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Contents

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This book is dedicated to the late Professor David A. G. Galton

PREFACE TO THE FOURTH EDITION

In this book we have set out to provide a practical guide to bone marrow diagnosis, based on an integrated assessment of peripheral blood and bone marrow aspirate films, trephine biopsy sections and supplementary investigations. We believe that a trephine biopsy specimen should not be examined and interpreted in isolation. We have therefore discussed the clinical context of bone marrow diagnosis and have given equal weight to cytological and histological features. Since bone marrow diagnosis is no longer based on morphological features alone we have also discussed in detail the role of immunophenotypic, 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 comprehensive, including information on uncommon 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 magnifications are given as the microscope objective used for photography rather than as the magnification on the printed page.

To facilitate use of the book in diagnostic laboratories we have extended the ‘Problems and pitfalls’ sections and have added new diagnostic algorithms and summary boxes, which we believe will be of value. We hope that haematologists 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, BSW

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 individually acknowledged in the legends of specific figures. In addition we should like to thank our technical and medical colleagues in St Mary's Hospital, Hammersmith Hospital, Nottingham University Hospital, Path Links and St Thomas'Hospital for the direct and indirect help they have given us in the preparation of this edition. We are also grateful for the comments and feedback given to us by readers of the previous editions and individuals attending the postgraduate courses on which we teach.

Our special thanks go to Dr Irvin Lampert, for his invaluable contributions as co-author of the first three editions of this book, and for the friendship and wisdom he has generously shared with us for more than 20 years.

This book is dedicated to the late Professor David Galton (1922-2006) who taught us and countless other haematologists and histopathologists a great deal over many years. Those who had the opportunity to work with him admired him for his exceptional diagnostic skills, his humility and his mindfulness of patients as individuals. He is much missed.

