Leukaemia Diagnosis E-Book

Barbara J. Bain

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1533

Veröffentlichungsjahr: 2024

Beschreibung

Leukaemia Diagnosis Authoritative reference on classifying and diagnosing leukaemia, with practical guidance on using various laboratory techniques included Leukaemia Diagnosis is a practical reference on the principles of leukaemia diagnosis and classification that illustrates and explains in a user-friendly way how different laboratory techniques are used to achieve an accurate interpretation. To aid in reader comprehension, over 300 high quality full colour digital images of abnormal cells in leukaemia and lymphoma are included, supplemented by histological, cytogenetic and immunophenotyping images. This newly revised and updated Sixth Edition includes recent developments, highlights the growing importance of molecular genetics, and incorporates the recent 5th edition of the WHO guidelines and the International Consensus Classification for leukaemia diagnosis and classification throughout the text. Information on cytogenetic and molecular genetic abnormalities in leukaemia is also included, along with characteristic immunophenotypic characteristics of different categories of leukaemia. Written by world-renowned authors in the field, Barbara Bain and Mike Leach, Leukaemia Diagnosis covers sample topics such as: * The nature of leukaemia, cytology, cytochemistry, and the morphological classification of acute leukaemia, with an index of commonly used abbreviations * Immunophenotyping and cytogenetic/molecular genetic analysis, and integration of morphological, immunophenotypic and genetic information with the WHO classifications * Acute lymphoblastic leukaemia, acute leukaemia of ambiguous lineage, and the myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms * Chronic myeloid leukaemias, lymphoid leukaemias of mature B, T, and natural killer cells, and leukaemia diagnosis in resource-poor countries The Sixth Edition of Leukaemia Diagnosis is a highly valuable resource for trainee haematologists and laboratory scientists in haematology and related disciplines. The text also serves as a useful reference and teaching aid for those who already have expertise in this field.

Leseprobe

Table of Contents

Cover

Table of Contents

Title Page

Copyright Page

Preface

Acknowledgements

Commonly Used Abbreviations

1 The Nature of Leukaemia, Cytology, Cytochemistry and the Morphological Classification of Acute Leukaemia

The nature of leukaemia

The aetiology of leukaemia

The importance of classification

The nature and classification of acute leukaemia

The nature and classification of the myelodysplastic syndromes

The nature and classification of chronic myeloid leukaemias and myelodysplastic/myeloproliferative neoplasms

The nature and classification of lymphoid neoplasms

Defining a blast cell, a promyelocyte and a promonocyte

The FAB classification of acute leukaemia

Automated full blood counts in acute leukaemia

References

2 Immunophenotyping and Cytogenetic/Molecular Genetic Analyis

Introduction

Immunophenotyping

Genetic analysis

Conclusions

References

3 Acute Myeloid Leukaemia: Integration of Morphological, Immunophenotypic and Genetic Information: the WHO and International Consensus Classifications

Introduction

The WHO classification of acute myeloid leukaemia

Acute myeloid leukaemia associated with antecedent and predisposing conditions

The International Consensus Classification of acute myeloid leukaemia

Other acute myeloid leukaemias and related conditions

Prognostic significance of cytogenetic and genetic abnormalities in acute myeloid leukaemia

The role of immunophenotyping

The diagnostic pathway

Conclusions

References

4 Acute Lymphoblastic Leukaemia and Acute Leukaemia of Mixed or Ambiguous Lineage

Introduction

The WHO classification of acute lymphoblastic leukaemia/lymphoblastic lymphoma of B lineage

The International Consensus Classification of acute lymphoblastic leukaemia/lymphoblastic lymphoma of B lineage

The WHO classification of acute lymphoblastic leukaemia/lymphoblastic lymphoma of T lineage

The International Consensus Classification of acute lymphoblastic leukaemia/lymphoblastic lymphoma of T lineage

Natural killer cell lymphoblastic leukaemia/lymphoma

Therapy‐related lymphoblastic leukaemia/lymphoma

Acute leukaemias of mixed or ambiguous lineage

Conclusions

References

5 The Myelodysplastic Syndromes, the Myelodysplastic/Myeloproliferative Neoplasms and Juvenile Myelomonocytic Leukaemia

MYELODYSPLASTIC SYNDROMES/NEOPLASMS

Recognition, nature and epidemiology

Classification

Cytochemistry

Immunophenotyping

Bone marrow trephine biopsy

Cytogenetic features

Molecular genetic features

Other laboratory tests

Disease evolution and prognosis

Differential diagnosis, CHIP, CCUS, ICUS and VEXAS

The WHO classification of the myelodysplastic syndromes/neoplasms

The International Consensus Classification of the myelodysplastic syndromes

Myelodysplastic syndromes with antecedent and predisposing conditions

MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS

Recognition, nature and epidemiology

Cytochemistry

Immunophenotyping

Cytogenetic and molecular genetic analysis

The WHO and International Consensus classifications of myelodysplastic/myeloproliferative neoplasms

Juvenile myelomonocytic leukaemia

Conclusions

References

6 Chronic Myeloid Leukaemias

Introduction

Chronic myeloid leukaemia

Chronic neutrophilic leukaemia

Chronic eosinophilic leukaemia

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

Chronic basophilic leukaemia

Chronic mast cell leukaemia

Conclusions

References

7 Lymphoid Leukaemias of Mature B, T and Natural Killer Cells

Diagnosis and classification of lymphoid leukaemias and leukaemic‐phase lymphomas of mature T, B and NK cells

Chronic leukaemias/lymphomas of B lineage

Leukaemias of mature T and NK cells

References

8 Leukaemia Diagnosis in Resource‐Poor Countries

Introduction

Diagnosis of specific leukaemias and related conditions

Supplementary tests

Training and continuing education

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Inherited susceptibility to acute myeloid leukaemia* [5–10].

