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Oxford Handbook of
Clinical Pathology
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Oxford Handbook of
Clinical
Pathology
SECOND EDITION

Edited by

James Carton
Consultant Histopathologist
Imperial College Healthcare NHS Trust
London, UK

1
1
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
Oxford University Press is a department of the University of Oxford.
It furthers the University’s objective of excellence in research, scholarship,
and education by publishing worldwide. Oxford is a registered trade mark of
Oxford University Press in the UK and in certain other countries
© Oxford University Press 2017
The moral rights of the authors have been asserted
First Edition published in 2012
Second Edition published in 2017
Impression: 1
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, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by licence or under terms agreed with the appropriate reprographics
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address above
You must not circulate this work in any other form
and you must impose this same condition on any acquirer
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America
British Library Cataloguing in Publication Data
Data available
Library of Congress Control Number: 2017931114
ISBN 978–​0–​19–​875958–​4
Printed and bound in China by
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Oxford University Press makes no representation, express or implied, that the
drug dosages in this book are correct. Readers must therefore always check
the product information and clinical procedures with the most up-​to-​date
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and the most recent codes of conduct and safety regulations. The authors and
the publishers do not accept responsibility or legal liability for any errors in the
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contained in any third party website referenced in this work.
 To my parents, Paul and Shirley,
for all they have done for me,
and to Rob for making me so happy.
vi

Preface to the second

edition
The first edition of the Oxford Handbook of Clinical Pathology was very well
received and I have been delighted to receive much positive feedback since
its publication.
Pathology continues to advance at a tremendous pace, particularly in the
field of tumour pathology, with new immunohistochemical and molecular
diagnostic tools transforming the way in which tumours are diagnosed and
classified. This new information has been a particular focus for the updates
in this second edition. A dedicated head and neck pathology chapter has
been written and colour photos have also been included.
An ever increasing burden in routine diagnostic work has meant that
updating the book by myself became an impossibility, so I have been aided
by a number of contributors, all of whom are experts in their particular
subspecialty. I thank them all for their help, without which this new edition
would not have been possible. I am also grateful to the team at Oxford
University Press, especially Liz Reeve and Michael Hawkes.
James Carton
2016
 vii

Contents

Contributors viii
Symbols and abbreviations ix

1 Basic pathology    1
2 Infectious diseases   15
3 Vascular pathology   29
4 Cardiac pathology   41
5 Lung pathology   63
6 Head and neck pathology   89
7 Gastrointestinal pathology 105
8 Hepatobiliary pathology 147
9 Pancreatic pathology 169
10 Renal pathology 179
11 Urological pathology 209
12 Gynaecological pathology 243
13 Breast pathology 281
14 Endocrine pathology 301
15 Haematopathology 327
16 Skin pathology 385
17 Osteoarticular pathology 415
18 Neuropathology 451
19 Multisystem diseases 491

Index 499
viii

Contributors

Dr Giuseppe Culora Dr Luis Perez-​Casanova-

Consultant Histopathologist, ​Gomez
Guys’ & St Thomas’ NHS Trust, Royal National Orthopaedic
London, UK Hospital NHS Trust,
Stanmore, UK
Professor Adrienne
Flanagan Dr Rathi Ramakrishnan
Royal National Orthopaedic Consultant Histopathologist,
Hospital NHS Trust, Imperial College Healthcare
Stanmore, UK NHS Trust, London, UK
Professor Robert Goldin Dr Manuel Rodriguez-​Justo
Professor of Liver and GI Consultant Histopathologist,
Pathology, Imperial College University College Hospitals
Healthcare NHS Trust, NHS Trust, London, UK
London UK
Dr Candice Roufosse
Dr Monika Hofer Consultant Histopathologist,
Consultant Neuropathologist, Imperial College Healthcare
Oxford University Hospitals NHS Trust, London, UK
NHS Trust, Oxford, UK
 ix

