Table of Contents
Cover
Dedication
Title page
Copyright page
Contributors
Foreword
Preface
About the companion website
PART 1: Oesophagus
CHAPTER 1 The normal oesophagus: anatomy, specimen dissection and histology relevant to pathological practice
Anatomy
Histology
Handling of endoscopic and resection oesophageal specimens
CHAPTER 2 Normal embryology, fetal development and developmental abnormalities
Embryology and fetal development
Anomalies of development
Atresia, stenosis and tracheo-oesophageal fistula
CHAPTER 3 Neuromuscular and mechanical disorders of the oesophagus
Classification
Progressive systemic sclerosis (scleroderma)
Primary muscle disorders
Diffuse oesophageal spasm and other motility disorders of the oesophagus
Achalasia
Diverticula, rings and webs
Acquired hiatus hernia
Muscular and connective tissue changes associated with eosinophilic oesophagitis
CHAPTER 4 Inflammatory disorders of the oesophagus
Classification
Reflux oesophagitis
Infective oesophagitis
Eosinophilic oesophagitis
Other forms of oesophagitis
CHAPTER 5 Barrett’s oesophagus
Introduction
Definition, diagnosis and histological appearances
SSCLO
USSCLO
Effects of treatment
Dysplasia in Barrett’s oesophagus
CHAPTER 6 Polyps and tumour-like lesions of the oesophagus
Inflammatory/hyperplastic polyp
Giant fibrovascular polyp
Glycogenic acanthosis
Diffuse leiomyomatosis
CHAPTER 7 Tumours of the oesophagus
Benign epithelial tumours
Malignant epithelial tumours
Well differentiated endocrine (carcinoid) tumour
Malignant melanoma
Mesenchymal tumours
Secondary tumours
Leukaemia and lymphoma
CHAPTER 8 Miscellaneous conditions of the oesophagus
Trauma
Oesophageal casts
Varices
Webs and rings
Barium sulphate in the oesophagus
PART 2: Stomach
CHAPTER 9 The normal stomach: anatomy, specimen dissection and histology relevant to pathological practice
Anatomy and specimen dissection
Histology
CHAPTER 10 Congenital abnormalities of the stomach
Normal development
Developmental abnormalities
CHAPTER 11 Inflammatory disorders of the stomach
Classification of ‘gastritis’ and ‘gastropathies’
Gastropathies
Gastritides
Peptic ulcer disease
Atrophic gastritis and gastric atrophy
Autoimmune gastritis
Acute gastritis
Uraemic gastropathy
Other forms of gastritis
CHAPTER 12 Polyps and tumour-like lesions of the stomach
Epidemiology
Classification of gastric polyps
Fundic gland polyps
Hyperplastic polyps
Adenoma
Polyps developing in the setting of polyposis
Non-epithelial and malformative polypoid lesions
Ménétrier’s disease
Polyp-like lesions
CHAPTER 13 Epithelial tumours of the stomach
Benign epithelial tumours
Malignant epithelial tumours
Staging gastric cancer
Hereditary gastric cancer syndromes
Molecular aspects of gastric carcinoma
Endocrine cell tumours
Secondary carcinoma in the stomach
CHAPTER 14 Stromal tumours of the stomach
Gastrointestinal stromal tumours
Tumours of neural origin
Tumours of smooth muscle origin
Vascular tumours
Tumours of adipose tissue
Other mesenchymal tumours
CHAPTER 15 Lymphoid tumours of the stomach
Introduction
Primary gastric lymphomas
Extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)
Primary gastric diffuse large B-cell lymphoma
Other primary gastric lymphomas
Secondary lymphomatous involvement
Miscellaneous haematological malignancies
CHAPTER 16 Miscellaneous conditions
Acute gastric dilatation
Motility disorders
Amyloidosis
Gastric bezoars
Gastric hyalinisation
Pseudo-lipomatosis
Pseudo-xanthoma elasticum
Graft-versus-host disease
Vascular disorders
PART 3: Small Intestine
CHAPTER 17 Normal small intestine: anatomy, specimen dissection and histology relevant to pathological practice
Gross anatomy
Physiology
Microscopic anatomy
Distinctive regional characteristics
CHAPTER 18 Congenital abnormalities of the small intestine
Normal development
Small intestinal development
Malformations
Maldevelopment
CHAPTER 19 Muscular and mechanical disorders of the small intestine
Intussusception
Internal (intra-abdominal) hernia
Volvulus
Perforation and rupture
Small intestinal obstruction
Intestinal pseudo-obstruction
CHAPTER 20 Inflammatory disorders of the small intestine
Inflammation due to identifiable micro-organisms
Bacterial infection
Fungal infection
Protozoal infection
Helminthic infection
Crohn’s disease
Drug-induced enteropathy
Miscellaneous inflammatory conditions of the small intestine
Radiation enteritis
Behçet’s disease
Ileal reservoirs and pouchitis
Ulcerative colitis in the small intestine
Ileostomy pathology and ileal conduits
Obstructive ileitis
Non-specific jejunitis
Chronic ‘non-specific’ duodenitis
CHAPTER 21 The pathology of malnutrition and malabsorption
Introduction
Histopathological diagnosis of malabsorptive states
Malnutrition due to unsatisfactory diet
Malnutrition due to defects in absorption and metabolism
Food intolerance
Miscellaneous causes of malnutrition
CHAPTER 22 Vascular disorders of the small intestine
Vascular anatomy of the small intestine
Vascular physiology of the small intestine
Pathogenesis of vascular disorders of the small intestine
Occlusive ischaemia
Non-occlusive ischaemia
