Robbins & Cotran Pathologic Basis of Disease (Robbins Pathology)

Cover
Endsheet
Robbins & Cotran Pathologic Basis of Disease
Copyright Page
Dedication
Contributors
Preface
Acknowledgments
Table Of Contents
1 The Cell as a Unit of Health and Disease
Chapter Contents
The Genome
Noncoding DNA
Histone Organization
Micro-RNA and Long Noncoding RNA
Micro-RNA
Long Noncoding RNA
Gene Editing
Cellular Housekeeping
Plasma Membrane: Protection and Nutrient Acquisition
Membrane Transport
Passive Diffusion.
Carriers and Channels (Fig. 1.8).
Receptor-Mediated and Fluid-Phase Uptake (see Fig. 1.8)
Cytoskeleton
Cell-Cell Interactions
Biosynthetic Machinery: Endoplasmic Reticulum and Golgi Apparatus
Waste Disposal: Lysosomes and Proteasomes
Cellular Metabolism and Mitochondrial Function
Cellular Activation
Cell Signaling
Signal Transduction Pathways
Modular Signaling Proteins, Hubs, and Nodes
Transcription Factors
Growth Factors and Receptors
Epidermal Growth Factor (EGF) and Transforming Growth Factor-α (TGF-α).
Hepatocyte Growth Factor (HGF).
Platelet-derived Growth Factor (PDGF).
Vascular Endothelial Growth Factor (VEGF).
Fibroblast Growth Factor (FGF).
Transforming Growth Factor β (TGF-β).
Extracellular Matrix
Components of the Extracellular Matrix (Fig. 1.15)
Collagens.
Elastin.
Proteoglycans and Hyaluronan (see Fig. 1.15B).
Adhesive Glycoproteins and Adhesion Receptors.
Maintaining Cell Populations
Proliferation and the Cell Cycle
Stem Cells
Regenerative Medicine
Concluding Remarks.
Suggested Readings
Genetics and Epigenetics
Cellular Housekeeping
Cellular Metabolism and Mitochondrial Function
Cellular Activation
Maintaining Cell Populations
2 Cell Injury, Cell Death, and Adaptations
Chapter Contents
Introduction to Pathology
Overview of Cellular Responses to Stress and Noxious Stimuli
Causes of Cell Injury
Oxygen Deprivation
Physical Agents
Chemical Agents and Drugs
Infectious Agents
Immunologic Reactions
Genetic Abnormalities
Nutritional Imbalances
The Progression of Cell Injury and Death
Reversible Cell Injury
Cell Death
Necrosis
Patterns of Tissue Necrosis
Apoptosis
Causes of Apoptosis
Apoptosis in Physiologic Situations
Apoptosis in Pathologic Conditions
Morphologic and Biochemical Changes in Apoptosis
Mechanisms of Apoptosis
The Mitochondrial (Intrinsic) Pathway of Apoptosis
The Extrinsic (Death Receptor–Initiated) Pathway of Apoptosis
The Execution Phase of Apoptosis
Removal of Dead Cells
Other Mechanisms of Cell Death
Autophagy
Mechanisms of Cell Injury
General Mechanisms of Cell Injury and Intracellular Targets of Injurious Stimuli
Mitochondrial Damage
Membrane Damage
Damage to DNA
Oxidative Stress: Accumulation of Oxygen-Derived Free Radicals
Generation of Free Radicals
Removal of Free Radicals
Pathologic Effects of Free Radicals
Disturbance in Calcium Homeostasis
Endoplasmic Reticulum Stress: the Unfolded Protein Response
Clinicopathologic Correlations: Selected Examples of Cell Injury and DEATH
Hypoxia and Ischemia
Mechanisms of Ischemic Cell Injury
Ischemia-Reperfusion Injury
Chemical (Toxic) Injury
Adaptations of Cellular Growth and Differentiation
Hypertrophy
Mechanisms of Hypertrophy
Hyperplasia
Mechanisms of Hyperplasia
Atrophy
Mechanisms of Atrophy
Metaplasia
Mechanisms of Metaplasia
Intracellular Accumulations
Lipids
Steatosis (Fatty Change)
Cholesterol and Cholesterol Esters
Proteins
Hyaline Change
Glycogen
Pigments
Exogenous Pigments
Endogenous Pigments
Pathologic Calcification
Dystrophic Calcification
Metastatic Calcification
Cellular Aging
DNA Damage.
Cellular Senescence.
Defective Protein Homeostasis.
Dysregulated Nutrient Sensing.
Suggested Readings
Mechanisms of Cell Injury
Cell Death
Apoptosis
Necroptosis and Pyroptosis
Autophagy
Adaptations
Aging
3 Inflammation and Repair
Chapter Contents
Overview of Inflammation: Definitions and General Features
Historical Highlights
Causes of Inflammation
Recognition of Microbes and Damaged Cells
Acute Inflammation
Reactions of Blood Vessels in Acute Inflammation
Changes in Vascular Flow and Caliber
Increased Vascular Permeability (Vascular Leakage)
Responses of Lymphatic Vessels and Lymph Nodes
Leukocyte Recruitment to Sites of Inflammation
Leukocyte Adhesion to Endothelium
Leukocyte Migration Through Endothelium
Chemotaxis of Leukocytes
Phagocytosis and Clearance of the Offending Agent
Phagocytosis
Phagocytic Receptors.
Engulfment.
Intracellular Destruction of Microbes and Debris
Reactive Oxygen Species.
Nitric Oxide.
Lysosomal Enzymes and Other Lysosomal Proteins.
Neutrophil Extracellular Traps
Leukocyte-Mediated Tissue Injury
Other Functional Responses of Activated Leukocytes
Termination of the Acute Inflammatory Response
Mediators of Inflammation
Vasoactive Amines: Histamine and Serotonin
Arachidonic Acid Metabolites
Prostaglandins
Leukotrienes
Lipoxins
Pharmacologic Inhibitors of Prostaglandins and Leukotrienes
Cytokines and Chemokines
Tumor Necrosis Factor and Interleukin-1
Chemokines
Other Cytokines in Acute Inflammation
Complement System
Other Mediators of Inflammation
Platelet-Activating Factor
Products of Coagulation
Kinins
Neuropeptides
Morphologic Patterns of Acute Inflammation
Serous Inflammation
Fibrinous Inflammation
Purulent (Suppurative) Inflammation and Abscess
Ulcers
Outcomes of Acute Inflammation
Summary of Acute Inflammation
Chronic Inflammation
Causes of Chronic Inflammation
Morphologic Features
Cells and Mediators of Chronic Inflammation
Role of Macrophages
Role of Lymphocytes
Other Cells in Chronic Inflammation
Granulomatous Inflammation
Systemic Effects of Inflammation
Tissue Repair
Overview of Tissue Repair
Cell and Tissue Regeneration
Cell Proliferation: Signals and Control Mechanisms
Mechanisms of Tissue Regeneration
Liver Regeneration
Repair by Connective Tissue Deposition
Steps in Scar Formation
Angiogenesis
Mechanisms of Angiogenesis.
Deposition of Connective Tissue
Remodeling of Connective Tissue
Factors That Influence Tissue Repair
Examples of Tissue Repair and Fibrosis
Healing of Skin Wounds
Healing by First Intention
Healing by Second Intention
Wound Strength
Fibrosis in Parenchymal Organs
Abnormalities in Tissue Repair
Defects in Healing: Chronic Wounds
Excessive Scarring
Suggested Readings
General Mechanisms of Inflammation
Sensors of Inflammatory Stimuli
Acute Inflammation: Vascular Reactions
Acute Inflammation: Role of Neutrophils
Mediators of Inflammation
Chronic Inflammation: Role of Macrophages and Other Cells
Sepsis
Tissue Repair: Regeneration and Fibrosis
4 Hemodynamic Disorders, Thromboembolic Disease, and Shock
Chapter Contents
Edema and Effusions
Increased Hydrostatic Pressure
Reduced Plasma Osmotic Pressure
Sodium and Water Retention
Lymphatic Obstruction
Clinical Features
Hyperemia and Congestion
Hemostasis, Hemorrhagic Disorders, and Thrombosis
Normal Hemostasis
Platelets
Coagulation Cascade
Factors That Limit Coagulation
Endothelium
Hemorrhagic Disorders
Thrombosis
Endothelial Injury
Alterations in Normal Blood Flow
Hypercoagulability
Heparin-Induced Thrombocytopenia (HIT) Syndrome
Antiphospholipid Antibody Syndrome (APS)
Fate of the Thrombus
Clinical Features
Venous Thrombosis (Phlebothrombosis).
Arterial and Cardiac Thrombosis.
Disseminated Intravascular Coagulation (DIC)
Embolism
Pulmonary Embolism (PE)
Systemic Thromboembolism
Fat Embolism
Air Embolism
Amniotic Fluid Embolism
Infarction
Factors That Influence Development of an Infarct.
Shock
Pathogenesis of Septic Shock
Stages of Shock
Clinical Features
Suggested Readings
Fluid Dynamics
Hemostasis and Bleeding
Thrombosis and Thromboembolism
Unusual Forms of Embolic Disease
Septic Shock
5 Genetic Disorders
Chapter Contents
Genes and Human Diseases
Mutations
Mendelian Disorders
Transmission Patterns of Single-Gene Disorders
Autosomal Dominant Disorders
Autosomal Recessive Disorders
X-Linked Disorders
Biochemical and Molecular Basis of Single-Gene (Mendelian) Disorders
Enzyme Defects and Their Consequences
Defects in Receptors and Transport Systems
Alterations in Structure, Function, or Quantity of Nonenzyme Proteins
Genetically Determined Adverse Reactions to Drugs
Disorders Associated With Defects in Structural Proteins
Marfan Syndrome
Pathogenesis
Clinical Features
Ehlers-Danlos Syndromes (EDSs)
Disorders Associated With Defects in Receptor Proteins
Familial Hypercholesterolemia
Normal Cholesterol Metabolism and Transport
Disorders Associated With Enzyme Defects
Lysosomal Storage Diseases
Tay-Sachs Disease (GM2 Gangliosidosis: Hexosaminidase α-Subunit Deficiency)
Clinical Features
Niemann-Pick Disease Types A and B
Niemann-Pick Disease Type C
Gaucher Disease
Clinical Features
Mucopolysaccharidoses
Clinical Features
Glycogen Storage Diseases (Glycogenoses)
Disorders Associated With Defects in Proteins That Regulate Cell Growth
Complex Multigenic Disorders
Chromosomal Disorders
Normal Karyotype
Commonly Used Cytogenetic Terminology
Structural Abnormalities of Chromosomes
Cytogenetic Disorders Involving Autosomes
Trisomy 21 (Down Syndrome)
Other Trisomies
Chromosome 22q11.2 Deletion Syndrome
Cytogenetic Disorders Involving Sex Chromosomes
Klinefelter Syndrome
Turner Syndrome
Hermaphroditism and Pseudohermaphroditism
Single-Gene Disorders With Nonclassic Inheritance
Diseases Caused by Trinucleotide-Repeat Mutations
Fragile X Syndrome (FXS)
Fragile X–Associated Tremor/Ataxia Syndrome and Fragile X–Associated Primary Ovarian Failure
Mutations in Mitochondrial Genes—Leber Hereditary Optic Neuropathy
Genomic Imprinting
Prader-Willi Syndrome and Angelman Syndrome
Gonadal Mosaicism
Molecular Genetic Diagnosis
Diagnostic Methods and Indications for Testing
Laboratory Considerations
Indications for Analysis of Inherited Genetic Alterations
Indications for Analysis of Acquired Genetic Alterations
PCR and Detection of DNA Sequence Alterations
Molecular Analysis of Genomic Alterations
Fluorescence in Situ Hybridization (FISH)
Cytogenomic Array Technology
Polymorphic Markers and Molecular Diagnosis
Epigenetic Alterations
RNA Analysis
Next-Generation Sequencing (NGS)
Bioinformatics
Clinical Applications of Next-Generation DNA Sequencing
Future Applications
Acknowledgment
Suggested Readings
Molecular Basis of Single-Gene Disorders—General
Disorders Associated With Defects in Structural Proteins
Disorders Associated With Defects in Receptor Proteins
Lysosomal Storage Disorders
Cytogenetic Disorders Affecting Autosomes
Cytogenetic Disorders Affecting Sex Chromosomes
Diseases Caused by Trinucleotide Mutations
Diseases Caused by Genomic Imprinting
6 Diseases of the Immune System
Chapter Contents
The Normal Immune Response
Innate Immunity
Components of Innate Immunity
Cellular Receptors for Microbes, Products of Damaged Cells, and Foreign Substances
Natural Killer Cells
Reactions of Innate Immunity
Adaptive Immunity
Cells of the Adaptive Immune System
Lymphocyte Diversity
T Lymphocytes
B Lymphocytes
Dendritic Cells (DCs)
Macrophages
Tissues of the Immune System
Primary Lymphoid Organs.
