BONE MARROW

PATHOLOGY
This book is dedicated to Professor David A.G. Galton
BONE MARROW
PATHOLOGY
BARBARA J. BAIN
MBBS, FRACP, FRCPath
Reader in Diagnostic Haematology
St Mary’s Hospital Campus of
Imperial College School of Medicine, London
and Honorary Consultant Haematologist
St Mary’s Hospital, London

DAVID M. CLARK
MD, MRCP, FRCPath
Consultant Histopathologist
United Lincolnshire Hospitals NHS Trust
Honorary Consultant Histopathologist
University Hospital, Nottingham
and Special Lecturer in Pathology
University of Nottingham

IRVIN A. LAMPERT
MB, ChB, DCP, FRCPath
Consultant Histopathologist
Ealing Hospital, London
Honorary Senior Lecturer,
Hammersmith Hospital Campus of
Imperial College School of Medicine
and Honorary Consultant Histopathologist
Hammersmith Hospital, London

BRIDGET S. WILKINS
DM, PhD, FRCPath
Consultant Histopathologist
Newcastle upon Tyne Hospitals NHS Trust
and Honorary Senior Lecturer
University of Newcastle

THIRD EDITION
© 1992, 1996, 2001
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A catalogue record for this title
is available from the British Library
ISBN 978-0-632-05578-4
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Cataloging-in-Publication Data
Bone marrow pathology/Barbara
J. Bain . . . [et al.].-3rd ed.
p. cm.
Rev. ed. of: Bone marrow pathology/
Barbara J. Bain, David M. Clark,
Irvin A. Lampert. 2nd ed. 1996.
Includes bibliographical references
and index.
ISBN 978-0-632-05578-4
1 Bone marrow-histopathology.
I Bain, Barbara J. II Bain, Barbara J.
Bone marrow pathology.
[DNLM: 1. Bone Marrow Diseasesa
pathology. 2. Bone Marrowa
pathology. WH 380 B7116 2001]
RC645.7.B35 2001
616.4’107adc21
00-051929
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CONTENTS

Preface to the third edition, vi

Acknowledgements, vii
Abbreviations, viii
1 The normal bone marrow, 1
2 Special techniques applicable to bone marrow diagnosis, 51
3 Infection and reactive changes, 90
4 Acute myeloid leukaemia, the myelodysplastic syndromes
and histiocytic neoplasms, 141
5 Chronic myeloproliferative and myeloproliferative/
myelodysplastic disorders, 191
6 Lymphoproliferative disorders, 231
7 Multiple myeloma and related disorders, 332
8 Disorders of erythropoiesis, granulopoiesis and thrombopoiesis, 360
9 Miscellaneous disorders, 391
10 Metastatic tumours, 430
11 Diseases of bone, 462
Appendix, 474
Index, 483

v
 PREFACE TO THE
THIRD EDITION
In this book we have set out to provide a practical
guide to bone marrow diagnosis, based on an inte-
grated assessment of peripheral blood and bone
marrow aspirate films, trephine biopsy sections and
various supplementary investigations. We believe
that a trephine biopsy specimen should not be ex-
amined and interpreted in isolation. We have there-
fore discussed the clinical context of bone marrow
diagnosis and have given equal weight to cytolog-
ical and histological features. Since bone marrow
diagnosis is no longer based on morphological fea-
tures alone we have also, in this edition, discussed
in considerable detail the role of immunopheno-
typic, cytogenetic and molecular genetic analysis.
We have dealt very fully with haematological
disorders for which bone marrow examination is
commonly performed. However, we have also
sought to be as comprehensive as possible, includ-
vi
ing whatever information is available on uncom-
mon and rare disorders so that the book will serve
as a useful reference source. When possible, we
have illustrated rare as well as common conditions
and have cited the relevant scientific literature
extensively.
In this edition we have introduced a new section
entitled ‘Problems and pitfalls’ which we believe
will be of value. We have also expanded the descrip-
tion of technical methods. We hope that haemato-
logists and histopathologists will continue to find
Bone Marrow Pathology a useful aid in their day-to-
day practice and that trainees in these disciplines
will find it indispensable.
BJB, DMC, IAL, BSW
December 2000
 ACKNOWLEDGEMENTS
We should like to thank our many friends and
colleagues in North America, Europe, Africa, Asia
and Australia who have provided illustrations or
have permitted us to photograph microscopic slides
from their personal collections. They are individu-
ally acknowledged in the legends of specific figures.
In addition we should like to thank our technical and
medical colleagues in St Mary’s Hospital, Hammer-
smith Hospital, Nottingham University Hospitals
and Southampton University Hospitals for the direct
and indirect help they have given us.
This book is dedicated to Professor Emeritus
David Galton who taught us and countless other
haematologists and histopathologists for a great
many years. Those who have worked with him have
admired him both for his diagnostic skills and for
his mindfulness of the individual patient. It is with
much pleasure that we make this dedication to him.
vii
 ABBREVIATIONS

