Introduction to Biopsy Interpretation and Surgical Pathology
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2 J.C.E. Underwood Introduction to Biopsy Interpretation and Surgical Pathology Second Edition With 85 Figures Springer-Verlag London Berlin Heidelberg New York Paris Tokyo
3 ].C.E. Underwood, MD, FRCPath. Joseph Hunter Professor of Pathology, University of Sheffield Medical School, and Honorary Consultant Histopathologist, Royal Hallamshire Hospital, Sheffield S10 2RX, England ISBN-13: e-isbn-13: DOl: / British Library Cataloguing in Publication Data Underwood, ].C.E. Introduction to biopsy interpretation and surgical pathology.-2nd ed. Pathological-Technique I. Title ' 583 RB43 1. Histology, Library of Congress Cataloging-in-Publication Data Underwood, ].C.E. (James Cressee Elphinstone) Introduction to biopsy interpretation and surgical pathology. Includes bibliographies and index. 1. Pathology, Surgical. 2. Biopsy. I. Title [DNLM: 1. Biopsy. 2. Diagnosis, Surgical. WO 142 U55i] RD57 U ' The work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying, machine or similar means, and storage in data banks. Springer-Verlag Berlin Heidelberg 1981,1987 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceuticalliterarure. Filmset and printed by BAS Printers Limited, Over Wallop, Hampshire. 2128/
4 Preface Preface to the Second Edition Since publication of the first edition, continuing developments in histopathology have motivated the inclusion of four new chapters: cytology, immunohistology, quality control and assessment, and the autopsy. The increasing use of cytology in clinical practice and advances in techniques and diagnostic interpretation justify the devotion of more space than formerly to this important topic. Immunohistology now merits a separate chapter because it has a status beyond that of being just another "special stain" and there are certain aspects of technique and interpretation that are peculiar to it. Quality control and assessment in histopathology are very topical and important now that greater attention is being paid to cost effectiveness and the auditing of many aspects of clinical practice. The autopsy is an integral part of the professional life of a histopathologist and, though it lacks the immediate clinical impact of the biopsy diagnosis, it nevertheless constitutes an important activity in all hospitals; without detailing dissection techniques I have provided some information and guidance about the autopsy which I believe will be useful to trainees and of interest to others. The remainder of the book has been thoroughly revised and updated, and illustrations and tables added where experience has shown that the text is insufficient. Sheffield, October 1986 J.C.E. Underwood Preface to the First Edition This book is primarily addressed to the needs of the trainee histopathologist. It is intended to bridge that gap between the descriptive histopathology taught as part of the undergraduate medical curriculum and the interpretative skills required of the diagnostician. My object is to convey the basic general principles, in theory and practice. Books are, however, only adjuncts to practical experience and not substitutes for it. Indeed, to obtain the maximum benefit from this book it is essential that the reader is actively involved in the work of a diagnostic laboratory. Only in this way can the trainee become thoroughly conversant with the rudiments of biopsy interpretation.
5 VI Preface To retain detailed knowledge of the histological appearances of the plethora of diseases and their permutations to which humans are subject is beyond the mental resources of most individuals. For this reason, histopathologists probably refer to books more often than do most other specialists. This book aims to provide a core of knowledge sufficient to master the fundamental aspects, while still encouraging the intelligent use of all those indispensable atlases, monographs and fascicles for which there is no substitute. I make no apologies for beginning the text with a brief account of the history of the biopsy. The origins of biopsy diagnosis might be dismissed as having little relevance to current practice, but it is often easier to understand a subject if one can see how it has evolved and recognise the various ways in which it may continue to develop. Also, it would have been easy to evade the need for a systematic consideration of the actual processes of interpretation. Having decided that the reader should be introduced to heuristics and pattern recognition, I was anxious to avoid giving an idiosyncratic account of something so personal and subjective. I hope I have succeeded in showing that there is nothing particularly arcane about the methods we use to interpret histological tmages. The histopathological diagnosis does not begin and end with the inert, twodimensional, brightly coloured artifact of the stained histological section. It begins with a living patient and ends with a credible report embodying a diagnosis or any other information that may guide the treatment of the patient. Modern investigative techniques may be needed to solve some diagnostic problems and for that reason I have included