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Front Matter IFC PATHOLOGIC BASIS of VETERINARY DISEASE PATHOLOGIC BASIS of VETERINARY DISEASE Copyright Contributors Preface CONTENTS Fundamentals for Understanding Veterinary Pathology Diagnoses in Veterinary Pathology Language of Veterinary Pathology Recognition and Interpretation of Lesions Colors of Normal Tissues and Organs Evaluation of Lesions Affecting Tissues and Organs Diagnostic Pathology I - Cellular and Molecular Mechanisms of Disease (General Pathology) 1 - Mechanisms and Morphology of Cellular Injury, Adaptation, and Deatha Causes of Cell Injury Oxygen Deficiency Physical Agents Infectious Agents Nutritional Imbalances Genetic Derangement Workload Imbalance Chemicals, Drugs, and Toxins Immunologic Dysfunction Aging Reversible Cell Injury Acute Cell Swelling Mechanisms of Acute Cell Swelling Acute Cell Swelling Resulting from Hypoxic Injury Acute Cell Swelling Resulting from Specific Types of Cell Membrane Injury Carbon Tetrachloride and Cell Membrane Injury Molecules of the Immune System and Cell Membrane Injury. Cell membranes can also be injured directly by the membrane attack comp... Morphology of Acute Cell Swelling Gross Appearance. Acute cell swelling increases the volume and weight of parenchymal organs and imparts pallor to them. It is im... Microscopic Appearance. The influx of water in hydropic degeneration dilutes the cytosol, separates its organelles, and distends... Ultrastructural Appearance. Ultrastructurally, the acutely swollen epithelial cell loses plasma membrane structures, such as cil... Significance and Fate of Acute Cell Swelling Irreversible Cell Injury and Cell Death Cell Death Cell Death by Apoptosis Extrinsic Apoptosis. Extrinsic apoptosis (see Fig. 1.14) is triggered by alterations in the extracellular milieu and begins with... Intrinsic Apoptosis. The intrinsic or mitochondrial pathway of apoptosis (see Fig. 1.14) does not entail ligation of a cell surf... Morphologic Appearance of Apoptosis. Morphologically, apoptosis is a process of chromatin condensation (pyknosis) and nuclear fr... Cell Death by Oncosis (Oncotic Necrosis) Regulated Cell Death (RCD) with Morphologic Features of Necrosis. With the discovery that inhibition of caspases did not rescue ... Cell Membrane Injury Leading to Cell Death. The failure to restore mitochondrial function and repair cell membrane damage is a c... Free Radical Injury. A free radical is any molecule with an unpaired electron, including ROS and reactive nitrogen species (e.g.... Morphologic Appearance of Necrotic Cells and Tissues (Oncotic Necrosis). The appearance of necrotic cells depends on the type of... Morphologic Appearance of Postmortem Changes Chronic Cell Injury and Cell Adaptations Cellular Survival during Sublethal Ischemia or Involution Autophagy Adaptations That Change Cell Size, Number, or Appearance Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia Intracellular Accumulations Lipids Glycogen Proteins Defects in Protein Folding. Newly synthesized proteins are moved into the ER lumen for folding and addition of disulfide bonds b... Other Intracellular Inclusions Autophagic Vacuoles. Autophagy (see previous section) is a response to injury in which cell membranes envelop portions of the cy... Crystalline Protein Inclusions. Rhomboidal crystalline protein inclusions, also known as crystalloids (see Fig. 1.31, B), are co... Viral Inclusion Bodies. Some types of viruses produce characteristic intranuclear or cytoplasmic inclusion bodies. Certain DNA v... Lead Inclusions. In some cases of lead poisoning, intranuclear inclusions develop in renal tubular epithelial cells. The inclusi... Extracellular Accumulations Hyaline Substances Amyloid. Increasingly diseases are attributed to the misfolding of soluble and functional peptides or proteins, converting them ... Other Extracellular Accumulations Fibrinoid Change. Fibrinoid change is the result of leakage of plasma proteins, such as immunoglobulin, complement, or fibrin, i... Collagen (Fibrosis). Fibrosis is an excess in fibrous collagen, predominantly type I collagen, in the interstitium of organs or ... Fatty Infiltration. Fatty infiltration is an increase in the number and/or volume of adipocytes in the