1. Front ..........................................................................................................................13

1.1 Cover .......................................................................................................................13

1.2 About This Book ......................................................................................................183

1.3 Frontmatter ..............................................................................................................183

1.4 Copyright .................................................................................................................185

1.5 Dedication ...............................................................................................................186

1.6 Contributors .............................................................................................................186

1.7 Preface: The Golden Jubilee Edition ......................................................................188

1.8 Acknowledgments ....................................................................................................190

2. I. General Pathology ...................................................................................................192

2.1 1. Cellular Responses to Stress & Toxic Insults: Adaptation, Injury & Death ............192

2.1.1 Introduction to Pathology .......................................................................................192

2.1.2 Overview: Cellular Responses to Stress & Noxious Stimuli ..................................193

2.1.3 Adaptations of Cellular Growth & Differentiation ....................................................196

2.1.4 Overview of Cell Injury & Cell Death ......................................................................204

2.1.5 Causes of Cell Injury ..............................................................................................204

2.1.6 Morphologic Alterations in Cell Injury .....................................................................206

2.1.7 Mechanisms of Cell Injury ......................................................................................216

2.1.8 Clinico-Pathologic Correlations: Selected Examples of Cell Injury & Necrosis .....228

2.1.9 Apoptosis ...............................................................................................................231

2.1.10 Autophagy ...........................................................................................................243

2.1.11 Intracellular Accumulations .................................................................................. 244

2.1.12 Pathologic Calcification ........................................................................................253

2.1.13 Cellular Aging .......................................................................................................255

2.1.14 References .................................................................................................................................................. 258

2.2 2. Acute & Chronic Inflammation ......................................................................................................................... 260

2.2.1 Overview of Inflammation .............................................................................................................................. 260

2.2.2 Historical Highlights ....................................................................................................................................... 261

2.2.3 Acute Inflammation ........................................................................................................................................ 262

2.2.4 Mediators of Inflammation ............................................................................................................................. 281

2.2.5 Outcomes of Acute Inflammation .................................................................................................................. 297

2.2.6 Morphologic Patterns of Acute Inflammation ................................................................................................ 298

2.2.7 Summary of Acute Inflammation ................................................................................................................... 301

2.2.8 Chronic Inflammation .................................................................................................................................... 302

2.2.9 Systemic Effects of Inflammation .................................................................................................................. 311

2.2.10 Consequences of Defective or Excessive Inflammation ............................................................................. 312

2.2.11 References .................................................................................................................................................. 312

2.3 3. Tissue Renewal, Regeneration & Repair ......................................................................................................... 314

2.3.1 Control of Normal Cell Proliferation & Tissue Growth ................................................................................... 314

2.3.2 Cell Cycle & the Regulation of Cell Replication ............................................................................................ 326

2.3.3 Mechanisms of Tissue & Organ Regeneration ............................................................................................. 336

2.3.4 Extracellular Matrix & Cell-Matrix Interactions .............................................................................................. 338

2.3.5 Healing by Repair, Scar Formation & Fibrosis .............................................................................................. 345

2.3.6 References .................................................................................................................................................... 360

2.4 4. Hemodynamic Disorders, Thromboembolic Disease & Shock ........................................................................ 362

2.4.1 Edema ........................................................................................................................................................... 362

2.4.2 Hyperemia & Congestion .............................................................................................................................. 367

2.4.3 Hemorrhage .................................................................................................................................................. 368

2.4.4 Hemostasis & Thrombosis ............................................................................................................................ 369

2.4.5 Embolism ....................................................................................................................................................... 387

2.4.6 Infarction ........................................................................................................................................................ 391

2.4.7 Shock ............................................................................................................................................................. 395

2.4.8 References .................................................................................................................................................... 400

2.5 5. Genetic Disorders ............................................................................................................................................ 401

2.5.1 Human Genetic Architecture ......................................................................................................................... 401

2.5.2 Genes & Human Diseases ............................................................................................................................ 404

2.5.3 Mendelian Disorders ..................................................................................................................................... 409

2.5.4 Complex Multigenic Disorders....................................................................................................................... 441

2.5.5 Chromosomal Disorders ................................................................................................................................ 441