Nomenclature of vascular pathology in the small intestine
Histopathology of intestinal ischaemia
Vasculitis and other primary vascular lesions in the small intestine
CHAPTER 23 Polyps and tumour-like lesions of the small intestine
Brunner’s gland hyperplasia/hamartoma/adenoma
Peri-ampullary myo-epithelial hamartoma/adenomyoma
Peutz–Jeghers polyps
Juvenile polyps
Cronkhite–Canada syndrome
Pyogenic granuloma
CHAPTER 24 Epithelial tumours of the small intestine
Introduction
Molecular genetics of small intestinal neoplasia
Adenomas
Adenocarcinoma
Endocrine tumours
Metastatic epithelial tumours
Acknowledgement
CHAPTER 25 Stromal tumours of the small intestine
Gastrointestinal stromal tumours
Smooth muscle tumours of the small intestine
Inflammatory myofibroblastic tumour/inflammatory fibrosarcoma
Tumours of adipose tissue
Vascular tumours
Neural tumours of the small intestine
Translocation sarcomas involving the small intestine
CHAPTER 26 Lymphoid and other tumours of the small intestine
Benign lymphoid proliferations
Primary malignant lymphoma of the small intestine
Leukaemic and secondary lymphomatous involvement of the small intestine
Metastatic disease to the small intestine
CHAPTER 27 Miscellaneous disorders of the small intestine
Amyloidosis
Bypass operations
Cholesterol ester storage disease
Endometriosis
Pneumatosis cystoides intestinalis
Malakoplakia
Systemic mastocytosis
Melanosis and pseudo-melanosis
Zinc deficiency
Pseudo-lipomatosis
Graft-versus-host disease
Small intestinal transplantation
PART 4: Appendix
CHAPTER 28 Normal appendix: anatomy, specimen dissection and histology relevant to pathological practice
Anatomy
Histology
Specimen dissection
CHAPTER 29 Inflammatory disorders of the appendix
Acute non-specific appendicitis
Other forms of appendicitis
CHAPTER 30 Tumours of the appendix
Low grade appendiceal mucinous neoplasms
Adenocarcinoma
Pseudomyxoma peritonei
Hyperplastic polyp, diffuse mucosal hyperplasia and sessile serrated adenoma
Traditional serrated adenoma
Colonic-type tubular adenomas
Endocrine (carcinoid) tumours
Goblet cell carcinoid
Mesenchymal tumours
Malignant lymphoma
Secondary tumours (other than lymphoma)
CHAPTER 31 Miscellaneous conditions of the appendix
Normal embryology and fetal development
Developmental abnormalities
Diverticular disease
Intussusception
Torsion
Endometriosis and conditions related to pregnancy
Cystic fibrosis
Foreign bodies
Melanosis
PART 5: Large Intestine
CHAPTER 32 Normal large intestine: anatomy, specimen dissection and histology relevant to pathological practice
Anatomy
Specimen handling
Histology
CHAPTER 33 Embryogenesis and developmental abnormalities (including the anal region)
Normal development
Malpositions
Vestigial remnants
Maldevelopments
Disturbances of innervation
CHAPTER 34 Neuromuscular and mechanical disorders of the large intestine
Diverticular disease of the colon
Diverticulosis of the right colon
The irritable bowel syndrome
Idiopathic constipation, megacolon, megarectum and pseudo-obstruction
Volvulus
Mucosal prolapse and the solitary ulcer syndrome
Intussusception and complete rectal prolapse
Trauma
Foreign bodies
CHAPTER 35 Inflammatory disorders of the large intestine
Inflammation due to viruses
Bacterial infection
Inflammation due to fungi
Protozoal infection
Helminthic infection
Inflammatory bowel diseases
Ulcerative colitis
Crohn’s disease of the large intestine
Diverticular disease and CIBD of the large intestine
Other granulomatous pathology in the large intestine
Biopsy in the differential diagnosis of CIBD and infective procto-colitis
Drug-induced procto-colitis
Pseudo-membranous colitis and antibiotic-associated diarrhoea and colitis
Brainerd diarrhoea
Focal active colitis
Radiation procto-colitis
Diversion procto-colitis
Necrotising colitis
Neutropaenic colitis
Neonatal necrotising enterocolitis
Microscopic colitis
Mastocytic enterocolitis
Phlegmonous colitis
Transient colitis and acute self-limiting (acute infectious type) colitis
Obstructive colitis
Behçet’s disease
CHAPTER 36 Vascular disorders of the large intestine
Anatomy
Nomenclature
Causes of ischaemic colitis
Ischaemic lesions
Endoscopic features and biopsy
Angiodysplasia
Portal (hypertensive) colopathy
Vasculitides
Idiopathic myointimal hyperplasia of mesenteric veins
CHAPTER 37 Polyps and tumour-like lesions of the large intestine
Conventional adenoma
Serrated polyps
Serrated polyposis
Familial adenomatous polyposis
MUTYH-associated polyposis
Juvenile polyp
Autosomal dominant inherited hamartomatous polyposis syndromes
Cronkhite–Canada syndrome
Inflammatory polyps
Other polyps
CHAPTER 38 Malignant epithelial neoplasms of the large bowel
Introduction
Epidemiology
Aetiology
Pathogenesis of colorectal neoplasia
The clinical pathology of colorectal adenocarcinoma
Endocrine tumours
Rare forms of colorectal cancer
Datasets and reporting standards
Screening for colorectal cancer
CHAPTER 39 Non-epithelial tumours of the large intestine
Tumours of lymphoid tissue
Connective tissue tumours
Miscellaneous tumours of the colorectum and retrorectal space