interstitium of an organ ... Gout Pseudogout Cholesterol. Cholesterol crystals are dissolved during histologic processing, leaving characteristic acicular (needle-shaped) cl... Pathologic Calcification Dystrophic Calcification Metastatic Calcification Heterotopic Ossification Pigments Exogenous Pigmented Substances Carbon and Other Dusts. Coal mine dust lung disease, also known as black lung, is the best-studied example of pneumoconiosis (lu... Carotenoid Pigments. Carotenoid pigments, such as β-carotene, are abundant in leafy green plants and impart a yellow coloration ... Tetracycline. The antibiotic tetracycline binds to calcium phosphate in teeth and bones. If administered to animals during the t... Nonhematogenous Endogenous Pigments Melanin. Melanin is the pigment responsible for the color of the hair, skin, and iris. It also colors the leptomeninges in sheep... Lipofuscin and Ceroid. Lipofuscin is a yellow-brown lipoprotein that accumulates as residual bodies in secondary lysosomes, espe... Hematogenous Pigments Hemoglobin. The hemoglobin molecule consists of four globular protein subunits, each folded around and tightly associated with a... Hematin. Hematin is a brown-black, Fe+3-containing pigment formed by the oxidation of hemoglobin Hemosiderin. Free iron is toxic to cells because it catalyzes the formation of ROS via the Fenton reaction. However, ferritin, a... Hematoidin. Hematoidin is a bright-yellow crystalline pigment that is derived from hemosiderin, presumably within macrophages, b... Bilirubin. Bilirubin is normally present in low amounts in the plasma as a breakdown product of erythrocytes (see Chapter 8, Hep... Porphyria. Porphyrias are heme synthesis disorders that result in deposition of porphyrin pigments in tissues. The porphyrin rin... Cell Cycle Cellular Aging Genetic Basis of Aging Telomeres Cellular Senescence Structural and Biochemical Changes with Cellular Aging Chromosome Structure and Function Nuclear Chromosomes Mitochondrial Chromosomes Gene Structure and Function Mechanisms of Genetic Disorders Single-Gene Disorders Single-Gene Disorders of Somatic Cells. Mutations that arise in somatic cells are not heritable but are important in the genesis... Single-Gene Disorders of Germ Cells. Mutations that affect germ cells are transmitted to the progeny and can give rise to inheri... Single-Gene Disorders of Mitochondria. Some single-gene disorders have a non-Mendelian pattern of inheritance and include disord... Chromosomal Disorders Errors in Cell Division. Most chromosomal disorders are caused by errors in cell division, which transfers the disorder within s... Numeric Alterations. Cells with normal chromosome numbers have euploid karyotypes (i.e., normal number of chromosomes for the sp... Structural Alterations. Changes in the structure of chromosomes are caused by deletion, inversion, duplication, or translocation... Complex Multigenic Disorders Components of Normal Cells and Their Vulnerabilities Cell Membranes (Cytocavitary Network) Second Messenger Systems. Cells are in continuous contact with a wide variety of extracellular molecules (see first messengers e... Cytosol versus Cytoplasm Nucleus Nucleolus. The nucleolus (see Fig. 1.1) is a non–membrane-bound structure within the nucleus that forms around chromosomal loci ... Rough Endoplasmic Reticulum Ribosomes. Ribosomes facilitate the synthesis of proteins in cells (i.e., translation) (see Figs. 1.1 and 1.3). Their function i... Golgi Complex Smooth Endoplasmic Reticulum Mitochondria Oxidative Phosphorylation Vaults Lysosomes and Peroxisomes Cytoskeleton: Microfilaments, Intermediate Filaments, and Microtubules Cellular Inclusions Intercellular Junctions and the Extracellular Matrix 2 - Vascular Disorders and Thrombosisa Rete Mirabile (plural, Retia Mirabilia) Microcirculation, Interstitium, and Cells Interstitium and Extracellular Matrix (ECM) Fluid Distribution and Homeostasis Abnormal Fluid Distribution Imbalance between Intracellular and Interstitial Compartments Imbalance between Intravascular and Interstitial Compartments (Edema) Mechanisms of Edema Formation Increased Microvascular Permeability Increased Intravascular Hydrostatic Pressure Decreased Intravascular Osmotic Pressure Decreased Lymphatic Drainage