Table 1.2 Constitutional and inherited susceptibility to acute lymphoblasti...

Table 1.3 Cytochemical stains of use in the diagnosis and classification of...

Table 1.4 Criteria for the diagnosis of acute myeloid leukaemia of M0 categ...

Table 1.5 Ultrastructural characteristics distinguishing blast cells and ot...

Table 1.6 Ultrastructural cytochemistry in the identification of blast cell...

Table 1.7 Criteria for the diagnosis of acute myeloid leukaemia of M1 categ...

Table 1.8 Criteria for the diagnosis of acute myeloid leukaemia of M2 categ...

Table 1.9 Criteria for the diagnosis of acute myeloid leukaemia of M4 categ...

Table 1.10 Criteria for the diagnosis of acute myeloid leukaemia of M5 cate...

Table 1.11 Criteria for the diagnosis of acute myeloid leukaemia of M6 cate...

Table 1.12 Criteria for the diagnosis of acute myeloid leukaemia of M7 cate...

Table 1.13 Morphological features of acute lymphoblastic leukaemia (ALL) su...

Chapter 2

Table 2.1 The fluorochromes most often used in flow cytometric immunophenot...

Table 2.2 Monoclonal (or polyclonal) antibodies useful in the diagnosis and...

Table 2.3 Panel of antibodies recommended by the European LeukemiaNet for t...

Table 2.4

P

attern of reactivity with monoclonal (or polyclonal) antibodies c...

Table 2.5 Monoclonal antibodies and polyclonal antisera useful in the diagn...

Table 2.6 European Group for the Immunological Characterization of Leukemia...

Table 2.7 European Group for the Immunological Characterization of Leukemia...

Table 2.8 A comparison of the immunophenotypic characteristics of haematogo...

Table 2.9 Typical antibody combinations for the identification of a leukaem...

Table 2.10 Abbreviations, terminology and symbols used in describing chromo...

Table 2.11 Some symbols, terminology and abbreviations used in describing f...

Table 2.12 A summary of molecular genetic techniques used in the investigat...

Table 2.13 Some examples demonstrating the role of cytogenetic analysis in ...

Table 2.14 Some examples demonstrating the role of molecular genetic analys...

Table 2.15 Class I and class II mutations that can interact in the pathogen...

Table 2.16 Prognostic significance of haematological, cytogenetic and molec...

Chapter 3

Table 3.1 The 2022 5th edition World Health Organization (WHO) classificati...

Table 3.2 The 2022 5th edition World Health Organization (WHO) classificati...

Table 3.3 Characteristics of acute myeloid leukaemia (AML) associated with ...

Table 3.4 Characteristics of acute leukaemia and related conditions associa...

Table 3.5 Further subtypes of acute myeloid leukaemia* with an 11q23.3 brea...

Table 3.6 Cytogenetic and genetic abnormalities that define myelodysplasia‐...

Table 3.7 Acute myeloid leukaemia with other defined genetic alterations [5...

Table 3.8 Cytogenetic abnormalities associated with therapy‐related acute l...

Table 3.9 The 2022 World Health Organization classification of germline pre...

Table 3.10 The International Consensus Classification of acute myeloid leuk...

Table 3.11 The International Consensus Classification categories of acute m...

Table 3.12 Prognostic classification based on United Kingdom Medical Resear...

Table 3.13 European LeukemiaNet prognostic scoring system.

Table 3.14 Recurring genetic abnormalities that influence outcome in acute ...

Table 3.15 Laboratory investigations required for precise diagnosis and man...

Chapter 4

Table 4.1 The WHO and International Consensus classifications of lymphoblas...

Table 4.2 The most frequent cytogenetic/genetic rearrangements in

KMT2A

‐rea...

Table 4.3 The 2022 WHO classifications of other types of B‐lineage lymphobl...

Table 4.4 Some genetic categories of T‐lineage ALL (derived from references...

Table 4.5 WHO 2022 criteria for a diagnosis of mixed phenotype and undiffer...

Table 4.6 Genetic categories of mixed phenotype and acute undifferentiated ...

Chapter 5

Table 5.1 Features of some inherited conditions predisposing to myelodyspla...

Table 5.2 Haematological features that may occur in the myelodysplastic syn...

Table 5.3 The 2022 World Health Organization (WHO) classification of the my...

Table 5.4 Cytogenetic abnormalities associated with the myelodysplastic syn...

Table 5.5 Factors that have been reported to have prognostic significance i...

Table 5.6 The International Prognostic Scoring System for myelodysplastic s...

Table 5.7 The World Health Organization (WHO) classification‐based Prognost...

Table 5.8 Outcome in two cohorts of patients according to the World Health ...

Table 5.9 The International Prognostic Scoring System for myelodysplastic s...

Table 5.10 The International Prognostic Scoring System for myelodysplastic ...

Table 5.11 The 2016, revised 4th edition, World Health Organization classif...

Table 5.12 The 2022 5th edition World Health Organization classification: c...

Table 5.13 The 2022 5th edition World Health Organization classification: c...

Table 5.14 The International Consensus Classification of the myelodysplasti...

Table 5.15 The 2022 5th edition World Health Organization (WHO) classificat...

Table 5.16 The 2022 5th edition World Health Organization (WHO) classificat...

