Textbook of Pathology (7th Edition) PDF

Textbook of PATHOLOGY tahir99 - UnitedVRG - vip.persianss.ir The photographs on the cover of the textbook depict images of corresponding diseases as under: Tuberculous lymphadenitis Plasma cell myeloma Nodal metastasis from breast carcinoma Apoptotic cells in squamous mucosa Aschoff body in the myocardium tahir99 - UnitedVRG - vip.persianss.ir Textbook of PATHOLOGY Seventh Edition Harsh Mohan MD, FAMS, FICPath, FUICC Professor & Head Department of Pathology Government Medical College Sector-32A, Chandigarh-160 031 INDIA E-mail: [email protected] Originally Released by tahir99 - UnitedVRG and http://vip.persianss.ir For more books visit: https://kat.cr/user/tahir99/ The Health Sciences Publishers New Delhi | London | Philadelphia | Panama tahir99 - UnitedVRG - vip.persianss.ir Jaypee Brothers Medical Publishers (P) Ltd. Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected] Overseas Offices Jaypee-Highlights Medical Publishers Inc. J.P. Medical Ltd. City of Knowledge, Bld. 237, Clayton 83, Victoria Street, London Panama City, Panama SW1H 0HW (UK) Phone: +1 507-301-0496 Phone: +44-20 3170 8910 Fax: +1 507-301-0499 Fax: +044(0)20 3008 6180 Email: [email protected] Email: [email protected] Jaypee Medical Inc. Jaypee Brothers Medical Publishers (P) Ltd. The Bourse 17/1-B, Babar Road, Block-B, Shaymali 111, South Independence Mall East Mohammadpur, Dhaka-1207 Suite 835, Philadelphia, PA 19106, USA Bangladesh Phone: +1 267-519-9789 Mobile: +08801912003485 Email: [email protected] Email: [email protected] Jaypee Brothers Medical Publishers (P) Ltd. Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 Email: [email protected] Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2015, Harsh Mohan The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photo copying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/ editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. Inquiries for bulk sales may be solicited at: [email protected] Textbook of Pathology First Edition : 1992 Second Edition : 1994 Third Edition : 1998 Fourth Edition : 2000 Fifth Edition : 2005 Sixth Edition : 2010 Reprint : 2013 Seventh Edition: 2015 Assistant Editors: Praveen Mohan, Tanya Mohan, Sugandha Mohan ISBN: 978-93-5152-369-7 Printed at tahir99 - UnitedVRG - vip.persianss.ir bbbbbbbbbbbbbbbbbbbbbbbb b b To deeds alone you have a right and b b b b never at all to its fruits; b b Let not the fruits of deeds be your motive; b b Neither let there be in you b b any detachment to performing your duty. b b The Bhagvadgita (Chapter II, verse 47) b b b bbbbbbbbbbbbbbbbbbbbbbbb b Dedicated to My loving soulmate, Praveen, for being there for me and with me always, Tanya-Vivek, for giving happiness of being together forever, Sugandha, for being the daughter who is my best friend, & To all my students and colleagues, present and past: For their enduring inspiration. tahir99 - UnitedVRG - vip.persianss.ir tahir99 - UnitedVRG - vip.persianss.ir Foreword vii Foreword This is the third time that I was asked to write a foreword to Dr Mohan's Textbook, and again I am at a loss for words to adequately express my enthusiasm for this book which has such a long history of excellence. Over all those years spanning the previous six editions, it has served as an introduction to clinical medicine to generations of medical students, and I am sure that it will continue in that function way into the twenty first century. A book of this caliber does not need introductions, forewords and endorsements for its continuous success. Its value has been proven over and over again by those for whom it was written and those who have used it in its previous editions—the medical students and their professors. For the new edition, Dr Mohan has thoroughly revised his previous text, expanding it with novel data selected judiciously from both laboratory and clinical research papers. Yet the basic structure of the book remains unchanged, with an unconditional dedication to the systematic coverage of the basics, strong clinical underpinning, and a good sense for didactics. It reflects the author's lifelong experience in the classroom and his passion for teaching of pathology to medical students. The text is illustrated with informative artists' drawings and photographs. It also contains highlighted summary boxes and valuable tables. At the end of each chapter there are clinical cases, designed to stimulate further studies and discussions. The condensed Quick Review Book, appended to the textbook as a lagniappe, will remain attractive to medical students preparing for their examinations. In a short foreword of this kind, it is not possible to mention all the strong points of this textbook. It should suffice to say that Dr Mohan's Textbook has retained all the features which have made previous editions so popular with medical students and their teachers alike. It was masterfully updated and with the new didactic elements it will be even more attractive to its readers. It will remain an essential must-have for all medical undergraduate students, serving them as a pathfinder and bridge during their transition from basic medical sciences to clinical medicine. Ivan Damjanov, MD, PhD Professor Department of Pathology The University of Kansas School of Medicine Kansas City, Kansas, USA tahir99 - UnitedVRG - vip.persianss.ir tahir99 - UnitedVRG - vip.persianss.ir Preface ix Preface As I sit down to put my thoughts into words for the 7th revised edition of my Textbook of Pathology, I look back with satisfaction how this book has grown phenomenally since its modest beginning in 1992. During these years, successive editions of the textbook have brought me closer to enumerable well-wishers, won me life-long friends, rewarded me with respect and faith of my colleagues, got me blessings of senior professionals, and earned me affection of innumerable students and fans. It has been really highly gratifying journey so far. At the same time, such an abiding trust by users of previous editions of my textbook certainly puts an onerous responsibility on me to come up to their expectations and make it better with every new edition. It is this motivation and zeal which I pursued while preparing the thoroughly transformed and updated 7th revised edition which I am pleased to present to users. Diagnostic pathology has been growing exponentially with advances in molecular methods, cytogenetics and immunology, besides the ready availability of immunohistochemistry. In fact, in the current era, immunophenotyping and cytogenetics have been recommended as defining criteria for classification, diagnosis and prognostication of growing number of cancers. In such a scenario, it is quite natural that undergraduate students of pathology should be made aware of what is happening in the realm of diagnostic science while at the same time not forgetting to lose hold of the fundamental aspects of pathology of diseases. Thus, for beginners in pathology, for whom this textbook is primarily meant, a balanced approach for learning of pathology is recommended i.e. the students must learn basic morphologic pathology including recent knowledge of etiology and pathogenesis of diseases, and simultaneously they should know the contribution of modern diagnostic techniques mentioned above towards achieving the goal of an objective ‘final diagnosis’ that is prognostically relevant as well. This philosophy for teaching and learning of pathology has been followed in the present edition but without disturbing the basic format of the book. Some of the Key Features of the Seventh Edition are as follows: Revised and Updated Text Most of the topics in chapters have undergone revision and updating of various aspects of diseases including their newer causes and recent mechanisms by insertion of latest information between the lines. Emphasis has also been placed on contemporary diagnostic modalities in a simple and lucid manner. In doing so, the basic accepted style of the book—simple, easy-to-understand and reproduce the subject matter, and emphasis on clarity and accuracy, has not been disturbed. Considering their utility, a dozen new tables have been added in different chapters in the revised edition while many others have been updated. Reorganisation of the Book The redistribution of the textbook into three sections (General Pathology, Haematology and Lymphoreticular