a general introduction to newer methods of histopathological analysis of proven clinical value. These include electron microscopy, immunological methods and stereology. Those who work in laboratories without such resources will, I hope, find guidance to the potential usefulness of these relatively sophisticated techniques. Perhaps they will be prompted to seek appropriate help and advice from colleagues who have access to the materials and skills that are necessary to solve some of the more difficult problems that may come their way. I have referred to published work liberally but not uncritically. I hope that the text will whet the reader's appetite for more information and give directions as to where it may be satiated. For the trainee, this will be an introduction to biopsy interpretation and surgical pathology in the context of contemporary clinical medicine. The text is an overview and commentary on current theory and practice in histopathology; I would, therefore, be well pleased if senior pathologists or clinicians also found something of interest and value in these pages. Sheffield, January I98I j.ce. Underwood
6 Acknowledgements I am very grateful to the many readers of the first edition who made helpful and positive comments, most of which I have been able to accommodate. Although the book continues to be aimed primarily at trainee histopathologists, it has been read by many of their more experienced seniors and I am indebted to them for their encouragement and advice in the preparation of this new edition. I continue to be indebted to Drs. M. E. Boxer, C. D. Franklin, J. R. Goepel and L. Harvey, whose guidance and comments during the preparation of the first edition was invaluable. The assistance of Mr. T. E. Durrant and Mr. T. Gray with aspects of electron microscopy and X-ray microanalysis is acknowledged, and Mr. G. Anderson's advice about special stains has continued to be indispensable. Dr. N. Rooney and Miss Patricia Mills helped with the selection of illustrative material for the new chapter on immunohistology, and Mr. J. Lawry provided the DNA profiles illustrating the section on flow cytometry. Many colleagues have allowed me to use illustrations prepared from their own case material, notably Drs. A. J. Coup, J. R. Goepel, P. Gray, A. S. Hill, M. A. Parsons, C. M. D. Ross and J. R. Shortland. Permission to reproduce illustrations from their published work or unpublished material was given generously by Dr. J. D. Davies of Bristol, Dr. B. Dixon of Leeds, Professor 1. R. H. Kramer of London and Dr. E. J. Wilkinson of Milwaukee. I am also grateful for permission from the Editor and publishers of the Lancet to reproduce extended quotations from the published works of J. H. Bennett and Ernest Shaw; the Editor of the American Journal of the Medical Sciences and Charles B. Slack, Inc. to reproduce the extended quotation from the published work of F. Donaldson; the Editor of the British Journal of Cancer and H. K. Lewis & Co. Ltd. to reproduce Fig. 1.I; Dr. J. E. Rhoads, Editor, Cancer, and the American Cancer Society to reproduce Figs. 2.4 and 3.I3; Professor R. E. Cotton, Editor, Histopathology, and Blackwell Scientific Publications Ltd. to reproduce Fig. 9.8; and the Editors and publishers of the Journal of Clinical Pathology to reproduce Fig. Io.6. Figure 9.I was kindly supplied by Philips of Eindhoven and Figure 10.3 is modified from an illustration provided by Becton Dickinson. The quality of the illustrations is to the credit of Mr. M. J. Eaton. My secretary, Mrs. Mary Hogg, and latterly Mrs. Brenda Barrass, deciphered and typed and sometimes retyped the script; for this and all their other help with the preparation of this edition, I am most grateful. The enthusiasm and
7 Vlll Acknowledgements guidance of Mr. Michael Jackson and his colleagues of Springer-Verlag continues to be much appreciated. This new edition would not have appeared without the personal support of my closest friends and family. I dedicate it to them.
8 Contents I Diagnostic Histopathology I Origins of Histopathology I The Objectives of Histopathology Clinical Diagnosis Epidemiology Treatment Selection and Monitoring Clinical Research Autopsies and Clinicopathological Correlation Medicolegal Aspects The Histopathological Diagnosis Diagnosis and Disease Diagnostic Processes Diagnostic Fallibility Adverse Effects of Biopsy Prospects for Histopathology Macroscopy, Microscopy and Sampling 17 Sampling Error... I7 Sampling Biopsies and Surgical Resections Suspected or Proven Neoplasia Ischaemic and Vascular Lesions Infection and Inflammatory Lesions Metabolic and Degenerative Diseases Specific Types of Biopsy Needle Biopsies Mucosal Biopsies Curettings Cone Biopsies Specimen Radiology Section Thickness Thick Sections I Thin Sections Imprints and Smears Information and Magnification