2.5.6 Single-Gene Disorders with Nonclassic Inheritance ..................................................................................... 455

2.5.7 Molecular Diagnosis of Genetic Diseases ..................................................................................................... 465

2.5.8 References .................................................................................................................................................... 478

2.6 6. Diseases of the Immune System ..................................................................................................................... 480

2.6.1 The Normal Immune Response .................................................................................................................... 480

2.6.2 Hypersensitivity & Autoimmune Disorders .................................................................................................... 503

2.6.3 Rejection of Tissue Transplants .................................................................................................................... 556

2.6.4 Immunodeficiency Syndromes ...................................................................................................................... 562

2.6.5 Amyloidosis ................................................................................................................................................... 592

2.6.6 References .................................................................................................................................................... 602

2.7 7. Neoplasia ......................................................................................................................................................... 606

2.7.1 Nomenclature ................................................................................................................................................ 606

2.7.2 Characteristics of Benign & Malignant Neoplasms ....................................................................................... 611

2.7.3 Epidemiology ................................................................................................................................................. 630

2.7.4 Molecular Basis of Cancer ............................................................................................................................ 639

2.7.5 Molecular Basis of Multistep Carcinogenesis................................................................................................ 691

2.7.6 Carcinogenic Agents & Their Cellular Interactions ....................................................................................... 692

2.7.7 Host Defense against Tumors: Tumor Immunity........................................................................................... 705

2.7.8 Clinical Aspects of Neoplasia ........................................................................................................................ 711

2.7.9 References .................................................................................................................................................... 724

2.8 8. Infectious Diseases .......................................................................................................................................... 729

2.8.1 General Principles of Microbial Pathogenesis............................................................................................... 729

2.8.2 Viral Infections ............................................................................................................................................... 758

2.8.3 Bacterial Infections ........................................................................................................................................ 775

2.8.4 Fungal Infections ........................................................................................................................................... 826

2.8.5 Parasitic Infections ........................................................................................................................................ 833

2.8.6 References .................................................................................................................................................... 855

2.9 9. Environmental & Nutritional Diseases ............................................................................................................. 858

2.9.1 The Global Burden of Disease ...................................................................................................................... 858

2.9.2 Health Effects of Climate Change ................................................................................................................. 860

2.9.3 Toxicity of Chemical & Physical Agents ........................................................................................................ 862

2.9.4 Environmental Pollution ................................................................................................................................. 864

2.9.5 Occupational Health Risks: Industrial & Agricultural Exposures ................................................................... 873

2.9.6 Effects of Tobacco ......................................................................................................................................... 875

2.9.7 Effects of Alcohol ........................................................................................................................................... 881

2.9.8 Injury by Therapeutic Drugs & Drugs of Abuse ............................................................................................. 885

2.9.9 Injury by Physical Agents .............................................................................................................................. 895

2.9.10 Nutritional Diseases .................................................................................................................................... 909

2.9.11 References .................................................................................................................................................. 937

2.10 10. Diseases of Infancy & Childhood ................................................................................................................. 939

2.10.1 Congenital Anomalies ................................................................................................................................. 939

2.10.2 Disorders of Prematurity .............................................................................................................................. 951

2.10.3 Perinatal Infections ...................................................................................................................................... 960

2.10.4 Fetal Hydrops .............................................................................................................................................. 961

2.10.5 Inborn Errors of Metabolism & Other Genetic Disorders ............................................................................ 968

2.10.6 Sudden Infant Death Syndrome (SIDS) ...................................................................................................... 984

2.10.7 Tumors & Tumor-like Lesions of Infancy & Childhood ................................................................................ 987

2.10.8 References ................................................................................................................................................ 1004

3. II. Systemic Pathology: Diseases of Organ Systems .............................................................................................. 1007

3.1 11. Blood Vessels .............................................................................................................................................. 1007

3.1.1 The Structure & Function of Blood Vessels ................................................................................................ 1007

3.1.2 Vessel Development, Growth & Remodeling .............................................................................................. 1009

3.1.3 Congenital Anomalies ................................................................................................................................. 1009

3.1.4 Vascular Wall Cells & Their Response to Injury.......................................................................................... 1010

3.1.5 Hypertensive Vascular Disease .................................................................................................................. 1014