CHAPTER 40 Miscellaneous disorders of the large intestine
Amyloid
Endometriosis
Melanosis coli
Muciphages
Pneumatosis coli
Pseudo-lipomatosis
Stercoral ulceration
Graft-versus-host disease
Cord colitis syndrome
Effects of bowel preparation
Torsion of appendices epiploicae
Barium granuloma
Malakoplakia
Squamous metaplasia of the colorectum
PART 6: The Anal Region
CHAPTER 41 Normal anal region: anatomy, histology relevant to pathological practice and specimen handling
Normal anal region: anatomy, histology relevant to pathological practice and specimen handling
CHAPTER 42 Inflammatory disorders of the anal region
Miscellaneous inflammatory conditions
Infectious disease of the anorectum
Inflammatory bowel disease involving the anorectum
CHAPTER 43 Tumours and tumour-like conditions of the anorectal region
Benign epithelial tumours and pre-cancerous lesions of the anorectal region
Malignant epithelial tumours of the anal canal
Malignant epithelial tumours of the anal margin
Miscellaneous tumours
CHAPTER 44 Miscellaneous conditions of the anal region
Haemorrhoids
Oleogranuloma
Ectopic tissue
Anal incontinence
PART 7: Peritoneum
CHAPTER 45 The normal peritoneum
Anatomy
Microscopic appearances
CHAPTER 46 Inflammatory disorders of the peritoneum
Acute diffuse peritonitis
Localised peritonitis
Special forms of peritonitis
Sclerosing mesenteritis
Fat necrosis after pancreatitis
CHAPTER 47 Tumours and tumour-like lesions of the peritoneum
Introduction
Mesothelial hyperplasia and mesothelial tumours
Epithelial tumours and metaplastic tumour-like lesions of the peritoneum
Primary tumours arising from the subserosal mesenchyme
Tumours of uncommitted stem cells or uncertain histogenesis
Tumour-like conditions of the peritoneum
Secondary tumours
Pseudomyxoma peritonei
CHAPTER 48 Miscellaneous conditions of the peritoneum
Ascites
Pneumo-peritoneum
Intra-peritoneal loose bodies
Torsion and segmental infarction of the greater omentum
Peritoneal pigmentation
Splenosis
Trophoblastic implants
Cartilaginous metaplasia
Index
This book is dedicated to the memory of two outstanding gastrointestinal pathologists,
Professor Jeremy Jass and Professor Bryan Warren.
This edition first published 2013 © 2013 by Blackwell Publishing Ltd.
Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell.
Registered office: John Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
Editorial offices: 9600 Garsington Road, Oxford, OX4 2DQ, UK
The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
111 River Street, Hoboken, NJ 07030-5774, USA
For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell
The right of the author to be identified as the author of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.
Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought.
The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom.
Library of Congress Cataloging-in-Publication Data
Morson and Dawson’s gastrointestinal pathology. – 5th ed. / edited by Neil A. Shepherd . . . [et al.].
p. ; cm.
Gastrointestinal pathology
Includes bibliographical references and index.
ISBN 978-1-4051-9943-8 (hardcover : alk. paper)
I. Shepherd, Neil A. II. Morson, Basil C. (Basil Clifford). Gastrointestinal pathology. III. Title: Gastrointestinal pathology.
[DNLM: 1. Gastrointestinal Diseases–pathology. WI 140]
616.3'3071–dc23
2012009760
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Cover images: Main image – Courtesy of Robert E. Petras and back image – Courtesy of Neil A. Shepherd
Cover design by Sarah Dickinson
Contributors
Richard L. Attanoos, BSc, MB BS, FRCPath
Consultant Histopathologist
Department of Histopathology
University Hospital Llandough
Penarth, UK
Shinichi Ban, MD, PhD
Head, Department of Pathology
Saiseikai Kawaguchi General Hospital
Saitama, Japan
Adrian C. Bateman, BSc, MD, FRCPath
Consultant Histopathologist and Honorary Senior Lecturer in Pathology
Southampton General Hospital
Southampton, UK
Lodewijk A.A. Brosens, MD, PhD
Chief Resident in Pathology
Department of Pathology
University Medical Centre Utrecht
Utrecht, The Netherlands
Ian Brown, FRCPA
Visiting Senior Specialist
Royal Brisbane and Women’s Hospital;
Specialist Pathologist
Envoi Specialist Pathologists
Brisbane, QLD, Australia
Fiona Campbell, BSc, MD, FRCPath
Honorary Professor and Consultant Gastrointestinal Pathologist
Department of Pathology
Royal Liverpool University Hospital
Liverpool, UK
Frank A. Carey, BSc, MD, FRCPath
Consultant Pathologist and Honorary Professor in Pathology
Department of Pathology
Ninewells Hospital and Medical School
Dundee, UK
Fátima Carneiro, MD, PhD
Professor of Pathology and Head of Department of Pathology
Faculty of Medicine of the University of Porto
Centro Hospitalar de São João and IPATIMUP
Porto, Portugal
Andrew D. Clouston, MBBS, PhD, FRCPA
Associate Professor, Molecular and Cellular Pathology
University of Queensland;
Visiting Senior Specialist, Royal Brisbane and Women’s Hospital;
Specialist Pathologist
Envoi Specialist Pathologists
Brisbane, QLD, Australia
Claude Cuvelier, MD, PhD
Head, Academic Department of Pathology
Ghent University
Ghent, Belgium