Morphologic Characteristics of Edema Hemostasis Hemostatic Process Primary Hemostasis Secondary Hemostasis Thrombolysis and Fibrinolysis Regulation of Hemostasis Coagulation Inhibitors Fibrinolytic Inhibitors Hemostasis and Other Host Responses Disorders of Hemostasis: Hemorrhage and Thrombosis Hemorrhage Thrombosis Normal Blood Flow, Distribution, and Perfusion Alterations in Blood Flow and Perfusion Increased Blood Flow Decreased Blood Flow Decreased Tissue Perfusion Shock Cardiogenic Shock Hypovolemic Shock Blood Maldistribution Stages and Progression of Shock Clinical and Morphologic Features of Shock 3 - Inflammation and Healinga Beneficial and Harmful Aspects of Inflammation Acute Inflammation Substances Inducing the Acute Inflammatory Response Fluidic (Exudative) Phase of the Acute Inflammatory Response Endothelial Cell Dynamics during the Acute Inflammatory Response Formation of Endothelial Cell Gaps Cellular Phase of the Acute Inflammatory Response Leukocyte Adhesion Cascade Leukocyte Adhesion Deficiencies Therapeutic Strategies to Modulate Leukocyte Infiltration Additional Regulation of Inflammation Inflammation and Pain Effector Cells of the Acute Inflammatory Response Neutrophils Eosinophils Basophils and Mast Cells Lymphocytes Natural Killer Cells and Natural Killer T Lymphocytes Plasma Cells Monocytes and Macrophages Vascular Endothelial Cells Chemical Mediators of the Acute Inflammatory Response Complement Cascade Arachidonic Acid Metabolites Prostaglandin Formation and Inhibition Leukotriene Formation and Inhibition Omega-3 Fatty Acids (Fish Oils) and Inhibition of Eicosanoid Activity Platelet-Activating Factor Cytokine Family Overview in Inflammation and Induction of CD4 TH Subsets Cytokine Receptors and Signaling Inflammatory Proteins Interferons. Interferons are glycoprotein cytokines produced by lymphocytes and many other cell types in response to viruses and... High Mobility Group Box Protein 1. High mobility group box protein 1 (HMGB-1) is a proinflammatory cytokine released by monocyte... Chemokines Classification of Chemokines Chemokine Receptors and Signaling Oxygen-Derived Free Radicals and Nitric Oxide Receptors for Exogenous and Endogenous Inflammatory Stimuli and Toll-Like Receptors Antimicrobial Peptides and Collectins Acute Phase Proteins Anti-inflammatory Mediators Summary of the Chemical Mediators of Acute Inflammation Reparative Phase of the Acute Inflammatory Response Outcomes of the Acute Inflammatory Response Nomenclature of the Inflammatory Response (Morphologic Diagnoses) Morphologic Classification of Exudates in Acute Inflammatory Lesions Serous Inflammation Catarrhal Inflammation Fibrinous Inflammation Suppurative Inflammation Chronic Inflammation Beneficial and Harmful Aspects of Chronic Inflammation Progression of the Acute Inflammatory Response to Chronic Inflammation, Fibrosis, and Abscess Formation Progression to Chronic/Granulomatous Inflammation Healing by Fibrosis Abscess Formation Granulomatous Inflammation and Granuloma Formation Nodular (Tuberculoid) Granulomas (TH1-Biased Granulomas) Diffuse (Lepromatous) Granulomas (TH2-Biased Granulomas) Sarcoids of Horses Eosinophilic Granulomas Other Chronic Inflammatory/Granulomatous Conditions Gross and Microscopic Lesions and Nomenclature of the Chronic Inflammatory Response Effector Cells and Cellular Mechanisms of Chronic Inflammatory Responses Lymphocytes Innate Lymphoid Cells γ/δ T Lymphocytes α/β T Lymphocytes (CD4/CD8) TH1, TH2, TH17, and T reg Immunologic Responses Monocytes/Macrophages Epithelium Mononuclear Cell Maturation and Trafficking in the Chronic Inflammatory Response Formation of Epithelioid Macrophages and Multinucleated Giant Cells (MGCs) Dendritic Cells Dendritic Cell Trafficking B Lymphocytes Plasma Cells Eosinophils Mast Cells Natural Killer Cells and Natural Killer T Lymphocytes Fibroblasts Endothelial Cells Platelets Trafficking of Naïve and Activated T and B Lymphocytes Homing of Naïve Lymphocytes via High Endothelial Venules Adherence and Transendothelial Migration of Activated T Lymphocytes Inflammation and the Sensation of Pain The Effect of Inflammation on the Febrile Response and Other Activities Unique Types of Inflammation Septicemia and Endotoxic Shock Septicemia Septic (Endotoxic) Shock