Secondary Lymphoid Organs.
Lymphocyte Recirculation
Major Histocompatibility Complex Molecules: the Peptide Display System of Adaptive Immunity
Cytokines: Messenger Molecules of the Immune System
Overview of Lymphocyte Activation and Immune Responses
Display and Recognition of Antigens
Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes
Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes
Decline of Immune Responses and Immunologic Memory
Hypersensitivity: Immunologically Mediated Tissue Injury
Classification of Hypersensitivity Reactions
Immediate (Type I) Hypersensitivity
Activation of Th2 Cells and Production of IgE Antibody
Sensitization and Activation of Mast Cells
Mediators of Immediate Hypersensitivity
Cytokines.
Late-Phase Reaction
Development of Allergies
Systemic Anaphylaxis
Local Immediate Hypersensitivity Reactions
Antibody-Mediated (Type II) Hypersensitivity
Opsonization and Phagocytosis
Inflammation
Cellular Dysfunction
Immune Complex–Mediated (Type III) Hypersensitivity
Systemic Immune Complex Disease
Local Immune Complex Disease
T Cell–Mediated (Type IV) Hypersensitivity
CD4+ T Cell–Mediated Inflammation
Activation of CD4+ T Cells
Responses of Differentiated Effector T Cells
Clinical Examples of CD4+ T Cell–Mediated Inflammatory Reactions
CD8+ T Cell–Mediated Cytotoxicity
Autoimmune Diseases
Immunologic Tolerance
Central Tolerance
Peripheral Tolerance
Mechanisms of Autoimmunity: General Principles
Role of Susceptibility Genes
Association of HLA Alleles With Disease
Association of Non-MHC Genes With Autoimmune Diseases
Role of Infections and Other Environmental Factors
General Features of Autoimmune Diseases
Systemic Lupus Erythematosus (SLE)
Spectrum of Autoantibodies in Systemic Lupus Erythematosus
Pathogenesis
Genetic Factors.
Immunologic Factors.
Environmental Factors.
A Model for the Pathogenesis of SLE.
Mechanisms of Tissue Injury.
Clinical Features
Chronic Discoid Lupus Erythematosus
Subacute Cutaneous Lupus Erythematosus
Drug-Induced Lupus Erythematosus
Rheumatoid Arthritis
Sjögren Syndrome
Pathogenesis
Clinical Features
Systemic Sclerosis (Scleroderma)
Pathogenesis
Clinical Features
Inflammatory Myopathies
Mixed Connective Tissue Disease
Polyarteritis Nodosa and Other Vasculitides
IgG4-Related Disease
Rejection of Tissue Transplants
Mechanisms of Recognition and Rejection of Allografts
Recognition of Graft Alloantigens by T and B Lymphocytes
Patterns and Mechanisms of Graft Rejection
Methods of Increasing Graft Survival
Transplantation of Hematopoietic Stem Cells (HSCs)
Immunodeficiency Diseases
Primary Immunodeficiencies
Defects in Innate Immunity
Defects in Leukocyte Function
Deficiencies Affecting the Complement System
Defects in Adaptive Immunity
Severe Combined Immunodeficiency
X-linked SCID.
Autosomal Recessive SCID.
X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia)
DiGeorge Syndrome (Thymic Hypoplasia)
Other Defects in Lymphocyte Maturation
Hyper-IgM Syndrome
Common Variable Immunodeficiency
Isolated IgA Deficiency
X-Linked Lymphoproliferative Disease
Other Defects in Lymphocyte Activation
Immunodeficiencies Associated With Systemic Diseases
Wiskott-Aldrich Syndrome
Ataxia Telangiectasia
Secondary Immunodeficiencies
Acquired Immunodeficiency Syndrome (AIDS)
Epidemiology
Etiology: the Properties of HIV
Structure of HIV
Pathogenesis of HIV Infection and AIDS
Life Cycle of HIV
Infection of Cells by HIV.
Viral Replication.
Mechanism of T-Cell Depletion in HIV Infection
HIV Infection of Non–T Cells
B-Cell Function in HIV Infection
Pathogenesis of Central Nervous System Involvement
Natural History of HIV Infection
Primary Infection, Virus Dissemination, and the Acute Retroviral Syndrome
Chronic Infection: Phase of Clinical Latency
AIDS
Clinical Features of AIDS
Opportunistic Infections
Tumors
Kaposi Sarcoma.
Lymphomas.
Other Tumors.
Central Nervous System Disease
Effect of Antiretroviral Drug Therapy
Amyloidosis
Properties of Amyloid Proteins
Physical Nature of Amyloid.
Chemical Nature of Amyloid.
Pathogenesis and Classification of Amyloidosis
Primary Amyloidosis: Plasma Cell Disorders Associated With Amyloidosis
Reactive Systemic Amyloidosis
Heredofamilial Amyloidosis
Hemodialysis-Associated Amyloidosis
Localized Amyloidosis
Endocrine Amyloid
Amyloid of Aging
Clinical Features
Suggested Readings
Innate Immunity
Cell-Mediated Immunity
Humoral Immunity
Immediate Hypersensitivity, Allergy
Other Hypersensitivity Reactions
Immunological Tolerance
Mechanisms of Autoimmunity: General
Systemic Lupus Erythematosus
Sjogren Syndrome, Systemic Sclerosis, and Other Systemic Autoimmune Diseases
Rejection of Transplants
Primary Immunodeficiency Diseases
HIV and AIDS
Amyloidosis
7 Neoplasia
Chapter Contents
Nomenclature
Benign Tumors
Malignant Tumors
Mixed Tumors
Characteristics of Benign and Malignant Neoplasms
Differentiation and Anaplasia
Metaplasia, Dysplasia, and Carcinoma In Situ
Local Invasion
Metastasis
Pathways of Spread
Seeding of Body Cavities and Surfaces.
Lymphatic Spread.
Hematogenous Spread.
Epidemiology of Cancer
The Global Impact of Cancer
Environmental Factors
Age
Acquired Predisposing Conditions
Genetic Predisposition and Interactions Between Environmental and Inherited Factors
Molecular Basis of Cancer: Role of Genetic and Epigenetic Alterations
Cellular and Molecular Hallmarks of Cancer
Self-Sufficiency in Growth Signals: Oncogenes
Oncoproteins and Cell Growth
Growth Factors.
Growth Factor Receptors.
Downstream Components of the Receptor Tyrosine Kinase Signaling Pathway.
Nonreceptor Tyrosine Kinases.
Transcription Factors.
MYC.
Cyclins and Cyclin-Dependent Kinases.
Insensitivity to Growth Inhibition: Tumor Suppressor Genes
RB: Governor of Proliferation.
TP53: Guardian of the Genome.
Other Tumor Suppressor Genes.
APC: Gatekeeper of Colonic Neoplasia.
E-Cadherin.
CDKN2A.
TGF-β Pathway.
PTEN.
VHL.
STK11.
Growth-Promoting Metabolic Alterations: The Warburg Effect
Autophagy.
Oncometabolism.
Evasion of Cell Death
Limitless Replicative Potential: The Stem Cell–Like Properties of Cancer Cells
Angiogenesis
Invasion and Metastasis
Invasion of Extracellular Matrix
Vascular Dissemination, Homing, and Colonization
Evasion of Immune Surveillance
Tumor Antigens
Antitumor Effector Mechanisms
Mechanisms of Immune Evasion by Cancers
Genomic Instability
DNA Mismatch Repair Factors.
Nucleotide Excision Repair Factors.
Homologous Recombination Repair Factors.
DNA Polymerase.
Regulated Genomic Instability in Lymphoid Cells.
Cancer-Enabling Inflammation
Dysregulation of Cancer-Associated Genes
Chromosomal Changes
Chromosomal Translocations.
Deletions.
Gene Amplification.
Complex Chromosomal Rearrangements.
Epigenetic Changes
Noncoding RNAs and Cancer
Molecular Basis of Multistep Carcinogenesis
Carcinogenic Agents and Their Cellular Interactions
Chemical Carcinogenesis
Direct-Acting Carcinogens
Indirect-Acting Carcinogens
Molecular Targets of Chemical Carcinogens.
Radiation Carcinogenesis
Ultraviolet Rays
Ionizing Radiation
Microbial Carcinogenesis
Oncogenic RNA Viruses
Human T-Cell Leukemia Virus Type 1.
Oncogenic DNA Viruses
Human Papillomavirus.
Epstein-Barr Virus.
Hepatitis B and C Viruses.
Helicobacter pylori
Clinical Aspects of Neoplasia
Clinical Manifestations
Local and Hormonal Effects
Cancer Cachexia
Paraneoplastic Syndromes
Grading and Staging of Tumors
Laboratory Diagnosis of Cancer
Histologic and Cytologic Methods.
Immunohistochemistry.
Flow Cytometry.
Circulating Tumor Cells.
Molecular Diagnostics and Cytogenetics.
Molecular Profiles of Tumors: The Future of Cancer Diagnostics
Tumor Markers
Suggested Readings
Cancer Epidemiology
Cancer Evolution and Genomics
Hallmarks of Cancer
Oncogenes
Tumor Suppressor Genes
Cancer Cell Metabolism
Autophagy
Evasion of Apoptosis
Cancer Stem Cells
Angiogenesis
Invasion and Metastasis
Evasion of Host Defense
Cancer Enabling Inflammation
Chromosomal Aberrations
Epigenetics and Cancer
Noncoding RNAs
Environmental Carcinogens
Microbial Carcinogenesis
Cancer Cachexia and Paraneoplastic Syndromes
Cancer Diagnostics
8 Infectious Diseases
Chapter Contents
General Principles of Microbial Pathogenesis
How Microorganisms Cause Disease
Routes of Entry of Microbes
Skin
Gastrointestinal Tract
Respiratory Tract
Urogenital Tract
Vertical Transmission
Spread and Dissemination of Microbes Within the Body
Release From the Body and Transmission of Microbes
Host-Pathogen Interactions
Immune Evasion by Microbes
Injurious Effects of Host Immunity
Infections in People With Immunodeficiencies
Host Damage by Microbes
Mechanisms of Viral Injury
Mechanisms of Bacterial Injury
Bacterial Virulence.
Bacterial Adherence to Host Cells.
Intracellular Bacteria.
Bacterial Toxins.
Spectrum of Inflammatory Responses to Infection
Suppurative (Purulent) Inflammation
Mononuclear and Granulomatous Inflammation
Cytopathic-Cytoproliferative Reaction
Tissue Necrosis
Chronic Inflammation and Scarring
Viral Infections
Acute (Transient) Infections
Measles
Pathogenesis
Mumps
Poliomyelitis
West Nile Virus Infections
Viral Hemorrhagic Fever
Zika Virus Infections
Dengue
Novel Coronavirus SARS-CoV-2 (COVID-19)
Latent Infections (Herpesvirus Infections)
Herpes Simplex Virus (HSV) Infections
Varicella-Zoster Virus (VZV) Infections
Cytomegalovirus (CMV) Infections
Congenital Infections.
Perinatal Infections.
CMV Mononucleosis.
CMV in Immunosuppressed Individuals.