Paola Domizio, BSc, MB BS, FRCPath
Professor of Pathology Education
Barts and The London School of Medicine and Dentistry
Queen Mary University of London;
Department of Cellular Pathology
The Royal London Hospital
London, UK
Erinn Downs-Kelly, DO, MS
Staff Pathologist
Department of Anatomic Pathology
Cleveland Clinic
Cleveland, OH, USA
David K. Driman, MBChB, FRCPC
Professor of Pathology
Department of Pathology
Schulich School of Medicine and Dentistry
Western University and London Health Sciences Centre
London, ON, Canada
Robert P. Eckstein, MB, BS, FRCPA
Associate Professor of Pathology
Department of Anatomical Pathology
Pacific Laboratory Medicine Services
Royal North Shore Hospital
St Leonards, NSW, Australia
Nadine Ectors, MD, PhD
Professor in Histopathology and Coordinator
Translational Cell and Tissue Research
AC Biobanking
University Hospitals and University Leuven
Leuven, Belgium
Hala El-Zimaity, MD, FRCPC, MSc
Associate Professor
Department of Laboratory Medicine and Pathobiology
University of Toronto
Toronto, ON, Canada
Jean-François Fléjou, MD, PhD
Professor of Pathology
Department of Pathology
Hôpital Saint-Antoine, AP-HP;
Faculté de Médecine Pierre et Marie Curie
Paris, France
Karel Geboes, MD, PhD, AGAF
Professor of Pathology
Department of Pathology
University Hospital and Medical School KU Leuven
Leuven, Belgium
Muriel Genevay, MD
Consultant Gastrointestinal Pathologist
Service of Clinical Pathology
University Hospitals of Geneva
Geneva, Switzerland
John R. Goldblum, MD
Chairman, Department of Anatomic Pathology
Cleveland Clinic;
Professor of Pathology
Cleveland Clinic Lerner College of Medicine
Cleveland, OH, USA
Joel K. Greenson, MD
Professor of Pathology
University of Michigan Medical School
Ann Arbor, MI, USA
Thomas Guenther, MD, PhD, FRCPath
Honorary Consultant Histopathologist
St Mark’s Hospital
North West London Hospitals NHS Trust
London, UK;
Professor of Pathology and Consultant Histopathologist
Otto-von-Guericke University
Magdeburg, Germany
Gordon Hutchins, BMedSci(Hons), MB BS
Academic SpR in Histopathology & Honorary Clinical Lecturer
Pathology and Tumour Biology
Leeds Institute of Molecular Medicine
University of Leeds
Leeds, UK
Dhanpat Jain, MBBS, MD
Associate Professor of Pathology and Medicine (Digestive Diseases)
Director, Program in Gastrointestinal and Liver Pathology
Department of Anatomic Pathology
Yale University School of Medicine
New Haven, CT, USA
Marnix Jansen, MD, MSc, PhD
Chief Resident, Pathology
Department of Pathology
Academic Medical Centre
Amsterdam, The Netherlands
Laura W. Lamps, MD
Professor and Vice-Chair
Department of Pathology
University of Arkansas for Medical Sciences
Little Rock, AZ, USA
Gregory Y. Lauwers, MD
Vice Chair of Pathology, Massachusetts General Hospital;
Professor of Pathology
Harvard Medical School
Boston, MA, USA
Laurence de Leval, MD, PhD
Professor of Pathology
Clinical Director, Institute of Pathology
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
Maurice B. Loughrey, BSc, MRCP, MD, FRCPath
Consultant Histopathologist and Honorary Lecturer
Royal Victoria Hospital
Queen’s University Belfast
Belfast, UK
Joanne E. Martin, MA, MB BS, PhD, FRCPath
Professor of Pathology
Barts and the London School of Medicine and Dentistry
Queen Mary University of London;
Department of Cellular Pathology
The Royal London Hospital
London, UK
Raymond F.T. McMahon, BSc, MD, FRCPath
Professor and Hospital Dean
Central Manchester NHS Foundation Trust;
Honorary Consultant Pathologist
Manchester Royal Infirmary
Manchester Medical School, University of Manchester
Manchester, UK
Joseph Misdraji, MD
Associate Professor of Pathology
Director, Histopathology
Massachusetts General Hospital
Harvard Medical School
Boston, MA, USA
Elizabeth Montgomery, MD
Professor of Pathology, Oncology, and Orthopedic Surgery
Johns Hopkins Medical Institutions
Baltimore, MD, USA
Cian Muldoon, MB BCh, MRCPI, FRCPath, FFacPathRCPI
Consultant Histopathologist
Department of Histopathology
St James’s Hospital
Dublin, Ireland
Amy E. Noffsinger, MD
Gastrointestinal Pathologist
Miraca Life Sciences
Camp Dennison, OH, USA
Marco R. Novelli, MB ChB, PhD, FRCPath
Professor of Gastrointestinal Pathology and Consultant Histopathologist
University College Hospital
London, UK
Robert D. Odze, MD, FRCPC
Professor of Pathology
Harvard Medical School;
Chief, GI Pathology Division
Brigham and Women’s Hospital
Boston, MA, USA
G. Johan A. Offerhaus, MD, MPH, PhD
Professor of Pathology
Department of Pathology
University Medical Centre Utrecht
Utrecht, The Netherlands
Scott R. Owens, MD
Assistant Professor
University of Pittsburgh Medical Center
Pittsburgh, PA, USA
Jeremy R. Parfitt, MD, FRCPC
Assistant Professor
Department of Pathology
Schulich School of Medicine and Dentistry
Western University and London Health Sciences Centre
London, ON, Canada
Do-Youn Park, MD, PhD
Professor
Department of Pathology
Pusan National University College of Medicine
Pusan National University Hospital
Busan, Republic of Korea
Robert E. Petras, MD
National Director for Gastrointestinal Pathology Services
AmeriPath, Inc.