Cytologic and Histologic Comparisons of Inflammatory Exudates Wound Healing and Angiogenesis First and Second Intention Healing First Intention Healing Second Intention Healing Impaired Wound Healing Expression of Genes Responsible for Wound Repair Degradation of Cells and Tissue Components in Wounds Degradation of the Extracellular Matrix (Interstitium) in Wounds Resynthesis of the Extracellular Matrix (Interstitium) with Wound Healing Synthesis of Collagen and Matrix Proteins Collagen Production by Fibroblasts Synthesis of Proteoglycans Fibroblasts and the Mechanistic Basis of Fibrosis Synthetic Matrices Morphology of Granulation Tissue and Fibrous Connective Tissue Granulation Tissue Hypertrophic Scars. Hypertrophic scars occur as a result of exuberant proliferation of fibroblasts and collagen in wounds that f... Fibrous Connective Tissue Wound Contraction The Scirrhous Reaction Myofibroblasts. Myofibroblasts are specialized fibroblasts with contractile activity. They form within wounds in response to tis... Angiogenesis in Wound Repair Initiation of Endothelial Cell Proliferation Endothelial Cell Growth Factors. The formation of new blood vessels in wounds begins from the proliferation of endothelial cell ... Endothelial Cell Migration Is Mediated by Integrins. Newly formed endothelial cells and fibroblasts migrate into wound sites and... Vascular Remodeling. Once blood vessels are initially formed, they are loosely arranged and require remodeling to become mature.... Regulators/Inhibitors of Endothelial Cell Growth. Inhibitors of angiogenesis are produced by endothelial cells, macrophages, and... Epithelialization in Wound Repair Intact Basement Membranes Enhance Reepithelialization Initiation of Cell Proliferation in Epithelia Senescent Cells Differentiation of Epithelia Remodeling Metaplasia in Wound Repair 4 - Mechanisms of Microbial Infectionsa Portals of Entry Portal of Entry: Alimentary System (Ingestion) Portal of Entry: Respiratory System (Inhalation) Portal of Entry: Urogenital System (Ascending Infection) Portal of Entry: Skin (Direct Contact and Cutaneous Penetration) Portal of Entry: Ear and Eye (Direct Contact and Cutaneous Penetration) Target Cells and Substances Epithelial Cells as Microbial Targets Mucosa-Associated Lymphoid Tissues as Microbial Targets Biologic Substances as Microbial Targets Pathways of Spread Mechanisms Used to Colonize Mucosae (or Biologic Substances) at Portals of Entry Colonize Mucus (Goblet Cells) Colonize Cilia (or Microvilli) of Mucosal Epithelial Cells Colonize the Cell (Endocytosis) Mechanisms Used to Cross Mucosae at Portals of Entry M Cell Entry Transcytosis and Endocytosis/Exocytosis Intercellular Direct Entry (Motility) Non–M Cell Transcytosis Entry Cell Polarity. In the alimentary and respiratory systems (and likely in other mucosae), the surface of an epithelial cell locate... Dendritic Cell Entry Leukocyte “Trojan Horse” Entry Nerve Ending Entry Mechanisms Used to Spread Systemically Defense Mechanisms Barrier Systems Structural (Physical) Barriers Functional (Biologic) Barriers Mucus Layer. Mucosae of the alimentary and respiratory systems are covered by a protective mucous gel composed predominantly of ... Immune System Innate and Adaptive Immune Responses Monocyte-Macrophage System Dendritic Cells Phagosome-Lysosome Fusion Genetic Resistance of Animals to Infectious Diseases Disorders of Barrier Systems Disorders of the Innate Immune Response Disorders of the Adaptive Immune Response Bacterial Diseases Morphology of Bacteria Pathogenicity Initial Encounters at Portals of Entry Adhesion, Colonization, Invasiveness, and Toxigenesis Adhesion, Colonization, and Invasiveness Toxigenesis (Toxins) Exotoxins and Lipoteichoic Acid. Exotoxins (usually from Gram-positive bacteria) are secreted from viable bacteria and are poten... Endotoxins. Gram-negative bacteria, such as E. coli, Salmonella spp., Pseudomonas spp., Haemophilus spp., and Bordetella spp. ca... Other Virulence Factors Secretion Systems. Secretion systems, of which nine types (type I to IX; aka: T1SS–T9SS) have been described, are bacterial orga... Siderophores. Some bacteria require iron for colonization of mucosae. Iron is plentiful in cells but unavailable to bacteria