Paediatric Pathology Springer London Berlin Heidelberg New York Barcelona Budapest Hong Kong Milan Paris Santa Clara Singapore Tokyo Colin L. Berry (Ed.) Paediatric Pathology Third Edition With 851 Figures Springer Sir Colin Berry, DSc, MD, PhD, FRCPath, FRCP Department of Morbid Anatomy, The Royal London Hospital. Whitechapel, London El J BB, UK. IS BN-13: 9 78-\-44 71-3027-7 e-ISBN-13: 978-\-4471-3025-3 DOl: 10.1007/978-1-447\-3025-3 British Library Cataloguing in Publication Data Paediatric Pathology. - 3Rev. ed I. Berry, Colin L. 618.92007 ISBN-13: 918-1-4411-3021-1 Library of Congress Cataloging-in-Publication Data Paediatric pathology 1C olin L. Berry (ed.). - 3rd cd p. cm. Includes bibliographical references and index. [S B N-13: 918-1-4411-3021-7 I. Pediatric pathology. I. Beny, Colin Leonard, 1937- {DNLM: I. Pediatrics. 2. Pathology. WS 200 PI255 1995J R149.P3 1995 618.92'007-dc20 DNLMlDCL for Library of Congress 95-33587 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permined under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced. stored or transmitted, in any form or by any means. with the prior permission in writing of the publishers. or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. e Springer-Verlag London Limited 1996 Softcover reprint of the hardcover 3rd edition 1996 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a spedfic statement, thaI such names arc: exempt from the reJevantlaws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof con tained in this book. In every individual case the respective uscr must check its accuracy by consulting other pharmaceuli callilerature. Typesetting: Expo Holdings. Malaysia 28/3830-543210 Printed on acid-free paper Preface to the First Edition The increased provision of facilities for neonatal and paediatric care in the last 25 years has been accompanied only in part by appropriate developments in pathology. Specialist pathologists are many fewer than paediatric departments, and details of the advances in knowledge of the pathogenesis of diseases in childhood and of ways of investigating them are not uniformly available. In many institutions an individual with a special interest rather than a special training will be responsible for paediatric pathology and it is to this group of histopathologists that this text is addressed. For this reason it is not written as a comprehensive text and is not intended for use as a reference volume. Areas which may produce particular difficulties for the individual with little specialist knowledge of the very young (e.g. the lung) are dealt with in more detail and, in general, entities in which the histopathology does not differ greatly from that of the adult disease are considered briefly. A brief account of developmental processes is included where prenatal considera tions are helpful in understanding a particular entity. A number of specialist topics which are known to trouble those who work in non-specialist departments are described fully (diseases of muscle) or with guides to investigation (metabolic disease). The value of investigation and careful description of abnormalities of development is also emphasized. The authors are from different backgrounds, paediatric pathologists (J.W. Keeling, J. Cox), pathologists in general departments with extensive experience in paediatric pathol ogy (C.L. Berry, R.A. Risdon, M. Becker, J. Smith) or specialists with an interest in the manifestation of diseases of which they have expert knowledge in the young (P.A. Revell, R.H. Anderson, C.L. Brown, M. Swash, A.E. Becker, B.D. Lake). All are valued and respected friends, who have been asked to contribute in a particular way; any errors or "design" faults are my own. Acknowledgements It is a pleasure to thank Professor A.E. Claireaux, a mentor of five of the authors, for his generosity in allowing us to use illustrations of many cases seen at The Hospital for Sick Children, Gt. Ormond Street. Our collective thanks are owed to Miss L. Singer who has made sense of many difficult manuscripts. Mr Michael Jackson and Mrs J. Dodsworth of Springer-Verlag have been unfailingly generous with help and advice in the preparation of the text. London Colin L. Berry 1981 Preface to the Second Edition Eight years have passed since the first edition of this book was published. It continues to be true that most autopsies in the paediatric age group are done by those who are not full time paediatric pathologists, but rather individuals with a particular interest in the pattern of disease in the young. Neonatal pathology is achieving deserved recognition as a speciality, but the provision of specialist posts lags behind the development of the subject For these reasons it is hoped that a text for the interested non-specialist histopathologist will still be useful. This edition has been modified in a number of ways: firstly by a simple updating - with change in knowledge more evident in some fields than others: secondly, by the addition of areas identified as deficient by kind (and critical) reviewers, notably in a new chapter on Infection by Professor R.O.c. Kaschula, but also in other fields, including the provision of more data helpful in estimating age in infants and chil dren at autopsy: thirdly, by modifying the structure of some chapters. Finally, the chapter on the placenta has been omitted as an Editorial decision; the text makes clear that detailed morphometric studies of the placenta are necessary to provide useful data with regard to the infant. These are beyond the scope of this book and detailed texts of placen tal changes per se are available elsewhere. A further Editorial decision has been made in citing only the first page of references. I am happy that all of the previous contributors agreed to revise their texts and glad to welcome R.O.C. Kaschula to their number. Professor R.A. Risdon is now Head of Department at Great Ormond Street, the pathological "base" of many of us. I thank Dr Mies Becker for her previous contributions and am glad that her careful studies will be published elsewhere. As before, design faults in the volume are my own. Acknowledgements Miss L. Singer has again made a valuable contribution to the production of the volume. I am grateful to Mr Michael Jackson and to Mr Roger Dobbing and the Production Department of Springer-Verlag for their help. London Colin L. Berry 1989 Preface to the Third Edition A shorter interval between the second and third editions of this book than between the first and second indicates both the rapid pace of change in pathology and the increasing requirement for all of us to involve ourselves in continuing education - a mandatory requirement for many. This is facilitated by better information and production systems, which now allow shorter intervals between editions, but it is important to note that this book is still intended to provide support for those who carry out paediatric pathology as part of their general duties in histopathology. However, no apologies are made for intro ducing new scientific concepts into the chapters on malformations and embryonic tumours and elsewhere; these concepts may underlie therapeutic and other interventions in the immediate future. The chapter on the central nervous system has been completely revised by a new author, Dr Jennian Geddes, and Professor Kaschula has written a new chapter on AIDS in this age group. The