Oakwood Village;
Associate Clinical Professor of Pathology
Northeast Ohio Medical University
Rootstown, OH, USA
Phil Quirke, BM, PhD, FRCPath
Yorkshire Cancer Research Centenary Professor of Pathology
Pathology and Tumour Biology
Leeds Institute of Molecular Medicine
University of Leeds
Leeds, UK
Robert H. Riddell, MD, FRCPath
Professor of Laboratory Medicine and Pathology
Mount Sinai Hospital
Toronto, ON, Canada
Brian P. Rubin, MD, PhD
Associate Professor of Pathology
Cleveland Clinic
Cleveland, OH, USA
Manuel Salto-Tellez, MD (LMS), FRCPath
Professor and Chair of Molecular Pathology
Clinical Consultant Pathologist
Centre for Cancer Research and Cell Biology
Queen’s University Belfast
Belfast, UK
D. Scott A. Sanders, MD, FRCPath
Consultant Histopathologist
Coventry and Warwickshire Pathology Services
Warwick, UK
Kieran Sheahan, MB, BSc, FRCPI, FRCPath
Associate Clinical Professor
University College Dublin;
Consultant Pathologist
St Vincent’s University Hospital
Dublin, Ireland
Neil A. Shepherd, DM, FRCPath
Professor of Gastrointestinal Pathology and Consultant Histopathologist
Gloucestershire Cellular Pathology Laboratory
Cheltenham, UK
Michio Shimizu, MD, PhD
Professor
Department of Pathology
Saitama Medical University
Saitama International Medical Center
Saitama, Japan
Amitabh Srivastava, MD
Assistant Professor
Harvard Medical School;
Department of Pathology
Brigham and Women’s Hospital
Boston, MA, USA
Kaiyo Takubo, MD, PhD
Team Leader
Research Team for Geriatric Pathology
Tokyo Metropolitan Institute of Gerontology;
Clinical Professor
Tokyo Medical and Dental University School of Medicine
Tokyo, Japan
Neal I. Walker, MD, BS, FRCPA
Specialist Pathologist
Envoi Specialist Pathologists;
Associate Professor
Molecular and Cellular Pathology
University of Queensland
Brisbane, QLD, Australia
Shaun V. Walsh, MB BCh BAO, FRCPath
Consultant Histopathologist
Department of Pathology
Ninewells Hospital and Medical School
Dundee, UK
†Bryan F. Warren, MB ChB, FRCP(London), FRCPath
Professor of Gastrointestinal Pathology
John Radcliffe Hospital
Oxford, UK
Kevin P. West, BSc, MB ChB, DMJ, FRCPath
Consultant Histopathologist
Honorary Senior Lecturer in Cancer Studies and Molecular Medicine
University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary
Leicester, UK
Nicholas P. West, BSc, PhD, MB ChB, PGCert
NIHR Academic Clinical Lecturer in Histopathology
Pathology and Tumour Biology
Leeds Institute of Molecular Medicine
University of Leeds
Leeds, UK
Geraint T. Williams, OBE, BSc, MD, MRCR, FRCP(London), FRCPath, FMedSci
Professor of Pathology
Cardiff University
Cardiff, UK
Alison M. Winstanley, BSc, MB BS, FRCPath
Consultant Cellular Pathologist
University College Hospital
London, UK
Note
†Deceased
Foreword
Since the first edition was published in 1972, there have been many changes in both the scope and the practice of gastrointestinal pathology.
Forty years ago gastrointestinal pathology as a subspecialty within general histopathology did not exist in contrast, for example, to gynaecological pathology and neuropathology. The picture today is very different. All academic departments will have one or more full-time gastrointestinal pathologists with time available for research and teaching in their subject. In the general hospitals serving large districts there is likely to be at least one pathologist with special expertise in gastrointestinal work. To what can these changes be attributed?
During the last 50 years there has been an increasing abundance of surgical specimens available for detailed examination. More important, perhaps, is the revolution in endoscopy. Virtually the entire gastrointestinal tract is now accessible to biopsy. As surgeons and gastroenterologists increasingly rely on biopsy interpretation for their practice, so the numbers of biopsies have escalated. The demand, therefore, for skilled gastrointestinal pathologists has hugely increased.
This book aims to provide an up-to-date contribution to training for this now fully acknowledged subspecialty of histopathology. It should also be helpful as a major point of resource in the practice of gastrointestinal pathology. The structure of this edition remains substantially the same as in previous ones except there are now six editors, including one lead editor. The inclusion of editors from North America and authors from North America, the European continent, Asia and Australia, is a deliberate attempt to internationalise the contributors.
The practice of gastrointestinal pathology has now reached a stage where there is sub-specialisation within our discipline, with the inclusion of authors who have a special diagnostic or research interest in particular parts and/or particular diseases of the gastrointestinal tract. This trend is likely to continue. Moreover, this further sub-specialisation is leading to rationalisation of pathology departments. One can also envisage the development of specialised technical support in the future for gastrointestinal pathologists.
It is extraordinary how, in contrast to other sub-specialties in general histopathology, molecular pathology has yet to make more than a very limited impact on day-to-day diagnostic work. Haematoxylin and eosin (H&E)-based technical support remains the mainstay of diagnosis but it is likely that new molecular analyses will break into the traditional approach, particularly in the management of colorectal cancer.