Tissues, and Systemic Pathology) done in the previous edition has been widely accepted and appreciated for its ease for locating material and has, therefore, been retained. In order to make space for addition of new information, topics of normal cell structure and function and laboratory techniques have been relocated, after editing them, to relevant chapters to which they belong. Newer and Revised Images Morphologic pathology has always been regarded as a highly visual branch of medicine, and therefore, there is always need and scope of doing more and making this aspect better in the new edition. In the revised edition, many newer illustrations have been added while some old ones have been replaced with better quality images or improved after eliminating their shortcomings. Inboxes have been incorporated in some photomicrographs for a close-up microscopic view. In general, the effort has been to give soft and pleasing colours for soothing visual look to the new edition. Gist Boxes In the revised edition, at the end of every topic a short summary of the subject covered has been given. These ‘Gist Boxes’ (226 in all) include salient must-know features of the covered topic in bulleted points for a rapid revision in ultrashort time. These Gist Boxes have been given a distinctive eye-catching colour throughout the book to be visible on a glance and for looking up quickly by turning the pages of the book for a last minute revision before facing an evaluation in examination. Clinical Focus on Learning A novel modality of learning and self-assessment has been added in the revised edition by including 30 structured clinical cases. At the end of most of the chapters, one or more clinical cases with history and findings of examination have been given based on a common or an important disease pertaining to the system of that chapter. Questions framed at the end of these cases have been rationally answered and discussed in an analytical manner in Appendix II. Revised Pathology Quick Review and MCQs The 7th edition of textbook is accompanied with the new revised baby-book popular with many students and interns. This small book has been found profoundly useful by the students just before practical examination to face viva voce when they need to revise huge course content in a short time, or by those preparing to take postgraduate entrance examinations. The revised edition has over 50 more new MCQs while some old ones have either been edited or replaced. A Word on Foreword Professor Ivan Damjanov, MD, PhD, Kansas University, USA, has been very generous and gracious in writing Foreword for the last three successive editions of my textbook which has brought the textbook closer to users in other tahir99 - UnitedVRG - vip.persianss.ir x parts of the world, which is appreciated and gratefully acknowledged. He is gifted with qualities of perfection, clarity of mind and meticulous approach, besides having an excellent knack for choosing measured words in his language. I wholeheartedly express my gratitude to this adorable teacher and an eminent author and editor. Textbook of Pathology In essence, the revised edition is a comprehensive text of pathology meant primarily for students of pathology; however, the practicing clinicians and students of other branches of medicine, dentistry, pharmacy, alternate system of medicine, and paramedical courses may also find it useful. ACKNOWLEDGEMENTS The magnitude of work pertaining to revision of the textbook after 5 years is massive and would not have been possible without active cooperation and support from friends and well-wishers in general, and my departmental colleagues in particular. The task of fresh photomicrography for the present edition was ably assisted by my colleagues, Dr Shilpa, Senior Resident, Department of Pathology; and Ms Agam Verma, Senior Lab Technician, which is greatly appreciated. Here, I wish to recall and put on record the sincere and selfless services rendered by my former students and colleagues in preparation of images in earlier editions of the book and thank them once again. As always, I remain indebted to those from whom I had the opportunity to learn basics of pathology—Professor K Joshi, MD, PhD, formerly at PGIMER, Chandigarh, Late Professor TS Jaswal, MD, and Professor Uma Singh, MD, formerly at PGIMS, Rohtak, Haryana, India. Constant strategic encouragement and support extended by the Department of Medical Education and Research, Chandigarh Administration, during the completion of this academic work is gratefully acknowledged. I have strived to be as accurate and perfect as possible, and in doing so, I may have been quite harsh and demanding with Production team at the M/s Jaypee Brothers Medical Publishers (P) Ltd. But I must appreciate their patience, cooperation and commitment in general, and Mr Manoj Pahuja, Senior Graphic Designer and Mrs Y Kapoor, Senior Desktop Operator, in particular, for acceding to all my requests for amendments smilingly and ungrudgingly till the very last minute, and to Mr Sunil Dogra, Production Executive, for overseeing the entire project vigilantly and efficiently. Lastly, the passionate involvement of Shri Jitendar P Vij (Group Chairman) and enthusiasm of Mr Ankit Vij (Group President), M/s Jaypee Brothers Medical Publishers (P) Ltd, in the revised edition of the textbook has raised the bar for a high standard for which I am deeply thankful to both of them. While the content and product quality of the revised edition of the textbook are of an uncompromising quality, the book continues to be of reasonable volume and has been kept affordable. Finally, I owe gratitude to the users of previous editions who have been generous in giving feedback and suggestions. Every suggestion helps me to introspect and attempt to make the textbook better. I request all the users of present edition to continue giving their valuable suggestions and point out errors, if any, to help me to improve it further. Government Medical College Harsh Mohan, MD, FAMS, FICPath, FUICC Sector-32A, Chandigarh-160031 Professor & Head INDIA Department of Pathology E-mail: [email protected] tahir99 - UnitedVRG - vip.persianss.ir Contents xi Contents Section I: GENERAL PATHOLOGY Chapter 1: Introduction to Pathology 1 Study of Pathology, 1: Health and Disease, 1; Common Terms in Pathology, 1 Evolution of Pathology, 2: Prehistoric Times to Medieval Period, 2; Human Anatomy and Era of Gross Pathology, 3; Era of Technology Development and Cellular Pathology, 4; Modern Pathology, 6; Telepathology and Virtual Microscopy, 7 Subdivisions of Pathology, 7: Morphological Branches, 7; Non-Morphological Branches, 8 Chapter 2: Cell Injury, Cellular Adaptations and Cellular Ageing 9 Cell Injury, 9: Etiology of Cell Injury, 9; Pathogenesis of Cell Injury, 10; Morphology of Reversible Cell Injury, 17; Intracellular Accumulations, 19; Pigments, 22; Morphology of Irreversible Cell Injury (Cell Death), 26; Changes after Cell Death, 32 Adaptive Disorders, 37: Atrophy, 37; Hypertrophy, 38; Hyperplasia, 39; Metaplasia, 39; Dysplasia, 41 Ageing, 42: Theories of Ageing, 42; Organ Changes in Ageing, 43 Chapter 3: Immunopathology Including Amyloidosis 44 The Immune System, 44: Organs and Cells of Immune System, 44; Cytokines, 48; HLA System and Major Histocompatibility Complex, 48; Transplant Rejection, 49 Diseases of Immunity, 50: Acquired Immunodeficiency Syndrome (AIDS), 51; Hypersensitivity Reactions (Immunologic Tissue Injury), 57; Autoimmune Diseases, 61 Amyloidosis, 66: Physical and Chemical Nature of Amyloid, 67; Pathogenesis of Amyloidosis, 69; Classification of Amyloidosis, 70; Staining Characteristics of Amyloid, 72; Diagnosis of Amyloidosis, 73; Morphologic Features of Amyloidosis of Organs, 73; Prognosis of Amyloidosis, 75 Chapter 4: Derangements of Homeostasis and Haemodynamics 78 Homeostasis, 78: Normal Water and Electrolyte Balance (Gibbs-Donnan Equilibrium), 79; Acid-Base Balance, 79; Pressure Gradients and Fluid Exchanges, 79 Disturbances of Body Water, 80: Oedema, 80; Dehydration, 87; Overhydration, 87 Disturbances of Electrolytes and pH of Blood, 88: Acid Base Imbalance, 89 Haemodynamic Derangements, 89: Disturbances in the Volume of Circulating Blood, 90; Circulatory Disturbances of Obstructive Nature, 99 Chapter 5: Inflammation and Healing 116 Acute Inflammation, 116: Acute Inflammatory Response, 116; Mediators of Inflammation, 