bec... Biofilms/Intracellular Bacterial Communities. Bacterial coloni­zation can occur through virulence factors that form an exopolysa... Capsules. Bacterial capsules are virulence factors that protect bacteria from phagocytosis by cells such as neutrophils and macr... Role of Bacterial Genes in Susceptibility and/or Resistance to Disease Virulence Factors Antibiotic Resistance Bacterial Gene Transfer Vertical Gene Transfer. Vertical gene transfer is the process through which bacteria pass virulence factors such as antibiotic r... Horizontal Gene Transfer. Bacteria can also transfer genes (e.g., antibiotic resistance genes) between variably related bacteria... Mechanisms of Genomic Change Bacterial Diseases of Organ Systems Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity E-Table 4.3 E-Table 4.3 E-Table 4.3 Hepatobiliary System and Exocrine Pancreas Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae Cardiovascular System and Lymphatic Vessels Urinary System Bone Marrow, Blood Cells, and Lymphoid/Lymphatic System Nervous System Skeletal Muscle Bone, Joints, Tendons, and Ligaments Integumentary System Female Reproductive System and Mammae Male Reproductive System Viral Diseases Morphology of Viruses Target Cells Viral Pathogenicity and Replication Cycle Virulence Factors Mechanisms of Genomic Change Defense Mechanisms Viral Diseases of Organ Systems Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity Hepatobiliary System and Exocrine Pancreas Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae Cardiovascular System and Lymphatic Vessels Bone Marrow, Blood Cells, and Lymphoid/Lymphatic System Nervous System Bone, Joints, Ligaments, and Tendons Integumentary System Female Reproductive System and Mammae Male Reproductive System The Eye Fungal Diseases (Mycoses) Morphology of Fungi Fungal Diseases of Organ Systems Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae Cardiovascular System and Lymphatic Vessels Nervous System Protozoan Diseases Morphology of Protozoa Protozoan Diseases of Organ Systems Nervous System Female Reproductive System and Mammae Prion Diseases (Spongiform Encephalopathies) Morphology of Prion Particles (Spongiform Encephalopathies) Prion Diseases of Organ Systems 5 - Diseases of Immunitya Innate Immunity (Nonspecific Immunity) Recognition Molecules of Innate Immunity (Pathogen-Associated Molecular Patterns) Toll-Like Receptors Adaptive Immunity (Specific Immunity) Cells and Tissues of the Immune System Lymphoid Tissues Innate Lymphoid Cells (ILCs) T Lymphocytes B Lymphocytes Mononuclear Phagocytic System (Monocyte-Macrophage System) Macrophages Dendritic Cells Natural Killer Cells Cytokines: Messenger Molecules of the Immune System General Properties of Cytokines Structure and Function of Histocompatibility Antigens Disorders of the Immune System Mechanisms of Immunologic Tissue Injury: Hypersensitivity Reactions Type I Hypersensitivity (Immediate Hypersensitivity) Systemic Type I Hypersensitivity (Anaphylaxis). Anaphylaxis refers to an acute systemic hypersensitivity reaction to an antigen ... Localized Type I Hypersensitivity. In a localized type I hypersensitivity reaction, the clinical signs and pathologic findings a... Type II Hypersensitivity (Cytotoxic Hypersensitivity) Type III Hypersensitivity (Immune Complex Hypersensitivity) Localized Type III Hypersensitivity. Localized type III hypersensitivity reactions are best exemplified by the Arthus reaction (... Generalized Type III Hypersensitivity. When antigen is present in the circulation at appropriate concentrations relative to circ... Type IV Hypersensitivity (Delayed-Type Hypersensitivity) Cytokine-Related Diseases Transplant Rejection General Features of Autoimmune Disease Immunologic Tolerance Mechanisms of Autoimmunity Failure of Peripheral Tolerance Genetic Factors in Autoimmunity Central Tolerance. Central tolerance occurs during T lymphocyte development in the thymus, in which self-reactive T lymphocytes ... Peripheral Tolerance. In peripheral tolerance, self-reactive T lymphocytes that are not eliminated as a result of negative selec... Microbial Agents in Autoimmunity Specific Autoimmune Diseases Systemic Lupus Erythematosus Etiology and Pathogenesis. The cause of SLE remains undetermined, although the