Chronic Productive Infections
Transforming Viral Infections
Epstein-Barr Virus (EBV) Infections
Pathogenesis
Clinical Features
Bacterial Infections
Gram-Positive Bacterial Infections
Staphylococcal Infections
Pathogenesis
S. aureus Toxins.
Streptococcal and Enterococcal Infections
Pathogenesis
Diphtheria
Listeriosis
Anthrax
Pathogenesis
Nocardial Infections
Gram-Negative Bacterial Infections
Neisserial Infections
Pathogenesis
Pertussis
Pathogenesis
Pseudomonal Infections
Pathogenesis
Plague
Chancroid (Soft Chancre)
Granuloma Inguinale
Mycobacterial Infections
Tuberculosis
Epidemiology
Pathogenesis
Clinical Features
Nontuberculous Mycobacterial Infections
Leprosy
Pathogenesis
Spirochete Infections
Syphilis
Pathogenesis
Primary Syphilis.
Secondary Syphilis.
Tertiary Syphilis.
Congenital Syphilis.
Serologic Tests for Syphilis.
Lyme Disease
Pathogenesis
Anaerobic Bacterial Infections
Abscesses
Clostridial Infections
Pathogenesis
Obligate Intracellular Bacterial Infections
Chlamydial Infections
Infections Caused by Other Intracellular Bacteria
Pathogenesis
Fungal Infections
Yeast Infections
Candidiasis
Pathogenesis
Candida auris Infections
Cryptococcosis
Pathogenesis
Pneumocystis Infections
Mold Infections
Aspergillosis
Pathogenesis
Mucormycosis (Zygomycosis)
Pathogenesis
Parasitic Infections
Protozoal Infections
Malaria
Pathogenesis
Babesiosis
Leishmaniasis
Pathogenesis
African Trypanosomiasis
Pathogenesis
Chagas Disease
Pathogenesis
Toxoplasmosis
Pathogenesis
Metazoal Infections
Strongyloidiasis
Cysticercosis and Hydatid Disease (Tapeworm Infections)
Trichinosis
Pathogenesis
Schistosomiasis
Pathogenesis
Lymphatic Filariasis
Pathogenesis
Onchocerciasis
Sexually Transmitted Infections
Emerging Infectious Diseases
Agents of Bioterrorism.
Special Techniques for Diagnosing Infectious Agents
Suggested Readings
General Principles of Microbial Pathogenesis
Virology
Bacteriology
Fungi
Parasitology
9 Environmental and Nutritional Diseases
Chapter Contents
Health Effects of Climate Change
Toxicity of Chemical and Physical Agents
Environmental Pollution
Air Pollution
Outdoor Air Pollution
Indoor Air Pollution
Metals as Environmental Pollutants
Lead
Mercury
Arsenic
Cadmium
Occupational Health Risks: Industrial and Agricultural Exposures
Effects of Tobacco
Smoking and Lung Cancer.
Smoking and Other Diseases.
Effects of Alcohol
Injury by Therapeutic Drugs and Drugs of Abuse
Injury by Therapeutic Drugs (Adverse Drug Reactions)
Anticoagulants
Menopausal Hormone Therapy
Oral Contraceptives
Acetaminophen
Aspirin (Acetylsalicylic Acid)
Injury by Nontherapeutic Agents (Drug Abuse)
Cocaine
Opioids and Opiates
Amphetamines and Related Drugs
Methamphetamine.
Marijuana
Other Drugs
Injury by Physical Agents
Mechanical Trauma
Thermal Injury
Thermal Burns
Hyperthermia
Hypothermia
Electrical Injury
Injury Produced by Ionizing Radiation
Radiation Units.
Main Determinants of Biologic Effects of Ionizing Radiation.
Total-Body Irradiation.
Acute Effects on Hematopoietic and Lymphoid Systems.
Fibrosis.
DNA Damage and Carcinogenesis.
Cancer Risks From Exposures to Radiation.
Nutritional Diseases
Dietary Insufficiency
Severe Acute Malnutrition
Marasmus.
Kwashiorkor.
Malnutrition in the Upper Income World.
Cachexia.
Anorexia Nervosa and Bulimia
Vitamin Deficiencies
Vitamin A
Function.
Vitamin A Deficiency.
Vitamin A Toxicity.
Vitamin D
Metabolism of Vitamin D.
Functions.
Effects of Vitamin D on Calcium and Phosphorus Homeostasis.
Deficiency States.
Nonskeletal Effects of Vitamin D.
Vitamin D Toxicity.
Vitamin C (Ascorbic Acid)
Function.
Deficiency States.
Vitamin C Excess.
Obesity
Leptin.
Adiponectin.
Gut Hormones.
Adipose Tissue.
Role of the Gut Microbiome.
Clinical Consequences of Obesity
Obesity and Cancer
Diet and Cancer
Diet and Systemic Diseases
Suggested Readings
Climate Change
Air Pollution
Heavy Metal Poisoning
Effects of Alcohol and Tobacco
Menopausal Hormone Therapy and Oral Contraceptives
Drugs of Abuse and Radiation Injury
Malnutrition
Vitamins
Obesity
10 Diseases of Infancy and Childhood
Chapter Contents
Congenital Anomalies
Definitions
Causes of Anomalies
Pathogenesis
Prematurity and Fetal Growth Restriction
Fetal Growth Restriction
Maternal Abnormalities
Fetal Abnormalities
Placental Abnormalities
Neonatal Respiratory Distress Syndrome
Pathogenesis
Clinical Features
Necrotizing Enterocolitis
Perinatal Infections
Transcervical (Ascending) Infections
Transplacental (Hematologic) Infections
Sepsis
Fetal Hydrops
Immune Hydrops
Etiology and Pathogenesis
Nonimmune Hydrops
Clinical Features
Inborn Errors of Metabolism and Other Genetic Disorders
Phenylketonuria
Galactosemia
Cystic Fibrosis (Mucoviscidosis)
Cystic Fibrosis Gene: Normal Structure and Function
Cystic Fibrosis Gene: Mutational Spectrum and Genotype-Phenotype Correlation
Genetic and Environmental Modifiers
Clinical Features
Sudden Infant Death Syndrome
Epidemiology
Pathogenesis
Tumors and Tumorlike Lesions of Infancy and Childhood
Benign Tumors and Tumorlike Lesions
Hemangioma
Fibrous Tumors
Teratomas
Malignant Tumors
Incidence and Types
Neuroblastic Tumors
Clinical Course and Prognostic Features (Table 10.7)
Wilms Tumor
Pathogenesis and Genetics
Clinical Features
Suggested Readings
Congenital Anomalies, Hydrops, and Infections
Cystic Fibrosis and Inborn Errors of Metabolism
Diseases of Prematurity and SIDS
Tumors of Infancy and Childhood
11 Blood Vessels
Chapter Contents
Vascular Structure and Function
Vascular Anomalies
Vascular Wall Response to Injury
Intimal Thickening: A Stereotyped Response to Vascular Injury
Hypertensive Vascular Disease
Blood Pressure Regulation
Pathogenesis of Hypertension
Mechanisms of Secondary Hypertension.
Mechanisms of Essential Hypertension.
Vascular Pathology in Hypertension
Arteriosclerosis
Atherosclerosis
Epidemiology.
Risk Factors
Constitutional Risk Factors
Modifiable Major Risk Factors
Additional Risk Factors
Pathogenesis of Atherosclerosis
Endothelial Injury.
Hemodynamic Disturbances.
Hypercholesterolemia.
Inflammation.
Infection.
Smooth Muscle Proliferation and Matrix Synthesis.
Overview.
Consequences of Atherosclerotic Disease
Atherosclerotic Stenosis.
Acute Plaque Change.
Aneurysms and Dissection
Pathogenesis
Abdominal Aortic Aneurysm
Clinical Features
Thoracic Aortic Aneurysm
Aortic Dissection
Pathogenesis
Clinical Features
Vasculitis
Noninfectious Vasculitis
Immune Complex–Associated Vasculitis
Antineutrophil Cytoplasmic Antibodies
Anti–Endothelial Cell Antibodies
Giant Cell (Temporal) Arteritis
Pathogenesis
Clinical Features
Takayasu Arteritis
Clinical Features
Polyarteritis Nodosa (PAN)
Clinical Features
Kawasaki Disease
Clinical Features
Microscopic Polyangiitis
Pathogenesis
Clinical Features
Granulomatosis With Polyangiitis (GPA)
Pathogenesis
Clinical Features
Churg-Strauss Syndrome
Thromboangiitis Obliterans (Buerger Disease)
Pathogenesis
Clinical Features
Vasculitis Associated With Other Noninfectious Disorders
Infectious Vasculitis
Disorders of Blood Vessel Hyperreactivity
Raynaud Phenomenon
Myocardial Vessel Vasospasm
Veins and Lymphatics
Varicose Veins
Clinical Features
Thrombophlebitis and Phlebothrombosis
Superior and Inferior Vena Caval Syndromes
Lymphangitis and Lymphedema
Vascular Tumors
Benign Tumors and Tumor-Like Conditions
Vascular Ectasias.
Hemangiomas.
Lymphangiomas.
Glomus Tumor (Glomangioma).
Bacillary Angiomatosis.
Intermediate-Grade (Borderline) Tumors
Kaposi Sarcoma.
Pathogenesis
Clinical Features
Hemangioendothelioma.
Malignant Tumors
Angiosarcoma.
Pathology of Vascular Intervention
Endovascular Stenting
Vascular Replacement
Suggested Readings
Vascular Structure and Function
Vascular Wall Response to Injury
Hypertensive Vascular Disease
Atherosclerosis
Aneurysms and Dissection
Vasculitis
Disorders of Blood Vessel Hyperreactivity
Veins and Lymphatics
Vascular Tumors
Pathology of Vascular Intervention
12 The Heart
Chapter Contents
Cardiac Structure and Specializations
Myocardium
Valves
Conduction System
Blood Supply
Cardiac Regeneration
Effects of Aging on the Heart
Overview of Cardiac Pathophysiology
Heart Failure
Cardiac Hypertrophy: Pathophysiology and Progression to Heart Failure
Left-Sided Heart Failure
Right-Sided Heart Failure
Cardiac Development
Congenital Heart Disease
Incidence
Etiology and Pathogenesis
Clinical Features
Left-to-Right Shunts
Atrial Septal Defect
Clinical Features
Patent Foramen Ovale
Ventricular Septal Defect
Clinical Features
Patent Ductus Arteriosus
Right-to-Left Shunts
Tetralogy of Fallot
Clinical Features
Transposition of the Great Arteries
Tricuspid Atresia
Obstructive Lesions
Coarctation of the Aorta
Clinical Features
Pulmonary Stenosis and Atresia
Aortic Stenosis and Atresia
Ischemic Heart Disease
Epidemiology
Pathogenesis
Chronic Vascular Occlusion
Acute Plaque Change
Consequences of Myocardial Ischemia
Angina Pectoris
Myocardial Infarction
Pathogenesis
Coronary Arterial Occlusion.
Myocardial Response.
Patterns of Infarction.
Infarct Modification by Reperfusion.