aCML atypical CML EMA epithelial membrane antigen

AIDS acquired immune deficiency syndrome ESR erythrocyte sedimentation rate
AILD angio-immunoblastic ET essential thrombocythaemia
lymphadenopathy (with FAB French–American–British (co-operative
dysproteinaemia) group)
ALCL anaplastic large cell lymphoma FICTION fluorescent immunophenotyping and
ALIP abnormal localization of immature interphase cytogenetics
precursors FISH fluorescence in situ hybridization
ALL acute lymphoblastic leukaemia G-CSF granulocyte colony-stimulating factor
AML acute myeloid leukaemia GM-CSF granulocyte–macrophage colony-
ATLL adult T-cell leukaemia/lymphoma stimulating factor
ATRA all-trans retinoic acid GMS Grocott’s methenamine silver (stain)
BCL2 B-cell leukaemia/lymphoma 2 GPI glycosyl phosphatidylinositol
BCR breakpoint cluster region GVHD graft-versus-host disease
BFU-E erythroid burst-forming unit H&E haematoxylin and eosin (stain)
BM bone marrow Hempas hereditary erythroid multinuclearity
B-PLL B-lineage prolymphocytic leukaemia with positive acidified serum test
CD cluster of differentiation HHV human herpesvirus
CDA congenital dyserythropoietic anaemia HIV human immunodeficiency virus
CFU colony-forming unit HLA human leucocyte antigen
CFU-GM granulocyte–monocyte CFU HTLV-I human T-cell lymphotropic virus I
CFU-Meg megakaryocyte CFU Ig immunoglobulin
CGL chronic granulocytic leukaemia IGH immunoglobulin heavy chain (gene)
CHAD cold haemagglutinin disease IL interleukin
CLL chronic lymphocytic leukaemia ISH in situ hybridization
CML chronic myeloid leukaemia JMML juvenile myelomonocytic leukaemia
CMML chronic myelomonocytic leukaemia LDH lactate dehydrogenase
CMV cytomegalovirus LE lupus erythematosus
CT computerized tomography LGL large granular lymphocyte
CyIg cytoplasmic immunoglobulin LGLL large granular lymphocyte leukaemia
DIC disseminated intravascular coagulation LTC-IC long-term culture-initiating cell
DNA deoxyribonucleic acid MALT mucosa-associated lymphoid tissue
EBER Epstein–Barr early RNA MBR major breakpoint region
EBNA Epstein–Barr nuclear antigen McAb monoclonal antibody
EBV Epstein–Barr virus MCR minor cluster region
EDTA ethylene diamine tetra-acetic acid MDS myelodysplastic syndromes
EGIL European Group for the Immunological M:E myeloid : erythroid ratio
Classification of Leukaemia MGG May–Grünwald–Giemsa (stain)

viii
 ABBREVIATIONS ix

MGUS monoclonal gammopathy of RAEB refractory anaemia with excess of blasts

undetermined significance RAEB-T refractory anaemia with excess of blasts
MIC morphologic, immunologic, cytogenetic in transformation
(classification) RARS refractory anaemia with ring
MIC-M morphological, immunological, sideroblasts
cytogenetic, molecular genetic REAL Revised European–American
(classification) Lymphoma (classification)
MPD myeloproliferative disorder RNA ribonucleic acid
MPO myeloperoxidase RT-PCR reverse transcriptase polymerase chain
mRNA messenger RNA reaction
NEC non-erythroid cells SBB Sudan black B (stain)
NHL non-Hodgkin’s lymphoma SD standard deviation
NK natural killer SKY spectral karyotyping
PAS periodic acid–Schiff (stain) SLVL splenic lymphoma with villous
PB peripheral blood lymphocytes
PCR polymerase chain reaction SmIg surface membrane immunoglobulin
Ph Philadelphia chromosome TAR thrombocytopenia-absent radii
PLL prolymphocytic leukaemia (syndrome)
PNET primitive neuro-ectodermal tumour TCR T-cell receptor
PNH paroxysmal nocturnal haemoglobinuria TdT terminal deoxynucleotidyl transferase
POEMS polyneuropathy, organomegaly, T-PLL T-lineage prolymphocytic leukaemia
endocrinopathy, M-protein, skin TRAP tartrate-resistant acid phosphatase
changes (syndrome) WBC white blood cell (count)
PRV polycythaemia rubra vera WHO World Health Organization
RA refractory anaemia ZN Ziehl–Neelsen