122; Regulation of Inflammation, 127; The Inflammatory Cells, 128; Acute Inflammation—Factors, Morphology, Effects, Fate, 131 Chronic Inflammation, 134: Granulomatous Inflammation, 135; Examples of Granulomatous Inflammation, 137 Healing, 155: Regeneration and Repair, 155; Healing of Skin Wounds, 158; Healing in Specialised Tissues, 161; Stem Cell Concept of Healing—Regenerative Medicine, 163 Chapter 6: Infectious and Parasitic Diseases 165 Diseases Caused by Bacteria, Spirochaetes and Mycobacteria, 167: Plague, 167; Anthrax, 168; Whooping Cough (Pertussis), 169; Donovanosis, 170; Lymphogranuloma Venereum, 170; Cat-Scratch Disease, 170; Staphylococcal Infections, 170; Streptococcal Infections, 171; Clostridial Diseases, 172 Diseases Caused by Fungi, 173: Mycetoma, 173; Candidiasis, 173; Cutaneous Superficial Mycosis, 174 Diseases Caused by Viruses, 174: Viral Haemorrhagic Fevers, 175; Influenza Virus Infections, 176; Varicella Zoster Virus Infection, 177; Herpes Simplex Virus Infection, 177; Rabies, 178 tahir99 - UnitedVRG - vip.persianss.ir xii Diseases Caused by Parasites, 178: Amoebiasis, 178; Malaria, 179; Filariasis, 180; Cysticercosis, 181 Torch Complex, 182: Textbook of Pathology Chapter 7: Neoplasia 184 Nomenclature and Classification, 184 Characteristics of Tumours, 186 I. Rate of Growth, 186; II. Cancer Phenotype and Stem Cells, 188; III. Clinical and Gross Features, 188; IV. Microscopic Features, 188; V. Spread of Tumours, 192; Grading and Staging of Cancer, 197 Epidemiology and Molecular Pathogenesis of Cancer, 197: Epidemiologic Factors, 198; Molecular Basis of Cancer, 201 Carcinogens and Carcinogenesis, 209: A. Chemical Carcinogenesis, 210; B. Physical Carcinogenesis, 214; C. Biologic Carcinogenesis, 216 Clinical Aspects of Neoplasia, 222: Host Response against Tumour (Tumour Immunology), 222; Effect of Tumour on Host, 224; Pathologic Diagnosis of Cancer, 226 Chapter 8: Environmental and Nutritional Diseases 231 Environmental Diseases, 231: Environmental Pollution, 231; Chemical and Drug Injury, 233; Injury by Physical Agents, 237 Nutritional Diseases, 238: Obesity, 238; Starvation, 240; Protein-Energy Malnutrition, 240; Metals and Trace Elements, 240; Disorders of Vitamins, 241; Diet and Cancer, 249 Chapter 9: Genetic and Paediatric Diseases 251 Genetic Diseases, 251: Developmental Defects, 251; Cytogenetic (Karyotypic) Abnormalities, 252; Single-Gene Defects (Mendelian Disorders), 254; Multifactorial Inheritance, 256; Storage Diseases (Inborn Errors of Metabolism), 256 Other Paediatric Diseases, 258: Tumours of Infancy and Childhood, 259 Section II: HAEMATOLOGY AND LYMPHORETICULAR TISSUES Chapter 10: Introduction to Haematopoietic System and Disorders of Erythroid Series 261 Bone Marrow and Haematopoiesis, 261: Haematopoietic Organs, 261; Haematopoietic Stem Cells, 262; Bone Marrow Examination, 262 Erythropoiesis, 264: Erythropoietin, 264; Erythroid Series, 265; The Red Cell, 265; Nutritional Requirements for Erythropoiesis, 266 Anaemia—General Considerations, 268: General Clinical Features, 268; General Scheme of Investigations of Anaemia, 269; Classification of Anaemias, 271 Hypochromic Anaemias, 272: Iron Deficiency Anaemia, 272; Sideroblastic Anaemia, 277; Anaemia of Chronic Disorders, 278 Megaloblastic Anaemias—Vitamin B12 and Folate Deficiency, 280: Megaloblastic Anaemia, 280; Pernicious Anaemia, 285 Haemolytic Anaemias and Anaemia due to Blood Loss, 286: General Aspects, 287; I. Acquired Haemolytic Anaemias, 288; II. Hereditary Haemolytic Anaemias, 291; Anaemia of Blood Loss, 301 Aplastic Anaemia and Other Primary Bone Marrow Disorders, 301: Aplastic Anaemia, 301; Myelophthisic Anaemia, 303; Pure Red Cell Aplasia, 303 Chapter 11: Disorders of Platelets, Bleeding Disorders and Basic Transfusion Medicine 305 Disorders of Platelets, 305: Investigations of Haemostatic Function, 306 Bleeding Disorders (Haemorrhagic Diathesis), 309: Haemorrhagic Diatheses due to Vascular Disorders, 309; Haemorrhagic Diatheses due to Platelet Disorders, 310; Coagulation Disorders, 313; Other Bleeding and Coagulation Disorders, 315 Blood Groups and Blood Transfusion, 317: Blood Transfusion, 318; Haemolytic Disease of Newborn, 319 tahir99 - UnitedVRG - vip.persianss.ir Chapter 12: Disorders of Leucocytes and Lymphoreticular Tissues 321 xiii Lymph Nodes: Normal and Reactive, 321: Reactive Lymphadenitis, 322 White Blood Cells: Normal and Reactive, 324: Granulopoiesis, 324; Lymphopoiesis, 326; Mature Leucocytes in Health and Reactive Proliferation in Disease, 326; Infectious Mononucleosis, 329; Contents Leukaemoid Reactions, 331 Lymphohaematopoietic Malignancies (Leukaemias-Lymphomas): General, 333: Etiology of Lymphohaematopoietic Malignancies, 334; Pathogenesis, 334 Myeloid Neoplasms, 335: Myeloproliferative Diseases, 335; Acute Myeloid Leukaemia, 340; Myelodysplastic Syndromes, 343 Lymphoid Neoplasms: General, 344: Common to ALL Lymphoid Malignancies, 347 Hodgkin’s Disease, 348 Non-Hodgkin’s Lymphomas-Leukaemias, 352: Precursor (Immature) B- and T-Cell Leukaemia/Lymphoma, 353; Peripheral (Mature) B-Cell Malignancies, 355; Peripheral (Mature) T-Cell Malignancies, 359; Staging of NHL, 360; Lymph Node Metastatic Tumours, 360 Plasma Cell Disorders, 360 Histiocytic Neoplasms: Langerhans Cell Histiocytosis, 365 Spleen, 366: Splenic Enlargement and Effects on Function, 367 Thymus, 368: Structural and Functional Changes in Thymus, 369 Section III: SYSTEMIC PATHOLOGY Chapter 13: The Blood Vessels and Lymphatics 370 Normal Structure, 370 Arteriosclerosis, 371: Senile Arteriosclerosis, 371; Hypertensive Arteriolosclerosis, 371; Mönckeberg’s Arteriosclerosis (Medial Calcific Sclerosis), 372; Atherosclerosis, 373 Vasculitis, 381: I. Infectious Arteritis, 381; II. Non-Infectious Arteritis, 382 Aneurysms, 386 Common Diseases of Veins, 389 Diseases of Lymphatics, 390 Tumours and Tumour-like Lesions, 391: A. Benign Tumours and Hamartomas, 391; B. Intermediate Grade Tumours, 394; C. Malignant Tumours, 394 Chapter 14: The Heart 397 Normal Structure and Classification, 397 Heart Failure, 399: Etiology, 399; Types of Heart Failure, 399; Compensatory Mechanisms: Cardiac Hypertrophy and Dilatation, 400 Congenital Heart Disease, 402: I. Malpositions of the Heart, 403; II. Shunts (Cyanotic Congenital Heart Disease), 403; III. Obstructions (Obstructive Congenital Heart Disease), 406 Ischaemic Heart Disease, 407: Etiopathogenesis, 407; Effects of Myocardial Ischaemia, 408 Hypertensive Heart Disease, 417 Cor Pulmonale, 418 Rheumatic Fever and Rheumatic Heart Disease, 418 Non-Rheumatic Endocarditis, 424: Atypical Verrucous (Libman-Sacks) Endocarditis, 424; Non-Bacterial Thrombotic (Cachectic, Marantic) Endocarditis, 425; Infective (Bacterial) Endocarditis, 425 Valvular Diseases and Deformities, 429 Myocardial Diseases, 432: Myocarditis, 432; Cardiomyopathy, 434 Pericardial Diseases, 437: Pericardial Fluid Accumulations, 437; Pericarditis, 437 Tumours of the Heart, 439 Pathology of Cardiovascular Interventions, 440 Chapter 15: The Respiratory System 442 Normal Structure of Lungs, 442 Paediatric Lung Disease, 443 Pulmonary Vascular Disease, 446 Pulmonary Infections, 448: Pneumonias, 448; Lung Abscess, 457; Pulmonary Tuberculosis, 457 Chronic Obstructive Pulmonary Disease, 458: Chronic Bronchitis, 458; Emphysema, 459; Bronchial Asthma, 463; Bronchiectasis, 465; Small Airways Disease, 466 tahir99 - UnitedVRG - vip.persianss.ir xiv Chronic Restrictive Pulmonary Disease, 467: Pneumoconioses, 467; ILDs Associated with Immunologic Lung Diseases, 474; ILDs Associated with Connective Tissue Diseases, 475; Idiopathic Pulmonary Fibrosis, 476; ILDs Associated with Smoking, 476 Textbook of Pathology Tumours of Lungs, 477: Bronchogenic Carcinoma, 477; Bronchial Carcinoid and Other Neuroendocrine Tumours, 483; Hamartoma, 484; Metastatic Lung Tumours, 484 Diseases of Pleura, 485: Inflammations, 485; Non-Inflammatory Pleural Effusions, 485; Pneumothorax, 485; Tumours of Pleura, 486; Secondary Pleural Tumours, 487 Chapter 16: The Eye, ENT and Neck 488 Eye, 488: Congenital Lesions, 488; Inflammatory Conditions, 489; Vascular Lesions, 489; Miscellaneous Conditions, 491; Tumours and Tumour-like Lesions, 492 Ear, 495: Inflammatory and Miscellaneous Lesions, 495; Tumours and Tumour-Like Lesions, 495 Nose and Paranasal Sinuses, 496: Inflammatory Conditions, 496; Tumours, 498 Pharynx, 499: Inflammatory Conditions, 499; Tumours, 