The gastrointestinal pathologist has an increasingly important part to play in the management of patients with gastrointestinal disorders. Surgeons, gastroenterologists and endoscopists know this and insist on access to the special skills of an experienced gastrointestinal pathologist as part of the team approach to patient care. It is important, therefore, that gastrointestinal pathologists take an active interest in the patient, not just the surgical specimen or biopsy. The view down the microscope should surely be interpreted with awareness that one is looking at part of a patient.
Basil C. Morson, CBE, VRD, MA, DM, FRCS, FRCP, FRCPath, FRACS(Hon)
Consulting Pathologist at St Mark’s Hospital London, UK
Preface
This, the fifth edition of ‘Morson & Dawson’, marks a radical departure from previous editions. Gastrointestinal pathology has developed into such a large and diverse subject that it becomes very difficult for a small group of authors to write the entire book. So, the remaining editors decided that, not only should the book become multi-author, but it should also become international in its authorship. We make no excuses for this because we believe this is the best way for this unique title to survive in the face of much excellent competition.
There have been very considerable changes to the editorship. Very sadly, Professor Jeremy Jass died of a brain tumour in November 2008. Jeremy was one of the world’s outstanding gastrointestinal pathologists and his incisive and creative writing and editing are very sorely missed. During production of this edition, Professor Bryan Warren also succumbed to cancer. Bryan was also one of the world’s great gastro-intestinal pathologists and has been a highly influential member of the Morson & Dawson team for two editions. His death leaves a huge void in UK and international gastrointestinal pathology that just cannot be filled. Furthermore, no less than four of our editorial colleagues have retired from practice and authorship in the last few years. They, too, are greatly missed. They are David Day, Ashley Price, Jimmy Sloan and Ian Talbot. So, we were delighted to be joined by our friend and colleague, Marco Novelli, who brings a touch of relative youth to the team. In line with internationalisation of the title, we were also delighted when two of North America’s top gastrointestinal pathologists, Joel Greenson and Gregory Lauwers, agreed to become editors. They have brought with them vitality, expertise and knowledge of the international scene that has been of very considerable value. They greatly complement the team at Morson & Dawson.
There have been other changes to Morson & Dawson. The title now features almost 100% colour photographs. In a lot of ways, we miss the striking quality and historical context of many of the black and white photographs that previous editions held but we cannot stand in the way of progress. The chapter titles have been standardised for the entire luminal gastrointestinal tract and we have restored the section on the ‘peritoneum’ to its rightful place in this book. The new edition also reflects the very considerable advances in molecular pathology, immunohistochemistry and pathological practice that have occurred since the fourth edition was published in 2003. Becoming multi-author and international does inevitably change a book. Nevertheless we are confident that the choice of authors, from four continents, has meant that the quality initiated by Basil Morson and Ian Dawson has been upheld.
We are delighted to report that Basil, now into his nineties, is well and still attends the lecture, bequeathed to him, each year at the British Society of Gastroenterology, amongst other attendances at UK functions. He has once again provided the Foreword and has told us how delighted he is to see the title he created, way back in 1972, still flourishing. In that regard, we were honoured when the fourth edition won First Prize in the ‘Multi-author Text Book’ section of the UK’s Society of Authors/RSM Medical Book Awards in 2004. No pressure on the fifth edition, then!
We would like to place on record our gratitude to all of our colleagues who have provided illustrations for this book. These are too numerous to mention individually but important acknowledgements have been made in the legends to the relevant illustrations. We would also record our grateful thanks to all of our colleagues and friends at Wiley-Blackwell, especially Oliver Walter, Elisabeth Dodds, Cathryn Gates, Julie Elliott, Annette Abel, Ruth Swan and Jane Sugarman for their endeavours. They have ensured safe passage of the book, through some stormy waters, and we wish to thank them all sincerely for their help, professionalism and bonhomie.
Neil A. Shepherd
Bryan F. Warren
Geraint T. Williams
Joel K. Greenson
Gregory Y. Lauwers
Marco R. Novelli
About the Companion Website
This book is accompanied by a companion website:
www.wiley.com/go/morsondawson
The website includes:
- Powerpoints of all figures from the book for downloading
PART 1
Oesophagus
CHAPTER 1
The Normal Oesophagus: Anatomy, Specimen Dissection and Histology Relevant to Pathological Practice
Kaiyo Takubo1 and Neil A. Shepherd2
1Tokyo Metropolitan Institute of Gerontology and Tokyo Medical and Dental University School of Medicine, Tokyo, Japan
2Gloucestershire Cellular Pathology Laboratory, Cheltenham, UK
Anatomy
The adult oesophagus is a muscular tube some 250 mm long, which extends from the pharynx, at the cricoid cartilage opposite the sixth cervical vertebra, to the oesophago-gastric junction, about 25 mm to the left of the midline, opposite the tenth or eleventh thoracic vertebra. The oesophagus has longitudinal mucosal folds and, when empty, a very narrow lumen. For endoscopists, the distance from the incisor teeth to the upper end of the oesophagus is about 150 mm and to the oesophago-gastric junction about 400 mm, depending, clearly, on the height of the person. The oesophagus pierces the left crus of the diaphragm and has an intra-abdominal portion about 15 mm in length. Its principal relations, important to the pathologist in assessing the local spread of cancer, are with the trachea, left main bronchus, aortic arch, descending aorta and left atrium.
