Textbook of Pathology PDF

TEXTBOOK OF P ATHOLOGY The photographs on the cover of the textbook depict images of common diseases: Squamous cell Chronic ischaemic carcinoma heart dis...

TEXTBOOK OF P ATHOLOGY The photographs on the cover of the textbook depict images of common diseases: Squamous cell Chronic ischaemic carcinoma heart disease Pap smear aerodigestive tract Blood smear Cavitary tuberculosis lung invasive carcinoma cervix acute myeloid leukaemia Nodular lesions in Aspergillosis lung diabetic kidney TEXTBOOK OF P ATHOLOGY Harsh Mohan MD, MNAMS, FICPath, FUICC Professor & Head Department of Pathology Government Medical College Sector-32 A, Chandigarh-160 031 INDIA E mail: [email protected] ® JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD St Louis (USA) Panama City (Panama) New Delhi Ahmedabad Bengaluru Chennai Hyderabad Kochi Kolkata Lucknow Mumbai Nagpur Published by Jitendar P Vij Jaypee Brothers Medical Publishers (P) Ltd Corporate Office 4838/24 Ansari Road, Daryaganj, New Delhi 110 002, India, Phone: +91-11-43574357, Fax: +91-11-43574314 Registered Office B-3 EMCA House, 23/23B Ansari Road, Daryaganj, New Delhi 110 002, India Phones: +91-11-23272143, +91-11-23272703, +91-11-23282021, +91-11-23245672, Rel: +91-11-32558559 Fax: +91-11-23276490, +91-11-23245683 e-mail: [email protected], Website: www.jaypeebrothers.com Branches  2/B, Akruti Society, Jodhpur Gam Road Satellite Ahmedabad 380 015 Phones: +91-79-26926233, Rel: +91-79-32988717 Fax: +91-79-26927094 e-mail: [email protected]  202 Batavia Chambers, 8 Kumara Krupa Road, Kumara Park East Bengaluru 560 001 Phones: +91-80-22285971, +91-80-22382956, +91-80-22372664, Rel: +91-80-32714073 Fax: +91-80-22281761 e-mail: [email protected]  282 IIIrd Floor, Khaleel Shirazi Estate, Fountain Plaza, Pantheon Road Chennai 600 008 Phones: +91-44-28193265, +91-44-28194897, Rel: +91-44-32972089 Fax: +91-44-28193231 e-mail: [email protected]  4-2-1067/1-3, 1st Floor, Balaji Building, Ramkote Cross Road Hyderabad 500 095 Phones: +91-40-66610020, +91-40-24758498, Rel:+91-40-32940929 Fax:+91-40-24758499, e-mail: [email protected]  No. 41/3098, B & B1, Kuruvi Building, St. Vincent Road Kochi 682 018, Kerala Phones: +91-484-4036109, +91-484-2395739, +91-484-2395740 e-mail: [email protected]  1-A Indian Mirror Street, Wellington Square Kolkata 700 013 Phones: +91-33-22651926, +91-33-22276404, +91-33-22276415 Fax: +91-33-22656075, e-mail: [email protected]  Lekhraj Market III, B-2, Sector-4, Faizabad Road, Indira Nagar Lucknow 226 016 Phones: +91-522-3040553, +91-522-3040554 e-mail: [email protected]  106 Amit Industrial Estate, 61 Dr SS Rao Road, Near MGM Hospital, Parel Mumbai 400012 Phones: +91-22-24124863, +91-22-24104532, Rel: +91-22-32926896 Fax: +91-22-24160828, e-mail: [email protected]  “KAMALPUSHPA” 38, Reshimbag, Opp. Mohota Science College, Umred Road Nagpur 440 009 (MS) Phone: Rel: +91-712-3245220 Fax: +91-712-2704275 e-mail: [email protected] North America Office 1745, Pheasant Run Drive, Maryland Heights (Missouri), MO 63043, USA, Ph: 001-636-6279734 e-mail: [email protected], [email protected] Central America Office Jaypee-Highlights Medical Publishers Inc., City of Knowledge, Bld. 237, Clayton, Panama City, Panama, Ph: 507-317-0160 Textbook of Pathology © 2010, Harsh Mohan All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the author and the publisher. This book has been published in good faith that the material provided by author is original. Every effort is made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters are to be settled under Delhi jurisdiction only. First Edition : 1992 Second Edition : 1994 Third Edition : 1998 Fourth Edition : 2000 Fifth Edition : 2005 Sixth Edition: 2010 Assistant Editors: Praveen Mohan, Tanya Mohan, Sugandha Mohan ISBN: 978-81-8448-702-2 Typeset at JPBMP typesetting unit Printed at Ajanta Press      To deeds alone you have a right and   never at all to its fruits;   Let not the fruits of deeds be your motive;   Neither let there be in you   any detachment to performing your duty.   The Bhagvadgita (Chapter II, verse 47)     Dedicated to My family: spouse Praveen and daughters Tanya and Sugandha, for their love and constant support; & To all the students and colleagues: whose inspiration has made this ordinary work seem extraordinary.  Foreword to the Sixth Edition vii Foreword A few years ago I wrote the Foreword to the Fifth Edition of this Textbook. For details and reasons why I liked Professor Mohan’s book and why I recommended it then, please refer to my previous foreword below. My positive reaction to the previous Edition probably gives some clues on why I accepted the second invitation, this time to introduce the Sixth Edition to new students of Pathology and other potential readers. Great French writer André Gide once said “le problème n’est pas comment réussir mais comment durer”, which in translation to English means: The problem is not how to succeed but how to last. The fact that Dr Mohan’s book has reached its Sixth Edition is the best sign that you are holding in your hands a very successful book, and probably one of the medical bestsellers published on the Indian subcontinent. Up to now, it has been used by thousands of students and I am sure that it will continue to be read and cherished in the new Edition as well. For the Sixth Edition, Dr Mohan has partially restructured the book, substantially revised it, and updated the text wherever it was necessary. Following the advances of basic sciences and clinical pathology, the revisions and addition are most evident in portions pertaining to molecular biology and genetics. Other aspects of modern pathology have not been neglected either and contain numerous novelties; even the seasoned specialists will learn something new from each and every chapter. Furthermore, the author has dramatically increased the number of illustrations, which are so essential for understanding Pathology. The distribution of illustrations has also been changed so that they are now much closer to the text to which they relate. For the new generation of modern students who have grown up next to the computers, the author has placed all the images and tables on the website with facility for downloading them. These images will serve the twin purpose of quick review and self-assessment for students and will appeal to Pathology teachers who could use them for their lectures, being assured that their students will have access to the same material for review and study. The Quick Review Book, the ever popular companion to the previous two Editions, was also updated, succinctly supplementing the main text. It will provide a helpful study material to many a student and help them review the subject for examinations. In summary, it is my distinct pleasure and honour to most enthusiastically endorse the new edition of an established textbook and salute its publication. Dr Mohan deserves kudos for the job well done and for providing the medical students with such an attractive, modern, up-to-date and useful Textbook of Pathology. Ivan Damjanov, MD, PhD Professor of Pathology Foreword to the Fifth Edition As the Book Review Editor of the journal Modern Pathology, the official journal of the United States-Canadian Academy of Pathology I am used to receiving medical books. These books are sent to my office from publishers, with a standard request for a potential review in the Journal. Nevertheless a recent package from New Delhi caught me by surprise. As you already might have guessed, the parcel contained a copy of the 5th Edition of the Textbook of Pathology written by Professor Harsh Mohan, together with the Second Edition of the pocket size companion Pathology Quick Review and MCQs. Included was also a friendly letter from Mr JP Vij, the Publisher. I acknowledged the receipt of the books by email, and also congratulated the Publisher on a job well done. A brief electronic exchange between Kansas City and New Delhi ensued, whereupon Mr Vij asked me to write a foreword for the Reprint of 5th Edition of the Textbook. I accepted the invitation with pleasure. Even though there were no specific instructions attached to