499 Larynx, 500: Inflammatory Conditions, 500; Tumours, 500 Neck, 501: Cysts of Neck, 502; Tumours, 502 Chapter 17: The Oral Cavity and Salivary Glands 504 Oral Soft Tissues, 504: Developmental Anomalies, 504; Mucocutaneous Lesions, 504; Inflammatory and Pigmentary Diseases, 504; Tumours and Tumour-like Lesions, 505 Teeth and Periodontal Tissues, 509: Inflammatory Diseases, 510; Epithelial Cysts of the Jaw, 511; Odontogenic Tumours, 513 Salivary Glands, 515: Inflammatory and Salivary Flow Diseases, 515; Tumours of Salivary Glands, 516 Chapter 18: The Gastrointestinal Tract 521 Oesophagus, 521: Congenital Anomalies, 521; Muscular Dysfunctions, 521; Haematemesis of Oesophageal Origin, 522; Inflammatory Lesions, 523; Tumours of Oesophagus, 524 Stomach, 526: Gastric Analysis, 527; Congenital and Miscellaneous Acquired Conditions, 529; Inflammatory Conditions, 529; Haematemesis and Melaena of Gastric Origin, 537; Tumours and Tumour-like Lesions, 537 Small Intestine, 544: Congenital Anomalies and Intestinal Obstruction, 544; Ischaemic Bowel Disease (Ischaemic Enterocolitis), 546; Inflammatory Bowel Disease (Crohn’s Disease and Ulcerative Colitis), 548; Infective and Other Enterocolitis, 552; Malabsorption Syndrome, 556; Small Intestinal Tumours, 559 Appendix, 561: Appendicitis, 561; Tumours of Appendix, 562 Large Bowel, 563: Congenital and Other Miscellaneous Conditions, 563; Polyps and Tumours of Large Bowel, 566; Causes of Gastrointestinal Bleeding, 573 Peritoneum, 574: Peritonitis, 574; Tumour-like Lesions and Tumours, 575 Chapter 19: The Liver, Biliary Tract and Exocrine Pancreas 577 Liver, 577: Liver Function Tests, 578; Jaundice—General, 581; Neonatal Jaundice, 585; Hepatic Failure, 587; Circulatory Disturbances, 589; Viral Hepatitis, 590; Other Infections and Infestations, 599; Chemical and Drug Injury, 601; Cirrhosis, 603; Portal Hypertension, 615; Hepatic Tumours and Tumour-like Lesions, 617 Biliary Tract, 623: Congenital Anomalies, 623; Cholelithiasis (Gallstones), 623; Cholecystitis, 626; Tumours of Biliary Tract, 628 Exocrine Pancreas, 630: Developmental Anomalies, 631; Pancreatitis, 631; Tumours and Tumour-like Lesions, 633 Chapter 20: The Kidney and Lower Urinary Tract 636 Kidney, 636: Renal Function Tests, 639; Pathophysiology of Renal Disease: Renal Failure, 640; Congenital Malformations, 643; Glomerular Diseases, 647; Pathogenesis of Glomerular Injury, 649; Specific Types of Glomerular Diseases, 652; Tubular and Tubulointerstitial Diseases, 666; Obstructive Uropathy, 672; Renal Vascular Diseases, 675; Tumours of Kidney, 680 Lower Urinary Tract, 685: Congenital Anomalies, 685; Inflammations, 685; Tumours, 686 tahir99 - UnitedVRG - vip.persianss.ir Chapter 21: The Male Reproductive System and Prostate 691 xv Testis and Epididymis, 691: Developmental Disorders, 691; Inflammations, 692; Miscellaneous Lesions, 694; Testicular Tumours, 694 Penis, 702: Developmental and Inflammatory Disorders, 702; Tumours, 702 Prostate, 703: Prostatitis, 704; Nodular Hyperplasia, 705; Carcinoma of Prostate, 706 Contents Chapter 22: The Female Genital Tract 710 Vulva, 710: Miscellaneous Conditions, 710; Vulval Tumours, 711 Vagina, 712: Vaginitis and Vulvovaginitis, 712; Tumours and Tumour-like Conditions, 713 Cervix, 713: Cervicitis, 713; Tumours, 714 Myometrium and Endometrium, 719: Effects of Hormones, 720; Endometritis and Myometritis, 721; Adenomyosis, 721; Endometriosis, 722; Endometrial Hyperplasias, 723; Tumours of Endometrium and Myometrium, 723 Fallopian Tubes, 728: Inflammations, 728; Ectopic Tubal Pregnancy, 729; Tumours and Tumour-like Lesions, 729 Ovaries, 729: Non-Neoplastic Cysts, 729; Ovarian Tumours, 730 Placenta, 741: Hydatidiform Mole, 741; Choriocarcinoma, 742 Chapter 23: The Breast 745 Non-Neoplastic Conditions, 746: Inflammations, 746; Fibrocystic Change, 746; Gynaecomastia (Hypertrophy of Male Breast), 748 Breast Tumours, 748: Fibroadenoma, 748; Phyllodes Tumour (Cystosarcoma Phyllodes), 749; Intraductal Papilloma, 749; Carcinoma of the Breast, 750 Chapter 24: The Skin 759 Dermatoses, 760: I. Genetic Dermatoses, 760; II. Non-Infectious Inflammatory Dermatoses, 761; III. Infectious Dermatoses, 762; IV. Granulomatous Diseases, 765; V. Connective Tissue Dermatoses, 765; VI. Non-Infectious Bullous Dermatoses, 766; VII. Scaling Dermatoses, 768; VIII. Metabolic Diseases of Skin, 769 Tumours and Tumour-like Lesions, 770: I. Tumours and Cysts of the Epidermis, 771; II. Adnexal (Appendageal) Tumours, 776; III. Melanocytic Tumours, 777; IV. Tumours of the Dermis, 779; V. Cellular Migrant Tumours, 780 Chapter 25: The Endocrine System 782 Basic Concept of Endocrines, 782: Neuroendocrine System, 782; The Endocrine System, 782 Pituitary Gland, 784: Hyperpituitarism, 784; Hypopituitarism, 785; Pituitary Tumours, 786 Adrenal Gland, 787: Adrenocortical Hyperfunction (Hyperadrenalism), 788; Adrenocortical Insufficiency (Hypoadrenalism), 789; Tumours of Adrenal Glands, 790 Thyroid Gland, 792: Functional Disorders, 793; Thyroiditis, 794; Graves’ Disease (Diffuse Toxic Goitre), 796; Goitre, 797; Thyroid Tumours, 800 Parathyroid Glands, 806: Hyperparathyroidism, 806; Hypoparathyroidism, 807; Parathyroid Tumours, 808 Endocrine Pancreas, 808: Diabetes Mellitus, 808; Islet Cell Tumours, 818 Miscellaneous Endocrine Tumours, 819 Chapter 26: The Musculoskeletal System 821 Skeletal System, 821: Infection, Necrosis, Fracture Healing, 822; Disorders of Bone Growth and Development, 825; Metabolic and Endocrine Bone Diseases, 826; Paget’s Disease of Bone (Osteitis Deformans), 828; Tumour-like Lesions of Bone, 829; Tumours of Bone and Cartilage, 831 Joints, 841: Degenerative Joint Disease (Osteoarthritis), 842; Inflammatory Joint Diseases, 843 Skeletal Muscles, 848: Neurogenic Diseases, 848; Myopathic Diseases (Myopathies), 850 Chapter 27: Soft Tissue Tumours 851 General Features, 851 Soft Tissue Tumours, 853: Tumours and Tumour-like Lesions of Fibrous Tissue, 853; Fibrohistiocytic Tumours, 855; Tumours of Adipose Tissue, 857; Skeletal Muscle Tumours, 859; Tumours of Uncertain Histogenesis, 861 tahir99 - UnitedVRG - vip.persianss.ir xvi Chapter 28: The Nervous System 863 Central Nervous System, 863: Developmental Anomalies and Hydrocephalus, 865; Textbook of Pathology Infections of CNS, 866; Cerebrovascular Diseases, 871; Miscellaneous Diseases, 875; Tumours of the CNS, 878 Peripheral Nervous System, 884: Pathologic Reactions to Injury, 884; Peripheral Neuropathy, 884; Nerve Sheath Tumours, 885 APPENDICES Appendix I: Basic Diagnostic Cytology 888 Exfoliative Cytology, 889: I. Gynaecologic Exfoliative Cytology, 889; II. Non-Gynaecologic Exfoliative Cytology, 894; Techniques in Exfoliative Cytology, 897 Interventional Cytology, 899: I. Fine Needle Aspiration Cytology, 899; II. Imprint Cytology, 905; III. Crush Smear Cytology, 905; IV. Biopsy Sediment Cytology, 905 Appendix II: Answers to Clinical Cases 906 Preamble, 906 Appendix III: Normal Values 915 Weights and Measurements of Normal Organs, 915 Laboratory Values of Clinical Significance, 916 Further Reading 923 Index 931 List of Clinical Cases 954 tahir99 - UnitedVRG - vip.persianss.ir 1 Section I GENERAL PATHOLOGY CHAPTER 1 1 Introduction to Pathology Introduction to Pathology STUDY OF PATHOLOGY The word ‘Pathology’ is derived from two Greek words—pathos (meaning suffering) and logos (meaning study). Pathology is, thus, scientific study of changes in the structure and function of the body in disease. In other words, pathology consists of the abnormalities in normal anatomy (including histology) and normal physiology owing to disease. Another commonly used term with reference to study of diseases is ‘pathophysiology’ (patho=suffering, physiology=study of normal function). Pathophysiology, thus, includes study of disordered function (i.e. physiological changes) and breakdown of homeostasis in diseases (i.e. biochemical changes). Pathologists contribute in patient management by providing final diagnosis of disease. Therefore, knowledge and understanding of pathology is essential for all would-be doctors, as well as general medical practitioners and specialists because unless they have knowledge and understanding of the language in the form of pathology laboratory reports, they would not be able to institute appropriate treatment or suggest preventive measures to the patient. For the student of any system of medicine, the discipline of pathology