Clinical Features
Consequences and Complications of Myocardial Infarction
Chronic Ischemic Heart Disease
Arrhythmias
Sudden Cardiac Death
Hypertensive Heart Disease
Systemic (Left-Sided) Hypertensive Heart Disease
Pulmonary (Right-Sided) Hypertensive Heart Disease (Cor Pulmonale)
Valvular Heart Disease
Calcific Valvular Degeneration
Calcific Aortic Stenosis
Clinical Features
Calcific Stenosis of Congenitally Bicuspid Aortic Valve
Mitral Annular Calcification
Mitral Valve Prolapse (Myxomatous Degeneration of the Mitral Valve)
Pathogenesis
Clinical Features
Rheumatic Fever and Rheumatic Heart Disease
Pathogenesis
Clinical Features
Infective Endocarditis (IE)
Pathogenesis
Clinical Features
Noninfected Vegetations
Nonbacterial Thrombotic Endocarditis (NBTE)
Endocarditis of Systemic Lupus Erythematosus (Libman-Sacks Disease)
Carcinoid Heart Disease
Pathogenesis
Complications of Prosthetic Valves
Cardiomyopathies
Dilated Cardiomyopathy (DCM)
Pathogenesis
Clinical Features
Arrhythmogenic Cardiomyopathy
Hypertrophic Cardiomyopathy
Pathogenesis
Clinical Features
Restrictive Cardiomyopathy
Amyloidosis
Myocarditis
Pathogenesis
Clinical Features
Other Causes of Myocardial Disease
Cardiotoxic Drugs
Radiation
Pericardial Disease
Pericardial Effusion and Hemopericardium
Pericarditis
Acute Pericarditis
Chronic or Healed Pericarditis
Tumors of the Heart
Primary Cardiac Tumors
Metastatic Neoplasms
Cardiac Transplantation
Cardiac Devices
Ventricular Assist Devices
Suggested Readings
General
Cardiac Structure and Specializations
Heart Failure
Congenital Heart Disease
Ischemic Heart Disease
Arrhythmias
Hypertensive Heart Disease
Valvular Heart Disease
Cardiomyopathies
Tumors of the Heart
Cardiac Transplantation
13 Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
Chapter Contents
Normal Hematopoiesis
Disorders of White Cells
Leukopenia
Neutropenia, Agranulocytosis
Pathogenesis
Clinical Features
Reactive Proliferations of White Cells and Lymph Nodes
Leukocytosis
Pathogenesis
Lymphadenitis
Acute Nonspecific Lymphadenitis
Chronic Nonspecific Lymphadenitis
Hemophagocytic Lymphohistiocytosis
Pathogenesis
Clinical Features
Neoplastic Proliferations of White Cells: Overview
Etiologic and Pathogenetic Factors in White Cell Neoplasia
Chromosomal Translocations and Other Acquired Mutations.
Inherited Genetic Factors.
Viruses.
Chronic Inflammation.
Iatrogenic Factors.
Smoking.
Lymphoid Neoplasms
Definitions and Classifications
Precursor B- and T-Cell Neoplasms
Acute Lymphoblastic Leukemia/Lymphoma
Pathogenesis
Immunophenotype.
Clinical Features
Peripheral B-Cell Neoplasms
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Pathogenesis
Immunophenotype.
Clinical Features
Follicular Lymphoma
Pathogenesis
Immunophenotype.
Clinical Features
Diffuse Large B-Cell Lymphoma
Pathogenesis
Immunophenotype.
Special Subtypes.
Clinical Features
Burkitt Lymphoma
Pathogenesis
Immunophenotype.
Clinical Features
Mantle Cell Lymphoma
Pathogenesis
Immunophenotype.
Clinical Features
Marginal Zone Lymphomas
Hairy Cell Leukemia
Pathogenesis
Immunophenotype.
Clinical Features
Peripheral T- and NK-Cell Neoplasms
Peripheral T-Cell Lymphoma, Unspecified
Anaplastic Large-Cell Lymphoma (ALK Positive)
Adult T-Cell Leukemia/Lymphoma
Mycosis Fungoides/Sézary Syndrome
Large Granular Lymphocytic Leukemia
Extranodal NK/T-Cell Lymphoma
Plasma Cell Neoplasms and Related Disorders
Multiple Myeloma
Pathogenesis
Immunophenotype.
Clinical Features
Smoldering Myeloma
Solitary Osseous Plasmacytoma
Monoclonal Gammopathy of Undetermined Significance
Lymphoplasmacytic Lymphoma
Pathogenesis
Immunophenotype.
Clinical Features
Hodgkin Lymphoma
Classification.
Pathogenesis
Clinical Features
Pathogenic Lessons From Lymphoid Neoplasms
Myeloid Neoplasms
Acute Myeloid Leukemia
Classification.
Pathogenesis
Immunophenotype.
Cytogenetics.
Clinical Features
Myelodysplastic Syndrome
Pathogenesis
Clinical Features
Myeloproliferative Neoplasms
Chronic Myeloid Leukemia
Pathogenesis
Clinical Features
Polycythemia Vera
Pathogenesis
Clinical Features
Essential Thrombocytosis
Pathogenesis
Clinical Features
Primary Myelofibrosis
Pathogenesis
Clinical Features
Langerhans Cell Histiocytosis
Pathogenesis
Clinical Features
Spleen
Splenomegaly
Nonspecific Acute Splenitis
Congestive Splenomegaly
Splenic Infarcts
Neoplasms
Congenital Anomalies
Rupture
Thymus
Developmental Disorders
Thymic Hyperplasia
Thymoma
Clinical Features
Suggested Readings
Hematopoietic Stem Cells
White Cell Neoplasms
14 Red Blood Cell and Bleeding Disorders
Chapter Contents
Anemias
Anemias of Blood Loss
Acute Blood Loss
Chronic Blood Loss
Hemolytic Anemias
Hereditary Spherocytosis
Pathogenesis
Clinical Features
Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase Deficiency
Sickle Cell Disease
Pathogenesis
Clinical Features
Thalassemia
β-Thalassemia
Molecular Pathogenesis
Clinical Syndromes
β-Thalassemia Major.
β-Thalassemia Minor.
α-Thalassemia
Clinical Syndromes
Silent Carrier State.
α-Thalassemia Trait.
Hemoglobin H (HbH) Disease.
Hydrops Fetalis.
Paroxysmal Nocturnal Hemoglobinuria
Immunohemolytic Anemia
Warm Antibody Type.
Cold Agglutinin Type.
Cold Hemolysin Type.
Hemolytic Anemia Resulting From Trauma to Red Cells
Anemias of Diminished Erythropoiesis
Megaloblastic Anemia
Vitamin B12 Deficiency Anemia: Pernicious Anemia
Normal Vitamin B12 Metabolism.
Biochemical Functions of Vitamin B12.
Pernicious Anemia
Incidence.
Pathogenesis
Clinical Features
Anemia of Folate Deficiency
Etiology
Iron Deficiency Anemia
Iron Metabolism.
Etiology.
Pathogenesis
Clinical Features
Anemia of Chronic Inflammation
Aplastic Anemia
Etiology.
Pathogenesis
Clinical Features
Pure Red Cell Aplasia
Other Forms of Marrow Failure
Polycythemia
Bleeding Disorders: Hemorrhagic Diatheses
Bleeding Disorders Caused by Vessel Wall Abnormalities
Bleeding Related to Reduced Platelet Number: Thrombocytopenia
Chronic Immune Thrombocytopenic Purpura
Pathogenesis
Clinical Features
Acute Immune Thrombocytopenic Purpura
Drug-Induced Thrombocytopenia
HIV-Associated Thrombocytopenia
Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS)
Bleeding Disorders Related to Defective Platelet Function
Hemorrhagic Diatheses Related to Abnormalities in Clotting Factors
Factor VIII–vWF Complex
Von Willebrand Disease
Hemophilia A (Factor VIII Deficiency)
Hemophilia B (Christmas Disease, Factor IX Deficiency)
Disseminated Intravascular Coagulation (DIC)
Etiology and Pathogenesis
Clinical Features
Complications of Transfusion
Allergic Reactions
Hemolytic Reactions
Transfusion-Related Acute Lung Injury
Infectious Complications
Suggested Readings
Red Cell Disorders
Bleeding Disorders
15 The Lung
Chapter Contents
Congenital Anomalies
Atelectasis (Collapse)
Pulmonary Edema
Hemodynamic Pulmonary Edema
Edema Caused by Microvascular (Alveolar) Injury
Acute Lung Injury and Acute Respiratory Distress Syndrome (Diffuse Alveolar Damage)
Pathogenesis
Clinical Features
Obstructive and Restrictive Lung Diseases
Obstructive Lung Diseases
Chronic Obstructive Pulmonary Disease
Emphysema
Pathogenesis
Chronic Bronchitis
Pathogenesis
Clinical Features of COPD
Other Forms of Emphysema
Asthma
Atopic Asthma.
Non-Atopic Asthma.
Drug-Induced Asthma.
Occupational Asthma.
Pathogenesis
Th2 Responses, IgE, and Inflammation.
Genetic Susceptibility.
Environmental Factors.
Clinical Features
Bronchiectasis
Pathogenesis
Clinical Features
Chronic Diffuse Interstitial (Restrictive) Diseases
Fibrosing Diseases
Idiopathic Pulmonary Fibrosis
Pathogenesis
Clinical Features
Nonspecific Interstitial Pneumonia
Clinical Features
Cryptogenic Organizing Pneumonia
Pulmonary Involvement in Autoimmune Diseases
Pneumoconioses
Pathogenesis
Coal Workers’ Pneumoconiosis
Clinical Features
Silicosis
Pathogenesis
Clinical Features
Asbestos-Related Diseases
Pathogenesis
Clinical Features
Complications of Therapies
Drug-Induced Lung Diseases.
Radiation-Induced Lung Diseases.
Granulomatous Diseases
Sarcoidosis
Pathogenesis
Clinical Features
Hypersensitivity Pneumonitis
Clinical Features
Pulmonary Eosinophilia
Smoking-Related Interstitial Diseases
Desquamative Interstitial Pneumonia
Respiratory Bronchiolitis–Associated Interstitial Lung Disease
Pulmonary Langerhans Cell Histiocytosis
Pulmonary Alveolar Proteinosis
Clinical Features
Surfactant Dysfunction Disorders
Diseases of Vascular Origin
Pulmonary Embolism and Infarction
Pathogenesis
Clinical Features
Pulmonary Hypertension
Pathogenesis
Clinical Features
Diffuse Pulmonary Hemorrhage Syndromes
Idiopathic Pulmonary Hemosiderosis
Goodpasture Syndrome (Anti–Glomerular Basement Membrane Antibody Disease With Pulmonary Involvement)
Pathogenesis
Clinical Features
Polyangiitis With Granulomatosis
Pulmonary Infections
Community-Acquired Bacterial Pneumonias
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Klebsiella pneumoniae
Pseudomonas aeruginosa
Legionella pneumophila
Mycoplasma pneumoniae
Clinical Features
Community-Acquired Viral Pneumonia
Influenza
Human Metapneumovirus
Human Coronaviruses
Clinical Features
Health Care–Associated Pneumonia
Hospital-Acquired Pneumonia
Aspiration Pneumonia
Lung Abscess
Etiology and Pathogenesis
Clinical Features
Chronic Pneumonia
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Pneumonia in the Immunocompromised Host
Pulmonary Disease in Human Immunodeficiency Virus Infection
Lung Transplantation
Tumors
Carcinomas
Etiology and Pathogenesis
Tobacco Smoking.
Industrial Hazards.
Air Pollution.
Acquired Mutations.
Lung Cancer in Never-Smokers.
Precursor (Preinvasive) Lesions.
Classification
Staging.
Clinical Features
Paraneoplastic Syndromes.
Neuroendocrine Proliferations and Tumors
Carcinoid Tumors
Clinical Features
Miscellaneous Tumors
Metastatic Tumors
Pleura
Pleural Effusion
Inflammatory Pleural Effusions
Noninflammatory Pleural Effusions
Pneumothorax
Pleural Tumors
Solitary Fibrous Tumor
Malignant Mesothelioma
Clinical Features
Suggested Readings
Acute Lung Injury
Obstructive Pulmonary Diseases
Emphysema
Chronic Bronchitis
Asthma
Bronchiectasis
Idiopathic Pulmonary Fibrosis
Nonspecific Interstitial Pneumonia
Organizing Pneumonia
Pneumoconiosis
Radiation Pneumonitis
Sarcoidosis
Hypersensitivity Pneumonia
Eosinophilic Lung Diseases
Smoking-Related Interstitial Diseases
Pulmonary Langerhans Cell Histiocytosis
Pulmonary Alveolar Proteinosis
Surfactant Dysfunction Disorders
Pulmonary Hypertension
Pulmonary Hemorrhage Syndromes
Pneumonia
Lung Transplantation
Lung Cancer
Pleura
16 Head and Neck
Chapter Contents
Oral Cavity
Diseases of Teeth and Supporting Structures
Caries (Tooth Decay)
Gingivitis
Periodontitis
Inflammatory/Reactive Lesions
Aphthous Ulcers (Canker Sores)
Fibrous Proliferative Lesions
Infections
Herpes Simplex Virus Infections
Oral Candidiasis (Thrush)
Deep Fungal Infections
Oral Manifestations of Systemic Disease
Hairy Leukoplakia
Precancerous and Cancerous Lesions
Leukoplakia and Erythroplakia
Squamous Cell Carcinoma
Molecular Biology of Squamous Cell Carcinoma.