presence of autoantibodies directed against a num... Lesions of Systemic Lupus Erythematosus. A wide spectrum of morphologic lesions are associated with canine SLE. The most common ... Genetic Factors. SLE in human beings is characterized as a disease with a complex genetic component with MHC and multiple non-MH... Environmental Factors. In addition to the genetic factors, SLE in human beings has also been associated with a number of environ... Immunologic Factors. As discussed previously, SLE is characterized by a number of immunologic abnormalities and is clinically no... Rheumatoid Arthritis Sjögren-Like Syndrome Etiology and Pathogenesis. The keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) result from the lymphocytic infi... Clinical Signs and Lesions. Dogs with Sjögren-like syndrome have an adult onset of conjunctivitis and keratitis. Other findings ... Inflammatory Myopathies Dermatomyositis. Dermatomyositis is an inflammatory disease of the skin, muscles, and vasculature affecting primarily young dogs... Vasculitis Clinical Signs and Immunologic Abnormalities. The classic presentation is a febrile (104° F to 107° F) young dog with anorexia, ... Lesions. Severe necrotizing vasculitis and perivasculitis with thrombosis of small- to medium-sized blood vessels in the leptome... Immunodeficiency Syndromes Primary Immunodeficiencies Primary Immunodeficiencies of Specific Immunity Severe Combined Immunodeficiency Disease. Severe combined immunodeficiency disease (SCID) is a family of genetic defects that ha... Common Variable Immunodeficiency. Common variable immunodeficiency is a primary immunodeficiency disease characterized by an adu... Agammaglobulinemia. Agammaglobulinemia is a primary immunodeficiency characterized by an inability to produce immunoglobulins an... Selective Immunoglobulin Deficiencies. Selective deficiencies are represented by several diseases characterized by a deficiency ... Thymic Hypoplasia. Thymic hypoplasia represents several immunodeficiency diseases characterized by a failure to develop a functi... Primary Immunodeficiencies of Nonspecific Immunity Deficiencies of the Complement System. The complement system contains more than 30 soluble and cell-bound proteins that influenc... Chédiak-Higashi Syndrome. Chédiak-Higashi syndrome is an inherited disease caused by defective lysosomes, melanosomes, platelet-... Leukocyte Adhesion Deficiency. Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency disease characterized by the in... Immune Checkpoints in Immunity and Cancer Amyloidosis Pathogenesis of Amyloidosis Chemical Nature of Amyloid Classification of Amyloidosis Primary Amyloidosis. Primary amyloidosis is the most common systemic form of amyloidosis in human beings and is of the AL type. ... Reactive Systemic Amyloidosis. Reactive systemic amyloidosis is the most common form in animals. This form of amyloidosis has a ... Familial Amyloidosis. Familial amyloidosis is a systemic form of AA amyloidosis that is hereditary in some breeds of cats and do... Localized Amyloidosis. Occasionally, amyloid deposits are limited to a single organ or tissue. In many instances, the localized ... Endocrine Amyloidosis. Deposition of amyloid in the pancreas of cats, nonhuman primates (macaques and baboons), and human beings... Amyloid of Aging. Amyloid deposition can occur as an age-related change in a number of organ systems. Similar to senile systemic... Morphology of Amyloidosis 6 - Neoplasia and Tumor Biologya Tumor Characteristics (Essential Concept 6.1) Benign Versus Malignant Tumors Differentiation of Tumors Gross Patterns of Tumor Growth Microscopic Tumor Morphology Tumor Cell Function Differentiation Therapy Tumor Cell Proliferation and Death Tumor Growth Cell Division Cell Senescence and Death Senescence. Senescent cells are somatic cells that can no longer divide; these cells stop dividing through a mechanism called re... Apoptosis. Apoptosis is a form of “programmed cell death” that serves both as a normal physiologic process and as a response to ... Autophagy. Autophagy refers to degradation of a cell’s own organelles within autophagosomes (see Fig. 1.24). Autophagy can be a ... Neoplastic Transformation (Essential Concept 6.2) Latency Stepwise Tumor Development