Table 5.17 The 2022 5th edition World Health Organization (WHO) classificat...

Table 5.18 The 2022 5th edition World Health Organization (WHO) criteria fo...

Table 5.19 The International Consensus Classification (ICC) criteria for a ...

Chapter 6

Table 6.1 The 2022 5th edition World Health Organization classification of t...

Table 6.2 Molecular variants of

BCR::ABL1

and associated clinicopathologica...

Table 6.3 The 2022 5th edition World Health Organization (WHO) and Internat...

Table 6.4 The 2022 5th edition World Health Organization classification of ...

Table 6.5 Chronic eosinophilic leukaemia and related conditions associated ...

Table 6.6 Chronic eosinophilic leukaemia and related conditions associated ...

Table 6.7 Lymphoid and myeloid neoplasms associated with rearrangement of

F

...

Chapter 7

Table 7.1 Monoclonal antibodies applicable to immunophenotyping chronic lym...

Table 7.2 Cytogenetic and molecular genetic abnormalities most characterist...

Table 7.3 Staging of Hodgkin and non‐Hodgkin lymphoma (Lugano modification ...

Table 7.4 International Prognostic Index for high‐grade non‐Hodgkin lymphom...

Table 7.5 Follicular Lymphoma International Prognostic Index (FLIPI).

Table 7.6 Some monoclonal antibodies used in the characterisation of chroni...

Table 7.7 Characteristic immunophenotype of chronic B‐cell leukaemias and B...

Table 7.8 A scoring system for the immunophenotypic diagnosis of chronic ly...

Table 7.9 Differences between chronic lymphocytic leukaemia subsets with un...

Table 7.10 The Rai staging system for chronic lymphocytic leukaemia.

Table 7.11 The Binet staging system for chronic lymphocytic leukaemia.*

Table 7.12 Criteria for a diagnosis of smouldering chronic lymphocytic leuk...

Table 7.13 Factors indicating worse prognosis in chronic lymphocytic leukae...

Table 7.14 Criteria proposed for the diagnosis of monoclonal B‐cell lymphoc...

Table 7.15 2022 World Health Organization subtyping of follicular lymphoma ...

Table 7.16 Comparison of usual features of classical mantle cell lymphoma a...

Table 7.17 Some monoclonal antibodies used in the characterisation of chron...

Table 7.18 Characteristic immunophenotype of chronic T‐cell leukaemias.

Table 7.19 A comparison of the clinicopathological features of T‐cell large...

Table 7.20 Subclassification of adult T‐cell leukaemia/lymphoma (ATLL) [531...

Table 7.21 International Society for Cutaneous Lymphomas criteria for diagn...

Chapter 8

Table 8.1 Websites giving useful information in the diagnosis of leukaemia ...

List of Illustrations

Chapter 1

Fig. 1.1 Peripheral blood (PB) film of a patient with acute myeloid leukaemi...

Fig. 1.2 PB film of a patient with AML showing: (a) a type II blast with sca...

Fig. 1.3 Bone marrow (BM) film of a patient with AML, French–American−Britis...

Fig. 1.4 BM film from a patient with FAB M2 AML showing: (a) a type I blast ...

Fig. 1.5 BM film from a patient with FAB M5 AML showing: (a) a monoblast and...

Fig. 1.6 BM film from a patient with FAB M5 AML showing a promonocyte and th...

Fig. 1.9 Ultrastructural cytochemistry showing peroxidase‐positive granules ...

Fig. 1.10 PB film of a patient with FAB M1 AML showing type I and type II bl...

Fig. 1.11 PB film of a patient with FAB M1 AML showing type I blasts with cy...

Fig. 1.12 Trephine biopsy section from a patient with FAB M1 AML. The majori...

Fig. 1.13 Cytochemical reactions in a patient with FAB M1 AML. (a) MGG‐stain...

Fig. 1.14 Unusual forms of Auer rod. (a) PB film showing an Auer rod within ...

Fig. 1.15 BM film of a patient with FAB M2 AML showing blasts (one of which ...

Fig. 1.16 BM film of a patient with FAB M2 AML stained by (a) MGG and (b) SB...

Fig. 1.17 BM film of a patient with FAB M2 AML showing unusually heavy granu...

Fig. 1.18 Clinical photograph of a patient with FAB M3 AML showing extensive...

Fig. 1.19 Computed tomography scan of the chest showing bilateral pulmonary ...

Fig. 1.20 BM film of a patient with FAB M3 AML showing hypergranular promyel...

Fig. 1.21 PB film of a patient with FAB M3 AML. One of the abnormal promyelo...

Fig. 1.22 Trephine biopsy section from a patient with FAB M3 AML. Paraffin e...

Fig. 1.23 BM film from a patient with acute promyelocytic leukaemia a few da...

Fig. 1.24 PB film of a patient with FAB M3 AML being treated with ATRA and g...

Fig. 1.25 (a) PB film and (b) film of cultured leukaemic cells from a patien...

Fig. 1.26 (a) PB film of a patient with FAB M3 variant AML showing cells wit...

Fig. 1.27 Ultrastructural examination of leukaemic cells of three patients w...

Fig. 1.28 BM film from a patient with the hyperbasophilic variant of acute p...

Fig. 1.29 Cytochemical reactions in a patient with FAB M3 variant AML. (a) P...

Fig. 1.30 (a) PB film of a patient with FAB M4 AML showing a myeloblast of m...

Fig. 1.31 Trephine biopsy section from a patient with M4Eo AML. Cells are ei...