the request, I assumed that I should address my notes primarily to undergraduate and graduate students of Pathology. Furthermore, I decided to write the Foreword in the form of answers to the questions that I would have had if I were a medical student entering the field of Pathology. I hope that these hypothetical questions and answers of mine will be of interest to the readers of this Textbook. Question 1: Is this a good book? Answer: Yes. This is a modern Textbook written by an expert who knows his pathology; an experienced teacher who knows what is important and what is not, and who has obviously taught pathology for many years; a well informed academician who is au courant with modern trends in medical education, and knows how to present pathology as a preparatory step for future clinical education of medical students. Question 2: How does the book compare with the leading textbooks of pathology in the USA, Great Britain and Germany? Answer: Very favorably. This Indian Textbook covers more or less the same topics as the equivalent Textbooks currently used in the Western Hemisphere. Like the Western textbooks it covers the traditional fields of General and Systemic Pathology: one-third of the book  viii is devoted to General Pathology, whereas the remaining two-thirds cover Systemic Pathology. The emphasis is on classical anatomic pathology. In that respect the Indian textbook resembles more the European than the American textbooks, which have become more clinically-oriented. In my opinion this approach gives excellent results, but only if the students have enough time to devote to Pathology. In Textbook of Pathology most US medical schools this is not the case any more, and thus pathology is not taught as extensively as before. Histopathology has been deleted from most curricula, and most American medical students do not know to use efficiently the microscope, which is unfortunate. Question 3: Is the material presented in a “student-friendly” manner? Answer: The material is presented in a systematic manner in the best tradition of classical British textbooks, a tradition that can be traced to the classical writers of ancient Greece and Rome. This time tested teaching will be most appreciated by students who are methodical and do not take shortcuts in their effort to acquire encyclopedic knowledge of pathology. On the other hand, even if your learning method is based on “cherry-picking”, i.e. you concentrate only on the most important facts in each chapter, the structure of the text will allow you to do it quite easily as well. There are no ideal books that would satisfy everybody in every respect, but there is no doubt that Professor Mohan’s book is close to ideal for a classical pathology course and I predict that it will be popular with many students. Question 4: What are the most salient features of this textbook? Answer: Clear writing. As we all know clear writing reflects clear thinking, and clear thinking in my opinion, is an absolute prerequisite for good teaching. Judging from the book at hand, Professor Mohan (whom I do not know personally) is not only a clear thinker, but he must be also an exceptionally talented teacher. Clear and visually pleasing presentation. The exposition is logical and well structured. Each chapter is subdivided into smaller entities, which are further divided into paragraphs, ideally suited for easy reading. Color coded headings and the added emphasis in form of words printed in bold or capital letters are additional attractions that facilitate learning. Exceptionally good illustrations, flow-charts and tables. Unique to this Textbook are the numerous hand-drawn color illustrations, including many renditions of histopathologic slides. These drawings are simple, but to the point and well annotated. Students will most likely understand them much easier than the relatively impersonal original microphotographs of the same histopathologic lesions. Flow-charts are most efficiently used to explicate the pathogenesis of various lesions or the pathophysiology of disease processes. The tables are good for classifications and comparative listings of closely related diseases and their pathologic features. Companion pocket book (baby-book of pathology). I always recommend to my students to buy a major textbook and a smaller review book containing a digest of the most important concepts; or a book of questions and answers, so that the student could test his/her knowledge of pathology and the understanding of the material in the main textbook. I was pleased to see that Professor Mohan shares my teaching philosophy and has taken upon himself to prepare for his students a shorter version of main text. This pocket book is also garnered with review questions. The medical students are thus getting a bargain— two books for the price of one. At the same time, they have a unique opportunity to see, from the example set by their teacher, on how the same material can be approached from two points of view, and presented in two formats. The old adage, that you have never learned anything unless you have seen it at least from two sides, is clearly illustrated here. For the students of medicine the message is clear: if you understand the material presented in both the shorter and the longer version you can be assured that you know your Pathology inside out; and you are ready for the final examination and clinical training. Question 5: Do I have to know all that is in this book for my final examination? Answer: No!! This is the most common question my students ask me and I hope that you believe me when I say that you do not have to know it all. First of all, neither I nor Professor Mohan know it all. Second, few of us have photographic memory and infinite storage space in our brains and thus even theoretically, very few of us could learn this book by heart. I can assure you that the book was not written for those geniuses, but for the average persons like most of us. Third, your goal should not be to memorize all the facts listed in the textbook, but rather to understand the main concepts. Since the concepts cannot be fully understood or taught without specific examples, by necessity you will have to learn “some nitty-gritty details”. The more details you know, the deeper your understanding of the basic concepts will be. Memorizing the details without the understanding of concepts that hold them together is not something that I would recommend. The beauty of it all is that you can decide for yourself how deep to dig in, when to stop, what to keep and memorize, and what to eliminate. And remember, deciding on what to eliminate is almost as important as choosing what to retain. As the educational gurus teach us, that is the gist of what they call active learning. And to repeat again, this Textbook is ideally suited for that approach. At the end, let me repeat how excited I was perusing this excellent book. I hope that you will be similarly excited and I hope that it will inspire in you enthusiasm for Pathology. Remember also the words of the great clinician William Osler, one of the founders of modern medicine in late 19th and early 20th Century, who said that our clinical practice will be only as good as our understanding of Pathology. I hope that I have answered most of the questions that you might have had while opening this book. If you have any additional questions that I did not anticipate, please feel free to send me an email at [email protected]. Good luck! Ivan Damjanov, MD, PhD Professor of Pathology The University of Kansas School of Medicine Kansas City, Kansas, USA Dr Damjanov is Professor of Pathology at the University of Kansas School of Medicine, Kansas City, Kansas, USA. He earned his Medical degree from the University of Zagreb, Croatia in 1964, and a PhD degree in Experimental Pathology from the same University in 1970. He received his Pathology training in Cleveland, New York and Philadelphia. Thereafter he served as Professor of Pathology at the University of Connecticut, Farmington, Connecticut, Hahnemann University and Thomas Jefferson University, Philadelphia, Pennsylvania. For the last ten years he has been on the Faculty of the University of Kansas School of Medicine dividing his time between teaching, practice of surgical pathology and medical publishing. He is the author of more than 300 biomedical articles, and has written or edited more than 20 medical books.  