9 x Contents 3 The Use of Stains Principles of Staining Indications for Special Stains Identification of Specific Substances and Cells Connective Tissues Carbohydrates Nucleic Acids Fats Minerals and Pigments Organisms Specific Cells Autoradiography Immunohistology Techniques for Immunohistology Direct Method Indirect Method Tracer-Complex Method Avidin-Biotin Method Hapten Method Enzyme-Bridge Method Labelled-Antigen Method Primary Antibodies Bridging Reagents Tracer Substances Fluorochromes Enzymes Gold Particles Double-Labelling Techniques Fixation Use of Enzymes to Unmask Antigens Endogenous Peroxidase Controls Common Applications Investigation of Lymphoproliferative Disorders Determination of Tumour Histogenesis Renal Biopsies Problems of Interpretation Immuno-electron Microscopy Interpretation of Histological Appearances Artifact of Sections Basic Microscopy Artifacts in Sections Methods of Interpretation Heuristic Analysis... " 75 Pattern Recognition Clinicopathological Integration
10 Contents Xl Morphology of Disease Processes Evolution of Lesions Modification by Treatment Significance of Specific Morphological Features Morphological Overlap Between Diseases Cytology Relative Merits of Cytology and Histology Cytological Preparations Exfoliation Aspiration Fine-Needle Aspiration Cytology Miscellaneous Methods Stains for Cytology Haematoxylin and Eosin Romanovsky Stains Papanicolaou Special Investigations... lor Immunohistochemistry Electron Microscopy Flow Cytometry Interpretation Applications Epithelial "Dysplasias" and Malignancy Serous Effusions Infective Lesions Solid Tumours Fat Embolism Inflammatory Lung Diseases Living Cells Reporting Cytology Borderline Lesions, Pseudomalignancy and Mimicry I II Borderline Lesions III Discrete Versus Continuous Diagnostic Categories III Use of Criteria II2 Mimicry of Histological Features I I 3 Pseudomalignancy and Related Diagnostic Problems lis Skin Soft Tissues Lymphoid Tissues Bone Breasts Urinary Tract Thyroid Male Genitalia Female Genital Tract Gastrointestinal Tract
11 xii Contents Respiratory Tract Serosal Surfaces Central Nervous System Conclusions Rapid Frozen Section Diagnosis Clinical Indications Methods Interpretation Common Applications Breast Lesions Thyroid Parathyroid Glands Gastrointestinal Tract Respiratory Tract Urinary Tract Bone and Soft Tissues Skin Reliability Diagnostic Electron Microscopy Principles of Transmission Electron Microscopy The Electron Microscope Specimen Processing... IF Diagnostic Value of Electron Microscopy Renal Disease Tumour Histogenesis Virus Identification Miscellaneous Applications Scanning Electron Microscopy X-ray Microanalysis Quantitative Methods Stereological Principles Stereological Methods Volumetric Analysis Surface Area Surface-to-Volume Ratios Particle Size and Density Automatic and Semi-automatic Image Analysis Microspectrophotometry Flow Cytometry Practical Applications Metabolic Bone Disease Jejunal Biopsies Respiratory Tract Tumours
12 Contents xiii II Reporting and Classification of Biopsy Diagnoses The Biopsy Report Gross Description..., 177 Histology Other Investigations Summary Reporting Tumours Disease Classifications "Lumping" and "Splitting" Nomenclature and Codes Problems in Tumour Classification and Grading Data Storage and Retrieval Clinical Assimilation I2 Quality Assessment and Control Sources of Diagnostic Error The "Correct" Diagnosis Evaluation of Diagnostic Methods Evaluation of Performance Illustrative Examples Liver Biopsy Interpretation Bladder Tumour Grading Breast Carcinoma Grading National and Institutional Schemes Self Assessment Assessment of Errors of Procedure and Communication Conclusions The Autopsy History of the Autopsy The Autopsy and Clinical Audit Role in Medical Education Hazards in the Autopsy Room Consent General Techniques Special Methods Microbiology Post-mortem Biochemistry The Needle Autopsy The Frozen Section Autopsy Post-mortem Histology Subject Index
13 Explanatory Note Some clarification of the words "biopsy", "surgical pathology" and "histopathology" is necessary at this point. "Biopsy" is derived from the Greek ~ i (life) o 8 and 6 ~ (view). 1 8 The word is used in two ways; first, to describe the process of removal of tissue from the living patient for diagnostic purposes (e.g. to biopsy the liver) and, secondly, to describe the actual tissue that has been removed (e.g. a liver biopsy). In both senses the emphasis is on diagnosis. "Biopsy" is also loosely used to describe the removal of any piece of tissue from the living body for examination; the examination may just be an assessment of a disease process that has been previously diagnosed (e.g. gastrectomy for endoscopically diagnosed carcinoma). "Surgical pathology" is a branch of anatomical pathology dealing with the examination of tissues for the diagnosis and guidance in the care of patients; this safely encompasses the strict and loose meanings of "biopsy". At the risk of being pedantic, it must be pointed out that "surgical pathology" is restricted by some dictionaries to the pathology of those diseases accessible to surgical procedures. "Histopathology" is the study of diseased tissue; strictly used, this applies only to the cytological and histological structure of the tissues, though some might prefer a broader definition that includes any investigation of diseased tissues. "Diagnostic histopathology" is the application of histopathology to the examination of tissues removed for the diagnosis and care of patients.
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