Odontogenic Cysts and Tumors
Upper Airways
Nose
Inflammatory Lesions
Infectious Rhinitis.
Allergic Rhinitis.
Nasal Polyps.
Chronic Rhinitis.
Sinusitis.
Necrotizing Lesions of the Nose and Upper Airways
Nasopharynx
Inflammatory Lesions
Tumors of the Nose, Sinuses, and Nasopharynx
Nasopharyngeal Angiofibroma.
Sinonasal (Schneiderian) Papilloma.
Olfactory Neuroblastoma (Esthesioneuroblastoma).
NUT Midline Carcinoma.
Nasopharyngeal Carcinoma.
Larynx
Inflammatory Lesions
Reactive Nodules (Vocal Cord Nodules and Polyps)
Squamous Papilloma and Papillomatosis
Carcinoma of the Larynx
Hyperplasia-Dysplasia-Carcinoma Sequence.
Ears
Inflammatory Lesions
Otosclerosis
Tumors
Neck
Branchial Cyst (Cervical Lymphoepithelial Cyst)
Thyroglossal Duct Cyst
Paraganglioma (Carotid Body Tumor)
Salivary Glands
Xerostomia
Inflammation (Sialadenitis)
Mucocele.
Sialolithiasis and Nonspecific Sialadenitis.
Neoplasms
Pleomorphic Adenoma
Warthin Tumor (Papillary Cystadenoma Lymphomatosum)
Mucoepidermoid Carcinoma
Other Salivary Gland Tumors
Adenoid cystic carcinomas.
Acinic cell carcinomas.
Suggested Readings
17 The Gastrointestinal Tract
Chapter Contents
Congenital Abnormalities
Atresia, Fistulae, and Duplications
Diaphragmatic Hernia, Omphalocele, and Gastroschisis
Ectopia
Meckel Diverticulum
Pyloric Stenosis
Hirschsprung Disease
Pathogenesis
Clinical Features
Esophagus
Esophageal Obstruction
Achalasia
Esophagitis and Related Disorders
Lacerations
Chemical and Infectious Esophagitis
Reflux Esophagitis
Pathogenesis
Clinical Features
Eosinophilic Esophagitis
Esophageal Varices
Pathogenesis
Clinical Features
Barrett Esophagus
Clinical Features
Esophageal Tumors
Adenocarcinoma
Pathogenesis
Clinical Features
Squamous Cell Carcinoma
Pathogenesis
Clinical Features
Stomach
Gastropathy and Acute Gastritis
Pathogenesis
Stress-Related Mucosal Disease
Pathogenesis
Clinical Features
Chronic Gastritis and its Complications
Helicobacter pylori Gastritis
Epidemiology.
Pathogenesis
Clinical Features
Autoimmune Atrophic Gastritis
Pathogenesis
Clinical Features
Uncommon Forms of Gastritis
Eosinophilic Gastritis.
Lymphocytic Gastritis.
Granulomatous Gastritis.
Peptic Ulcer Disease
Epidemiology.
Pathogenesis
Clinical Features
Other Complications of Chronic Gastritis
Mucosal Atrophy and Intestinal Metaplasia
Dysplasia
Gastritis Cystica
Hypertrophic Gastropathies
Ménétrier Disease
Zollinger-Ellison Syndrome
Gastric Polyps and Tumors
Inflammatory and Hyperplastic Polyps
Fundic Gland Polyps
Gastric Adenoma
Gastric Adenocarcinoma
Epidemiology.
Pathogenesis
Clinical Features
Lymphoma
Pathogenesis
Clinical Features
Neuroendocrine Neoplasms
Clinical Features
Gastrointestinal Stromal Tumor
Epidemiology.
Pathogenesis
Clinical Features
Small Intestine and Colon
Intestinal Obstruction
Hernias
Adhesions
Volvulus
Intussusception
Ischemic Bowel Disease
Pathogenesis
Clinical Features
Angiodysplasia
Malabsorption and Diarrhea
Cystic Fibrosis
Celiac Disease
Pathogenesis
Clinical Features
Environmental Enteric Dysfunction
Autoimmune Enteropathy
Lactase (Disaccharidase) Deficiency
Microvillus Inclusion Disease
Abetalipoproteinemia
Infectious Enterocolitis
Cholera
Pathogenesis
Clinical Features
Campylobacter Enterocolitis
Pathogenesis
Clinical Features
Shigellosis
Pathogenesis
Clinical Features
Salmonella
Pathogenesis
Clinical Features
Typhoid Fever
Pathogenesis
Clinical Features
Yersinia
Pathogenesis
Clinical Features
Escherichia coli
Enterotoxigenic Escherichia coli.
Enteropathogenic Escherichia coli.
Enterohemorrhagic Escherichia coli.
Enteroinvasive Escherichia coli.
Enteroaggregative Escherichia coli.
Pseudomembranous Colitis
Pathogenesis
Clinical Features
Whipple Disease
Pathogenesis
Viral Gastroenteritis
Norovirus.
Rotavirus.
Adenovirus.
Parasitic Enterocolitis
Ascaris lumbricoides.
Strongyloides.
Necator duodenale and Ancylostoma duodenale.
Trichuris trichiura.
Enterobius vermicularis and Enterobius gregorii.
Schistosomiasis.
Intestinal Cestodes.
Entamoeba histolytica.
Giardia lamblia.
Cryptosporidium.
Irritable Bowel Syndrome
Pathogenesis
Clinical Features
Inflammatory Bowel Disease (IBD)
Epidemiology.
Pathogenesis
Crohn Disease
Clinical Features
Ulcerative Colitis
Clinical Features
Indeterminate Colitis
Colitis-Associated Neoplasia
Other Causes of Chronic Colitis
Diversion Colitis
Microscopic Colitis
Graft-Versus-Host Disease
Sigmoid Diverticular Disease
Pathogenesis
Clinical Features
Polyps
Hyperplastic Polyps
Inflammatory Polyps
Hamartomatous Polyps
Juvenile Polyps
Peutz-Jeghers Syndrome
Pathogenesis
Clinical Features
Neoplastic Polyps
Familial Adenomatous Polyposis
Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Adenocarcinoma
Epidemiology.
Pathogenesis
Clinical Features
Tumors of the Anal Canal
Hemorrhoids
Acute Appendicitis
Pathogenesis
Clinical Features
Tumors of the Appendix
Peritoneal Cavity
Inflammatory Disease
Peritoneal Infection
Sclerosing Retroperitonitis
Tumors
Suggested Readings
Congenital Abnormalities
Esophagus
Esophageal Obstruction
Esophagitis
Barrett Esophagus
Esophageal Tumors
Stomach
Gastropathy and Acute Gastritis
Chronic Gastritis
Hypertrophic Gastropathies
Gastric Polyps and Tumors
Small Intestine and Colon
Intestinal Obstruction
Ischemic Bowel Disease and Angiodysplasia
Malabsorption and Diarrhea
Infectious Enterocolitis
Irritable Bowel Syndrome
Inflammatory Bowel Disease
Other Causes of Colitis
Diverticulitis
Polyps
Adenocarcinoma
Hemorrhoids
Acute Appendicitis and Tumors of the Appendix
Peritoneal Cavity
18 Liver and Gallbladder
Chapter Contents
The Liver and Bile Ducts
General Features of Liver Disease
Mechanisms of Injury and Repair
Hepatocyte and Parenchymal Responses
Scar Formation and Regression
Liver Failure
Acute Liver Failure
Clinical Features
Chronic Liver Failure and Cirrhosis
Clinical Features
Portal Hypertension
Ascites
Portosystemic Shunts
Splenomegaly
Pulmonary Complications of Liver Failure and Portal Hypertension.
Acute-on-Chronic Liver Failure
Infectious Disorders
Viral Hepatitis
Hepatitis A Virus
Epidemiology
Pathogenesis
Clinical Features
Hepatitis B Virus
Epidemiology
Pathogenesis
Clinical Features
Hepatitis C Virus
Epidemiology
Pathogenesis
Clinical Features
Hepatitis D Virus
Epidemiology
Pathogenesis
Clinical Features
Hepatitis E Virus
Epidemiology
Pathogenesis
Clinical Features
Clinicopathologic Syndromes of Viral Hepatitis
Bacterial, Fungal, and Parasitic Infections
Autoimmune Hepatitis
Pathogenesis
Clinical Features
Drug- and Toxin-Induced Liver Injury
Pathogenesis
Clinical Features
Fatty Liver Disease
Alcoholic Liver Disease
Pathogenesis
Clinical Features
Nonalcoholic Fatty Liver Disease (NAFLD)
Pathogenesis
Clinical Features
Inherited Liver Disease
Hemochromatosis
Pathogenesis
Clinical Features
Wilson Disease
Pathogenesis
Clinical Features
α1-Antitrypsin Deficiency
Pathogenesis
Clinical Features
Cholestatic Disease
Bile Formation and Secretion
Pathophysiology of Hyperbilirubinemia
Clinical Features
Physiologic Jaundice of the Newborn
Hereditary Hyperbilirubinemia
Large Bile Duct Obstruction
Cholestasis of Sepsis
Primary Hepatolithiasis
Neonatal Cholestasis
Extrahepatic Biliary Atresia
Clinical Features
Nonobstructive Neonatal Cholestasis
Autoimmune Cholangiopathies
Primary Biliary Cholangitis (PBC)
Pathogenesis
Clinical Features
Primary Sclerosing Cholangitis (PSC)
Pathogenesis
Clinical Features
Structural Anomalies of the Biliary Tree
Choledochal Cyst
Fibropolycystic Disease
Circulatory Disorders
Impaired Blood Flow Into the Liver
Hepatic Artery Compromise
Portal Vein Obstruction and Thrombosis
Impaired Blood Flow Through the Liver
Hepatic Venous Outflow Obstruction
Hepatic Vein Thrombosis
Clinical Features
Sinusoidal Obstruction Syndrome
Pathogenesis
Clinical Features
Passive Congestion and Centrilobular Necrosis
Hepatic Disease Associated With Pregnancy
Preeclampsia and Eclampsia
Clinical Features
Acute Fatty Liver of Pregnancy
Pathogenesis
Clinical Features
Intrahepatic Cholestasis of Pregnancy
Nodules and Tumors
Non-Neoplastic Mass Lesions
Focal Nodular Hyperplasia
Pathogenesis
Clinical Features
Other Non-Neoplastic Mass Lesions
Benign Neoplasms
Cavernous Hemangioma
Hepatocellular Adenoma
Pathogenesis
Clinical Features
Primary Malignant Neoplasms
Hepatoblastoma
Clinical Features
Hepatocellular Carcinoma (HCC)
Pathogenesis
Clinical Features
Malignant Biliary Tumors
Pathogenesis
Clinical Features
Other Primary Hepatic Malignant Tumors
Metastasis
Gallbladder
Congenital Anomalies
Cholelithiasis (Gallstones)
Epidemiology
Pathogenesis of Cholesterol Stones
Pathogenesis of Pigment Stones
Clinical Features
Cholecystitis
Acute Cholecystitis
Pathogenesis
Clinical Features
Chronic Cholecystitis
Clinical Features
Gallbladder Carcinoma
Pathogenesis
Clinical Features
Suggested Readings
Mechanisms of Liver Injury and Repair
Acute, Chronic, Acute-On-Chronic Liver Failure
Viral Hepatitis
Autoimmune Liver Diseases
Drug- and Toxin-Induced Liver Injury
Fatty Liver Disease
Inherited Liver Diseases
Cholestatic Syndromes
Circulatory Disorders
Benign and Malignant Liver Tumors
19 The Pancreas
Chapter Contents
Congenital Anomalies
Pancreas Divisum.