Preface ix Preface The overwhelming success and all-round acceptance of the last edition of the textbook was very encouraging and quite stimulating but at the same time put an onerous responsibility and expectation to do better in the new edition than the best of last edition. In preparing 6th revised edition of my Textbook of Pathology, I pursued this goal with profound enthusiasm and passionate zeal. I am, thus, pleased to present to users a wholly transformed appearance and updated contents in the revised edition. While full colour printing had been introduced in the last edition 5 years back maturing the book into an international edition, the present redesigned and revised edition has utlilised the contemporary technological advances in its full form in illustrations, lay-out and in printing. The revised edition has almost thrice the number of illustrations of large number of common diseases placed along with the text, and it is hoped that it will enhance understanding and learning of the subject readily, besides being a visual treat. In recent times, advances in genetics, immunology and molecular biology have heightened our understanding of the mechanisms of diseases. As a result, mention of ‘idiopathic’ in etiology and pathogenesis of most diseases in the literature is slowly disappearing. Surely, the students of current times need to be enlightened on these modern advances in diseases; these aspects have been dealt in the revised edition with a simple and lucid approach. Some of the Key Features of the Sixth Edition are as follows: Thorough Textual Revision and Updating: All the chapters and topics have undergone thorough revision and updating of various aspects, including contemporary diagnostic modalities. While most of the newer information has been inserted between the lines, a few topics have been rewritten, e.g. current concepts on cell injury, immunopathology, carcinogenesis, newer infectious diseases, lymphomas-leukaemias, hypertension, interstitial lung diseases, etc. to name a few. 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. Past experience has shown that the readers find tables on contrasting features and listing of salient features as a very useful medium for quick learning; considering their utility 15 new tables have been added in different chapters in the revised edition. Reorganisation of the Book: In a departure from the conventional division of study of the subject into General and Systemic Pathology, the revised edition has been reorganised into 3 major sections—General Pathology and Basic Techniques (Chapters 1 to 11), Haematology and Lymphoreticular Tissues (Chapters 12 to 14) and Systemic Pathology (Chapters 15 to 30), followed by Appendix (containing Normal Values), Further Readings for references and Index. In my considered judgement, a separate section on haematology and lymphoid tissues and redistribution of their subtopics was necessitated for two reasons—firstly, reclassification of leukaemias-lymphomas by the WHO as an integrated topic, making the segregation of study of diseases of ‘circulating’ and ‘tissue’ leucocytes superfluous; and secondly, due to advances in haematology, transfusion medicine and diseases of lymphoreticular tissues, these subspecialties of pathology have developed a lot in recent times, requiring the students to focus on them separately for learning and they are evaluated too on these topics by separate experts. Similarly, in the revised edition, two chapters on laboratory techniques—Techniques for the Study of Pathology (Chapter 2) and Basic Diagnostic Cytology (Chapter 11) have been included in Section-I in view of technological advances in pathology which have gone beyond remaining confined as research tool but have increasingly become part of diagnostic work-up. Profusely Illustrated: Majority of illustrations in the revised Edition are new additions while a few old ones have been done again. All the line-drawing and schematic cartoons have been updated and improved in content as well as their presentation by preparing them again on CorelDraw in soft colours, eliminating the shortcomings noticed in them in previous edition. All free-hand labelled sketches of gross specimens and line-drawings of microscopic features of an entity have been placed alongside the corresponding specimen photograph and the photomicrograph respectively, enhancing the understanding of the subject for the beginner students in pathology. In doing so, the number of figures has gone up by about three-folds in the present edition, some incorporated as an inset with focus on a close-up microscopic view. Truly User-friendly: Rational use of various levels of headings and subheadings in different colours, bold face and in italics has been done in the text in order to highlight key points. All the citations of figures and tables in the text have been shown in colour now to make the related text vividly visible and to help user locate the same quickly on a page. It is hoped that these features will enable the user with rapid revision at the end of a topic, making the book truly user-friendly. Much More Content but Unaltered Volume: While the new edition has a lot more updated textual material, more tables and a marked increase in the number of figures than the previous edition, a meticulous and rational page management has helped in retaining almost the same girth of the book as before.  x Images and Tables on the Web: All the illustrations and tables included in this edition are being put on the website with a scratch key word on the inner page of the cover jacket. The students would find these useful for quick review and for self- assessment in which an unlabelled image (gross specimen or a photomicrograph) appears, followed by the labelled image Textbook of Pathology with diagnosis corresponding to the same figure and table in the textbook. Besides, ready availability of these downloadable images and tables would be useful to fellow teachers for possibly including the same in their lectures. Revised Pathology Quick Review and MCQs: The sixth 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 100 more new MCQs while some old ones have either been edited or replaced. A Word on Foreword: The Foreword by Prof Ivan Damjanov, MD, PhD, from Kansas University, US, for the previous edition and now for the sixth edition so generously and meticulously prepared with an eye to the details of the book, has been most welcome development, and has helped to bring the book closer to users in other parts of the world; I express our sincere gratitude to this eminent teacher and well-known author whom I have yet to meet in person. 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 revision work was indeed a mammoth task to accomplish and would not have been possible without active cooperation from friends and colleagues and continuous encouragement from well-wishers in general, and my departmental staff in particular who could bear with me for prolonged spells of my sabbatical leave. All the photomicrographs included in the present edition have been exposed afresh which has been made possible by the most valuable and selfless assistance rendered by my colleagues, Drs Shailja, Tanvi and Ujjawal, Senior Residents in Pathology, all of whom worked tirelessly for endless hours for months, much to the sacrifice of their personal comfort and time of their families, for which I am indebted to them. Here, I also recall the help accorded by my former students and colleagues in preparation of earlier editions of the book and thank once again, even though much of that may have been replaced. As always, I remain indebted to those from whom I had the opportunity to learn pathology; in particular to Prof K Joshi, MD, PhD, PGIMER, Chandigarh, Late Prof TS Jaswal, MD, and Prof Uma Singh, MD, formerly at PGIMS, Rohtak. Constant strategic support and encouragement extended by the Department of