3.1.6 Arteriosclerosis ............................................................................................................................................ 1019

3.1.7 Atherosclerosis ............................................................................................................................................ 1020

3.1.8 Aneurysms & Dissection ............................................................................................................................. 1035

3.1.9 Vasculitis ..................................................................................................................................................... 1043

3.1.10 Raynaud Phenomenon.............................................................................................................................. 1055

3.1.11 Veins & Lymphatics ................................................................................................................................... 1056

3.1.12 Tumors ...................................................................................................................................................... 1059

3.1.13 Pathology of Vascular Interventions .......................................................................................................... 1068

3.1.14 References ................................................................................................................................................ 1071

3.2 12. The Heart ..................................................................................................................................................... 1073

3.2.1 Cardiac Structure & Specializations ............................................................................................................ 1073

3.2.2 Effects of Aging on the Heart ...................................................................................................................... 1076

3.2.3 Heart Disease: Overview of Pathophysiology ............................................................................................. 1077

3.2.4 Heart Failure ................................................................................................................................................ 1077

3.2.5 Congenital Heart Disease ........................................................................................................................... 1085

3.2.6 Ischemic Heart Disease .............................................................................................................................. 1099

3.2.7 Hypertensive Heart Disease........................................................................................................................ 1123

3.2.8 Valvular Heart Disease ................................................................................................................................ 1126

3.2.9 Cardiomyopathies ....................................................................................................................................... 1142

3.2.10 Pericardial Disease ................................................................................................................................... 1159

3.2.11 Tumors of the Heart .................................................................................................................................. 1164

3.2.12 Cardiac Transplantation ............................................................................................................................ 1167

3.2.13 References ................................................................................................................................................ 1168

3.3 13. Diseases of White Blood Cells, Lymph Nodes, Spleen & Thymus .............................................................. 1171

3.3.1 Development & Maintenance of Hematopoietic Tissues ............................................................................ 1171

3.3.2 Disorders of White Cells .............................................................................................................................. 1174

3.3.2.1 Leukopenia ........................................................................................................................................... 1175

3.3.2.2 Reactive (Inflammatory) Proliferations of White Cells & Lymph Nodes ............................................... 1176

3.3.2.3 Neoplastic Proliferations of White Cells ................................................................................................ 1182

3.3.3 Spleen ......................................................................................................................................................... 1249

3.3.3.1 Splenomegaly ....................................................................................................................................... 1251

3.3.3.2 Neoplasms ............................................................................................................................................ 1254

3.3.3.3 Congenital Anomalies ........................................................................................................................... 1254

3.3.3.4 Rupture ................................................................................................................................................. 1254

3.3.4 Thymus ........................................................................................................................................................ 1254

3.3.4.1 Developmental Disorders ..................................................................................................................... 1255

3.3.4.2 Thymic Hyperplasia .............................................................................................................................. 1255

3.3.4.3 Thymomas ............................................................................................................................................ 1255

3.3.5 References .................................................................................................................................................. 1257

3.4 14. Red Blood Cell & Bleeding Disorders .......................................................................................................... 1259

3.4.1 Anemias....................................................................................................................................................... 1259

3.4.2 Polycythemia ............................................................................................................................................... 1312

3.4.3 Bleeding Disorders: Hemorrhagic Diatheses .............................................................................................. 1313

3.4.4 References .................................................................................................................................................. 1327

3.5 15. The Lung ...................................................................................................................................................... 1328

3.5.1 Congenital Anomalies ................................................................................................................................. 1328

3.5.2 Atelectasis (Collapse) .................................................................................................................................. 1332

3.5.3 Pulmonary Edema ....................................................................................................................................... 1334

3.5.4 Acute Lung Injury & Acute Respiratory Distress Syndrome (Diffuse Alveolar Damage) ............................ 1335

3.5.5 Obstructive versus Restrictive Pulmonary Diseases .................................................................................. 1340

3.5.6 Obstructive Pulmonary Diseases ................................................................................................................ 1340

3.5.7 Chronic Diffuse Interstitial (Restrictive) Diseases ....................................................................................... 1359

3.5.8 Diseases of Vascular Origin ........................................................................................................................ 1384