forms a vital bridge between initial learning phase of preclinical sciences and the final phase of clinical subjects. The role and significance of learning of pathology in clinical Figure 1.1 Sir William Osler (1849–1919). Canadian physician and one medicine is quite well summed up by Sir William Osler (1849- of the four founding Professors of Johns Hopkins Hospital, Baltimore, 1919), acclaimed physician and teacher in medicine considered US, is regarded as ‘Father of Modern Medicine’, Sir Osler had keen interest in pathology, was an acclaimed teacher and is also remembered for his as ‘Father of Modern Medicine’ by his famous quote “your famous quotations. practice of medicine will be as good as is your understanding of pathology” (Fig. 1.1). HEALTH AND DISEASE healthy state. The term syndrome (meaning running together) is used for a combination of several clinical features caused by Before there were humans on earth, there was disease, albeit in altered physiologic processes. early animals. Since pathology is the study of disease, then what is disease? In simple language, disease is opposite of health i.e. what is not healthy is disease. Health may be defined as a COMMON TERMS IN PATHOLOGY condition when the individual is in complete accord with the It is important for a beginner in pathology to be familiar with surroundings, while disease is loss of ease (or comfort) to the the language used in pathology (Fig.1.2): body (i.e. dis+ease). However, it must be borne in mind that in Patient is the person affected by disease. health there is a wide range of ‘normality’ e.g. in height, weight, Lesions are the characteristic changes in tissues and cells blood and tissue chemical composition etc. It also needs to be produced by disease in an individual or experimental animal. appreciated that at cellular level, the cells display wide range Pathologic changes or morphology consist of examination of activities within the broad area of health similar to what is of diseased tissues. These can be recognised with the naked seen in diseased cells. Thus, a disease or an illness means a eye (gross or macroscopic changes) or studied by microscopic condition marked by pronounced deviation from the normal examination of tissues. tahir99 - UnitedVRG - vip.persianss.ir 2 SECTION I General Pathology Figure 1.2 Diagrammatic depiction of disease and various terms used in pathology. Causal factors responsible for the lesions are included in PREHISTORIC TIMES TO MEDIEVAL PERIOD etiology of disease (i.e. ‘why’ of disease). Mechanism by which the lesions are produced is termed Present-day knowledge of primitive culture which was prevalent in the world in prehistoric times reveals that religion, pathogenesis of disease (i.e. ‘how’ of disease). Functional implications of the lesion felt by the patient magic and medical treatment were quite linked to each other in those times. The earliest concept of disease understood by are symptoms and those discovered by the clinician are the physical signs. the patient and the healer was the religious belief that disease Clinical significance of the morphologic and functional was the outcome of ‘curse from God’ or the belief in magic that the affliction had supernatural origin from ‘evil eye of spirits.’ changes together with results of other investigations help to arrive at an answer to what is wrong (diagnosis), what is going To ward them off, priests through prayers and sacrifices, and to happen (prognosis), what can be done about it (treatment), magicians by magic power used to act as faith-healers and and finally what should be done to avoid complications and invoke supernatural powers and please the gods. Remnants spread (prevention) (i.e. ‘what’ of disease). of ancient superstitions still exist in some parts of the world. The link between medicine and religion became so firmly established throughout the world that different societies had EVOLUTION OF PATHOLOGY their gods and goddesses of healing; for example: mythological Pathology as the scientific study of disease processes has its Greeks had Aesculapius and Apollo as the principal gods of deep roots in medical history. Since the beginning of mankind, healing, Dhanvantri as the deity of medicine in India, and there has been desire as well as need to know more about orthodox Indians’ belief in Mata Sheetala Devi as the pox the causes, mechanisms and nature of diseases. The answers goddess. to these questions have evolved over the centuries—from The insignia of healing, the Caduceus, having snake and supernatural beliefs to the present state of our knowledge staff, is believed to represent the god Hermes or Mercury, of modern pathology. However, pathology is not separable which according to Greek mythology has power of healing from other multiple disciplines of medicine and owes its since snake has regenerative powers expressed by its periodic development to interaction and interdependence on advances sloughing of its skin. God of Greek medicine, Aesculapius, in diverse neighbouring branches of science, in addition to performed his functions with a staff having a single serpent the strides made in medical technology. As we shall see in the wound around it. Later (around AD1800), however, the pages that follow, pathology has evolved over the years as a Caduceus got replaced with twin-serpents wound around distinct discipline from anatomy, medicine and surgery, in that a staff topped by a round knob and flanked by two wings sequence. and now represents the symbol of medicine instead of cross The following brief review of fascinating history of pathology (Fig. 1.3). and its many magnificent personalities with their outstanding The period of ancient religious and magical beliefs was contribution in the form of a disease or a process known by followed by the philosophical and rational approach to disease their names, is meant to stimulate and generate interest in by the methods of observations. This happened at the time the inquisitive beginner in pathology as to how this colourful when great Greek philosophers—Socrates, Plato and Aristotle, specialty has emerged. introduced philosophical concepts to all natural phenomena. tahir99 - UnitedVRG - vip.persianss.ir But the real practice of medicine began with Hippocrates 3 (460–370 BC), the great Greek clinical genius of all times and regarded as ‘the father of medicine’ (Fig. 1.4). Hippocrates dissociated medicine from religion and magic. Instead, he CHAPTER 1 firmly believed in study of patient’s symptoms and described methods of diagnosis. He recorded his observations on cases in the form of collections of writings called Hippocratic Corpus which remained the mainstay of learning of medicine for nearly two thousand years. However, the prevailing concept at that time on mechanism of disease based on disequilibrium of four basic humors (water, air, fire, and earth) was propagated by Hippocates too but this concept was later abandoned. Hippocrates followed rational and ethical attitudes in practice and teaching of medicine and is revered by the medical Introduction to Pathology profession by taking ‘Hippocratic oath’ at the time of entry into practice of medicine. After Hippocrates, Greek medicine reached Rome (now Italy) which controlled Greek world after 146 BC and, therefore, it dominated the field of development of medicine in ancient Europe then. In fact, since old times, many tongue-twisting terminologies in medicine have their origin from Latin language which was the official language of countries included in ancient Roman empire (Spanish, Portuguese, Italian, French and Greek languages have their origin from Latin). In Rome, Hippocratic teaching was propagated by Roman physicians, notably by Cornelius Celsus (53 BC-7 AD) and Figure 1.4 Hippocrates (460–370 BC). The great Greek clinical genius Claudius Galen (130–200 AD). Celsus first described four and regarded as ‘the Father of Medicine’. He introduced ethical aspects cardinal signs of inflammation—rubor (redness), tumor to medicine. (swelling), calor (heat), and dolor (pain). Galen postulated humoral theory, later called Galenic theory. This theory suggested that the illness resulted from imbalance between book of surgical sciences by Sushruta, and includes about 700 four humors (or body fluids): blood, lymph, black bile (believed plant-derived medicines. at that time to be from the spleen), and biliary secretion from The end of Medieval period was marked by back ward the liver. steps in medicine. There were widespread and devastating The hypothesis of disequilibrium of four elements consti epidemics which reversed the process of rational thinking tuting the body (Dhatus) similar to Hippocratic doctrine finds again to supernatural concepts and divine punishment for mention in ancient Indian medicine books compiled about ‘sins.’ The dominant belief during this period was that life was 200 AD—Charaka Samhita, a finest document by Charaka on due to influence of vital substance under the control of soul medicine listing 500 remedies, and Sushruta Samhita, similar (theory of vitalism). Thus, dissection of human body was strictly forbidden at that time as that would mean hurting the ‘soul.’ HUMAN ANATOMY AND ERA OF GROSS PATHOLOGY The backwardness of Medieval period was followed by the Renaissance period i.e. revival of learning. The Renaissance began from Italy in late 15th century and spread to whole of Europe. During this period, there was quest for advances in art and science. Since there was freedom of thought, there was emphasis on philosophical and rational attitudes again. The beginning of the development of human anatomy took place during this period with the art works and drawings of human muscles and embryos by famous Italian painter Leonardo da Vinci (1452–1519). Dissection of human body was started by Vesalius (1514–1564) on freshly executed criminals. His pupils, Gabriel Fallopius (1523–1562) who described human oviducts (Fallopian tubes) and Fabricius who discovered lymphoid tissue around the intestine of birds (bursa of Fabricius) further popularised the practice of Figure 1.3 The Caduceus, representing symbol of medicine, is the human anatomic dissection for which special postmortem traditional symbol of god Hermes or Mercury. It features twin serpents amphitheatres came in to existence in various parts of ancient winding around a winged staff. Europe. tahir99 - UnitedVRG - vip.persianss.ir 4 Antony van Leeuwenhoek (1632–1723), a cloth merchant French physician, dominated the early part of 19th century by by profession in Holland, during his spare time invented the his numerous discoveries. He described several lung diseases first ever microscope by grinding the lenses himself through (tubercles, caseous lesions, miliary lesions, pleural effusion, which he recognised male spermatozoa as tiny preformed men and bronchiectasis), chronic sclerotic liver disease (later called (or “homunculi”) and other single-celled organisms which he Laennec’s cirrhosis) and invented stethoscope. SECTION I called animalcules. He also introduced histological staining in Morbid anatomy attained its zenith with appearance of Carl 1714 using saffron to examine muscle fibres. F. von Rokitansky (1804–1878), self-taught German pathologist Marcello Malpighi (1624–1694) used microscope exten who performed nearly 30,000 autopsies himself. He described sively and observed the presence of capillaries and described acute yellow atrophy of the liver, wrote an outstanding the malpighian layer of the skin, and lymphoid tissue in the monograph on diseases of arteries and congenital heart spleen (malpighian corpuscles). Malpighi is known as ‘the defects. Unlike most other surgeons of that time, Rokitansky did father of histology.’ not do clinical practice of surgery but instead introduced the The credit for beginning of the study of morbid anatomy concept that pathologists should confine themselves to making (pathologic anatomy), however, goes to Italian anatomist- diagnosis which became the accepted role of pathologist later. General Pathology pathologist, Giovanni B. Morgagni (1682–1771). Morgagni was an excellent teacher in anatomy, a prolific writer and ERA OF TECHNOLOGY DEVELOPMENT a practicing clinician. By his work, Morgagni demolished AND CELLULAR PATHOLOGY the ancient humoral theory of disease and published his life-time experiences based on 700 postmortems and their Up to middle of the 19th century, correlation of clinical corresponding clinical findings. He, thus, laid the foundations manifestations of disease with gross pathological findings of clinicopathologic methodology in the study of disease and at autopsy became the major method of study of disease. introduced the concept of clinicopathologic correlation (CPC), Sophistication in surgery led to advancement in pathology. The establishing a coherent sequence of cause, lesions, symptoms, anatomist-surgeons of earlier centuries got replaced largely and outcome of disease (Fig. 1.5). with surgeon-pathologists in the 19th century. Sir Percivall Pott (1714–1788), famous surgeon in England, Pathology started developing as a diagnostic discipline described arthritic tuberculosis of the spine (Pott’s disease) in later half of the 19th century with the evolution of cellular and identified the first ever occupational cancer (cancer of pathology which was closely linked to technology advance scrotal skin) in the chimney sweeps in 1775 and discovered ments in machinery manufacture for cutting thin sections chimney soot as the first carcinogenic agent. The study of of tissue, improvement in microscope, and development of anatomy in England during the latter part of 18th Century was chemical industry and dyes for staining. dominated by the two Hunter brothers. These were John Hunter The discovery of existence of disease-causing micro- (1728–1793), a student of Sir Percivall Pott, who rose to become organisms was made by French chemist Louis Pasteur (1822– the greatest surgeon-anatomist of all times (Fig. 1.6) and his 1895), thus demolishing the prevailing theory of spontaneous elder brother William Hunter (1718–1788) who was a reputed generation of disease and firmly established germ theory anatomist-obstetrician. These brothers together started the of disease. Subsequently, G.H.A. Hansen (1841–1912) in first ever museum by collection of surgical specimens from Germany identified Hansen’s bacillus in 1873 as the first their flourishing practice, arranged them into separate organ microbe causative for leprosy (Hansen’s disease). While the systems, made comparison of specimens from animals and study of infectious diseases was being made, the concept of plants with humans, and included many clinical pathology immune tolerance and allergy emerged which formed the specimens as well, and thus developed the first museum basis of immunisation initiated by Edward Jenner. Metchnikoff of comparative anatomy and pathology in the world which (1845-1916), a Russian zoologist, introduced the existence of became the Hunterian Museum, now housed in Royal College phenomenon of phagocytosis by human defense cells against of Surgeons of London. Among many pupils of John Hunter invading microbes. was Edward Jenner (1749–1823) whose work on inoculation in Developments in chemical industry helped in switch over smallpox is well known. Another prominent English pathologist from earlier dyes of plant and animal origin to synthetic dyes; was Matthew Baillie (1760–1823), nephew of Hunter brothers, aniline violet being the first such synthetic dye prepared by who published first-ever systematic textbook of morbid Perkin in 1856. This led to emergence of a viable dye industry anatomy in 1793. The era of gross pathology had three more for histological and bacteriological purposes. The impetus for illustrious and brilliant physician-pathologists in England who the flourishing and successful dye industry came from the were colleagues at Guy’s Hospital in London: works of numerous pioneers as under: Richard Bright (1789–1858) who described non-suppurative Paul Ehrlich (1854–1915), German physician, conferred nephritis, later termed glomerulonephritis or Bright’s disease; Nobel prize in 1908 for his work in immunology, described Thomas Addison (1793–1860) who gave an account of Ehrlich’s test for urobilinogen using Ehrlich’s aldehyde chronic adrenocortical insufficiency termed Addison’s disease; reagent, staining techniques of cells and bacteria, and laid the and foundations of clinical pathology (Fig. 1.7). Thomas Hodgkin (1798–1866), who observed the complex of Christian Gram (1853–1938), Danish physician, developed chronic enlargement of lymph nodes, often with enlargement bacteriologic staining by crystal violet. of the liver and spleen, later called Hodgkin’s disease. D.L. Romanowsky (1861–1921), Russian physician, Towards the end of 18th century, Xavier Bichat (1771–1802) developed stain for peripheral blood film using eosin and in France described that organs were composed of tissue methylene blue derivatives. and divided the study of morbid anatomy into General Pathology Robert Koch (1843–1910), German bacteriologist, besides and Systemic Pathology. R.T.H. Laennec (1781–1826), another Koch’s postulate and Koch’s phenomena, developed techniques tahir99 - UnitedVRG - vip.persianss.ir FATHER OF CPCs FATHER OF MUSEUM IN PATHOLOGY FATHER OF CLINICAL PATHOLOGY 5 CHAPTER 1 Introduction to Pathology Figure 1.5 Giovanni B. Morgagni (1682– Figure 1.6 John Hunter (1728–1793). Figure 1.7 Paul Ehrlich (1854–1915). German 1771), an Italian physician-anatomist who Scottish surgeon, regarded as the greatest physician, conferred Nobel prize for his work introduced clinicopathologic methodology surgeon-anatomist of all times who estab in immunology, described Ehrlich’s test for in the study of disease by correlation of li shed first ever unique collection of urobilinogen, staining techniques of cells clinical findings with findings at postmortem pathological specimens that later resulted in and bacteria, and laid the foundations of examination. the Hunterian Museum of the Royal College haematology and clinical pathology. of Surgeons, London. of fixation and staining for identification of bacteria, discovered microscopy had been laid which was followed and promoted tubercle bacilli in 1882 and cholera vibrio organism in 1883. by numerous brilliant successive workers. This gave birth to May-Grünwald in 1902 and Giemsa in 1914 developed biopsy pathology and thus emerged the discipline of surgical blood stains and applied them for classification of blood cells pathology. Virchow also described etiology of embolism and bone marrow cells. (Virchow’s triad—slowing of blood-stream, changes in the Sir William Leishman (1865–1926) described Leishman’s vessel wall, changes in the blood itself), metastatic spread stain for blood films in 1914 and observed Leishman-Donovan of tumours (Virchow’s lymph node), and components and bodies (LD bodies) in leishmaniasis. diseases of blood (fibrinogen, leukocytosis, leukaemia). Robert Feulgen (1884–1955) described Feulgen reaction for The concept of frozen section examination while the patient DNA staining and laid the foundations of cytochemistry and was still on the operation table was introduced by Virchow’s histochemistry. student, Julius Cohnheim (1839–1884). In fact, during the Simultaneous technological advances in machinery initial period of development of surgical pathology around the manufacture led to development and upgrading of microtomes turn of the 19th century, frozen section was considered more for obtaining thin sections of organs and tissues for staining by acceptable by the surgeons. dyes for enhancing detailed study of sections. The concept of surgeon and physician doubling up in Though the presence of cells in thin sections of non-living the role of pathologist which started in the 19th century object cork had been first demonstrated much earlier by continued as late as the middle of the 20th century in most Robert Hooke in 1667, it was revived as a unit of living matter in the 19th century by F.T. Schwann (1810–1882), the first clinical departments. Assigning biopsy pathology work to neurohistologist, and Claude Bernarde (1813–1878), pioneer in some faculty member in the clinical department was common pathophysiology. practice; that is why some of the notable pathologists of the Until the end of the 19th century, the study of morbid first half of 20th century had background of clinical training anatomy had remained largely autopsy-based and thus had e.g. James Ewing (1866–1943), A.P. Stout (1885–1967) remained a retrospective science. Rudolf Virchow (1821–1905) and Lauren Ackerman (1905–1993) in US, Pierre Masson in Germany is credited with the beginning of microscopic (1880–1958) in France, and R.A. Willis in Australia. examination of diseased tissue at cellular level and thus A few other landmarks in further evolution of modern began histopathology as a method of investigation. Virchow pathology in this era are as follows: hypothesised cellular theory having following two components: Karl Landsteiner (1863–1943) described the existence of All cells come from other cells. major human blood groups in 1900 and is considered “father Disease is an alteration of normal structure and function of of blood transfusion”; he was awarded Nobel prize in 1930 these cells. (Fig. 1.9). Virchow was revered as Pope in pathology in Europe and Ruska and Lorries in 1933 developed electron microscope is aptly known as the ‘father of cellular pathology’ (Fig. 1.8). which aided the pathologist to view ultrastructure of cell and Thus, sound foundation of diagnostic pathology based on its organelles. tahir99 - UnitedVRG - vip.persianss.ir 6 FATHER OF CELLULAR PATHOLOGY FATHER OF BLOOD TRANSFUSION FATHER OF EXFOLIATIVE CYTOLOGY SECTION I General Pathology Figure 1.8 Rudolf Virchow (1821–1905). Figure 1.9 Karl Landsteiner (1863–1943). An Figure 1.10 George N Papanicolaou (1883– German pathologist who proposed cellular Austrian pathologist who first discovered the 1962). An American pathologist, who deve theory of disease and initiated biopsy existence of major human blood groups in loped Pap test for diagnosis of cancer of pathology for diagnosis of diseases. 1900 and was recipient of Nobel prize in 1930. uterine cervix. The development of exfoliative cytology for early detection MODERN PATHOLOGY of cervical cancer began with George N. Papanicolaou The strides made in the latter half of 20th century until recent (1883–1962), a Greek-born, American pathologist, in 1930s and times in 21st century have made it possible to study diseases is known as ‘father of exfoliative cytology’ (Fig. 1.10). at genetic and molecular level, and provide an evidence- Another pioneering contribution in pathology in the based and objective diagnosis that may enable the physician 20th century was by an eminent teacher-author, William to institute targeted therapy. The major impact of advances in Boyd (1885–1979), psychiatrist-turned pathologist, whose molecular biology are in the field of diagnosis and treatment textbooks—‘Pathology for Surgeons’ (first edition 1925) and of genetic disorders, immunology and in cancer. Some of ‘Textbook of Pathology’ (first edition 1932), dominated and the revolutionary discoveries during this time are as under inspired the students of pathology all over the world due to (Fig. 1.11): his flowery language and lucid style for a few generations. Description of the structure of DNA of the cell by Watson M.M. Wintrobe (1901–1986), a pupil of Boyd who discovered and Crick in 1953. haematocrit technique, regarded him as a very stimulating Identification of chromosomes and their correct number in teacher. humans (46) by Tijo and Levan in 1956. Figure 1.11 Molecular structure of human chromosome. tahir99 - UnitedVRG - vip.persianss.ir Identification of Philadelphia chromosome t(9;22) in Method of image capture, commonly a camera mounted 7 chronic myeloid leukaemia by Nowell and Hagerford in 1960 on light microscope. as the first chromosomal abnormality in any cancer. Telecommunications link between sending and receiving In Situ hybridization (ISH) introduced in 1969 in which side. CHAPTER 1 a labelled probe is employed to detect and localise specific Workstation at receiving end with a high quality monitor. RNA or DNA sequences ‘in situ’ (i.e. in the original place). Its Depending upon need and budget, telepathology system is later modification employs use of fluorescence microscopy of two types: (FISH) to detect specific localisation of the defect on chromosomes. Static (store-and-forward, passive telepathology) In this, Recombinant DNA technique developed in 1972 using selected images are captured, stored and then transmitted restriction enzymes to cut and paste bits of DNA. over the internet via e-mail attachment, file transfer protocol, Introduction of polymerase chain reaction (PCR) i.e. web page or CD-ROM. It is quite inexpensive and is more common but suffers from disadvantage of having sender’s bias “xeroxing” of DNA fragments by Kary Mullis in 1983 has in selection of transmitted images. Introduction to Pathology