Fig. 1.32 PB film of a patient with FAB M4 AML – M4Eo/inv(16) – who had both...

Fig. 1.33 PB film of a patient with FAB M5a AML showing three monoblasts. MG...

Fig. 1.34 PB film of a patient with FAB M5b AML showing a monocyte and a pro...

Fig. 1.35 PB and BM films of a patient with FAB M5b AML in whom the PB cells...

Fig. 1.36 Trephine biopsy section from a patient with FAB M5b AML and myelod...

Fig. 1.37 Clinical photograph of a patient with FAB M5a AML showing infiltra...

Fig. 1.38 Clinical photograph of a patient with FAB M5b AML showing skin inf...

Fig. 1.39 BM film of a patient with leukaemic cells showing histiocytic or m...

Fig. 1.40 (a) BM film of a patient with FAB M5a AML stained for ANAE activit...

Fig. 1.41 PB film in a patient with FAB M6 AML showing anaemia, severe throm...

Fig. 1.42 BM film from a patient with FAB M6 AML (erythroleukaemia) showing ...

Fig. 1.43 BM film from a patient with FAB M6 AML showing marked erythroid hy...

Fig. 1.44 BM film from a patient with FAB M6 AML showing: (a) a binucleated ...

Fig. 1.45 A cytospin preparation of BM cells of a patient with FAB M6 AML sh...

Fig. 1.46 (a, b) BM film in FAB M6 AML showing diffuse PAS positivity in lat...

Fig. 1.47 BM trephine biopsy section in FAB M6 AML showing primitive erythro...

Fig. 1.48 Ultrastructural examination of peripheral blood cells from a patie...

Fig. 1.49 Ultrastructural cytochemistry of a blast cell showing a positive p...

Fig. 1.50 PB and BM films from a patient with FAB M7 AML presenting as acute...

Fig. 1.51 Trephine biopsy section from a patient with FAB M7 AML showing inc...

Fig. 1.52 BM film in FAB M7 AML showing a micromegakaryocyte with cytoplasmi...

Fig. 1.53 PB film in acute eosinophilic leukaemia with abnormal eosinophil p...

Fig. 1.54 Trephine biopsy section in acute eosinophilic leukaemia showing nu...

Fig. 1.55 BM film from a patient with acute eosinophilic leukaemia showing a...

Fig. 1.56 BM film in acute basophilic leukaemia. (a) Vacuolated blast with l...

Fig. 1.57 PB film in mast cell leukaemia showing a neutrophil and four mast ...

Fig. 1.58 Trephine biopsy section from a patient with acute mast cell leukae...

Fig. 1.59 BM film from a patient with acute leukaemia showing mast cell and ...

Fig. 1.60 BM film from a patient with acute mast cell leukaemia showing a ma...

Fig. 1.61 Langerhans’ cell leukaemia. MGG ×100.

Fig. 1.62 PB film of a patient with FAB L1 acute lymphoblastic leukaemia (AL...

Fig. 1.63 BM film from a patient with FAB L1 ALL. MGG ×100.

Fig. 1.64 Ultrastructure of lymphoblasts in FAB L1 ALL.

Fig. 1.65 BM film from a patient with FAB L2 ALL showing large pleomorphic b...

Fig. 1.66 BM film from a patient with FAB L2 ALL showing medium to large ple...

Fig. 1.67 Trephine biopsy section from a patient with FAB L2 ALL. Note the p...

Fig. 1.68 PB film of a patient with FAB L3 ALL with the immunological phenot...

Fig. 1.69 BM film of a patient with FAB L3 ALL with the immunological phenot...

Fig. 1.70 PB film a patient with FAB L3 ALL which was unusual in being of T ...

Fig. 1.71 Trephine biopsy section from a patient with FAB L3 ALL, B‐cell phe...

Fig. 1.72 PB film of a patient with B‐lineage ALL showing two cup‐shaped bla...

Fig. 1.73 PB film of a patient with B‐lineage ALL showing two lymphoblasts w...

Fig. 1.74 Printouts from Bayer‐Technicon H.1 series instruments on blood sam...

Chapter 2

Fig. 2.1 French–American–British (FAB) M0 acute myeloid leukaemia (AML) inve...

Fig. 2.2 Immunophenotyping of a case of acute lymphoblastic leukaemia (ALL) ...

Fig. 2.3 Four‐colour flow cytometric immunophenotyping showing characteristi...

Fig. 2.4 Flow cytometric immunophenotyping in a patient with mantle cell lym...

Fig. 2.5 Dot plots of flow cytometric immunophenotyping of bone marrow cells...

Fig. 2.6 Flow cytometry histogram showing the number of signals plotted agai...

Fig. 2.7 Diagram showing expression of surface membrane and cytoplasmic anti...

Fig. 2.8 Diagram showing expression of surface membrane antigens at various ...

Fig. 2.9 Diagram showing expression of surface membrane antigens at various ...

Fig. 2.10 Flow cytometric immunophenotyping in ALL showing aberrant antigen ...

Fig. 2.11 Flow cytometric immunophenotyping in AML showing aberrant antigen ...

Fig. 2.12 Flow cytometric immunophenotyping in acute promyelocytic leukaemia...

Fig. 2.13 Karyogram from a patient with Burkitt lymphoma showing chromosomes...

Fig. 2.14 Fluorescence

in situ

hybridisation (FISH) using a dual‐colour, bre...

Fig. 2.15 FISH using a dual‐colour, dual‐fusion technique. Normal cells woul...

Fig. 2.16 FISH of chromosomes of a patient with ALL and the common transloca...