3.5.9 Pulmonary Infections ................................................................................................................................... 1395

3.5.10 Lung Transplantation ................................................................................................................................. 1413

3.5.11 Tumors ...................................................................................................................................................... 1415

3.5.12 Pleura ........................................................................................................................................................ 1435

3.5.13 References ................................................................................................................................................ 1442

3.6 16. Head & Neck ................................................................................................................................................ 1446

3.6.1 Oral Cavity ................................................................................................................................................... 1446

3.6.1.1 Teeth & Supporting Structures ............................................................................................................. 1447

3.6.1.2 Inflammatory/Reactive Tumor-like Lesions .......................................................................................... 1449

3.6.1.3 Infections .............................................................................................................................................. 1453

3.6.1.4 Oral Manifestations of Systemic Disease ............................................................................................. 1454

3.6.1.5 Tumors & Precancerous Lesions ......................................................................................................... 1455

3.6.1.6 Odontogenic Cysts & Tumors ............................................................................................................... 1461

3.6.2 Upper Airways ............................................................................................................................................. 1463

3.6.2.1 Nose...................................................................................................................................................... 1463

3.6.2.2 Nasopharynx ......................................................................................................................................... 1466

3.6.2.3 Tumors of the Nose, Sinuses & Nasopharynx ..................................................................................... 1467

3.6.2.4 Larynx ................................................................................................................................................... 1470

3.6.3 Ears ............................................................................................................................................................. 1473

3.6.3.1 Inflammatory Lesions ............................................................................................................................ 1473

3.6.3.2 Otosclerosis .......................................................................................................................................... 1473

3.6.3.3 Tumors .................................................................................................................................................. 1474

3.6.4 Neck ............................................................................................................................................................ 1474

3.6.4.1 Branchial Cyst (Cervical Lymphoepithelial Cyst) .................................................................................. 1474

3.6.4.2 Thyroglossal Duct Cyst ......................................................................................................................... 1474

3.6.4.3 Paraganglioma (Carotid Body Tumor) .................................................................................................. 1475

3.6.5 Salivary Glands ........................................................................................................................................... 1477

3.6.5.1 Xerostomia ............................................................................................................................................ 1477

3.6.5.2 Inflammation (Sialadenitis) ................................................................................................................... 1477

3.6.5.3 Neoplasms ............................................................................................................................................ 1478

3.6.6 References .................................................................................................................................................. 1484

3.7 17. The Gastrointestinal Tract ............................................................................................................................ 1486

3.7.1 Congenital Abnormalities ............................................................................................................................ 1486

3.7.1.1 Atresia, Fistulae & Duplications ............................................................................................................ 1486

3.7.1.2 Diaphragmatic Hernia, Omphalocele & Gastroschisis ......................................................................... 1487

3.7.1.3 Ectopia .................................................................................................................................................. 1488

3.7.1.4 Meckel Diverticulum .............................................................................................................................. 1488

3.7.1.5 Pyloric Stenosis .................................................................................................................................... 1489

3.7.1.6 Hirschsprung Disease ........................................................................................................................... 1489

3.7.2 Esophagus .................................................................................................................................................. 1491

3.7.2.1 Esophageal Obstruction ....................................................................................................................... 1492

3.7.2.2 Esophagitis ........................................................................................................................................... 1493

3.7.2.3 Barrett Esophagus ................................................................................................................................ 1497

3.7.2.4 Esophageal Tumors .............................................................................................................................. 1502

3.7.3 Stomach ...................................................................................................................................................... 1506

3.7.3.1 Acute Gastritis ...................................................................................................................................... 1506

3.7.3.2 Chronic Gastritis ................................................................................................................................... 1509

3.7.3.3 Complications of Chronic Gastritis ....................................................................................................... 1517

3.7.3.4 Hypertrophic Gastropathies .................................................................................................................. 1520

3.7.3.5 Gastric Polyps & Tumors ...................................................................................................................... 1523

3.7.4 Small Intestine & Colon ............................................................................................................................... 1536

3.7.4.1 Intestinal Obstruction ............................................................................................................................ 1536

3.7.4.2 Ischemic Bowel Disease ....................................................................................................................... 1539

3.7.4.3 Angiodysplasia ...................................................................................................................................... 1542