The arterial supply of the oesophagus is by the inferior thyroid, bronchial, left phrenic and left gastric arteries and by small branches directly from the aorta. Its veins form a well-developed submucosal plexus draining into the thyroid, azygos, hemiazygos and left gastric veins. It, thus, provides an important link between the systemic and portal venous systems. Lymphatic channels from the pharynx and upper third of the oesophagus drain to the deep cervical lymph nodes, either directly or through the paratracheal nodes, and also to the infrahyoid lymph nodes; from the lower two-thirds they drain to the posterior mediastinal (para-oesophageal) lymph nodes and thence to the thoracic duct. From the infra-diaphragmatic portion of the oesophagus, drainage is to the left gastric lymph nodes and to a ring of lymph nodes around the cardia. Some lymph vessels may drain directly into the thoracic duct. In its upper part the oesophagus is innervated by the glossopharyngeal nerve and, throughout its length, it is supplied by fibres from the vagus nerve and local sympathetic ganglia.
The lower end of the oesophagus is anchored posteriorly to the pre-aortic fascia and is surrounded by the phreno-oesophageal ligament, which blends into the muscularis propria of the oesophagus. This arrangement allows some degree of movement and rebound. Dissection studies indicate that no discrete anatomical sphincter is present but there are differences of opinion as to whether, and if so how, the muscle at the oesophago-gastric junction is modified. One careful anatomical study [1] has ruled out the presence of any thickening of the muscularis mucosae or of the circular muscle coat but has described the separation of obliquely arranged inner circular muscle fibres into fascicles, which continue into the stomach to form the circular muscle layer. However, another equally thorough investigation [2] describes a definite thickening of the inner circular muscle coat. Both studies have concluded that the arrangements that they describe might, and probably do, act as a functional sphincter.
The oesophageal wall in cross-section can be divided macroscopically into stratified squamous epithelium, lamina propria, muscularis mucosae, and the submucosa, muscularis propria and adventitia (Figure 1.1). Gross inspection of cut sections of tumours in the oesophagus generally reveals the depth of tumour invasion and this assessment of depth, through the various layers of the wall, is of critical importance for staging and prognostication.
Histology
Mucosa
The squamous-lined mucosa is about 500–800 µm thick and is composed of non-keratinising stratified squamous epithelium with a subjacent lamina propria resting on the underlying muscularis mucosae.
Epithelium
Resection specimens usually have a thinner squamous epithelium compared with biopsy specimens because the superficial layers are likely to be lost during surgical handling. The squamous epithelium (Figure 1.2) has a basal zone consisting of several layers of cuboidal or rectangular basophilic cells, with dark nuclei, in which glycogen is absent. It occupies about 10–15% of the thickness of the normal epithelium, although it may be thicker in the last 20 mm or so of the squamous-lined oesophagus. Occasional mitoses are evident in the basal and parabasal cell layers. Above the basal zone, the epithelial cells are larger and become progressively flattened but, even on the surface, they retain their nuclei. Keratohyaline granules are not usually present in the surface cells of the normal epithelium. However, glycogen is abundant. Ki-67 (monoclonal antibody MIB-1) immunostaining usually shows a negative reaction in the basal layer, on the basement membrane, and a positive reaction in the parabasal layers. Epithelial stem cells may be present in the basal layer. The presence of Ki-67-positive cells in more than three cell layers is an abnormal feature, consistent with gastro-oesophageal reflux disease (Figure 1.3).
Single intra-epithelial lymphocytes (‘squiggle’ cells) lying between the squamous cells are common, particularly in the lower half of the mucosa, and in this situation their convoluted nuclei may be confused with the nuclei of neutrophils. They are a normal feature. Characterisation using monoclonal antibodies has shown them to be T lymphocytes [3]. Langerhans’ cells are antigen-presenting cells that are demonstrable, by electron microscopy and metal impregnation techniques, as sparsely distributed ovoid forms with radiating dendritic processes, occurring in all layers of the oesophageal epithelium [4]. They are positively stained with antibodies against S-100 protein and react with monoclonal antibodies against HLA-DR (major histocompatibility complex [MHC] class II) and OKT6 (CD1). They also contain calcitonin gene-related peptide (CGRP), which may serve as an immunomodulator. The number of Langerhans’ cells and the intensity of their immunoreactivity for CGRP are increased in reflux oesophagitis [5]. They contain Langerhans’ granules (Birbeck’s granules), seen on electron microscopic examination.
Both melanocytes and non-melanocyte argyrophil cells are randomly distributed in the basal layer of the epithelium, the former usually as small groups and the latter singly [6,7]. These cell types are presumably the origin of primary malignant melanomas and small cell undifferentiated (oat cell) carcinomas, respectively, that occur at this site. Merkel’s cells are also present in the epithelium.
Transmission electron microscopy (TEM) studies of the squamous epithelium have broadened our understanding of the micro-anatomy [8–13]. Basal cells are cuboidal or columnar with large, centrally placed nuclei and relatively simple cytoplasm containing few organelles. They are attached to the basement membrane by frequent hemi-desmosomes. Prickle cells show numerous keratin filaments, relatively abundant glycogen, a prominent Golgi apparatus and more numerous desmosomes. The squamous cells of the superficial or functional zone become increasingly flattened towards the lumen, contain some phospholipid material and have a coating of acid mucosubstance which is likely to have a protective function. Scanning electron microscopy shows a complex pattern of micro-ridges lining the lumen. Membrane-coated granules, 0.1–0.3 µm in diameter, are present in the intermediate and superficial zones of the oesophageal epithelium. As well as being the source of mucosubstances, they also contain acid hydrolases which, when secreted into the intercellular space, may be responsible for the reduction of desmosomes exhibited by squamous cells as they approach the luminal surface.