Annular Pancreas.
Ectopic Pancreas.
Agenesis.
Pancreatitis
Acute Pancreatitis
Pathogenesis
Clinical Features
Chronic Pancreatitis
Pathogenesis
Clinical Features
Nonneoplastic Cysts
Congenital Cysts
Pseudocysts
Neoplasms
Cystic Neoplasms
Pancreatic Carcinoma
Precursors to Pancreatic Cancer
Pathogenesis
Epidemiology and Inheritance.
Clinical Features
Acinar Cell Carcinoma
Pancreatoblastoma
Suggested Readings
Congenital Anomalies
Acute Pancreatitis
Chronic Pancreatitis
Pseudocysts
Cystic Neoplasms
Pancreatic Carcinoma
20 The Kidney
Chapter Contents
Clinical Manifestations of Renal Diseases
Glomerular Diseases
Structure of the Glomerulus
Pathologic Responses of the Glomerulus to Injury
Hypercellularity
Basement Membrane Thickening
Hyalinosis and Sclerosis
Pathogenesis of Glomerular Injury
Diseases Caused by In Situ Formation of Immune Complexes
Disease Caused by Antibodies Directed Against Normal Components of the Glomerular Basement Membrane
Glomerulonephritis Resulting From Deposition of Circulating Immune Complexes
Mechanisms of Glomerular Injury Following Immune Complex Formation
Cell-Mediated Immunity in Glomerulonephritis
Activation of Alternative Complement Pathway
Mediators of Glomerular Injury
Cells
Soluble Mediators
Epithelial Cell Injury
Mechanisms of Progression in Glomerular Diseases
Glomerulosclerosis
Tubular Injury and Interstitial Fibrosis
Nephritic Syndrome
Acute Proliferative (Postinfectious and Infection-Associated) Glomerulonephritis
Pathogenesis
Clinical Features
Crescentic (Rapidly Progressive) Glomerulonephritis
Pathogenesis
Clinical Features
Nephrotic Syndrome
Pathophysiology
Pathogenesis
Membranous Nephropathy
Pathogenesis
Clinical Features
Minimal Change Disease
Pathogenesis
Clinical Features
Focal Segmental Glomerulosclerosis
Classification and Types
Pathogenesis
Clinical Features
HIV-Associated Nephropathy
Membranoproliferative Glomerulonephritis
Pathogenesis
Clinical Features
Secondary Membranoproliferative Glomerulonephritis
Dense Deposit Disease
Clinical Features
Fibrillary Glomerulonephritis
Other Glomerular Diseases
IgA Nephropathy (Berger Disease)
Pathogenesis
Clinical Features
Hereditary Nephritis
Alport Syndrome
Pathogenesis
Clinical Features
Thin Basement Membrane Nephropathy (Benign Familial Hematuria)
Glomerular Lesions Associated With Systemic Diseases
Lupus Nephritis
Henoch-Schönlein Purpura
Diabetic Nephropathy
Other Systemic Disorders
Tubular and Interstitial Diseases
Acute Tubular Injury/Necrosis
Pathogenesis
Clinical Features
Tubulointerstitial Nephritis
Pyelonephritis and Urinary Tract Infection
Pathogenesis
Acute Pyelonephritis
Clinical Features
Chronic Pyelonephritis and Reflux Nephropathy
Clinical Features
Tubulointerstitial Nephritis Induced by Drugs and Toxins
Acute Drug-Induced Interstitial Nephritis
Pathogenesis
Clinical Features
Nephropathy Associated With NSAIDs
Other Tubulointerstitial Diseases
Urate Nephropathy
Hypercalcemia and Nephrocalcinosis
Autosomal Dominant Tubulointerstitial Kidney Disease
Light-Chain Cast Nephropathy (“Myeloma Kidney”)
Clinical Features
Bile Cast Nephropathy
Vascular Diseases
Nephrosclerosis
Pathogenesis
Clinical Features
Renal Artery Stenosis
Pathogenesis
Clinical Features
Thrombotic Microangiopathies
Pathogenesis
Endothelial Injury.
Platelet Aggregation.
Typical (Epidemic, Classic, Diarrhea-Positive) Hemolytic Uremic Syndrome
Atypical (Non-Epidemic, Diarrhea-Negative) Hemolytic Uremic Syndrome
Thrombotic Thrombocytopenic Purpura
Other Vascular Disorders
Atherosclerotic Ischemic Renal Disease
Atheroembolic Renal Disease
Sickle Cell Nephropathy
Renal Infarcts
Congenital and Developmental Anomalies
Agenesis of the Kidney.
Hypoplasia.
Ectopic Kidneys.
Horseshoe Kidneys.
Cystic Diseases of the Kidney
Autosomal Dominant (Adult) Polycystic Kidney Disease
Genetics and Pathogenesis
Clinical Features
Autosomal Recessive (Childhood) Polycystic Kidney Disease
Genetics and Pathogenesis
Cystic Diseases of the Renal Medulla
Medullary Sponge Kidney
Nephronophthisis
Genetics and Pathogenesis
Multicystic Renal Dysplasia
Acquired Cystic Disease
Simple Cysts
Urinary Tract Obstruction (Obstructive Uropathy)
Clinical Features
Urolithiasis (Renal Calculi, Stones)
Etiology and Pathogenesis
Clinical Features
Neoplasms of the Kidney
Benign Neoplasms
Renal Papillary Adenoma
Angiomyolipoma
Oncocytoma
Malignant Neoplasms
Renal Cell Carcinoma
Epidemiology
Classification of Renal Cell Carcinoma: Histology, Cytogenetics, and Genetics
Clinical Features
Urothelial Carcinoma of the Renal Pelvis
Suggested Readings
Pathogenesis of Immune-Mediated Glomerular Injury
Mechanisms of Progression in Glomerular Diseases
Nephrotic Syndrome
Nephritic Syndrome
Rapidly Progressive (Crescentic) Glomerulonephritis
Isolated Urinary Abnormalities
Acute Tubular Injury/Necrosis
Tubulointerstitial Nephritis
Vascular Diseases
Cystic Diseases of the Kidney
Neoplasms of the Kidney
21 The Lower Urinary Tract and Male Genital System
Chapter Contents
The Lower Urinary Tract
Ureters
Congenital Anomalies
Tumors and Tumor-Like Lesions
Obstructive Lesions
Sclerosing Retroperitoneal Fibrosis
Urinary Bladder
Congenital Anomalies
Inflammation
Acute and Chronic Cystitis
Clinical Features
Special Forms of Cystitis
Interstitial Cystitis (Chronic Pelvic Pain Syndrome).
Malakoplakia.
Polypoid Cystitis.
Metaplastic Lesions
Neoplasms
Urothelial Neoplasms
Epidemiology.
Pathogenesis
Clinical Features
Other Epithelial Bladder Tumors
Mesenchymal Tumors
Benign Tumors.
Sarcomas.
Secondary Tumors
Obstruction
Urethra
Inflammation
Tumors and Tumor-Like Lesions
The Male Genital Tract
Penis
Congenital Anomalies
Hypospadias and Epispadias
Phimosis
Inflammation
Tumors
Benign Tumors and Tumor-Like Conditions
Condyloma Acuminatum
Peyronie Disease
Malignant Tumors
Squamous Carcinoma in situ/Penile Intraepithelial Neoplasia
Invasive Squamous Cell Carcinoma
Pathogenesis
Clinical Features
Testis and Epididymis
Congenital Anomalies
Cryptorchidism
Clinical Features
Regressive Changes
Atrophy and Decreased Fertility
Inflammation and Infections
Nonspecific Epididymitis and Orchitis
Granulomatous (Autoimmune) Orchitis
Infections
Gonorrhea
Mumps
Tuberculosis
Syphilis
Other Infections
Vascular Disorders
Torsion
Spermatic Cord and Paratesticular Tumors
Testicular Tumors
Germ Cell Tumors
Pathogenesis
Environmental Factors.
Genetic Factors.
Steps in the Development of Germ Cell Tumors.
Classification.
Seminoma
Spermatocytic Tumor
Embryonal Carcinoma
Yolk Sac Tumor
Choriocarcinoma
Teratoma
Mixed Tumors
Clinical Features of Testicular Germ Cell Tumors.
Serum Biomarkers in Germ Cell Tumors.
Tumors of Sex Cord–Gonadal Stroma
Leydig Cell Tumors
Sertoli Cell Tumors
Gonadoblastoma
Testicular Lymphoma
Lesions of Tunica Vaginalis
Prostate
Inflammation
Benign Enlargement
Benign Prostatic Hyperplasia
Etiology and Pathogenesis
Clinical Features
Neoplasms
Adenocarcinoma
Epidemiology and Pathogenesis.
Environmental Factors.
Inherited Genetic Factors.
Androgens.
Acquired Genetic and Epigenetic Alterations.
Precursor Lesions.
Grading and Staging.
Clinical Features
Miscellaneous Tumors
Suggested Readings
Penile Disorders
Testicular Disorders
Bladder Disorders
Prostatic Disorders
22 The Female Genital Tract
Chapter Contents
Infections
Infections of the Lower Genital Tract
Herpes Simplex Virus
Other Lower Female Genital Tract Infections
Infections Involving the Lower and Upper Genital Tract
Pelvic Inflammatory Disease (PID)
Vulva
Bartholin Cyst
Non-Neoplastic Epithelial Disorders
Lichen Sclerosus
Squamous Cell Hyperplasia
Benign Exophytic Lesions
Condyloma Acuminatum
Squamous Neoplastic Lesions
Vulvar Intraepithelial Neoplasia and Vulvar Carcinoma
Glandular Neoplastic Lesions
Papillary Hidradenoma
Extramammary Paget Disease
Vagina
Developmental Anomalies
Premalignant and Malignant Neoplasms of the Vagina
Vaginal Intraepithelial Neoplasia and Squamous Cell Carcinoma
Embryonal Rhabdomyosarcoma
Cervix
Inflammations
Acute and Chronic Cervicitis
Endocervical Polyps
Premalignant and Malignant Neoplasms of the Cervix
Pathogenesis
Cervical Intraepithelial Neoplasia (Squamous Intraepithelial Lesions)
Cervical Carcinoma
Clinical Features
Cervical Cancer Screening and Prevention
Body of Uterus and Endometrium
Endometrial Histology in the Menstrual Cycle
Functional Endometrial Disorders (Dysfunctional Uterine Bleeding)
Anovulatory Cycle
Inflammatory Disorders
Acute Endometritis
Chronic Endometritis
Endometriosis and Adenomyosis
Pathogenesis
Clinical Features
Endometrial Polyps
Endometrial Hyperplasia
Malignant Tumors of the Endometrium
Carcinoma of the Endometrium
Pathogenesis
Endometrioid Endometrial Carcinoma
Serous Endometrial Carcinoma
Pathogenesis
Clinical Features
Carcinosarcoma (Malignant Mixed Müllerian Tumors)
Tumors of Endometrial Stroma
Adenosarcoma
Stromal Tumors
Tumors of the Myometrium
Leiomyoma
Leiomyosarcoma
Fallopian Tubes
Inflammations
Tumors and Cysts
Ovaries
Non-Neoplastic and Functional Cysts
Follicle and Luteal Cysts
Polycystic Ovaries and Stromal Hyperthecosis
Ovarian Tumors
Classification
Epithelial Tumors
Serous Tumors
Pathogenesis
Mucinous Tumors
Pathogenesis
Endometrioid Ovarian Tumors
Pathogenesis
Clear Cell Carcinoma
Cystadenofibroma
Transitional Cell Tumors
Clinical Course, Detection, and Prevention of Ovarian Epithelial Tumors
Germ Cell Tumors
Teratoma
Mature (Benign) Teratomas
Monodermal or Specialized Teratomas
Immature Malignant Teratomas
Dysgerminoma
Yolk Sac Tumors
Choriocarcinoma
Other Germ Cell Tumors
Sex Cord–Stromal Tumors
Granulosa Cell Tumors
Fibromas, Thecomas, and Fibrothecomas
Sertoli-Leydig Cell Tumors
Other Sex Cord–Stromal Tumors
Metastatic Tumors
Gestational and Placental Disorders
Disorders of Early Pregnancy
Spontaneous Abortion
Ectopic Pregnancy
Clinical Features
Disorders of Late Pregnancy
Twin Placentas
Abnormalities of Placental Implantation
Placental Infections
Preeclampsia and Eclampsia
Pathogenesis
Clinical Features
Gestational Trophoblastic Disease
Hydatidiform Mole
Complete Mole
Partial Mole
Clinical Features
Invasive Mole
Choriocarcinoma
Clinical Features
Placental Site Trophoblastic Tumors
Suggested Readings
Infectious Diseases of Lower Genital Tract
Vulva
Vagina
Cervix
Uterus and Endometrium
Ovary
Placenta
23 The Breast
Chapter Contents
Disorders of Development
Milk Line Remnants
Accessory Axillary Breast Tissue
Congenital Nipple Inversion
Clinical Presentations of Breast Disease
Inflammatory Disorders
Acute Mastitis
Squamous Metaplasia of Lactiferous Ducts
Duct Ectasia
Fat Necrosis
Lymphocytic Mastopathy (Sclerosing Lymphocytic Lobulitis)
Granulomatous Mastitis
Benign Epithelial Lesions
Nonproliferative Breast Changes (Fibrocystic Changes)
Proliferative Breast Disease Without Atypia
Gynecomastia
Proliferative Breast Disease With Atypia
Clinical Significance of Benign Epithelial Changes
Carcinoma of the Breast
Incidence and Epidemiology
Risk Factors
Molecular Classification and Pathogenesis
Pathogenesis of Familial Breast Cancer
Pathogenesis of Sporadic Breast Cancer
Types of Breast Carcinoma
Carcinoma in Situ
Ductal Carcinoma in Situ.