Symbols and abbreviations

& and
7 approximately
% per cent
= equal to
× multiply
± plus/​minus
> greater than
< less than
≥ greater than or equal to
≤ less than or equal to
Δ delta
α alpha
β beta
ε epsilon
γ gamma
κ kappa
♀ female
♂ male
d decreased
i increased
l leading to
0 warning
2 important
3 don’t dawdle
®
registered trademark
E cross-​reference
ACTH adrenocorticotropic hormone
ADH atypical ductal hyperplasia
AFP alpha-​fetoprotein
AIDP atypical intraductal proliferation; acute inflammatory
demyelinating polyneuropathy
AIDS acquired immune deficiency syndrome
AIH autoimmune hepatitis
AIN anal intraepithelial neoplasia
AITL angioimmunoblastic T-​cell lymphoma
AKI acute kidney injury
ALCL anaplastic large cell lymphoma
ALH atypical lobular hyperplasia
x SYMBOLS AND ABBREVIATIONS

ALL acute lymphoblastic leukaemia

ALS amyotrophic lateral sclerosis
ALT atypical lipomatous tumour
ALVAL aseptic lymphocytic vasculitis-​associated lesion (score)
AMAN acute motor axonal neuropathy
AML acute myeloid leukaemia
AMSAN acute motor sensory axonal neuropathy
ANCA anti-​neutrophil cytoplasmic antibody
APKD adult polycystic kidney disease
APOE apolipoprotein E
APP amyloid precursor protein
APTT activated partial thromboplastin time
ARDS acute respiratory distress syndrome
ARF acute renal failure
ASD atrial septal defect
ASH alcoholic steatohepatitis
ATLL adult T-​cell lymphoma
ATM ataxia-​telangiectasia mutated (gene)
AVSD atrioventricular septal defect
BAL bronchoalveolar lavage
B-​ALL acute B-​lymphoblastic leukaemia
BL Burkitt’s lymphoma
BPH benign prostatic hyperplasia
BSE bovine spongiform encephalopathy
CADASIL cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy
CD Crohn’s disease
CF cystic fibrosis
CFTR cystic fibrosis transmembrane conductance regulator
CGIN cervical glandular intraepithelial neoplasia
CHD congenital heart disease
cHL classical Hodgkin’s lymphoma
CIN cervical intraepithelial neoplasia
CIS carcinoma in situ
CJD Creutzfeldt–​Jacob disease
CKD chronic kidney disease
CLL chronic lymphocytic leukaemia
cm centimetre
CML chronic myelogenous leukaemia
CMV cytomegalovirus
CNS central nervous system
 SYMBOLS AND ABBREVIATIONS xi

COPD chronic obstructive pulmonary disease

CPPD calcium pyrophosphate crystal deposition
CSF cerebrospinal fluid
CT computed tomography
CVID common variable immunodeficiency
DCIS ductal carcinoma in situ
DDD dense deposit disease
DFSP dermatofibrosarcoma protuberans
DIC disseminated intravascular coagulation
dL decilitre
DLBCL diffuse large B-​cell lymphoma
DNA deoxyribonucleic acid
DPLD diffuse parenchymal lung disease
EATL enteropathy-​associated T-​cell lymphoma
EBV Epstein–​Barr virus
ECG electrocardiogram
e.g. exempli gratia (for example)
ELISA enzyme-​linked immunosorbent assay
EMA eosin-​5-​maleimide
EPA eosinophilic granulomatosis with polyangiitis
ER oestrogen receptor
ERCP endoscopic retrograde cholangiopancreatography
ESR erythrocyte sedimentation rate
ET essential thrombocythaemia
ETEC enterotoxigenic Escherichia coli
FAB French–​American–​British (scheme)
FAP familial adenomatous polyposis
FEV1 forced expiratory volume in 1 second
FGF fibroblast growth factor
FIGO International Federation of Gynaecology and Obstetrics
FiO2 fraction of inspired oxygen
FISH fluorescence in situ hybridization
FMTC familial medullary thyroid carcinoma
FNA fine-​needle aspiration
FOB faecal occult blood
FS-​DSFP fibrosarcomatous dermatofibrosarcoma protuberans
FSGS focal segmental glomerulosclerosis
FSH follicle-​stimulating hormone
ft foot
FVC forced vital capacity
g gram
xii SYMBOLS AND ABBREVIATIONS