Medical Education and Research, Chandigarh Administration, during the completion of work is gratefully acknowledged. I may have been hard-task master and highly demanding on quality and accuracy from all staff members of the M/s Jaypee Brothers Medical Publishers (P) Ltd, at times losing my patience, but all of them have been very cooperative and quite accommodating. In particular, I would like to thank profusely Mr Manoj Pahuja, Computer Art Designer, for carrying out Herculean job on figures as per my requirements conscientiously and patiently with competence; Mrs Y Kapoor, Senior Desktop Operator, for overall lay-out of the book and acceding to all my requests for amendments smilingly and ungrudgingly till the very last minute; and Ms Chetna Malhotra, MBA, Senior Business Development Manager, for overseeing the entire project vigilantly and efficiently. All through this period, Mr Tarun Duneja, (Director-Publishing), M/s Jaypee Brothers Medical Publishers (P) Ltd, has been highly cooperative and supportive. Lastly, the vision of Shri JP Vij, Chairman and Managing Director of M/s Jaypee Brothers Medical Publishers (P) Ltd, has been to see the revised edition as unmatched internationally and keeping it affordable at the same time, much above his business interests, and I do hope his dream comes true. Full credit goes to M/s Ajanta Printers, Faridabad, for the admirably high quality of printing. Finally, the users of previous editions are gratefully acknowledged for having brought this textbook at this pedestal. In the past, I have gained profitably by suggestions from colleagues and students and I urge them to continue giving their valuable suggestions and point out errors, if any, so that I may continue to improve it. Government Medical College Harsh Mohan, MD, MNAMS, FICPath, FUICC Sector-32 A, Chandigarh-160031 Professor & Head INDIA Department of Pathology E mail: [email protected]  Contents xi Contents CHAPTER 5 GENERAL PATHOLOGY Section I AND BASIC TECHNIQUES Derangements of Homeostasis and 93 Haemodynamics CHAPTER 1 Homeostasis, 93 Introduction to Pathology 01 Disturbances of Body Fluids, 96 Study of Diseases, 1 Oedema, 96 Evolution of Pathology, 1 Dehydration, 102 Overhydration, 102 Subdivisions of Pathology, 7 Disturbances of Electrolytes, 103 CHAPTER 2 Acid-base Imbalance (Abnormalities in pH Techniques for the Study of Pathology 09 of Blood), 103 Haemodynamic Derangements, 104 Autopsy Pathology, 9 Disturbances in the Volume of Circulating Blood, 105 Surgical Pathology, 9 Haemorrhage, 107 Special Stains (Histochemistry), 11 Shock, 108 Circulatory Disturbances of Obstructive Nature, 113 Enzyme Histochemistry, 13 Thrombosis, 113 Basic Microscopy, 13 Embolism, 119 Immunofluorescence, 14 Ischaemia, 124 Electron Microscopy, 14 Infarction, 126 Immunohistochemistry, 15 Cytogenetics, 16 CHAPTER 6 Diagnostic Molecular Pathology, 17 Inflammation and Healing 130 Other Modern Aids in Diagnostic Pathology, 18 Inflammation, 130 CHAPTER 3 Introduction, 130 Cell Injury and Cellular Adaptations 21 Acute Inflammation, 130 Chemical Mediators of Inflammation, 136 The Normal Cell, 21 The Inflammatory Cells, 141 Etiology of Cell Injury, 27 Morphology of Acute Inflammation, 144 Chronic Inflammation, 147 Pathogenesis of Cell Injury, 28 General Features of Chronic Inflammation, 147 Morphology of Cell Injury, 34 Systemic Effects of Chronic Inflammation, 147 Intracellular Accumulations, 37 Types of Chronic Inflammation, 147 Pigments, 40 Granulomatous Inflammation, 148 Morphology of Irreversible Cell Injury Examples of Granulomatous Inflammation, 149 (Cell Death), 44 Tuberculosis, 149 Cellular Adaptations, 53 Leprosy, 157 Cellular Aging, 59 Syphilis, 161 Actinomycosis, 163 CHAPTER 4 Sarcoidosis (Boeck’s Sarcoid), 164 Immunopathology Including Healing, 165 Amyloidosis 61 Regeneration, 165 Repair, 166 Introduction, 61 Wound Healing, 167 Structure of Immune System, 61 Healing in Specialised Tissues, 171 HLA System and Major Histocompatibility CHAPTER 7 Complex, 64 Transplant Rejection, 65 Infectious and Parasitic Diseases 174 Diseases of Immunity, 66 Introduction, 174 Immunodeficiency Diseases, 67 Diseases Caused by Bacteria, Spirochaetes Acquired Immunodeficiency Syndrome (AIDS), 67 Hypersensitivity Reactions (Immunologic and Mycobacteria, 175 Tissue Injury), 73 Diseases Caused by Fungi, 181 Autoimmune Diseases, 77 Diseases Caused by Viruses, 183 Types and Examples of Autoimmune Diseases, 78 Diseases Caused by Parasites, 187 Amyloidosis, 82 Torch Complex, 190  xii CHAPTER 8 CHAPTER 11 Neoplasia 192 Basic Diagnostic Cytology 266 Textbook of Pathology Nomenclature and Classification, 192 Introduction, 266 Characteristics of Tumours, 194 Exfoliative Cytology, 267 Rate of Growth, 194 Female Genital Tract, 267 Cancer Phenotype and Stem Cells, 196 Respiratory Tract, 272 Clinical and Gross Features, 196 Gastrointestinal Tract, 273 Microscopic Features, 196 Urinary Tract, 273 Local Invasion (Direct Spread), 200 Body Fluids, 273 Metastasis (Distant Spread), 200 Buccal Smears for Sex Chromatin Bodies, 274 Grading and Staging of Cancer, 204 Techniques in Exfoliative Cytology, 275 Epidemiology and Predisposition to Interventional Cytology, 277 Neoplasia, 205 Fine Needle Aspiration Cytology, 277 Cancer Incidence, 205 Imprint Cytology, 283 Epidemiologic Factors, 205 Crush Smear Cytology, 283 Carcinogenesis: Etiology and Pathogenesis Biopsy Sediment Cytology, 283 of Cancer, 208 Molecular Pathogenesis of Cancer HAEMATOLOGY AND (Genetic Mechanism of Cancer), 208 Section II LYMPHORETICULAR TISSUES Chemical Carcinogenesis, 216 Physical Carcinogenesis, 220 CHAPTER 12 Biologic Carcinogenesis, 222 Introduction to Haematopoietic System Viruses and Human Cancer: A Summary, 228 Clinical Aspects of Neoplasia, 228 and Disorders of Erythroid Series 284 Tumour-host Inter-relationship, 228 Bone Marrow, 284 Pathologic Diagnosis of Cancer, 232 Haematopoiesis, 284 Haematopoietic Stem Cells, 285 CHAPTER 9 Bone Marrow Examination, 285 Environmental and Red Blood Cells, 287 Nutritional Diseases 236 Erythropoiesis, 287 Anaemia—General Considerations, 291 Introduction, 236 Anaemia of Blood Loss, 294 Environmental Pollution, 236 Hypochromic Anaemia, 295 Air Pollution, 236 Megaloblastic Anaemia, 303 Tobacco Smoking, 237 Pernicious Anaemia, 309 Chemical and Drug Injury, 238 Haemolytic Anaemias, 310 Therapeutic (Iatrogenic) Drug Injury, 238 Acquired (Extracorpuscular) Haemolytic Non-therapeutic Toxic Agents, 238 Anaemias, 311 Environmental Chemicals, 242 Hereditary (Intracorpuscular) Haemolytic Injury by Physical Agents, 242 Anaemia, 314 Thermal and Electrical Injury, 242 Aplastic Anaemia and Other Primary Bone Injury by Radiation, 242 Marrow Disorders, 324 Nutritional Diseases, 243 CHAPTER 13 Obesity, 243 Starvation, 245 Disorders of Platelets, Bleeding 327 Protein-energy Malnutrition, 245 Disorders and Basic Transfusion Disorders of Vitamins, 246 Medicine Metals and Trace Elements, 254 Thrombopoiesis, 327 Diet and Cancer, 254 Bleeding Disorders CHAPTER 10 (Haemorrhagic Diathesis), 328 Investigations of Haemostatic Function, 328 Genetic and Paediatric Diseases 256 Haemorrhagic Diatheses Due to Vascular Developmental Defects, 256 Disorders, 331 Haemorrhagic Diatheses Due to Platelet Cytogenetic (Karyotypic) Abnormalities, 257 Disorders, 331 Single-gene Defects (Mendelian Disorders), 259 Coagulation Disorders, 335 Storage Diseases (Inborn Errors of Haemorrhagic Diathesis Due to Fibrinolytic Metabolism), 260 Defects, 337 Multifactorial Inheritance, 263 Disseminated Intravascular Coagulation (DIC), 337 Other Paediatric Diseases, 263 Blood Groups and Blood Transfusion, 339  CHAPTER 14 Obstructions (Obstructive Congenital Heart xiii Disorders of Leucocytes and 342 Disease), 426 Ischaemic Heart Disease, 427 Lymphoreticular Tissues Contents Etiopathogenesis, 427 Lymph Nodes: Normal and Reactive, 342 Effects of Myocardial Ischaemia, 428 Normal Structure, 342 Angina Pectoris, 429 Reactive Lymphadenitis, 343 Acute Myocardial Infarction, 429 White Blood Cells: Normal and Reactive, 345 Chronic Ischaemic Heart Disease, 436 Sudden Cardiac Death, 436 Granulopoiesis, 345 Lymphopoiesis, 346 Hypertensive Heart Disease, 437 