BJB, DMC, BSW

ABBREVIATIONS

aCML atypical chronic myeloid leukaemiaalternating current
AIDS acquired immune deficiency syndromealternating current
AILD angioimmunoblastic lymphadenopathy with dysproteinaemiaalternating current
ALCL anaplastic large cell lymphomaalternating current
ALIP abnormal localization of immature precursorsalternating current
ALL acute lymphoblastic leukaemiaalternating current
ALPS autoimmune lymphoproliferative syndromealternating current
AML acute myeloid leukaemiaalternating current
ANAE alpha-naphthyl acetate esterasealternating current
APAAP alkaline phosphatase-anti-alkaline phosphatasealternating current
ATLL adult T-cell leukaemia/lymphomaalternating current
ATRA all-trans-retinoic acidalternating current
BFU burst-forming unitalternating current
BL Burkitt lymphomaalternating current
BM bone marrowalternating current
BSAP B-cell-specific activator proteinalternating current
c cytoplasmicalternating current
CAE chloroacetate esterasealternating current
CD cluster of differentiationalternating current
CDA congenital dyserythropoietic anaemiaalternating current
CEA carcino-embryonic antigenalternating current
CEL chronic eosinophilic leukaemiaalternating current
CFU colony-forming unitalternating current
CGH comparative genomic hybridizationalternating current
CGL chronic granulocytic leukaemiaalternating current
CHAD cold haemagglutinin diseasealternating current
CK cytokeratinalternating current
CLL chronic lymphocytic leukaemiaalternating current
CML chronic myeloid leukaemiaalternating current
CMML chronic myelomonocytic leukaemiaalternating current
CMV cytomegalovirusalternating current
CNS central nervous systemalternating current
CT computerized tomography del deletionalternating current
DIC disseminated intravascular coagulationalternating current
DLBCL diffuse large B-cell lymphomaalternating current
DNA deoxyribonucleic acidalternating current
EBER Epstein-Barr early RNAalternating current
EBNA Epstein-Barr nuclear antigenalternating current
EBV Epstein-Barr virusalternating current
EDTA ethylene diamine tetra-acetic acidalternating current
EGIL European Group for the Immunological Classification of Leukaemiaalternating current
EMA epithelial membrane antigenalternating current
ER oestrogen receptoralternating current
ET essential thrombocythaemiaalternating current
FAB French-American-British (co-operative group)alternating current
FBC full blood countalternating current
FISH fluorescence in situ hybridizationalternating current
G-CSF granulocyte colony-stimulating factoralternating current
GM-CSF granulocyte-macrophage colony-stimulating factoralternating current
GMS Grocott's methenamine silver (stain)alternating current
GPI glycosyl phosphatidylinositolalternating current
GVHD graft-versus-host diseasealternating current
Hb haemoglobin concentrationalternating current
H&E haematoxylin and eosin (stain)alternating current
HEMPAS hereditary erythroid multinuclearity with positive acidified serum lysis testalternating current
HER2 human epidermal growth factor receptor 2alternating current
HHV human herpesvirusalternating current
HIV human immunodeficiency virusalternating current
HL Hodgkin lymphomaalternating current
HLA human leucocyte antigenalternating current
HTLV-I human T-cell lymphotropic virus Ialternating current
i isochromosomealternating current
idic isodicentric chromosomealternating current
Ig immunoglobulinalternating current
IGH immunoglobulin heavy chain (gene locus)alternating current
IHC immunohistochemistryalternating current
IL interleukinalternating current
inv inversionalternating current
IPSID immunoproliferative small intestinal diseasealternating current
IPSS International Prognostic Scoring Systemalternating current
ISH in situ hybridizationalternating current
ITD internal tandem duplicationalternating current
JMML juvenile myelomonocytic leukaemiaalternating current
KIR killer inhibitory receptoralternating current
LDH lactate dehydrogenasealternating current
LGL large granular lymphocyte/salternating current
LMP latent membrane proteinalternating current
MALT mucosa-associated lymphoid tissuealternating current
McAb monoclonal antibodyalternating current
MDS myelodysplastic syndrome/salternating current
M : E myeloid : erythroidalternating current
MGG May-Grünwald-Giemsa (stain)alternating current
MGUS monoclonal gammopathy of undetermined significancealternating current
MPAL mixed phenotype acute leukaemiaalternating current
MPN myeloproliferative neoplasm/salternating current
MPO myeloperoxidasealternating current
MRD minimal residual diseasealternating current
mRNA messenger ribonucleic acidalternating current
MSB Martius scarlet blue (stain)alternating current
NEC non-erythroid cell/salternating current
NHL non-Hodgkin lymphomaalternating current
NK natural killeralternating current
NLPHL nodular lymphocyte-predominant Hodgkin lymphomaalternating current
NOS not otherwise specifiedalternating current
NSE non-specific esterasealternating current
PAS periodic acid-Schiff (stain)alternating current
PB peripheral bloodalternating current
PBS phosphate-buffered salinealternating current
PcAb polyclonal antibodyalternating current
PCR polymerase chain reactionalternating current
PEL primary effusion lymphomaalternating current
PET positron emission tomographyalternating current
Ph Philadelphia (chromosome)alternating current
PLL prolymphocytic leukaemiaalternating current
PMF primary myelofibrosisalternating current
PNET primitive neuroectodermal tumour/salternating current
PNH paroxysmal nocturnal haemoglobinuriaalternating current
POEMS polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (syndrome)alternating current
PSA prostate-specific antigenalternating current
PSAP prostate-specific acid phosphatasealternating current
PV polycythaemia veraalternating current
RA refractory anaemiaalternating current
RAEB refractory anaemia with excess of blastsalternating current
RAEB-T refractory anaemia with excess of blasts in transformationalternating current
RARS refractory anaemia with ring sideroblastsalternating current
RARS-T refractory anaemia with ring sideroblasts and thrombocytosisalternating current
RCC refractory cytopenia of childhoodalternating current
RCMD refractory cytopenia with multilineage dysplasiaalternating current
RCUD refractory cytopenia with unilineage dysplasiaalternating current
REAL Revised European American Lymphoma (classification)alternating current
RN refractory neutropeniaalternating current
RNA ribonucleic acidalternating current
RQ-PCR real time quantitative polymerase chain reactionalternating current
RT refractory thrombocytopeniaalternating current
RT-PCR reverse transcriptase polymerase chain reactionalternating current
SB Southern blotalternating current
SBB Sudan black Balternating current
SD standard deviationalternating current
SLL small lymphocytic lymphomaalternating current
SLVL splenic lymphoma with villous lymphocytesalternating current
SM-AHNMCD systemic mastocytosis with associated clonal, haematological non-mast cell lineage disease (WHO classification)alternating current
SmIg surface membrane immunoglobulinalternating current
SMZL splenic marginal zone lymphomaalternating current
SNP single nucleotide polymorphismalternating current
t translocationalternating current
TAR thrombocytopenia-absent radii (syndrome)alternating current
TBS Tris-buffered salinealternating current
TCR T-cell receptoralternating current
TCR T-cell receptor (gene locus)alternating current
TdT terminal deoxynucleotidyl transferasealternating current
TNF tumour necrosis factoralternating current
TPO thrombopoietinalternating current
TRAP tartrate-resistant acid phosphatasealternating current
TTF1 thyroid transcriptase factor 1alternating current
WBC white blood cell countalternating current
WHO World Health Organizationalternating current
ZN Ziehl-Neelsen (stain)alternating current