singular features of bone marrow disease in childhood are considered by Professor van den Tweel in more new text. New entities have been identified since 1989, and new data which help in dating fetuses are now available. As an example of changes in viewpoint, the pathogenesis of cystic fibrosis is becoming clearer as our knowledge of genetics increases, and this new understanding will modify the book more radically in the future. I hope it will help pathologists to understand disease processes better and inform their own careful studies, which have helped to define phenotypes accu rately enough to facilitate good genetic work. I am glad to welcome new authors and to be able to thank my long-term supporters. The radical changes in hospital and university organization which envelop all of us have not made writing or revising text an easy task, but almost everyone produced their text on time and the publishers have worked very effectively. Acknowledgements I am glad to be able to thank Miss Lorraine Singer once again for her help in establishing order where there was chaos and in identifyng areas where expected sections of text had failed to arrive, or where illustrations had disappeared. The Production Department at Springer-Verlag have worked very hard and I would like to thank Roger Dobbing who heads the team. It is with regret that I remember the former contributions of Mr Michael Jackson to the success of earlier editions of this book; medical publishing has lost a great deal by his untimely death. London Colin L. Berry 1995 Contents List of Contributors .................................................................................................... xv 1 Examination of the Fetus and the Neonatal Autopsy Colin L. Berry...................................................................................................... 1 History................................................................................................................. 1 Dimensions....................................... ................................................................... 2 Weights................................................................................................................ 2 Dating.................................................................................................................. 4 Chronology of Early Pregnancy .......................................................................... 4 External Examination .......................................................................................... 5 Internal Examination....... .................................................................................... 6 Abnormalities of Specific Systems................................ ...................................... 6 Blighted Ova ....................................................................................................... 8 Normal Organ Weights in the Fetus .................................................................... 8 Some Normal Historical Appearances During Development.............................. 9 The Neonatal Autopsy ......................................................................................... 32 Checklist for Paediatric Autopsy.......... ................... ....... ..................................... 40 2 Congenital Malformations Colin L. Berry...................................................................................................... 43 Genetics of Common Malformations .. ............... ....... ...................................... .... 46 Chromosomal Abnormality and Malformations.................................................. 53 Human Teratogens............................................................................................... 55 Infectious Causes of Abnormal Development..................................................... 61 Paternal Effects of Teratogens........ ............................ ......................................... 62 3 Cardiac Pathology Anton E. Becker and Robert H. Anderson.. ... ... ................. .................................. 67 Autopsy Technique.............................................................................................. 67 Examination of the Arrangement of the Organs (Situs) ...................................... 67 Sequential Segmental Analysis of the Heart ....................................................... 71 Congenital Heart Disease......................... .............................. ............................. 82 Congenital Malformations of the Aorta.... ... ....... ................................................ 113 Congenital Malformations of the Central Pulmonary Arteries............................ 115 Isolated Congenital Abnormalities of Endocardium, Myocardium and Pericardium ..................................................................................................... 115 xii Contents Congenital Heart Block....................................................................................... 116 Complications of Congenital Heart Disease........................................................ 117 Syndromes Commonly Associated with Cardiovascular Malformations ............ 122 Cardiac Tumours ... ... .... .......... ... ....... ....... ............. ....................... ............. ... ........ 125 4 Central Nervous System Jennian Geddes ................................................................................................... 131 Cell Populations in the CNS and their Reactions ...... ....... ......... .................... ...... 131 Assessment of Gestational Age ........................................................................... 134 Malformations ..................................................................................................... 135 Encephaloclastic Lesions........ ... ........... ............. ....... ................... ... .......... .... ...... 144 Hypoxic-ischaemic Brain Damage ...................................................................... 145 Cerebral Palsy ..................................................................................................... 150 Hydrocephalus..................................................................................................... 151 Raised Intracranial Pressure and Space-occupying Lesions................................ 153 Epilepsy .......................................................... ;.................................................... 156 Lead Poisoning.................................................................................................... 156 Inherited Metabolic Disease ................................................................................ 157 Non-inherited Metabolic Encephalopathies ........................................................ 164 Miscellaneous Neurodegenerative Conditions .................................................... 165 Neurocutaneous Syndromes ................................................................................ 166 Infections............................................................................................................. 170 Demyelination .......... ............. ....... .... ... ....... ... .............. ....... ......................... .... .... 181 Cerebrovascular Disease........ .......... .... ........................ .................. .......... .... ....... 