Clinical Features
Lobular Carcinoma in Situ.
Invasive (Infiltrating) Carcinoma
Special Histologic Types of Invasive Carcinoma
Prognostic and Predictive Factors for Invasive Carcinoma
Male Breast Cancer
Stromal Tumors
Fibroadenoma
Clinical Features
Phyllodes Tumor
Clinical Features
Lesions of Interlobular Stroma
Malignant Tumors of Interlobular Stroma
Other Malignant Tumors of the Breast
Suggested Readings
The Social, Historical, and Political Significance of Breast Cancer
General Sources of Information About Breast Cancer
Large Internet Breast Cancer Datasets
Breast Cancer Biology
Resources for Classification, Staging, Reporting, and Treating Breast Cancer
24 The Endocrine System
Chapter Contents
Pituitary Gland
Clinical Manifestations of Pituitary Disease
Pituitary Adenomas and Hyperpituitarism
Pathogenesis
Clinical Features
Lactotroph Adenoma
Clinical Features
Somatotroph Adenoma
Clinical Features
Corticotroph Adenoma
Clinical Features
Other Anterior Pituitary Tumors
Hypopituitarism
Posterior Pituitary Syndromes
Hypothalamic Suprasellar Tumors
Thyroid Gland
Hyperthyroidism
Clinical Features
Hypothyroidism
Cretinism
Myxedema
Thyroiditis
Hashimoto Thyroiditis
Pathogenesis
Clinical Features
Subacute Lymphocytic (Painless) Thyroiditis
Clinical Features
Granulomatous Thyroiditis
Pathogenesis
Clinical Features
Graves Disease
Pathogenesis
Clinical Features
Diffuse and Multinodular Goiter
Diffuse Nontoxic (Simple) Goiter
Clinical Features
Multinodular Goiter
Pathogenesis
Clinical Features
Neoplasms of the Thyroid
Thyroid Adenomas
Pathogenesis
Clinical Features
Thyroid Carcinomas
Pathogenesis
Driver Mutations.
Environmental Factors.
Papillary Carcinoma and Follicular Variants, Including Invasive Encapsulated Follicular Variant of PTC and Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features
Clinical Features
Follicular Carcinoma
Clinical Features
Poorly Differentiated and Anaplastic (Undifferentiated) Carcinoma
Clinical Features
Medullary Carcinoma
Clinical Features
Congenital Anomalies
Parathyroid Glands
Hyperparathyroidism
Primary Hyperparathyroidism
Clinical Features
Secondary Hyperparathyroidism
Clinical Features
Hypoparathyroidism
Clinical Features
Pseudohypoparathyroidism
The Endocrine Pancreas
Diabetes Mellitus
Diagnosis
Classification
Glucose Homeostasis
Regulation of Insulin Release
Insulin Action and Insulin-Signaling Pathways
Pathogenesis of Type 1 Diabetes
Genetic Susceptibility
Environmental Factors
Mechanisms of β-Cell Destruction
Pathogenesis of Type 2 Diabetes
Genetic Factors
Environmental Factors
Metabolic Defects in Type 2 Diabetes
Insulin Resistance
Obesity
β-Cell Dysfunction
Monogenic Forms of Diabetes
Genetic Defects in β-Cell Function
Genetic Defects That Impair Tissue Response to Insulin
Diabetes and Pregnancy
Clinical Features of Diabetes
The Classic Triad of Diabetes
Acute Metabolic Complications of Diabetes
Chronic Complications of Diabetes
Pathogenesis
Morphology of Chronic Complications of Diabetes
Diabetic Macrovascular Disease
Diabetic Microangiopathy
Diabetic Nephropathy
Capillary Basement Membrane Thickening.
Diffuse Mesangial Sclerosis.
Nodular Glomerulosclerosis.
Diabetic Ocular Complications
Diabetic Neuropathy
Clinical Manifestations of Chronic Diabetes
Pancreatic Neuroendocrine Tumors
Pathogenesis
Hyperinsulinism (Insulinoma)
Clinical Features
Zollinger-Ellison Syndrome (Gastrinoma)
Clinical Features
Other Rare Pancreatic Endocrine Neoplasms
Adrenal Glands
Adrenal Cortex
Adrenocortical Hyperfunction (Hyperadrenalism)
Hypercortisolism (Cushing Syndrome)
Pathogenesis
Clinical Features
Primary Hyperaldosteronism
Clinical Features
Adrenogenital Syndromes
Clinical Features
Adrenocortical Insufficiency
Primary Acute Adrenocortical Insufficiency
Waterhouse-Friderichsen Syndrome
Primary Chronic Adrenocortical Insufficiency (Addison Disease)
Pathogenesis
Clinical Features
Secondary Adrenocortical Insufficiency
Adrenocortical Neoplasms
Other Adrenal Lesions
Adrenal Medulla
Pheochromocytoma
Clinical Features
Multiple Endocrine Neoplasia Syndromes
Multiple Endocrine Neoplasia, Type 1
Multiple Endocrine Neoplasia, Type 2
Pineal Gland
Pinealoma
Suggested Readings
Pituitary
Thyroid
Parathyroid
Pancreas—Diabetes
Pancreas—Neuroendocrine Tumors
Adrenal Cortex
Adrenal Medulla
Multiple Endocrine Neoplasia
25 The Skin
Chapter Contents
The Skin: More Than a Mechanical Barrier
Disorders of Pigmentation and Melanocytes
Freckle (Ephelis)
Lentigo
Melanocytic Nevus (Pigmented Nevus, Mole)
Pathogenesis
Dysplastic Nevi
Pathogenesis
Melanoma
Pathogenesis
Clinical Features
Benign Epithelial Tumors
Seborrheic Keratosis
Pathogenesis
Acanthosis Nigricans
Pathogenesis
Fibroepithelial Polyp
Epithelial or Follicular Inclusion Cyst (Wen)
Adnexal (Appendage) Tumors
Premalignant and Malignant Epidermal Tumors
Actinic Keratosis
Squamous Cell Carcinoma
Pathogenesis
Basal Cell Carcinoma
Pathogenesis
Tumors of the Dermis
Benign Fibrous Histiocytoma (Dermatofibroma)
Dermatofibrosarcoma Protuberans
Pathogenesis
Tumors of Cellular Migrants to the Skin
Mycosis Fungoides (Cutaneous T-Cell Lymphoma)
Mastocytosis
Pathogenesis
Disorders of Epidermal Maturation
Ichthyosis
Pathogenesis
Acute Inflammatory Dermatoses
Urticaria
Pathogenesis
Acute Eczematous Dermatitis
Pathogenesis
Erythema Multiforme
Pathogenesis
Chronic Inflammatory Dermatoses
Psoriasis
Pathogenesis
Seborrheic Dermatitis
Pathogenesis
Lichen Planus
Pathogenesis
Blistering (Bullous) Diseases
Inflammatory Blistering Disorders
Pemphigus
Pathogenesis
Bullous Pemphigoid
Pathogenesis
Dermatitis Herpetiformis
Pathogenesis
Noninflammatory Blistering Disorders
Epidermolysis Bullosa and Porphyria
Epidermolysis Bullosa.
Porphyria.