Chapter 3

Fig. 3.1 Algorithm showing how the 2022 World Health Organization (WHO) clas...

Fig. 3.2 A diagrammatic representation of the t(8;21)(q22;q22.1) abnormality...

Fig. 3.3 Peripheral blood (PB) and bone marrow (BM) films of a patient with ...

Fig. 3.4 BM film from a patient with AML associated with t(8;21)(q22;q22.1),...

Fig. 3.5 BM film of a patient with AML associated with t(8;21)(q22;q22.1), F...

Fig. 3.6 BM film from a patient with AML associated with t(8;21)(q22;q22.1),...

Fig. 3.7 BM film of a patient with t(8;21)(q22;q22.1), FAB M2 AML with eosin...

Fig. 3.8 Four‐colour flow cytometry immunophenotyping in a patient with AML ...

Fig. 3.9 Karyogram showing the translocation between chromosome 8 and chromo...

Fig. 3.10 Diagrammatic representation of dual‐colour, dual‐fusion fluorescen...

Fig. 3.11 Metaphase spread and interphase nucleus from a patient with FAB M2...

Fig. 3.12 A diagrammatic representation of the t(15;17)(q24.1;q21.2) abnorma...

Fig. 3.13 BM aspirate in acute promyelocytic leukaemia (PML) showing hypergr...

Fig. 3.14 BM aspirate in PML showing hypergranular promyelocytes, two with g...

Fig. 3.15 PB film in the variant form of PML showing an erythroblast and a v...

Fig. 3.16 PB film of a patient with PML, showing abnormal maturation of leuk...

Fig. 3.17 Four‐colour flow cytometry immunophenotyping from a patient with A...

Fig. 3.18 Karyogram showing the translocation between chromosomes 15 and 17 ...

Fig. 3.19 Immunofluorescence technique using 5E10, a monoclonal antibody to ...

Fig. 3.20 Diagrammatic representation of two FISH strategies for the detecti...

Fig. 3.21 BM film from a patient with FAB M2/M3 AML with t(11;17)(q23.2;q21....

Fig. 3.22 PB film from a patient with AML with t(11;17)(q23.2;q21.2);

ZBTB16

Fig. 3.23 (a) A diagrammatic representation of inv(16)(p13.1q22); this is an...

Fig. 3.24 PB film from a patient with FAB M4Eo AML associated with inv(16)(p...

Fig. 3.25 PB film from a patient with FAB M4Eo AML associated with t(16;16)(...

Fig. 3.26 BM film from a patient with AML FAB M4Eo/inv(16)(p13.1q22). (a, b)...

Fig. 3.27 BM film from a patient with AML M4Eo/inv(16)(p13.1q22) showing Cha...

Fig. 3.28 BM film from a patient with FAB M4Eo AML and t(16;16)(p13.1;q22) s...

Fig. 3.29 Four‐colour flow cytometry immunophenotyping in a patient with AML...

Fig. 3.30 A karyogram showing inv(16)(p13.1q22).

Fig. 3.31 A karyogram showing t(16;16)(p13.1;q22).

Fig. 3.32 Diagrammatic representation of a dual‐colour, break‐apart FISH tec...

Fig. 3.33 FISH of a metaphase from a patient with inv(16)(p13.1q22) using a ...

Fig. 3.34 PB film from a patient with FAB M5a AML associated with t(9;11)(p2...

Fig. 3.35 BM film from a patient with FAB M4 AML associated with t(9;11)(p21...

Fig. 3.36 Diagrammatic representation of t(9;11)(p21.3;q23.3).

Fig. 3.37 A karyogram showing t(9;11)(p21.3;q23.3).

Fig. 3.38 BM film from a patient with FAB M4 AML associated with t(4;11)(q21...

Fig. 3.39 BM film from a patient with FAB M5a AML associated with t(11;19)(q...

Fig. 3.40 Diagrammatic representation of t(6;9)(p23;q34.1).

Fig. 3.41 PB and BM films from a patient with FAB M2Baso AML associated with...

Fig. 3.42 Karyogram of the patient with FAB M2Baso AML and t(6;9)(p23;q34.1)...

Fig. 3.43 A diagrammatic representation of inv(3)(q21.3q26.2); this is an ex...

Fig. 3.44 A diagrammatic representation of t(3;3)(q21.3;q26.2).

Fig. 3.45 BM film from a patient with inv(3)(q21.3q26.2) showing increased n...

Fig. 3.46 BM film from a patient with t(3;3)(q21.3;q26.2) showing hypogranul...

Fig. 3.47 Karyogram showing inv(3)(q21.3q26.2).

Fig. 3.48 Karyogram showing t(3;3)(q21.3;q26.2).

Fig. 3.49 Composite photograph of PB film of an infant with acute megakaryob...

Fig. 3.50 Trephine biopsy section from a patient with FAB M7 AML associated ...

Fig. 3.51 Karyogram showing t(1;22)(p13.3;q13.1).

Fig. 3.52 Diagrammatic representation of t(9;22)(q34.1;q11.2).

Fig. 3.53 PB film from a patient with acute monocytic leukaemia with

NPM1

an...

Fig. 3.54 PB film from a patient with AML with a normal karyotype who had bo...

Fig. 3.55 PB (a) and BM (b) films from a patient with biallelic

CEBPA

mutati...

Fig. 3.56 A diagram illustrating that, in the 2008 WHO classification, cases...

Fig. 3.57 PB film from a patient with myelodysplasia‐related AML showing a b...