Initiation Promotion Progression Tumor Heterogeneity and Clonal Selection Stem Cells and Cancer Tumor Microenvironment (Essential Concept 6.3) Tumor Stroma Composition of the Stroma Tumor-Stromal Interactions Angiogenesis Inflammation Tumor Immunity (see Essential Concept 6.3) Immunosurveillance Tumor Antigens Antitumor Effector Mechanisms Natural Killer Cells Macrophages T Lymphocytes B Lymphocytes Evasion of the Immune Response Altered Major Histocompatibility Complex Expression Antigen Masking Tolerance Immunosuppression Tumor Immunotherapy Tumor Dissemination (Essential Concept 6.4) Significance of Tumor Metastasis Mechanisms of Tumor Invasion and Metastasis Adhesion Migration Stromal Invasion Epithelial-Mesenchymal Transition Intravasation Tumor Emboli Extravasation Pathways of Tumor Spread Lymphatic Spread Hematogenous Spread Transcoelomic Spread Transmissible Tumors Metastasis Suppression Systemic Clinical Effects on the Animal (see Essential Concept 6.3) Direct Effects Paraneoplastic Effects Cachexia Endocrinopathies Endocrine Tumors. A functioning endocrine tumor produces the hormonal products of the tissue of origin. For example, thyroid fol... Nonendocrine Tumors. A variety of nonendocrine neoplasms may also produce hormonally active substances not normally found in the... Skeletal Syndromes Vascular and Hematologic Syndromes Additional Neoplastic Syndromes Neurologic Syndromes. Paraneoplastic neurologic disease in veterinary cancer patients is usually related to hypercalcemia, hypog... Cutaneous Syndromes. There are only a few reports of cutaneous manifestations of paraneoplastic disease in dogs and cats. Clinic... Miscellaneous Syndromes. Mast cell tumors are very common in dogs. Release of excess histamine from the neoplastic mast cells ca... Heritable Alterations in Cancer (Essential Concept 6.5) Genetic Changes in Cancer Point Mutations DNA Strand Breaks Insertions and Deletions Amplifications Aneuploidy Chromosomal Instability Germline Mutations and Cancer Syndromes Acquired Somatic Mutations and Sporadic Cancers Epigenetic Changes in Cancer DNA Methylation Histone Modification Imprinting Noncoding RNAs and Cancer Molecular Determinants of Cancer Oncogenes Tumor Suppressor Genes Modifier Genes Defects in DNA Repair Multistage Carcinogenesis Therapeutic Implications Mechanisms of Carcinogenesis Intrinsic Factors Extrinsic Factors Chemicals Radiation Viruses Dominant Oncogene Mechanism. The genomes of many rapidly transforming oncogenic viruses include a dominant oncogene that drives ... Insertional Mutagenesis Mechanism. Viruses that do not carry their own oncogenes can instead activate the expression of oncogene... Hit-and-Run Mechanism. In the two mechanisms discussed previously, the viral genome or portions of it persist in the infected ce... Indirect Mechanisms. Viruses may also stimulate tumorigenesis by suppression of the animal’s immune system or by stimulation of ... Cancer in Animals Naturally Occurring Tumors Animal Models of Cancer Experimentally Induced Tumors in Laboratory Animals Tumor Diagnosis and Prognosis Cytologic Tumor Diagnosis Limitations of Cytology. Cytology samples are generally easy to collect and often provide useful information to the clinician, b... Cytologic Evaluation of Malignant Potential. As tissue architecture cannot be assessed cytologically, cytologic estimation of th... Cytologic Categories of Neoplasia. As with histopathology, neoplastic cells are categorized as epithelial, mesenchymal, or round... Cytomorphology and Histomorphology of Selected Neoplasms. The goal of this section is to compare and illustrate the morphologic ... Histopathologic Tumor Diagnosis Sample Collection for Histopathologic Tumor Evaluation. For optimal sample quality, regions of inflammation, hemorrhage, necrosi... Histopathologic Evaluation of Tumors. Biopsy specimens undergo extensive processing; ultimately a 3- to 5-μm thick section of ti... Surgical Margin Evaluation Grading Staging Miscellaneous Techniques in Tumor Diagnosis Clonality Assays. Sometimes it is difficult to distinguish benign lymphoid hyperplasia from lymphoma by morphologic features alo... Flow Cytometry. Flow cytometry is a method available through many academic or commercial veterinary diagnostic laboratori