GBM glioblastoma
GBS Guillain–​Barré syndrome
GCNIS germ cell neoplasia in situ
GFR glomerular filtration rate
GH growth hormone
GI gastrointestinal
GN glomerulonephritis
GPA granulomatosis with polyangiitis
G6PD glucose-​6-​phosphate dehydrogenase
h hour
HAV hepatitis A virus
Hb haemoglobin
HBcAg hepatitis B core antigen
HbF fetal haemoglobin
HbS sickle haemoglobin
HBsAg hepatitis B surface antigen
HBV hepatitic B virus
HCC hepatocellular carcinoma
HCG human chorionic gonadotrophin
HCM hypertrophic cardiomyopathy
HCT haematocrit
HCV hepatitis C virus
HDV hepatitis D virus
HEV hepatitis E virus
HHV human herpesvirus
HIF hypoxia inducible factor
HIV human immunodeficiency virus
HLA human leucocyte antigen
HMA homovanilic acid
HNPCC hereditary non-​polyposis colorectal carcinoma
hpf high-​power field
HPV human papillomavirus
HRS Hodgkin/​Reed Sternberg
HRT hormone replacement therapy
HSV herpes simplex virus
HUS haemolytic uraemic syndrome
i.e. id est (that is)
IFN interferon
Ig immunoglobulin
IgA immunoglobulin A
IgAN IgA nephropathy
 SYMBOLS AND ABBREVIATIONS xiii

IgE immunoglobulin E
IgG immunoglobulin G
IgM immunoglobulin M
IL interleukin
in inch
IPF idiopathic pulmonary fibrosis
IPMN intraductal papillary neoplasm
IPSID immunoproliferative small intestinal disease
ISUP International Society of Urologic Pathologists
ITP idiopathic thrombocytopenic purpura
JAK2 Janus kinase 2
kDa kilodalton
kg kilogram
kPa kilopascal
L litre
LCIS lobular carcinoma in situ
LDH lactate dehydrogenase
LDL low-​density lipoprotein
LEF1 lymphoid-​enhancer-​binding factor 1
LFT liver function test
LH luteinizing hormone
LLETZ large loop excision of the transformation zone
LP lymphocyte-​predominant
LPL lymphoplasmacytic lymphoma
LRPP4 low-​density lipoprotein receptor-​related protein 4
LUTS lower urinary tract symptoms
LVF left ventricular failure
m metre
MALT mucosa-​associated lymphoid tissue
MASP mannose-​binding lectin-​associated serine protease
MCD minimal change disease
MCHC mean corpuscular haemoglobin concentration
MCV mean corpuscular volume
MDS myelodysplastic syndrome
MDS-​U myelodysplastic syndrome, unclassified
MEN multiple endocrine neoplasia
MFH malignant fibrous histiocytoma
mg milligram
MGUS monoclonal gammopathy of undetermined significance
MHC major histocompatibility complex
min minute
xiv SYMBOLS AND ABBREVIATIONS

mL millilitre
mm millimetre
mmHg millimetre of mercury
mmol millimole
MMSE Mini-​Mental State Examination
MoM metal-​on-​metal (prosthesis)
MPA microscopic polyangiitis
MPNST malignant peripheral nerve sheath tumour
MRI magnetic resonance imaging
MRSA meticillin-​resistant Staphylococcus aureus
nAChR nicotinic acetylcholine receptor
NADH nicotinamide adenine dinucleotide dehydrogenase
NAFLD non-​alcoholic fatty liver disease
NASH non-​alcoholic steatohepatitis
NF-​κB nuclear factor kappa B
NHS National Health Service
NIFTP non-​invasive follicular thyroid neoplasm with papillary-​like
nuclear features
NK natural killer
NLPHL nodular lymphocyte-​predominant Hodgkin’s lymphoma
NOD2 nucleotide oligomerization binding domain 2
NOS not otherwise specified
NSAID non-​steroidal anti-​inflammatory drug
PaO2 partial pressure of oxygen in arterial blood
PaCO2 partial pressure of carbon dioxide in arterial blood
PAN polyarteritis nodosa
PanIN pancreatic intraepithelial neoplasia
PAS periodic acid–​Schiff
PBC primary biliary cirrhosis/​cholangitis
PCR polymerase chain reaction
PCV packed cell volume
PDA patent ductus arteriosus
PET positron emission tomography
PID pelvic inflammatory disease
PIN prostatic intraepithelial neoplasia
PMF primary myelofibrosis
PR progesterone receptor
PrP prion protein
PSA prostate-​specific antigen
PSC primary sclerosing cholangitis
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