Fig. 3.58 BM film from a patient with myelodysplasia‐related AML (same patie...

Fig. 3.59 BM film from a patient with myelodysplasia‐related AML showing mar...

Fig. 3.60 Diagrammatic representation of t(8;16)(p11.2;p13.3).

Fig. 3.61 BM aspirate from a patient with FAB M5 AML associated with t(8;16)...

Fig. 3.62 BM aspirate from a patient with FAB M5 AML associated with t(8;16)...

Fig. 3.63 PB film in acute basophilic leukaemia showing blast cells that sta...

Fig. 3.64 PB film in acute basophilic leukaemia showing heavily granulated b...

Fig. 3.65 PB film in acute basophilic leukaemia showing a vacuolated blast c...

Fig. 3.66 PB film of a patient with therapy‐related AML associated with t(8;...

Fig. 3.67 PB of a neonate with transient abnormal myelopoiesis (TAM) of Down...

Fig. 3.68 BM film of the same patient as shown in Fig. 3.67 showing a lympho...

Fig. 3.69 PB film from another neonate with TAM in whom differentiation was ...

Fig. 3.70 PB film of a neonate with TAM with megakaryoblastic/megakaryocytic...

Fig. 3.71 PB film from a patient with Down syndrome with FAB M7 AML; blasts ...

Fig. 3.72 Flow chart showing how the International Consensus Classification ...

Fig. 3.73 Blastic plasmacytoid dendritic cell neoplasm. (a) PB film showing ...

Fig. 3.74 Blastic plasmacytoid dendritic cell neoplasm. (a) PB film showing ...

Chapter 4

Fig. 4.1 Peripheral blood (PB) film from a child with hyperdiploid acute lym...

Fig. 4.2 Karyogram of a child with ALL and a high hyperdiploid clone, 56,XXY...

Fig. 4.3 PB film of a patient with t(12;21)(p13.2;q22.1);

ETV6::RUNX1

showin...

Fig. 4.4 Bone marrow (BM) film of a child with t(12;21)(p13.2;q22.1);

ETV6::

...

Fig. 4.5 Fluorescence

in situ

hybridisation (FISH) demonstrating

ETV6::RUNX1

Fig. 4.6 Diagrammatic representation of extra‐signal, dual‐colour FISH for d...

Fig. 4.7 Graph showing the rising incidence of Ph‐positive ALL with age.

Fig. 4.8 PB film from a patient with French–American–British (FAB) L1 Ph‐pos...

Fig. 4.9 FISH in a patient with hyperdiploid

BCR::ABL1

‐positive ALL using a ...

Fig. 4.10 A karyogram showing t(4;11)(q21.3;q23.3).

Fig. 4.11 A subtle t(11;19)(q23.3;p13.3) demonstrated by FISH: (a) metaphase...

Fig. 4.12 BM film in ALL with t(1;19)(q23;p13.3) and FAB L3 cytological feat...

Fig. 4.13 Diagrammatic representation of balanced and unbalanced forms of t(...

Fig. 4.14 ALL with eosinophilia associated with t(5;14)(q31.1;q32.1). (a) PB...

Fig. 4.15 Demonstration of internal amplification of chromosome 21q sequence...

Fig. 4.16 Chest radiograph (a) and computed tomography scan (b) of a child w...

Fig. 4.17 PB film of a patient with T‐ALL with a cortical T phenotype. There...

Fig. 4.18 PB film in mixed phenotype (B‐myeloid) acute leukaemia showing thr...

Chapter 5

Fig. 5.1 Peripheral blood (PB) film of a patient with therapy‐related myelod...

Fig. 5.2 A binucleated micromegakaryocyte in the BM of a patient with refrac...

Fig. 5.3 Agranular neutrophil in the PB of a patient with refractory anaemia...

Fig. 5.4 PB film of a patient with RCMD/MDS‐MLD showing marked poikilocytosi...

Fig. 5.5 Granulocyte precursors with abnormally heavy granules from a patien...

Fig. 5.6 PB film showing a normal neutrophil and a macropolycyte, probably a...

Fig. 5.7 The relationship between the myelodysplastic neoplasms (MDS), the m...

Fig. 5.8 Immunocytochemistry of a BM film from a patient with refractory ana...

Fig. 5.9 Histological section of a trephine biopsy specimen from a patient w...

Fig. 5.10 Histological section of a trephine biopsy specimen from a patient ...

Fig. 5.11 Histological section of a trephine biopsy specimen from a patient ...

Fig. 5.12 Histological section of a trephine biopsy specimen from a patient ...

Fig. 5.13 Histological section of a trephine biopsy specimen from a patient ...

Fig. 5.14 Histological section of a trephine biopsy specimen from a patient ...

Fig. 5.15 Karyogram of a male patient with MDS showing a partial deletion of...

Fig. 5.16 Diagram showing the development of idic(17)(p11.2), the commonest ...

Fig. 5.17 Histograms and scatterplots produced by a Bayer H.1 automated coun...

Fig. 5.18 Application of the 2022 WHO classification of MDS in adults. MDS‐h...

Fig. 5.19 PB film of a patient with the 5q− syndrome showing macrocytes and ...

Fig. 5.20 BM aspirate film from a patient with the 5q– syndrome showing a me...

Fig. 5.21 PB film of a patient with RARS/MDS‐RS‐SLD. The film is dimorphic a...

Fig. 5.22 PB film of a patient with RARS/MDS‐RS‐SLD with acquired haemoglobi...

Fig. 5.23 BM aspirate films of a patient with RARS/MDS‐RS‐SLD. (a) Erythroid...