3.7.4.4 Malabsorption & Diarrhea ..................................................................................................................... 1542

3.7.4.5 Infectious Enterocolitis .......................................................................................................................... 1548

3.7.4.6 Irritable Bowel Syndrome...................................................................................................................... 1565

3.7.4.7 Inflammatory Bowel Disease ................................................................................................................ 1566

3.7.4.8 Other Causes of Chronic Colitis ........................................................................................................... 1578

3.7.4.9 Sigmoid Diverticulitis ............................................................................................................................. 1580

3.7.4.10 Polyps ................................................................................................................................................. 1582

3.7.4.11 Familial Syndromes ............................................................................................................................ 1593

3.7.4.12 Adenocarcinoma ................................................................................................................................. 1595

3.7.4.13 Tumors of the Anal Canal ................................................................................................................... 1602

3.7.4.14 Hemorrhoids ....................................................................................................................................... 1603

3.7.4.15 Acute Appendicitis .............................................................................................................................. 1604

3.7.4.16 Tumors of the Appendix...................................................................................................................... 1605

3.7.5 Peritoneal Cavity ......................................................................................................................................... 1605

3.7.5.1 Inflammatory Disease ........................................................................................................................... 1605

3.7.5.2 Tumors .................................................................................................................................................. 1606

3.7.6 References .................................................................................................................................................. 1607

3.8 18. Liver & Biliary Tract ...................................................................................................................................... 1610

3.8.1 The Liver...................................................................................................................................................... 1610

3.8.1.1 General Features of Hepatic Disease .................................................................................................. 1612

3.8.1.2 Infectious Disorders .............................................................................................................................. 1627

3.8.1.3 Autoimmune Hepatitis ........................................................................................................................... 1647

3.8.1.4 Drug- & Toxin-Induced Liver Disease ................................................................................................... 1649

3.8.1.5 Metabolic Liver Disease........................................................................................................................ 1655

3.8.1.6 Intrahepatic Biliary Tract Disease ......................................................................................................... 1667

3.8.1.7 Circulatory Disorders ............................................................................................................................ 1675

3.8.1.8 Hepatic Complications of Organ or Bone Marrow Transplantation ...................................................... 1683

3.8.1.9 Hepatic Disease Associated with Pregnancy ....................................................................................... 1684

3.8.1.10 Nodules & Tumors .............................................................................................................................. 1686

3.8.2 The Biliary Tract .......................................................................................................................................... 1698

3.8.2.1 Congenital Anomalies ........................................................................................................................... 1698

3.8.2.2 Disorders of the Gallbladder ................................................................................................................. 1699

3.8.2.3 Disorders of the Extrahepatic Bile Ducts .............................................................................................. 1708

3.8.2.4 Tumors .................................................................................................................................................. 1709

3.8.3 References .................................................................................................................................................. 1712

3.9 19. The Pancreas ............................................................................................................................................... 1714

3.9.1 Congenital Anomalies ................................................................................................................................. 1714

3.9.2 Pancreatitis .................................................................................................................................................. 1717

3.9.3 Non-Neoplastic Cysts .................................................................................................................................. 1726

3.9.4 Neoplasms................................................................................................................................................... 1727

3.9.5 References .................................................................................................................................................. 1735

3.10 20. The Kidney ................................................................................................................................................. 1737

3.10.1 Clinical Manifestations of Renal Diseases ................................................................................................ 1737

3.10.2 Glomerular Diseases ................................................................................................................................. 1740

3.10.3 Tubular & Interstitial Diseases .................................................................................................................. 1789

3.10.4 Vascular Diseases ..................................................................................................................................... 1816

3.10.5 Congenital Anomalies ............................................................................................................................... 1829

3.10.6 Cystic Diseases of the Kidney ................................................................................................................... 1831

3.10.7 Urinary Tract Obstruction (Obstructive Uropathy) ..................................................................................... 1839

3.10.8 Urolithiasis (Renal Calculi, Stones) ........................................................................................................... 1843

3.10.9 Tumors of the Kidney ................................................................................................................................ 1845

3.10.10 References .............................................................................................................................................. 1853

3.11 21. The Lower Urinary Tract & Male Genital System ...................................................................................... 1856