Infectious Mononucleosis, 350 Cor Pulmonale, 437 Leukaemoid Reactions, 352 Rheumatic Fever and Rheumatic Heart Haematologic Neoplasms Disease, 438 (Leukaemias-lymphomas): General, 353 Non-rheumatic Endocarditis, 444 Classification: Current Concepts, 353 Valvular Diseases and Deformities, 449 Myeloid Neoplasms, 356 Myocardial Disease, 452 Myeloproliferative Diseases, 356 Myocarditis, 452 Myelodysplastic Syndromes, 361 Cardiomyopathy, 454 Acute Myeloid Leukaemia, 362 Pericardial Disease, 456 Lymphoid Neoplasms, 365 Pericardial Fluid Accumulations, 456 General Comments on Lymphoid Malignancies, 368 Pericarditis, 457 Hodgkin’s Disease, 369 Tumours of the Heart, 459 Precursor (Immature) B- and T-cell Leukaemia/ Pathology of Cardiovascular Interventions, 459 Lymphoma (Synonym: Acute Lymphoblastic Leukaemia), 373 CHAPTER 17 Peripheral (Mature) B-cell Malignancies, 374 The Respiratory System 461 Peripheral (Mature) T-cell Malignancies, 379 Plasma Cell Disorders, 380 Lungs, 461 Lymph Node Metastatic Tumours, 385 Normal Structure, 461 Histiocytic Neoplasms: Paediatric Lung Disease, 462 Langerhans’ Cell Histiocytosis, 385 Pulmonary Vascular Disease, 465 Spleen, 386 Pulmonary Infections, 467 Thymus, 388 Pneumonias, 467 Lung Abscess, 475 Fungal Infections of Lung, 476 Section III SYSTEMIC PATHOLOGY Pulmonary Tuberculosis, 477 Chronic Obstructive Pulmonary Disease, 477 Chronic Bronchitis, 477 CHAPTER 15 Emphysema, 478 The Blood Vessels and Lymphatics 390 Bronchial Asthma, 483 Bronchiectasis, 484 Arteries, 390 Chronic Restrictive Pulmonary Disease, 486 Normal Structure, 390 Pneumoconioses, 487 Arteriosclerosis, 391 ILD Associated with Immunologic Lung Arteritis, 400 Diseases, 493 Aneurysms, 405 ILD Associated with Connective Tissue Fibromuscular Dysplasia, 409 Diseases, 495 Veins, 409 Idiopathic Pulmonary Fibrosis, 495 Lymphatics, 410 ILD Associated with Smoking, 496 Tumours and Tumour-like Lesions, 411 Tumours of Lungs, 496 Pleura, 504 CHAPTER 16 The Heart 417 CHAPTER 18 The Eye, ENT and Neck 507 Normal Structure, 417 Patterns and Classification of Heart Eye, 507 Diseases, 418 Ear, 513 Heart Failure, 419 Nose And Paranasal Sinuses, 515 Congenital Heart Disease, 422 Pharynx, 517 Malpositions of the Heart, 423 Larynx, 519 Shunts (Cyanotic Congenital Heart Disease), 423 Neck, 520  xiv CHAPTER 19 CHAPTER 21 The Oral Cavity and Salivary Glands 522 The Liver, Biliary Tract and 592 Exocrine Pancreas Textbook of Pathology Oral Soft Tissues, 522 Normal Structure, 522 Liver, 592 Developmental Anomalies, 522 Normal Structure, 592 Mucocutaneous Lesions, 522 Liver Function Tests, 593 Inflammatory Diseases, 522 Jaundice—General, 596 Pigmentary Lesions, 523 Neonatal Jaundice, 600 Tumours and Tumour-like Lesions, 523 Hepatic Failure, 602 Teeth and Periodontal Tissues, 527 Circulatory Disturbances, 603 Normal Structure, 527 Liver Cell Necrosis, 604 Dental Caries, 528 Viral Hepatitis, 605 Periodontal Disease, 529 Other Infections and Infestations, 614 Epithelial Cysts of the Jaw, 529 Chemical and Drug Injury, 617 Odontogenic Tumours, 531 Cirrhosis, 618 Salivary Glands, 533 Clinical Manifestations and Complications of Normal Structure, 533 Cirrhosis, 630 Salivary Flow Disturbances, 533 Portal Hypertension, 630 Sialadenitis, 533 Hepatic Tumours and Tumour-like Lesions, 632 Tumours of Salivary Glands, 534 Biliary System, 638 Normal Structure, 638 CHAPTER 20 Congenital Anomalies, 638 The Gastrointestinal Tract 538 Cholelithiasis (Gallstones), 638 Cholecystitis, 641 Oesophagus, 538 Tumours of Biliary System, 643 Normal Structure, 538 Exocrine Pancreas, 644 Congenital Anomalies, 538 Normal Structure, 644 Muscular Dysfunctions, 538 Developmental Anomalies, 645 Haematemesis of Oesophageal Origin, 539 Pancreatitis, 646 Inflammatory Lesions, 540 Tumours and Tumour-like Lesions, 647 Tumours of Oesophagus, 541 Stomach, 543 CHAPTER 22 Normal Structure, 543 The Kidney and Lower Urinary Tract 649 Gastric Analysis, 544 Congenital Anomalies, 545 Kidney, 649 Miscellaneous Acquired Conditions, 546 Normal Structure, 649 Inflammatory Conditions, 546 Renal Function Tests, 652 Haematemesis and Melaena of Gastric Origin, 554 Pathophysiology of Renal Disease: Tumours and Tumour-like Lesions, 554 Renal Failure, 653 Small Intestine, 560 Congenital Malformations, 656 Normal Structure, 560 Glomerular Diseases, 660 Congenital Anomalies, 561 Pathogenesis of Glomerular Injury, 662 Intestinal Obstruction, 562 Specific Types of Glomerular Diseases, 665 Ischaemic Bowel Disease Tubular and Tubulointerstitial Diseases, 678 (Ischaemic Enterocolitis), 563 Renal Vascular Diseases, 685 Inflammatory Bowel Disease Obstructive Uropathy, 690 (Crohn’s Disease and Ulcerative Colitis), 565 Tumours of Kidney, 693 Other Inflammatory Lesions of the Bowel, 569 Lower Urinary Tract, 698 Malabsorption Syndrome, 573 Normal Structure, 698 Small Intestinal Tumours, 576 Congenital Anomalies, 698 Appendix, 577 Inflammations, 698 Normal Structure, 577 Tumours, 700 Appendicitis, 578 Tumours of Appendix, 579 CHAPTER 23 Large Intestine, 579 The Male Reproductive System and 703 Normal Structure, 579 Prostate Congenital Malformations, 580 Colitis, 580 Testis and Epididymis, 703 Miscellaneous Lesions, 581 Normal Structure, 703 Miscellaneous Inflammatory Conditions, 581 Congenital Anomalies, 703 Large Intestinal Polyps and Tumours, 581 Inflammations, 705 Causes of Gastrointestinal Bleeding, 590 Miscellaneous Lesions, 706 Peritoneum, 590 Testicular Tumours, 706 Penis, 714 CHAPTER 26 xv Normal Structure, 714 The Skin 768 Congenital Anomalies, 714 Contents Inflammations, 714 Normal Structure, 768 Tumours, 714 Histopathologic Terms, 769 Prostate, 716 Dermatoses, 769 Normal Structure, 716 Genetic Dermatoses, 769 Prostatitis, 716 Non-infectious Inflammatory Dermatoses, 770 Nodular Hyperplasia, 717 Infectious Dermatoses, 771 Carcinoma of Prostate, 718 Granulomatous Diseases, 774 Connective Tissue Diseases, 774 CHAPTER 24 Non-infectious Bullous Dermatoses, 775 The Female Genital Tract 721 Scaling Dermatoses, 778 Metabolic Diseases of Skin, 778 Vulva, 721 Tumours and Tumour-like Lesions, 779 Normal Structure, 721 Tumours and Cysts of the Epidermis, 780 Bartholin’s Cyst and Abscess, 721 Adnexal (Appendageal) Tumours, 785 Non-neoplastic Epithelial Disorders, 721 Melanocytic Tumours, 787 Vulval Tumours, 722 Tumours of the Dermis, 789 Vagina , 723 Cellular Migrant Tumours, 790 Normal Structure, 723 Vaginitis and Vulvovaginitis, 723 CHAPTER 27 Tumours and Tumour-like Conditions, 723 The Endocrine System 791 Cervix , 724 Normal Structure, 724 Endocrines: The Basic Concept , 791 Cervicitis, 724 Pituitary Gland , 792 Tumours, 725 Normal Structure, 792 Myometrium and Endometrium , 730 Hyperpituitarism, 793 Normal Structure, 730 Hypopituitarism, 794 Normal Cyclic Changes, 730 Pituitary Tumours, 795 Effects of Hormones, 730 Adrenal Gland , 796 Dysfunctional Uterine Bleeding (DUB), 731 Normal Structure, 796 Endometritis and Myometritis, 732 Adrenocortical Hyperfunction Adenomyosis , 732 (Hyperadrenalism), 797 Endometriosis, 732 Adrenocortical Insufficiency (Hypoadrenalism), 798 Endometrial Hyperplasias, 733 Tumours of Adrenal Glands, 799 Tumours of Endometrium and Myometrium, 735 Thyroid Gland , 801 Fallopian Tubes, 738 Normal Structure, 801 Normal Structure, 738 Functional Disorders, 802 Inflammations, 738 Thyroiditis, 804 Ectopic Tubal Pregnancy, 739 Graves’ Disease (Diffuse Toxic Goitre), 806 Tumours and Tumour-like Lesions, 739 Goitre, 807 Ovaries, 739 Thyroid Tumours, 810 Normal Structure, 739 Parathyroid Glands, 815 Non-neoplastic Cysts, 740 Normal Structure, 815 Ovarian Tumours, 740 Hyperparathyroidism, 816 Placenta , 751 Hypoparathyroidism, 817 Normal Structure, 751 Parathyroid Tumours, 817 Hydatidiform Mole, 751 Endocrine Pancreas, 818 Choriocarcinoma, 753 Normal Structure, 818 Diabetes Mellitus, 818 CHAPTER 25 Islet Cell Tumours, 828 The Breast 754 Miscellaneous Endocrine Tumours, 829 Multiple Endocrine Neoplasia (MEN) Normal Structure, 754 Syndromes, 829 Non-neoplastic Conditions, 755 Polyglandular Autoimmune (PGA) Syndromes, 829 Inflammations, 755 Fibrocystic Change, 755 CHAPTER 28 Gynaecomastia (Hypertrophy of Male Breast), 757 The Musculoskeletal System 