Fig. 5.24 PB film from a patient with refractory cytopenia with multilineage...

Fig. 5.25 BM aspirate film of a patient with MDS‐MLD‐RS, showing erythroid d...

Fig. 5.26 BM aspirate film of a patient with RCMD/MDS‐MLD showing one blast ...

Fig. 5.27 BM aspirate film of a patient with RCMD/MDS‐MLD showing platelets,...

Fig. 5.28 BM aspirate film of a patient with RAEB/MDS‐EB showing increased, ...

Fig. 5.29 BM aspirate film from a patient with RAEB/MDS‐EB/MDS‐IB showing a ...

Fig. 5.30 BM aspirate film from a patient with RAEB‐2/MDS‐EB‐2 showing: (a) ...

Fig. 5.31 PB film of a patient with MDS‐EB with acquired haemoglobin H disea...

Fig. 5.32 PB film of a patient with chronic myeloid leukaemia evolving from ...

Fig. 5.33 PB film of a patient with atypical chronic myeloid leukaemia,

BCR:

...

Fig. 5.34 PB film of a patient with aCML/MDS/MPN‐N showing abnormal chromati...

Fig. 5.35 BM film of a patient with aCML/MDS/MPN‐N (same patient as Fig. 5.3...

Fig. 5.36 BM film of a patient with aCML/MDS/MPN‐N showing a multinucleated ...

Fig. 5.37 PB film of a patient with CMML showing a monocyte, a lymphocyte an...

Fig. 5.38 PB film of a patient with CMML showing a binucleated macropolycyte...

Fig. 5.39 PB film of a patient with CMML showing large immature and dysplast...

Fig. 5.40 BM film from a patient with CMML showing predominantly an increase...

Fig. 5.41 BM film of a patient with CMML showing granulocytic dysplasia. The...

Fig. 5.42 PB film of a child with JMML showing a blast cell and several cyto...

Fig. 5.43 High performance liquid chromatography on a Bio‐Rad Variant II ins...

Chapter 6

Fig. 6.1 Diagrammatic representation of the typical differential count in 50...

Fig. 6.2 Peripheral blood (PB) film of a patient with CML showing two promye...

Fig. 6.3 Bone marrow (BM) film of a patient with CML showing increased granu...

Fig. 6.4 Karyogram of a patient with CML showing t(9;22)(q34.1;q11.2). The 2...

Fig. 6.5 Diagrammatic representation of three fluorescence

in situ

hybridisa...

Fig. 6.6 Dual‐colour, dual‐fusion FISH in CML. The green probe is for

BCR

on...

Fig. 6.7 Dual‐fusion, tricolour FISH probe in CML with a supplementary aqua ...

Fig. 6.8 Dual‐fusion, tricolour FISH probe in CML with a supplementary aqua ...

Fig. 6.9 PB film of a patient with CML presenting in lymphoid blast crisis. ...

Fig. 6.10 PB film of a patient with megakaryoblastic transformation of CML s...

Fig. 6.11 BM film of a patient with megakaryoblastic transformation of CML s...

Fig. 6.12 PB film of a patient with neutrophilic leukaemia showing an increa...

Fig. 6.13 PB film of a patient with neutrophilic leukaemia showing an increa...

Fig. 6.14 BM film from a patient with chronic neutrophilic leukaemia showing...

Fig. 6.15 PB film of a patient with chronic eosinophilic leukaemia (CEL) wit...

Fig. 6.16 PB film of a patient with CEL showing three eosinophils, one of wh...

Fig. 6.17 BM film from a patient with eosinophilic leukaemia showing a Charc...

Fig. 6.18 PB film in a patient with

FIP1L1::PDGFRA

showing: (a) three eosino...

Fig. 6.19 BM film in a patient with

FIP1L1::PDGFRA

showing eosinophil precur...

Fig. 6.20 Trephine biopsy sections from a patient with a

FIP1L1::PDGFRA

‐asso...

Fig. 6.21 Diagrams illustrating the loss of

CHIC2

when a

FIP1L1::PDGFRA

fusi...

Fig. 6.22 PB film from a patient with CEL with t(5;12)(q33;p13). One of the ...

Fig. 6.23 BM film from a patient with CEL with t(5;12)(q33;p13) showing a ma...

Fig. 6.24 Karyogram of a patient with CEL with t(5;12)(q33;p13) (same patien...

Fig. 6.25 BM film from a 27‐year‐old man with a myeloid and lymphoid neoplas...

Fig. 6.26 BM trephine biopsy section from a patient with a myeloid and lymph...

Fig. 6.27 Lymph node biopsy from a patient with a myeloid and lymphoid neopl...

Fig. 6.28 Karyogram showing t(8;13)(p11;q12).

Fig. 6.29 FISH analysis from a patient with an MPN associated with t(8;13)(p...

Fig. 6.30 BM film from a patient with

PCM1::JAK2

showing increased eosinophi...

Chapter 7

Fig. 7.1 Patterns of bone marrow (BM) infiltration observed in lymphoprolife...

Fig. 7.2 Lymph node regions used for staging of Hodgkin and non‐Hodgkin lymp...

Fig. 7.3 Clinical photograph of a patient with chronic lymphocytic leukaemia...

Fig. 7.4 Peripheral blood (PB) film in CLL showing two mature lymphocytes an...

Fig. 7.5 PB film from a patient with CLL showing: (a) a smear cell and four ...

Fig. 7.6 PB film from a patient with CLL showing the negative image of an im...