3.11.1 The Lower Urinary Tract ............................................................................................................................ 1856

3.11.1.1 Ureters ................................................................................................................................................ 1856

3.11.1.2 Urinary Bladder ................................................................................................................................... 1860

3.11.1.3 Urethra ................................................................................................................................................ 1878

3.11.2 The Male Genital Tract .............................................................................................................................. 1880

3.11.2.1 Penis ................................................................................................................................................... 1880

3.11.2.2 Testis & Epididymis ............................................................................................................................ 1887

3.11.2.3 Prostate .............................................................................................................................................. 1904

3.11.3 References ................................................................................................................................................ 1922

3.12 22. The Female Genital Tract .......................................................................................................................... 1926

3.12.1 Development ............................................................................................................................................. 1926

3.12.2 Anatomy .................................................................................................................................................... 1927

3.12.3 Infections of the Female Genital Tract ...................................................................................................... 1929

3.12.4 Vulva .......................................................................................................................................................... 1933

3.12.4.1 Bartholin Cyst ..................................................................................................................................... 1934

3.12.4.2 Non-Neoplastic Epithelial Disorders ................................................................................................... 1934

3.12.4.3 Benign Exophytic Lesions................................................................................................................... 1936

3.12.4.4 Squamous Neoplastic Lesions ........................................................................................................... 1937

3.12.4.5 Glandular Neoplastic Lesions ............................................................................................................. 1940

3.12.4.6 Malignant Melanoma .......................................................................................................................... 1943

3.12.5 Vagina ....................................................................................................................................................... 1943

3.12.5.1 Developmental Anomalies .................................................................................................................. 1943

3.12.5.2 Premalignant & Malignant Neoplasms ............................................................................................... 1944

3.12.6 Cervix ........................................................................................................................................................ 1946

3.12.6.1 Inflammations ..................................................................................................................................... 1946

3.12.6.2 Endocervical Polyps ........................................................................................................................... 1946

3.12.6.3 Premalignant & Malignant Neoplasms ............................................................................................... 1947

3.12.7 Body of Uterus & Endometrium ................................................................................................................. 1957

3.12.7.1 Endometrial Histology in the Menstrual Cycle .................................................................................... 1957

3.12.7.2 Functional Endometrial Disorders (Dysfunctional Uterine Bleeding) ................................................. 1959

3.12.7.3 Inflammation ....................................................................................................................................... 1962

3.12.7.4 Endometriosis & Adenomyosis ........................................................................................................... 1962

3.12.7.5 Endometrial Polyps ............................................................................................................................. 1965

3.12.7.6 Endometrial Hyperplasia .................................................................................................................... 1965

3.12.7.7 Malignant Tumors of the Endometrium .............................................................................................. 1968

3.12.7.8 Tumors of the Endometrium with Stromal Differentiation ................................................................... 1974

3.12.7.9 Tumors of the Myometrium ................................................................................................................. 1975

3.12.8 Fallopian Tubes ......................................................................................................................................... 1978

3.12.8.1 Inflammations ..................................................................................................................................... 1978

3.12.8.2 Tumors & Cysts .................................................................................................................................. 1978

3.12.9 Ovaries ...................................................................................................................................................... 1978

3.12.9.1 Non-Neoplastic & Functional Cysts .................................................................................................... 1978

3.12.9.2 Ovarian Tumors .................................................................................................................................. 1981

3.12.10 Gestational & Placental Disorders .......................................................................................................... 2003

3.12.10.1 Disorders of Early Pregnancy ........................................................................................................... 2005

3.12.10.2 Disorders of Late Pregnancy ............................................................................................................ 2006

3.12.10.3 Gestational Trophoblastic Disease ................................................................................................... 2012

3.12.11 References .............................................................................................................................................. 2019

3.13 23. The Breast.................................................................................................................................................. 2022

3.13.1 The Female Breast .................................................................................................................................... 2022

3.13.1.1 Disorders of Development .................................................................................................................. 2025

3.13.1.2 Clinical Presentations of Breast Disease ............................................................................................ 2025

3.13.1.3 Inflammatory Disorders....................................................................................................................... 2029

3.13.1.4 Benign Epithelial Lesions ................................................................................................................... 2032