830 Breast Tumours, 757 Fibroadenoma, 757 Skeletal System, 830 Phyllodes Tumour (Cystosarcoma Phyllodes), 758 Normal Structure of Bone, 830 Intraductal Papilloma, 759 Normal Structure of Cartilage, 831 Carcinoma of the Breast, 759 Osteomyelitis, 831  xvi Avascular Necrosis (Osteonecrosis) , 833 CHAPTER 30 Fracture Healing, 834 The Nervous System 871 Disorders of Bone Growth and Development Textbook of Pathology (Skeletal Dysplasias), 834 Central Nervous System, 871 Metabolic and Endocrine Bone Diseases, 834 Normal Structure, 871 Paget’s Disease of Bone (Osteitis Deformans), 837 Developmental Anomalies, 872 Tumour-like Lesions of Bone, 837 Hydrocephalus, 873 Bone Tumours, 839 Infections, 874 Joints, 850 Cerebrovascular Diseases, 879 Normal Structure, 850 Trauma to the CNS, 882 Osteoarthritis, 850 Demyelinating Diseases, 883 Rheumatoid Arthritis, 851 Miscellaneous Diseases, 884 Suppurative Arthritis, 853 Tumours of the CNS, 886 Tuberculous Arthritis, 853 Peripheral Nervous System, 891 Gout and Gouty Arthritis, 853 Normal Structure, 891 Pigmented Villonodular Synovitis and Pathologic Reactions to Injury, 891 Tenosynovial Giant Cell Tumour, 855 Peripheral Neuropathy, 892 Cyst of Ganglion, 855 Nerve Sheath Tumours, 893 Bursitis, 856 Skeletal Muscles, 856 CHAPTER 29 Soft Tissue Tumours 860 APPENDIX General Features, 860 Tumours and Tumour-like Lesions of APPENDIX Fibrous Tissue, 861 Normal Values 896 Fibrohistiocytic Tumours, 864 Weights and Measurements of Tumours of Adipose Tissue, 865 Normal Organs, 896 Skeletal Muscle Tumours, 867 Tumours of Uncertain Histogenesis, 868 Laboratory Values of Clinical Significance, 897 Further Readings 904 Index 911  1 Section I GENERAL PATHOLOGY AND CHAPTER 1 BASIC TECHNIQUES Introduction to Pathology Chapter 1 Introduction to Pathology A term commonly confused with disease is illness. While STUDY OF DISEASES disease suggests an entity with a cause, illness is the reaction DEFINITION OF PATHOLOGY of the individual to disease in the form of symptoms (complaints of the patient) and physical signs (elicited by The word ‘Pathology’ is derived from two Greek words—pathos the clinician). Though disease and illness are not separable, meaning suffering, and logos meaning study. Pathology is, thus, the study of diseases is done in pathology while the learning scientific study of structure and function of the body in disease; and management of illnesses is done in wards and clinics. or in other words, pathology consists of the abnormalities that In addition to disease and illness, there are syndromes occur in normal anatomy (including histology) and physiology (meaning running together) characterised by combination owing to disease. Another commonly used term with reference of symptoms caused by altered physiologic processes. to study of diseases is ‘pathophysiology’ comprised by two words: patho=suffering; physiology=study of normal function. TERMINOLOGY IN PATHOLOGY Pathophysiology, thus, includes study of disordered function or breakdown of homeostasis in diseases. Pathologists are the It is important for a beginner in pathology to be familiar diagnosticians of disease. Therefore, knowledge and with the language used in pathology: understanding of pathology is essential for all would-be doctors, Patient is the person affected by disease. general medical practitioners and specialists since unless they Lesions are the characteristic changes in tissues and cells know the causes, mechanisms, nature and type of disease, and produced by disease in an individual or experimental understand the language spoken by the pathologist in the form animal. of laboratory reports, they would not be able to institute Pathologic changes or morphology consist of examination appropriate treatment or suggest preventive measures to the of diseased tissues. patient. For the student of any system of medicine, the discipline Pathologic changes can be recognised with the naked of pathology forms a vital bridge between initial learning phase eye (gross or macroscopic changes) or studied by microscopic of preclinical sciences and the final phase of clinical subjects. examination of tissues. Remember the prophetic words of one of the eminent founders of modern medicine in late 19th and early 20th century, Sir Causal factors responsible for the lesions are included William Osler, “Your practice of medicine will be as good as in etiology of disease (i.e. ‘why’ of disease). your understanding of pathology.” Mechanism by which the lesions are produced is termed pathogenesis of disease (i.e. ‘how’ of disease). HEALTH AND DISEASE Functional implications of the lesion felt by the patient Before there were humans on earth, there was disease, albeit in are symptoms and those discovered by the clinician are the early animals. Since pathology is the study of disease, then what physical signs. is disease? In simple language, disease is opposite of health i.e. Clinical significance of the morphologic and functional what is not healthy is disease. Health may be defined as a changes together with results of other investigations help condition when the individual is in complete accord with the to arrive at an answer to what is wrong (diagnosis), what is surroundings, while disease is loss of ease (or comfort) to the going to happen (prognosis), what can be done about it body (i.e. dis-ease). However, it must be borne in mind that in (treatment), and finally what should be done to avoid health there is a wide range of ‘normality’ e.g. in height, weight, complications and spread (prevention) (i.e. ‘what’ of disease). blood and tissue chemical composition etc. It also needs to be appreciated that at cellular level, the cells display wide range of activities within the broad area of health similar to what is EVOLUTION OF PATHOLOGY seen in diseased cells. Thus, health and disease are not absolute Pathology as the scientific study of disease processes has but are considered as relative states. its deep roots in medical history. Since the beginning of  2 mankind, there has been desire as well as need to know more about the causes, mechanisms and nature of diseases. The answers to these questions have evolved over the centuries— from supernatural beliefs to the present state of our SECTION I knowledge of modern pathology. However, pathology is not separable from other multiple disciplines of medicine and owes its development to interaction and interdependence on advances in diverse neighbouring branches of science, in addition to the strides made in medical technology. As we shall see in the pages that follow, pathology has evolved over the years as a distinct discipline from anatomy, medicine and General Pathology and Basic Techniques surgery, in that sequence. The brief review of fascinating history of pathology and its many magnificent personalities with their outstanding contribution in the opening pages of the book is meant to pay our obeisance to those great personalities who have laid glorious foundations of our speciality. Life and works of those whose names are mentioned below are linked to some disease or process—the aim being to stimulate the inquisitive beginner in pathology as to how this colourful specialty has emerged. FROM RELIGIOUS BELIEFS AND MAGIC TO RATIONAL APPROACH (PREHISTORIC TIME TO AD 1500) Figure 1.1 Hippocrates (460-370 BC). The great Greek clinical Present-day knowledge of primitive culture prevalent in the genius and regarded as ‘the father of medicine’. He introduced ethical world in prehistoric times reveals that religion, magic and aspects to medicine. medical treatment were quite linked to each other in those times. The earliest concept of disease understood by the two thousand years (Hippocratic aphorism). Some of the patient and the healer was the religious belief that disease major Hippocratic methods can be summarised as under: was the outcome of ‘curse from God’ or the belief in magic Observe all objectively. that the affliction had supernatural origin from ‘evil eye of Study the patient rather than the disease. spirits.’ To ward them off, priests through prayers and Evaluate honestly. sacrifices, and magicians by magic power used to act as faith- Assist nature. healers and invoke supernatural powers and please the gods. Hippocrates introduced ethical concepts in the practice Remnants of ancient superstitions still exist in some parts of of medicine and is revered by the medical profession by taking the world. The link between medicine and religion became ‘Hippocratic oath’ at the time of entry into practice of medicine. so firmly established throughout the world that different Greek medicine after Hippocrates reached Rome (now societies had their gods and goddesses of healing; for example: Italy), which controlled Greek world after 146 BC and therefore mythological Greeks had Asclepios and Apollo as the principal dominated the field of development of medicine in ancient gods of healing, Dhanvantri as the deity of medicine in India, Europe then. In fact, since ancient times, many tongue- and orthodox Indians’ belief in Mata Sheetala Devi as the pox twisting terminologies in medicine have their origin from goddess. Latin language which was the official language of countries The period of ancient religious and magical beliefs was included in ancient Roman empire (Spanish, Portugese, followed by the philosophical and rational approach to disease Italian, French and Greek languages have their origin from by the methods of observations. This happened at the time Latin). when great Greek philosophers—Socrates, Plato and Aristotle, Hippocratic teaching was propagated in Rome by Roman introduced philosophical concepts to all natural phenomena. physicians, notably by Cornelius Celsus (53 BC-7 AD) and But the real practice of medicine began with Hippocrates Cladius Galen (130–200 AD). Celsus first described four cardinal (460–370 BC), the great Greek clinical genius of all times and signs of inflammation—rubor (redness), tumor (swelling), regarded as ‘the father of medicine’ (Fig. 1.1). Hippocrates calor (heat), and dolor (pain). Galen postulated humoral followed rational and ethical attitudes in practice and teaching theory, later called Galenic theory. This theory suggested that of medicine as expressed in the collection of writings of that the illness resulted from imbalance between four humors (or era. He firmly believed in study of patient’s symptoms and body fluids): blood, lymph, black bile (believed to be from described methods of diagnosis. The prevailing concept of the spleen), and biliary secretion from the liver. mechanism of disease based on disequilibrium of four basic The hypothesis of disequilibrium of four elements consti- humors (water, air, fire, and earth) was propagated by tuting the body (Dhatus) similar to Hippocratic doctrine finds Hippocates too. He recorded his observations on cases in mention in ancient Indian medicine books compiled about writing which remained the mainstay of medicine for nearly 200 AD—Charaka Samhita, a finest document by Charaka on medicine listing 500 remedies, and Sushruta Samhita, similar Marcello Malpighi (1624–1694) used microscope extensively 3 book of surgical sciences by Sushruta, and includes about 700 and observed the presence of capillaries and described the plant-derived medicines. malpighian layer of the skin, and lymphoid tissue in the spleen CHAPTER 1 The end of Medieval period was marked by backward (malpighian corpuscles). Malpighi is known as ‘the father of steps in medicine. There were widespread and devastating histology.’ epidemics which reversed the process of rational thinking The credit for beginning of the study of morbid anatomy again to supernatural concepts and divine punishment for (pathologic anatomy), however, goes to Italian anatomist- ‘sins.’ The dominant belief during this period was that life pathologist, Giovanni B. Morgagni (1682–1771). Morgagni was was due to influence of vital substance under the control of an excellent teacher in anatomy, a prolific writer and a soul (theory of vitalism). Thus, dissection of human body was practicing clinician. By his work, Morgagni demolished the strictly forbidden as that would mean hurting the ‘soul.’ ancient humoral theory of disease and published his life-time Introduction to Pathology experiences based on 700 postmortems and their FROM HUMAN ANATOMY TO ERA OF corresponding clinical findings. He, thus, laid the foundations GROSS PATHOLOGY (AD 1500 to 1800) of clinicopathologic methodology in the study of disease and introduced the concept of clinicopathologic correlation (CPC), The backwardness of Medieval period was followed by the establishing a coherent sequence of cause, lesions, symptoms, Renaissance period i.e. revival of leaning. The Renaissance and outcome of disease (Fig. 1.3). began from Italy in late 15th century and spread to whole of Sir Percival Pott (1714–1788), famous surgeon in England, Europe. During this period, there was quest for advances in identified the first ever occupational cancer in the chimney art and science. Since there was freedom of thought, there sweeps in 1775 and discovered chimney soot as the first was emphasis on philosophical and rational attitudes again. carcinogenic agent. However, the study of anatomy in The beginning of the development of human anatomy England during the latter part of 18th Century was took place during this period with the art works and drawings dominated by the two Hunter brothers: John Hunter (1728– of human muscles and embryos by famous Italian painter 1793), a student of Sir Percival Pott, rose to become greatest Leonardo da Vinci (1452–1519). Dissection of human body was surgeon-anatomist of all times and he, together with his elder started by Vesalius (1514–1564) on executed criminals. His brother William Hunter (1718–1788) who was a reputed pupils, Gabriel Fallopius (1523–1562) who described human anatomist-obstetrician (or man-midwife), started the first oviducts (Fallopian tubes) and Fabricius who discovered ever museum of pathologic anatomy. John Hunter made a lymphoid tissue around the intestine of birds (bursa of collection of more than 13,000 surgical specimens from his Fabricius) further popularised the practice of human anatomic flourishing practice, arranged them into separate organ dissection for which special postmortem amphitheatres came systems, made comparison of specimens from animals and in to existence in various parts of ancient Europe (Fig. 1.2). plants with humans, and included many clinical pathology Antony van Leeuwenhoek (1632–1723), a cloth merchant by specimens as well, and thus developed the first museum of profession in Holland, during his spare time invented the first comparative anatomy and pathology in the world which ever microscope by grinding the lenses himself through which became the Hunterian Museum, now housed in Royal he recognised male spermatozoa as tiny preformed men (or College of Surgeons of London (Fig. 1.4). Amongst many “homunculi”) and blood corpuscles. He also introduced pupils of John Hunter was Edward Jenner (1749–1823) whose histological staining in 1714 using saffron to examine muscle work on inoculation in smallpox is well known. Another fibres. prominent English pathologist was Matthew Baillie (1760– 1823), nephew of Hunter brothers, who published first-ever systematic textbook of morbid anatomy in 1793. The era of gross pathology had three more illustrious and brilliant physician-pathologists in England who were colleagues at Guy’s Hospital in London: Richard Bright (1789–1858) who described non- suppurative nephritis, later termed glomerulonephritis or Bright’s disease; Thomas Addison (1793–1860) who gave an account of chronic adrenocortical insufficiency termed Addison’s disease; and Thomas Hodgkin (1798–1866), who observed the complex of chronic enlargement of lymph nodes, often with enlargement of the liver and spleen, later called Hodgkin’s disease. Towards the end of 18th century, Xavier Bichat (1771–1802) in France described that organs were composed of tissue and divided the study of morbid anatomy into Figure 1.2 In 16th Century, postmortem amphitheatre in Europe General Pathology and Systemic Pathology. R.T.H. Laennec was a place of learning human anatomic dissection conducted and demonstrated by professors to eager learners and spectators. (1781–1826), another French physician, dominated the early  4 FATHER OF CPCs FATHER OF MUSEUM IN PATHOLOGY FATHER OF CLINICAL PATHOLOGY SECTION I General Pathology and Basic Techniques Figure 1.3 Giovanni B. Morgagni (1682– Figure 1.4 John Hunter (1728-1793). Figure 1.5 Paul Ehrlich (1854-1915). 