Disorders of Epidermal Appendages
Acne Vulgaris
Pathogenesis
Rosacea
Pathogenesis
Panniculitis
Erythema Nodosum and Erythema Induratum
Other Types of Panniculitis
Infection
Verrucae (Warts)
Pathogenesis
Molluscum Contagiosum
Impetigo
Pathogenesis
Superficial Fungal Infections
Suggested Readings
Melanoma and Dysplastic Nevi
Epidermal Skin Tumors
Mastocytosis and Cutaneous T-Cell Lymphoma
Autoimmune and Inflammatory Skin Disorders
Blistering Disorders
Disorders of Skin Appendages and Subcutis
26 Bones, Joints, and Soft Tissue Tumors
Chapter Contents
Bone
Basic Structure and Function of Bone
Matrix
Cells
Development
Homeostasis and Remodeling
Developmental Disorders of Bone and Cartilage
Defects in Nuclear Proteins and Transcription Factors
Defects in Hormones and Signal Transduction Proteins
Defects in Extracellular Structural Proteins
Type 1 Collagen Diseases (Osteogenesis Imperfecta)
Defects in Metabolic Pathways (Enzymes, Ion Channels, and Transporters)
Osteopetrosis
Pathogenesis
Clinical Features
Diseases Associated With Defects in Degradation of Macromolecules
Mucopolysaccharidoses
Metabolic Diseases of Bone
Osteopenia and Osteoporosis
Pathogenesis
Clinical Features
Osteomalacia and Rickets
Hyperparathyroidism
Renal Osteodystrophy
Pathogenesis
Paget Disease (Osteitis Deformans)
Pathogenesis
Clinical Features
Fractures
Healing of Fractures
Osteonecrosis (Avascular Necrosis)
Clinical Features
Osteomyelitis
Pyogenic Osteomyelitis
Clinical Features
Mycobacterial Osteomyelitis
Skeletal Syphilis
Bone Tumors and Tumor-Like Lesions
Bone-Forming Tumors
Osteoid Osteoma and Osteoblastoma
Osteosarcoma
Pathogenesis
Clinical Features
Cartilage-Forming Tumors
Osteochondroma
Pathogenesis
Clinical Features
Chondroma
Pathogenesis
Clinical Features
Chondrosarcoma
Pathogenesis
Clinical Features
Tumors of Unknown Origin
Ewing Sarcoma
Pathogenesis
Clinical Features
Giant Cell Tumor
Pathogenesis
Clinical Features
Aneurysmal Bone Cyst
Pathogenesis
Clinical Features
Lesions Simulating Primary Neoplasms
Fibrous Cortical Defect and Nonossifying Fibroma
Clinical Features
Fibrous Dysplasia
Pathogenesis
Clinical Features
Metastatic Tumors
Joints
Arthritis
Osteoarthritis
Pathogenesis
Clinical Features
Rheumatoid Arthritis
Pathogenesis
Clinical Features
Juvenile Idiopathic Arthritis
Seronegative Spondyloarthropathies
Ankylosing Spondylitis
Reactive Arthritis
Infectious Arthritis
Suppurative Arthritis
Mycobacterial Arthritis
Viral Arthritis
Lyme Arthritis
Crystal-Induced Arthritis
Gout
Pathogenesis
Clinical Features
Calcium Pyrophosphate Crystal Deposition Disease (Pseudogout)
Pathogenesis
Clinical Features
Joint Tumors and Tumor-Like Conditions
Ganglion and Synovial Cysts
Tenosynovial Giant Cell Tumor
Pathogenesis
Clinical Features
Soft Tissue Tumors
Pathogenesis
Tumors of Adipose Tissue
Lipoma
Liposarcoma
Pathogenesis
Clinical Features
Fibrous Tumors
Nodular Fasciitis
Fibromatoses
Superficial Fibromatosis
Deep Fibromatosis (Desmoid Tumors)
Clinical Features
Skeletal Muscle Tumors
Rhabdomyosarcoma
Clinical Features
Smooth Muscle Tumors
Leiomyoma
Leiomyosarcoma
Clinical Features
Tumors of Uncertain Origin
Synovial Sarcoma
Clinical Features
Undifferentiated Pleomorphic Sarcoma
Clinical Features
Acknowledgment
Suggested Readings
Basic Structure and Biology of Bone
Skeletal Dysplasias
Osteoporosis
Hyperparathyroidism
Paget Disease
Osteonecrosis
Osteosarcoma
Chondrogenic Tumors
Ewing Sarcoma
Giant Cell Tumor of Bone
Aneurysmal Bone Cyst
Fibrous Dysplasia
Osteoarthritis
Rheumatoid Arthritis and Related Conditions
Lyme Disease
Gout and Pseudogout
Tenosynovial Giant Cell Tumor
Soft Tissue Sarcomas
27 Peripheral Nerves and Skeletal Muscles
Chapter Contents
Diseases of Peripheral Nerves
General Types of Peripheral Nerve Injury
Axonal Neuropathies
Demyelinating Neuropathies
Neuronopathies
Anatomic Patterns of Peripheral Neuropathies
Specific Peripheral Neuropathies
Inflammatory Neuropathies
Guillain-Barré Syndrome (Acute Inflammatory Demyelinating Polyneuropathy)
Pathogenesis
Clinical Features
Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy
Pathogenesis
Neuropathy Associated With Systemic Autoimmune Diseases
Neuropathy Associated With Vasculitis
Infectious Neuropathies
Leprosy (Hansen Disease)
Lyme Disease
HIV/AIDS
Diphtheria
Varicella-Zoster Virus
Metabolic, Hormonal, and Nutritional Neuropathies
Diabetes
Pathogenesis
Clinical Features
Other Metabolic, Hormonal, and Nutritional Neuropathies
Toxic Neuropathies
Neuropathies Associated With Malignancy
Neuropathies Caused by Physical Forces
Inherited Peripheral Neuropathies
Hereditary Motor and Sensory Neuropathies/Charcot-Marie-Tooth Disease
Hereditary Sensory Neuropathies With or Without Autonomic Neuropathy
Familial Amyloid Polyneuropathies
Diseases of the Neuromuscular Junction
Antibody-Mediated Diseases of the Neuromuscular Junction
Myasthenia Gravis
Pathogenesis
Clinical Features
Lambert-Eaton Myasthenic Syndrome
Congenital Myasthenic Syndromes
Disorders Caused by Toxins
Diseases of Skeletal Muscle
Skeletal Muscle Atrophy
Neurogenic and Myopathic Changes in Skeletal Muscle
Inflammatory Myopathies
Dermatomyositis
Pathogenesis
Clinical Features
Immune-Mediated Necrotizing Myopathy (IMNM)
Polymyositis
Pathogenesis
Inclusion Body Myositis
Toxic Myopathies
Inherited Diseases of Skeletal Muscle
Muscular Dystrophies
X-Linked Muscular Dystrophy With Dystrophin Mutation Including Duchenne and Becker Muscular Dystrophy
Pathogenesis
Clinical Features
Limb-Girdle Muscular Dystrophy
Myotonic Dystrophy
Pathogenesis
Emery-Dreifuss Muscular Dystrophy (EMD)
Fascioscapulohumeral Dystrophy
Pathogenesis
Diseases of Lipid or Glycogen Metabolism
Mitochondrial Myopathies
Clinical Features
Spinal Muscular Atrophy and Differential Diagnosis of a Hypotonic Infant
Ion Channel Myopathies (Channelopathies)
Peripheral Nerve Sheath Tumors
Schwannomas
Clinical Features
Neurofibromas
Pathogenesis
Malignant Peripheral Nerve Sheath Tumors
Neurofibromatosis Type 1 and Type 2
Neurofibromatosis Type 1
Neurofibromatosis Type 2
Suggested Readings
Neuropathies and Other Non-Neoplastic Disorders of Peripheral Nerves
Muscular Dystrophies and Other Disorders of Muscle
Tumors of Peripheral Nerves
28 The Central Nervous System
Chapter Contents
Cellular Pathology of the Central Nervous System
Reactions of Neurons to Injury
Reactions of Astrocytes to Injury
Reactions of Microglia to Injury
Reactions of Other Glial Cells to Injury
Cerebral Edema, Hydrocephalus, Raised Intracranial Pressure, and Herniation
Cerebral Edema
Hydrocephalus
Raised Intracranial Pressure and Herniation
Malformations and Developmental Disorders
Neural Tube Defects
Clinical Features
Forebrain Anomalies
Posterior Fossa Anomalies
Syringomyelia and Hydromyelia
Perinatal Brain Injury
Trauma
Skull Fractures
Parenchymal Injuries
Concussion
Direct Parenchymal Injury
Diffuse Axonal Injury
Traumatic Vascular Injury
Epidural Hematoma
Subdural Hematoma
Clinical Features
Sequelae of Brain Trauma
Spinal Cord Injury
Cerebrovascular Disease
Hypoxia and Ischemia
Focal Cerebral Ischemia
Lacunar Infarcts
Clinical Features
Global Cerebral Hypoxia/Ischemia
Intracranial Hemorrhage
Intraparenchymal Hemorrhage
Clinical Features
Subarachnoid Hemorrhage and Ruptured Saccular Aneurysm
Pathogenesis
Clinical Features
Vascular Malformations
Clinical Features
Vascular Dementia
Infections
Acute Meningitis
Acute Pyogenic (Bacterial) Meningitis
Acute Aseptic (Viral) Meningitis
Acute Focal Suppurative Infections
Brain Abscess
Clinical Features
Subdural Empyema
Extradural Abscess
Chronic Bacterial Meningoencephalitis
Tuberculosis
Clinical Features
Neurosyphilis
Neuroborreliosis (Lyme Disease)
Viral Meningoencephalitis
Arthropod-Borne Viral Encephalitis
Herpes Simplex Virus Type 1
Herpes Simplex Virus Type 2
Varicella-Zoster Virus
Cytomegalovirus
Poliomyelitis
Clinical Features
Rabies
Clinical Features
Human Immunodeficiency Virus
Clinical Features
Progressive Multifocal Leukoencephalopathy
Fungal Meningoencephalitis
Other Infectious Diseases of the Nervous System
Demyelinating Diseases
Multiple Sclerosis (MS)
Pathogenesis
Clinical Features
Neuromyelitis Optica
Acute Disseminated Encephalomyelitis and Acute Necrotizing Hemorrhagic Encephalomyelitis
Central Pontine Myelinolysis
Neurodegenerative Diseases
Prion Diseases
Pathogenesis
Creutzfeldt-Jakob Disease (CJD)
Variant Creutzfeldt-Jakob Disease
Alzheimer Disease (AD)
Pathogenesis
Clinical Features
Frontotemporal Lobar Degenerations (FTLDs)
FTLD-tau
Pathogenesis
FTLD-TDP
Pathogenesis
Parkinson Disease (PD)
Pathogenesis
Dementia With Lewy Bodies
Atypical Parkinsonian Syndromes
Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)
Multiple System Atrophy (MSA)
Pathogenesis
Huntington Disease (HD)
Pathogenesis
Clinical Features
Spinocerebellar Degenerations
Spinocerebellar Ataxias (SCA)
Pathogenesis
Friedreich Ataxia
Ataxia-Telangiectasia
Clinical Features
Amyotrophic Lateral Sclerosis (ALS)
Pathogenesis
Clinical Features
Other Motor Neuron Diseases
Spinal and Bulbar Muscular Atrophy (Kennedy Disease)
Spinal Muscular Atrophy (SMA)
Genetic Metabolic Diseases
Neuronal Storage Diseases
Leukodystrophies
Mitochondrial Encephalomyopathies
Toxic and Acquired Metabolic Diseases
Vitamin Deficiencies
Thiamine (Vitamin B1) Deficiency
Vitamin B12 Deficiency
Neurologic Sequelae of Metabolic Disturbances
Hypoglycemia
Hyperglycemia
Hepatic Encephalopathy
Toxic Disorders
Carbon Monoxide
Ethanol
Radiation
Tumors
Gliomas
Astrocytoma
Infiltrating Astrocytomas (WHO Grades II to IV)
Pathogenesis
Clinical Features
Oligodendroglioma
Pathogenesis
Clinical Features
Pilocytic Astrocytoma
Ependymoma
Pathogenesis
Clinical Features
Choroid Plexus Tumors
Neuronal and Glioneuronal Tumors
Embryonal Neoplasms
Medulloblastoma
Pathogenesis
Clinical Features
Primary CNS Lymphoma
Meningiomas
Pathogenesis
Clinical Features
Metastatic Tumors
Paraneoplastic Syndromes
Familial Tumor Syndromes
Neurofibromatoses and Schwannomatosis
Tuberous Sclerosis Complex
Von Hippel-Lindau Disease
Acknowledgment
Suggested Readings
General
Response to Injury
Malformations and Developmental Diseases
Trauma
Cerebrovascular Disease
Infections
Demyelinating Diseases
Prion Diseases
Neurodegenerative Diseases
Genetic Metabolic Diseases
Tumors
29 The Eye
Chapter Contents
Orbit
Functional Anatomy and Proptosis
Thyroid Ophthalmopathy (Graves Disease)
Other Orbital Inflammatory Conditions
Neoplasms
Eyelid
Functional Anatomy
Neoplasms
Conjunctiva
Functional Anatomy
Conjunctival Scarring
Pinguecula and Pterygium
Neoplasms
Sclera
Cornea
Functional Anatomy
Keratitis and Ulcers
Corneal Degenerations and Dystrophies
Band Keratopathies
Keratoconus
Fuchs Endothelial Dystrophy
Anterior Segment
Functional Anatomy
Cataract
Anterior Segment and Glaucoma
Endophthalmitis and Panophthalmitis
Uvea
Uveitis
Neoplasms
Uveal Nevi and Melanomas
Epidemiology and Pathogenesis
Clinical Features
Retina and Vitreous
Functional Anatomy
Retinal Detachment
Retinal Vascular Disease
Hypertension
Diabetes Mellitus
Retinopathy of Prematurity (Retrolental Fibroplasia)
Sickle Retinopathy, Retinal Vasculitis, and Radiation Retinopathy
Retinal Artery and Vein Occlusions
Age-Related Macular Degeneration (AMD)
Other Retinal Degenerations
Retinitis Pigmentosa
Retinitis
Retinal Neoplasms
Retinoblastoma
Retinal Lymphoma
Optic Nerve
Anterior Ischemic Optic Neuropathy
Papilledema
Glaucomatous Optic Nerve Damage
Other Optic Neuropathies
Optic Neuritis
The End-Stage Eye: Phthisis Bulbi
Suggested Readings
Orbit
Eyelid and Conjunctiva
Cornea
Glaucoma
Uvea
Retina
Optic Nerve
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z