revolutionised the diagnostic molecular genetics. PCR analysis is more rapid than ISH, can be automated by thermal cyclers Dynamic (Robotic interactive telepathology) Here, the and requires much lower amount of starting DNA. images are transmitted in real-time from a remote microscope. Invention of flexibility and dynamism of DNA by Barbara Robotic movement of stage of microscope is controlled remotely McClintock for which she was awarded Nobel prize in 1983. and the desired images and fields are accessioned from a Mammalian cloning started in 1997 by Ian Wilmut and his remote/local server. Thus, it almost duplicates to perfection the colleagues at Roslin Institute in Edinburgh, by successfully examination of actual slides under the microscope, hence is using a technique of somatic cell nuclear transfer to create referred to as Virtual Microscopy. However, image quality and the clone of a sheep named Dolly. Reproductive cloning for speed of internet can be major hurdles. human beings, however, is very risky besides being absolutely The era of “digital pathology” in 21st Century has reached its unethical. zenith with availability of technology for preparation of virtual The era of stem cell research started in 2000s by harvesting pathology slides (VPS) by high speed scanners and then storing the scanned data in large memory output computers. VPS these primitive cells isolated from embryos and maintaining their growth in the laboratory. There are 2 types of sources of stored in the memory of the computer can then be examined stem cells in humans: embryonic stem cells and adult stem and reported at any place on computer, without having to use cells, the former being more numerous. Stem cells are seen by microscope. However, the moot question remains whether many researchers as having virtually unlimited applications current pathologists used to conventional microscopy will get in the treatment of many human diseases such as Alzheimer’s the same perception on monitor. At present, this technology disease, diabetes, cancer, strokes, etc. At some point of time, holds potential for pathology education, storage for records, stem cell therapy may be able to replace whole organ transplant clinical meetings and quality control. and instead stem cells ‘harvested’ from the embryo may be used. SUBDIVISIONS OF PATHOLOGY Human Genome Project (HGP) consisting of a consortium of Human pathology is conventionally studied under two broad countries was completed in April 2003 coinciding with 50 years divisions: General Pathology dealing with general principles of of description of DNA double helix by Watson and Crick in April disease, and Systemic Pathology that includes study of diseases 1953. The sequencing of human genome reveals that human pertaining to the specific organs and body systems. In general, genome contains approximately 3 billion base pairs of amino the study of pathology includes morphological and non- acids, which are located in the 23 pairs of chromosomes within morphological disciplines as follows: the nucleus of each human cell. Each chromosome contains an estimated 30,000 genes in the human genome which carry MORPHOLOGICAL BRANCHES the instructions for making proteins. The HGP has given us the ability to read nature’s complete genetic blueprint used These branches essentially involve application of microscope in making of each human being (i.e. gene mapping). Clinical as an essential tool for the study and include histopathology, trials by gene therapy on treatment of some single gene defects cytopathology and haematology. have resulted in some success, especially in haematological A. HISTOPATHOLOGY Histopathology, used synonymously and immunological diseases. Future developments in genetic with anatomic pathology, pathologic anatomy, morbid engineering may result in designing new and highly effective anatomy, or tissue pathology, is the classic method of study individualised treatment options for genetic diseases as well as and still the most useful one which has stood the test of time. suggest prevention against diseases. The study includes structural changes observed by naked eye examination referred to as gross or macroscopic changes, and TELEPATHOLOGY AND VIRTUAL MICROSCOPY the changes detected by microscopy, which may be further supported by numerous special staining methods such as Telepathology is defined as the practice of diagnostic pathology histochemistry and immunohistochemistry to arrive at the by a remote pathologist utilising images of tissue specimens most accurate diagnosis. Modern time anatomic pathology transmitted over a telecommunication network. The main includes sub-specialities such as cardiac pathology, pulmo components of a telepathology system are as under: nary pathology, neuropathology, renal pathology, gynaeco Conventional light microscope. logic pathology, breast pathology, dermatopathology, tahir99 - UnitedVRG - vip.persianss.ir 8 gastrointestinal pathology, oral pathology, and so on. Anatomic Obviously, there is likely to be overlapping between clinical pathology includes the following subdivisions: pathology and clinical biochemistry. 1. Surgical pathology It deals with the study of tissues C. MICROBIOLOGY This is study of disease-causing removed from the living body by biopsy or surgical resection. microbes implicated in human diseases. Depending upon the SECTION I Surgical pathology forms the bulk of tissue material for the type of microorganims studied, it has further developed into pathologist and includes study of tissue by conventional such as bacteriology, parasitology, mycology, virology etc. paraffin embedding technique; intraoperative frozen section D. IMMUNOLOGY Detection of abnormalities in the may be employed for rapid diagnosis. immune system of the body comprises immunology and 2. Experimental pathology This is defined as production of immunopathology. disease in the experimental animal and study of morphological E. MEDICAL GENETICS This is the branch of human changes in organs after sacrificing the animal. However, all the genetics that deals with the relationship between heredity findings of experimental work in animals may not be applicable and disease. There have been important developments in the General Pathology to human beings due to species differences. field of medical genetics e.g. in blood groups, inborn errors 3. Forensic pathology and autopsy work This includes of metabolism, chromosomal aberrations in congenital the study of organs and tissues removed at postmortem for malformations and neoplasms etc. medicolegal work and for determining the underlying sequence F. MOLECULAR PATHOLOGY The detection and diagnosis and cause of death. By this, the pathologist attempts to of abnormalities at the level of DNA of the cell is included in reconstruct the course of events how they may have happened molecular pathology such as in situ hybridisation, PCR etc. in the patient during life which culminated in his death. These methods are now not only used for research purposes but Postmortem anatomical diagnosis is helpful to the clinician to are also being used as a part of diagnostic pathology reports. enhance his knowledge about the disease and his judgement The above divisions of pathology into several subspeciali while forensic autopsy is helpful for medicolegal purposes. ties are quite artificial since overlapping of disciplines is likely, The significance of a careful postmortem examination is ultimate aim of pathologist being to establish the final diagnosis appropriately summed up in the old saying ‘the dead teach the and learn the causes and mechanisms of disease. Towards this living’. aim, the beginner as well as the teacher in pathology remain life-long students of pathology, eager to learn more in their B. CYTOPATHOLOGY Though a branch of anatomic quest to become better with every passing day. pathology, cytopathology has developed as a distinct subspeciality in recent times. It includes study of cells shed off from the lesions (exfoliative cytology) and fine-needle GIST BOX 1.1 Introduction to Pathology aspiration cytology (FNAC) of superficial and deep-seated lesions for diagnosis (Appendix I). Pathology is the study of structural and functional changes in disease. C. HAEMATOLOGY Haematology dea

Textbook of Pathology (7th Edition) PDF

Document Details

Tags

Related

Summary

Full Transcript

Upgrade to continue