1771), an Italian physician-anatomist who Scottish surgeon, regarded as the greatest German physician, conferred Nobel prize for introduced clinicopathologic methodology in the surgeon-anatomist of all times who established his work in immunology, described Ehrlich’s test study of disease by correlation of clinical first ever unique collection of pathological for urobilinogen, staining techniques of cells findings with findings at postmortem exami- specimens that later resulted in the Hunterian and bacteria, and laid the foundations of nation. Museum of the Royal College of Surgeons, haematology and clinical pathology. London. part of 19th century by his numerous discoveries. He spontaneous generation of disease and firmly established described several lung diseases (tubercles, caseous lesions, germ theory of disease. Subsequently, G.H.A. Hansen miliary lesions, pleural effusion, bronchiectasis), chronic (1841–1912) in Germany identified Hansen’s bacillus as sclerotic liver disease (later called Laennec’s cirrhosis) and causative agent for leprosy (Hansen’s disease) in 1873. While invented stethoscope. the study of infectious diseases was being made, the concept Morbid anatomy attained its zenith with appearance of of immune tolerance and allergy emerged which formed the Carl F. von Rokitansky (1804–1878), self-taught German basis of immunisation initiated by Edward Jenner. Ilya pathologist who performed nearly 30,000 autopsies himself. Metchnikoff (1845-1916), a Russian zoologist, introduced the He described acute yellow atrophy of the liver, wrote an existence of phenomenon of phagocytosis by human defense outstanding monograph on diseases of arteries and cells against invading microbes. congenital heart defects. Unlike most other surgeons of that Developments in chemical industry helped in switch over time, Rokitansky did not do clinical practice of surgery but from earlier dyes of plant and animal origin to synthetic dyes; instead introduced the concept that pathologists should aniline violet being the first such synthetic dye prepared by confine themselves to making diagnosis which became the Perkin in 1856. This led to emergence of a viable dye industry accepted role of pathologist later. for histological and bacteriological purposes. The impetus for the flourishing and successful dye industry came from the ERA OF TECHNOLOGY DEVELOPMENT AND works of numerous pioneers as under: CELLULAR PATHOLOGY (AD 1800 TO 1950s) Paul Ehrlich (1854–1915), German physician, conferred Nobel prize in 1908 for his work in immunology, described Ehrlich’s Up to middle of the 19th century, correlation of clinical test for urobilinogen using Ehrlich’s aldehyde reagent, staining manifestations of disease with gross pathological findings techniques of cells and bacteria, and laid the foundations of at autopsy became the major method of study of disease. clinical pathology (Fig. 1.5). Sophistication in surgery led to advancement in pathology. Christian Gram (1853–1938), Danish physician, who The anatomist-surgeons of earlier centuries got replaced developed bacteriologic staining by crystal violet. largely with surgeon-pathologists in the 19th century. D.L. Romanowsky (1861–1921), Russian physician, who Pathology started developing as a diagnostic discipline developed stain for peripheral blood film using eosin and in later half of the 19th century with the evolution of cellular methylene blue derivatives. pathology which was closely linked to technology Robert Koch (1843–1910), German bacteriologist who, besides advancements in machinery manufacture for cutting thin Koch’s postulate and Koch’s phenomena, developed techniques sections of tissue, improvement in microscope, and of fixation and staining for identification of bacteria, discovered development of chemical industry and dyes for staining. tubercle bacilli in 1882 and cholera vibrio organism in 1883. The discovery of existence of disease-causing micro- May-Grunwald in 1902 and Giemsa in 1914 developed blood organisms was made by French chemist Louis Pasteur stains and applied them for classification of blood cells and bone (1822–1895), thus demolishing the prevailing theory of marrow cells.  Sir William Leishman (1865–1926) who described Leishman’s of tumours (Virchow’s lymph node), and components and 5 stain for blood films in 1914 and observed Leishman-Donovan diseases of blood (fibrinogen, leukocytosis, leukaemia). bodies (LD bodies) in leishmaniasis. The concept of frozen section examination when the CHAPTER 1 Robert Feulgen (1884–1955) who described Feulgen reaction patient was still on the operation table was introduced by for DNA staining and laid the foundations of cytochemistry and Virchow’s student, Julius Cohnheim (1839–1884). In fact, histochemistry. during the initial period of development of surgical Simultaneous technological advances in machinery pathology around the turn of the 19th century, frozen manufacture led to development and upgradation of section was considered more acceptable by the surgeons. microtomes for obtaining thin sections of organs and tissues Then there was the period when morphologic examination for staining by dyes for enhancing detailed study of sections. of cells by touch imprint smears was favoured for diagnostic Though the presence of cells in thin sections of non-living purposes than actual tissue sections. Subsequently, further Introduction to Pathology object cork had been first demonstrated much earlier by Robert advances in surgical pathology were made possible by Hooke in 1667, it was revived as a unit of living matter in the improved machinery and development of dyes and stains. 19th century by F.T. Schwann (1810–1882), the first The concept of surgeon and physician doubling up in neurohistologist, and Claude Bernarde (1813–1878), pioneer in the role of pathologist which started in the 19th century pathophysiology. continued as late as the middle of the 20th century in most Until the end of the 19th century, the study of morbid clinical departments. Assigning biopsy pathology work to anatomy had remained largely autopsy-based and thus had some faculty member in the clinical department was remained a retrospective science. Rudolf Virchow (1821–1905) in common practice; that is why some of the notable Germany is credited with the beginning of microscopic pathologists of the first half of 20th century had background examination of diseased tissue at cellular level and thus began of clinical training e.g. James Ewing (1866–1943), A.P. Stout histopathology as a method of investigation. Virchow gave two (1885–1967) and Lauren Ackerman (1905–1993) in US, Pierre major hypotheses: Masson (1880–1958) in France, and RA Willis in Australia. All cells come from other cells. A few other landmarks in further evolution of modern Disease is an alteration of normal structure and function of pathology in this era are as follows: these cells. Karl Landsteiner (1863–1943) described the existence of Virchow came to be referred as Pope in pathology in Europe major human blood groups in 1900 and was awarded Nobel and is aptly known as the ‘father of cellular pathology’ prize in 1930 and is considered father of blood transfusion (Fig. 1.6). Thus, sound foundation of diagnostic pathology had (Fig. 1.7). been laid which was followed and promoted by numerous Ruska and Lorries in 1933 developed electron microscope brilliant successive workers. Thus, knowledge and skill gained which aided the pathologist to view ultrastructure of cell by giving accurate diagnosis on postmortem findings started and its organelles. being applied to surgical biopsy and thus emerged the discipline The development of exfoliative cytology for early of surgical pathology. Virchow also described etiology of detection of cervical cancer began with George N. Papanicolaou embolism (Virchow’s triad—slowing of blood-stream, changes