181 Trauma ................................................................................................................ 183 Sudden Infant Death Syndrome (SIDS) .............................................................. 184 Tumours ....... .......... ....... ....................... ....... ....... ................. ........... .... .......... ....... 184 5 Gastrointestinal System Colin L. Berry and Jean W. Keeling ........................................ ............................ 207 Embryology........... .......... ............. ....... .......... ........... ..................... ...... ................ 207 Facial and Oral Abnormalities ... ................. ....... ....... ....... ... .................. ....... ....... 210 Salivary Glands ................................................................................................... 212 Oesophagus ............. .......... ......... ....... .... ............. ....... .......................................... 216 Stomach............................................................................................................... 220 Duodenum ........................................................................................................... 225 Pancreas ............. .......... ................ .................... .............. ......... ................ ............ 227 Small Bowel.... ... ....... ....... .......................... ... ... .... ... ....... ......... ............................ 231 Malformations of the Anus and Rectum.................................. ............................ 258 Polypoid Lesions of the Large Bowel ................................................................. 260 Appendix.............. ................... ....... ....... .......... ................. ......... ................ .......... 263 Ulcerative Colitis................................................................................................. 263 Crohn's Disease ................................................... ;............................................... 264 Perforation of the Large Bowel....... .............. .......... .......... ......... ......................... 264 Hernias ................................................................................................................ 265 Pneumatosis Intestinalis ........................... ....... ............. ... ......... ....... .................... 266 Malignant Tumours ....................................... , ..................................................... 266 Contents xiii 6 Liver and Gallbladder Colin L. Berry and Jean W. Keeling .................................................................... 275 Embryology ......................................................................................................... 275 Anomalies of Position, Form and Size ................................................................ 276 Cystic Disease................... ....................................................................... ........... 277 Erythroblastosis Fetalis ................... ................................................ .................... 280 Neonatal Jaundice ............................................................................................... 280 Metabolic Defects Causing Unconjugated Hyperbilirubinaemia ... ..................... 281 Inherited Metabolic Disease. ....... ............. ... .......... .................. ............................ 281 Giant Cell Transformation and Intrahepatic Cholestasis .................................. ... 286 Obstructive Jaundice ........................................................................................... 288 Intravenous Alimentation .................................................................................... 291 Infections............................................................................................................. 292 Reye's Syndrome ................................................................................................. 296 Kwashiorkor ........................................................................................................ 298 Cirrhosis ..................... ............. ....................... ................. .................................... 298 Thalassaemia............................... ..................................................... ................... 299 Mucoviscidosis...... ....... ....................................................................................... 299 Nodular Regenerative Hyperplasia...................................................................... 301 Budd-Chiari Syndrome ....................................................................................... 301 Aflatoxicosis........................................................................................................ 301 Tumours .............................................................................................................. 301 Gallbladder .............. ............................................................................................ 308 Cholecystitis......................... ....... .......... ......................................... ..................... 308 Cholelithiasis .... ....... ................ .............. ... ............. ....... ....................................... 309 7 Respiratory System Jerry N. Cox ........................................................................................................ 313 Development and Structure ................................................................................. 313 Nose and Nasopharynx ........................................................................................ 320 Larnyx and Trachea ............................................................................................. 332 Lungs ................................................................................................................... 347 Bronchial Lesions................................................................................................ 403 Lung Involvement in Metabolic Diseases ........................................................... 411 Tumours..... .................... ................. ........................................ ............................ 411 8 Kidney and Lower Urinary Tract R. Anthony Risdon...... .................................... ..................................................... 449 Embryology ......................................................................................................... 449 Congenital Anomalies..................... ............. .......... ............................................. 450 Cystic Diseases of the Kidney............................................... .............................. 459 Renal Diseases Principally Affecting the Glomeruli ........................................... 470 Renal Vascular Disease.................................. ......................... ............................ 486 Renal Infection ... ........................... ................... .............. ........................... .......... 490 Urolithiasis .......................................................................................................... 496 Hereditary Abnormalities of Renal Tubular Transport........................................ 497