Free-ending nerves are located in the intercellular spaces of the squamous epithelium and reach the subepithelial nerve plexus. These nerves probably mediate oesophageal pain. Cell proliferation studies have demonstrated a slower cell cycle time in basal cells overlying papillae, in comparison with the interpapillary basal cells [14]. The turnover time of the oesophageal epithelium is about 4–7 days in rats and mice. The corresponding period in humans is said to be 10 days or less, although no definitive data are available.
Lamina Propria
The lamina propria consists of loose connective tissue containing a sprinkling of lymphocytes, mostly helper T cells, plasma cells, and occasional eosinophils and mast cells. Focal collections of lymphocytes and plasma cells may be aggregated around the ducts of the oesophageal submucosal glands. There are numerous vascular papillae (also known as intrapapillary vessels or intrapapillary capillary loops), associated with connective tissue, which project upwards for two-thirds of the total thickness of the epithelium. Changes in the vascular pattern are evident by magnifying endoscopy under various pathological conditions.
Relatively large vessels are observed more frequently in the lamina propria than in the submucosa in cross-sections of the lower oesophageal sphincter. These vessels are considered to be the longitudinal palisade vessels visible at endoscopy and helpful in defining the true oesophago-gastric junction.
Muscularis Mucosae
The muscularis mucosae shows a variable pattern. In its upper part it commonly consists of isolated or irregularly arranged muscle bundles, rather than forming a continuous sheet, but in the middle and lower thirds it forms a continuum of longitudinal and transverse fibres and may reach up to 300 µm in thickness at the squamo-columnar junction. In the resected oesophagus, thick collections of fine irregular muscle fibres are evident at sites of previous biopsy.
Submucosa
The submucosa contains the oesophageal submucosal glands (deep glands, oesophageal glands proper), Meissner’s plexus and a ramifying lymphatic plexus within a loose connective tissue network, which accounts for the early and extensive submucosal spread of oesophageal carcinoma. The oesophageal submucosal glands tend to be arranged in rows parallel to the long axis [15] and, although scattered, they are relatively concentrated at the upper and lower ends of the oesophagus. The glands are compound tubulo-alveolar in type and resemble labial salivary glands, containing both mucous and serous secretory cells and oncocytes, with surrounding myo-epithelial cells, anchoring them to the underlying basement membrane. The mucous cells contain sulphomucins. Many glands do not contain serous cells. From two to five lobules drain into a common duct lined by a flattened cuboidal epithelium initially, which becomes stratified squamous in type, and surrounded by lymphocytes and plasma cells after passing obliquely through the muscularis mucosae (Figure 1.4). The presence of oesophageal submucosal glands and/or their ducts is presumptive evidence that any sampled biopsy material derives from the true anatomical oesophagus.
Muscularis Propria
The muscularis propria consists of well-developed circular and longitudinal coats. In its upper part these are striated and both oxidative (fast twitch) and glycolytic (slow twitch) fibres are present [16]. There is a gradual change to smooth muscle in the upper and middle thirds, although, in the lower third, both coats are entirely composed of smooth muscle with no clear evidence of sphincter formation. A well-defined myenteric nerve (Auerbach’s) plexus is present at all levels but there appears to be no well-formed submucosal plexus. Three types of neuron are identifiable [17,18]. One is argyrophilic, multi-axonal and, probably, sympathetic, and sends out numerous dendrites and axons to surround other neurons in the same and adjacent ganglia but does not directly supply muscle. The second type is not argyrophilic but cholinergic and probably parasympathetic, supplying the muscle. It is likely that the former has a coordinating function and the latter a motor function. A third type of fibre, probably part of the communicating system, is rich in vasoactive inhibitory peptide (VIP). Such fibres are commonly associated with sphincteric mechanisms [18]. There are also numerous intrinsic fibres containing neuropeptide Y [19]. Ganglion cells decrease in number with age [20] but the smooth muscle does not appear to undergo corresponding atrophy.
Adventitia
The adventitia of the oesophagus is a thick layer of coarse connective tissue around the oesophagus and is seen to surround the oesophagus in resection specimens. It contains blood vessels, lymphatics and lymph nodes, multiple branches, anterior and posterior, of the vagus nerve and other neural structures. Its comprehensive examination is of particular importance in such resection specimens because here proximity of tumour to the circumferential surgical resection margin and the pleural surfaces will be evident and assessable (see below). The adventitia is in continuity with the adjacent mediastinal connective tissues.
Tissues Adjacent to the Oesophagus, Including the Pleura
These are of some importance because they are or may be present in resected oesophagus specimens. The proximal stomach is almost universally present in such specimens whereas pharynx and spleen are occasionally seen in specimens resected with the oesophagus. The trachea, bronchus, lung, diaphragm, azygos vein, thoracic duct, thymus and aorta can also be present in oesophageal resection specimens. Although usually termed the circumferential resection margin of the oesophagus, it is important to note that, especially on the right but also on the left, a sizable proportion of the circumference of oesophageal resection specimens is actually invested not by adventitial connective tissues, thus constituting a true surgical margin, but by pleura, which all radical oesophago-gastrectomy specimens will possess. Involvement of the circumferential margin can be influenced by surgical quality but a surgeon can do little about pleural involvement. We advocate accurate identification of the pleura, on both sides, and painting, preferably by coloured gelatin, of only the true circumferential surgical margin to allow differentiation of these structures in histological sections.
Location of the Oesophago-Gastric Junction