3.13.1.5 Carcinoma of the Breast ..................................................................................................................... 2040

3.13.2 The Male Breast ........................................................................................................................................ 2071

3.13.2.1 Gynecomastia ..................................................................................................................................... 2071

3.13.2.2 Carcinoma .......................................................................................................................................... 2072

3.13.3 References ................................................................................................................................................ 2073

3.14 24. The Endocrine System ............................................................................................................................... 2075

3.14.1 Pituitary Gland ........................................................................................................................................... 2075

3.14.1.1 Clinical Manifestations of Pituitary Disease ........................................................................................ 2077

3.14.1.2 Pituitary Adenomas & Hyperpituitarism .............................................................................................. 2078

3.14.1.3 Hypopituitarism ................................................................................................................................... 2086

3.14.1.4 Posterior Pituitary Syndromes ............................................................................................................ 2088

3.14.1.5 Hypothalamic Suprasellar Tumors ..................................................................................................... 2088

3.14.2 Thyroid Gland ............................................................................................................................................ 2089

3.14.2.1 Hyperthyroidism .................................................................................................................................. 2091

3.14.2.2 Hypothyroidism ................................................................................................................................... 2094

3.14.2.3 Thyroiditis ........................................................................................................................................... 2097

3.14.2.4 Graves Disease .................................................................................................................................. 2102

3.14.2.5 Diffuse & Multinodular Goiters ............................................................................................................ 2105

3.14.2.6 Neoplasms of the Thyroid ................................................................................................................... 2108

3.14.2.7 Congenital Anomalies ......................................................................................................................... 2125

3.14.3 Parathyroid Glands .................................................................................................................................... 2125

3.14.3.1 Hyperparathyroidism ........................................................................................................................... 2126

3.14.3.2 Hypoparathyroidism ............................................................................................................................ 2131

3.14.3.3 Pseudohypoparathyroidism ................................................................................................................ 2132

3.14.4 The Endocrine Pancreas ........................................................................................................................... 2132

3.14.4.1 Diabetes Mellitus ................................................................................................................................ 2133

3.14.4.2 Pancreatic Endocrine Neoplasms ...................................................................................................... 2162

3.14.5 Adrenal Glands .......................................................................................................................................... 2166

3.14.5.1 Adrenal Cortex .................................................................................................................................... 2166

3.14.5.2 Adrenal Medulla .................................................................................................................................. 2189

3.14.6 Multiple Endocrine Neoplasia Syndromes ................................................................................................ 2195

3.14.7 Pineal Gland .............................................................................................................................................. 2197

3.14.7.1 Pinealomas ......................................................................................................................................... 2197

3.14.8 References ................................................................................................................................................ 2197

3.15 25. The Skin ..................................................................................................................................................... 2199

3.15.1 The Skin: More Than a Mechanical Barrier............................................................................................... 2199

3.15.2 Disorders of Pigmentation & Melanocytes ................................................................................................ 2203

3.15.3 Benign Epithelial Tumors .......................................................................................................................... 2214

3.15.4 Premalignant & Malignant Epidermal Tumors .......................................................................................... 2219

3.15.5 Tumors of the Dermis ................................................................................................................................ 2225

3.15.6 Tumors of Cellular Migrants to the Skin .................................................................................................... 2227

3.15.7 Disorders of Epidermal Maturation ............................................................................................................ 2230

3.15.8 Acute Inflammatory Dermatoses ............................................................................................................... 2231

3.15.9 Chronic Inflammatory Dermatoses ............................................................................................................ 2236

3.15.10 Blistering (Bullous) Diseases .................................................................................................................. 2239

3.15.11 Disorders of Epidermal Appendages ...................................................................................................... 2248

3.15.12 Panniculitis .............................................................................................................................................. 2250

3.15.13 Infection ................................................................................................................................................... 2251

3.15.14 References .............................................................................................................................................. 2256

3.16 26. Bones, Joints & Soft-Tissue Tumors ......................................................................................................... 2259

3.16.1 Bones ........................................................................................................................................................ 2259

3.16.1.1 Bone Modeling, Remodeling & Peak Bone Mass ............................................................................... 2264

