyloidosis Associated with Insulin and Enfuvirtide Administration

Iatrogenic Insulin-Associated Amyloidosis (AIns)

Iatrogenic Enfuvirtide-Associated Amyloidosis (AEnf)

References

Part VI: Clinical Issues and Therapy

36: Clinical and Pathologic Issues in Patients with Amyloidosis: Summary and Practical Comments

Introduction

Suspicion of Amyloidosis

Biopsy Types

Diagnosis

Staging

Localized Amyloidosis

Systemic Amyloidosis

Cardiac Staging

Bone Marrow Evaluation

Therapy

Systemic AL Amyloidosis

High-Dose Chemotherapy and Autologous Bone Marrow Transplantation

Melphalan-Based Therapies

The Immunomodulatory Derivatives

Proteasome Inhibitors

Aggresome Inhibition

Monoclonal Antibodies

Other Systemic Amyloidoses

Transplantation in the Management of Patients with Non-hereditary Systemic Amyloidoses

Examples of Patients with Different Types of Systemic Amyloidosis, Illustrating the Different E

Reevaluation

The Future

References

37: Emerging Therapies for Amyloidosis

References

38: Modern Therapies in AA Amyloidosis

References

39: Medicolegal Issues of Amyloidosis

Diagnostic and Therapeutic Amyloidosis Advances

Increased Medical-Legal Risk Due to Alleged Diagnostic Delay or Misdiagnosis

Medical Malpractice Basics

The Expansion of the “Loss-of-­Chance” Doctrine

Conclusion

References

40: Amyloidosis from the Patient’s Perspective

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