3.16.1.2 Bone Growth & Development ............................................................................................................. 2264

3.16.1.3 Developmental Abnormalities in Bone Cells, Matrix & Structure........................................................ 2266

3.16.1.4 Fractures ............................................................................................................................................. 2285

3.16.1.5 Osteonecrosis (Avascular Necrosis) .................................................................................................. 2287

3.16.1.6 Infections: Osteomyelitis ..................................................................................................................... 2289

3.16.1.7 Bone Tumors & Tumor-Like Lesions .................................................................................................. 2292

3.16.1.8 Miscellaneous Tumors ........................................................................................................................ 2314

3.16.2 Joints ......................................................................................................................................................... 2320

3.16.2.1 Arthritis ................................................................................................................................................ 2320

3.16.2.2 Tumors & Tumor-Like Lesions ........................................................................................................... 2341

3.16.3 Soft-Tissue Tumors & Tumor-Like Lesions ............................................................................................... 2344

3.16.3.1 Pathogenesis & General Features ..................................................................................................... 2345

3.16.3.2 Fatty Tumors ....................................................................................................................................... 2347

3.16.3.3 Fibrous Tumors & Tumor-Like Lesions .............................................................................................. 2349

3.16.3.4 Fibrohistiocytic Tumors ....................................................................................................................... 2355

3.16.3.5 Tumors of Skeletal Muscle ................................................................................................................. 2356

3.16.3.6 Tumors of Smooth Muscle .................................................................................................................. 2358

3.16.3.7 Synovial Sarcoma ............................................................................................................................... 2359

3.16.4 References ................................................................................................................................................ 2360

3.17 27. Peripheral Nerve & Skeletal Muscle .......................................................................................................... 2362

3.17.1 General Reactions of the Motor Unit ......................................................................................................... 2362

3.17.2 Diseases of Peripheral Nerve ................................................................................................................... 2368

3.17.3 Diseases of Skeletal Muscle ..................................................................................................................... 2377

3.17.4 References ................................................................................................................................................ 2393

3.18 28. The Central Nervous System ..................................................................................................................... 2394

3.18.1 Cellular Pathology of the Central Nervous System ................................................................................... 2394

3.18.2 Cerebral Edema, Hydrocephalus & Raised Intracranial Pressure & Herniation ....................................... 2398

3.18.3 Malformations & Developmental Diseases ............................................................................................... 2402

3.18.4 Perinatal Brain Injury ................................................................................................................................. 2408

3.18.5 Trauma ...................................................................................................................................................... 2409

3.18.6 Cerebrovascular Diseases ........................................................................................................................ 2416

3.18.7 Infections ................................................................................................................................................... 2430

3.18.8 Transmissible Spongiform Encephalopathies (Prion Diseases) ............................................................... 2447

3.18.9 Demyelinating Diseases ............................................................................................................................ 2451

3.18.10 Degenerative Diseases ........................................................................................................................... 2457

3.18.11 Genetic Metabolic Diseases .................................................................................................................... 2478

3.18.12 Toxic & Acquired Metabolic Diseases ..................................................................................................... 2483

3.18.13 Tumors .................................................................................................................................................... 2487

3.18.14 Metastatic Tumors, Paraneoplastic Syndromes, Peripheral Nerve Sheath Tumors, Familial Tumor

Syndromes ........................................................................................................................................................... 2504

3.18.15 References .............................................................................................................................................. 2511

3.19 29. The Eye ...................................................................................................................................................... 2514

3.19.1 Orbit ........................................................................................................................................................... 2514

3.19.2 Eyelid ......................................................................................................................................................... 2518

3.19.3 Conjunctiva ................................................................................................................................................ 2520

3.19.4 Sclera ........................................................................................................................................................ 2523

3.19.5 Cornea ....................................................................................................................................................... 2523

3.19.6 Anterior Segment ...................................................................................................................................... 2528

3.19.7 Uvea .......................................................................................................................................................... 2533

3.19.8 Retina & Vitreous ...................................................................................................................................... 2538

3.19.9 Optic Nerve ............................................................................................................................................... 2550

3.19.10 The End-Stage Eye: Phthisis Bulbi ......................................................................................................... 2554

3.19.11 References .............................................................................................................................................. 2554