Fig. 7.7 PB film from a patient with CLL with unusual cytological features. ...

Fig. 7.8 PB film in CLL complicated by autoimmune haemolytic anaemia showing...

Fig. 7.9 Histograms and scatterplots on a Bayer‐Technicon H2 automated count...

Fig. 7.10 Scatterplots on a Coulter Electronics Gen‐S automated counter of P...

Fig. 7.11 Bone marrow aspirate in CLL showing a fragment containing numerous...

Fig. 7.12 PB film in prolymphocytoid transformation of CLL.

Fig. 7.13 (a) PB film in Richter syndrome showing residual mature small lymp...

Fig. 7.14 Immunocytochemistry showing a high proliferative fraction in Richt...

Fig. 7.15 Diagrammatic representation of two mechanisms of transformation in...

Fig. 7.16 Immunophenotyping by flow cytometry in CLL using a CD19 monoclonal...

Fig. 7.17 Fluorescence

in situ

hybridisation (FISH) in CLL using directly la...

Fig. 7.18 PB film in CLL, mixed cell type, showing small mature lymphocytes ...

Fig. 7.19 PB film in B prolymphocytic leukaemia (B‐PLL) showing cells that a...

Fig. 7.20 Ultrastructural examination in B‐PLL showing a prominent nucleolus...

Fig. 7.21 PB film in hairy cell leukaemia. Cells have round nuclei with cond...

Fig. 7.22 PB film in hairy cell leukaemia showing a hairy cell containing a ...

Fig. 7.23 Film prepared from a buffy coat of the PB of a patient with hairy ...

Fig. 7.24 BM trephine biopsy section in hairy cell leukaemia showing cells w...

Fig. 7.25 PB film in the variant form of hairy cell leukaemia (hairy cell le...

Fig. 7.26 PB film in splenic lymphoma with villous lymphocytes. The cells ha...

Fig. 7.27 PB film in splenic lymphoma with villous lymphocytes showing two v...

Fig. 7.28 PB film in the leukaemic phase of follicular lymphoma. One cell is...

Fig. 7.29 Flow cytometric immunophenotyping in follicular lymphoma showing e...

Fig. 7.30 Scatter plots showing flow cytometric immunophenotyping in follicu...

Fig. 7.31 Trephine biopsy section in follicular lymphoma showing paratrabecu...

Fig. 7.32 A karyogram showing t(14;18)(q32;q21.3).

Fig. 7.33 PB film in mantle cell lymphoma. The cells are markedly pleomorphi...

Fig. 7.34 PB film from a patient with mantle cell lymphoma showing a range o...

Fig. 7.35 PB film from a patient with mantle cell lymphoma whose lymphoma ce...

Fig. 7.36 PB film in blastoid variant of mantle cell lymphoma showing medium...

Fig. 7.37 PB film from a patient with blastoid variant of mantle cell lympho...

Fig. 7.38 A karyogram showing t(11;14)(q13.3;q32).

Fig. 7.39 BM aspirate from a patient with Burkitt lymphoma showing medium si...

Fig. 7.40 Diagrammatic representation of tricolour, dual‐fusion FISH for the...

Fig. 7.41 Composite image of PB film in ‘double‐hit’ diffuse large B‐cell ly...

Fig. 7.42 PB film in diffuse large B‐cell lymphoma of centroblastic type. MG...

Fig. 7.43 A clump of lymphoma cells and a macrophage in a blood film of a pa...

Fig. 7.44 A skin biopsy from a patient with intravascular large B‐cell lymph...

Fig. 7.45 PB film in Waldenström macroglobulinaemia; this term describes a l...

Fig. 7.46 PB film in plasma cell leukaemia. The malignant cells are identifi...

Fig. 7.47 PB film in plasma cell leukaemia showing lymphoplasmacytoid cytolo...

Fig. 7.48 PB film in plasma cell leukaemia with cells showing plasmablastic ...

Fig. 7.49 PB film in plasma cell leukaemia in a patient with multiple myelom...

Fig. 7.50 PB film in plasma cell leukaemia showing a leukaemic cell with a l...

Fig. 7.51 PB film in

de novo

plasma cell leukaemia showing rouleaux formatio...

Fig. 7.52 PB film in large granular lymphocytic leukaemia. The cells have ab...

Fig. 7.53 PB film in natural killer (NK)‐like large granular T‐cell lymphoma...

Fig. 7.54 PB and BM in aggressive NK cell leukaemia: (a) the PB shows a medi...

Fig. 7.55 (a, b) PB film in extranodal NK/T‐cell lymphoma, nasal type showin...

Fig. 7.56 Ultrastructural examination in T prolymphocytic leukaemia (T‐PLL) ...

Fig. 7.57 PB film in T‐PLL. In this case the nuclei are more irregular and t...

Fig. 7.58 PB film in T‐PLL showing a leukaemic cell with a flower‐shaped nuc...

Fig. 7.59 Flow cytometric immunophenotyping in T‐PLL showing characteristic ...

Fig. 7.60 Clinical photograph showing skin lesions in a Japanese woman with ...

Fig. 7.61 Clinical photograph showing skin lesions in an Afro‐Caribbean woma...

Fig. 7.62 PB film in ATLL. Cells are pleomorphic with polylobulated nuclei, ...

Fig. 7.63 Ultrastructural examination in ATLL showing the multiple lobes of ...

Fig. 7.64 Ascitic fluid of a patient with ATLL showing pleomorphic cells wit...

Fig. 7.65 Clinical photograph showing skin lesions of Sézary syndrome.

Fig. 7.66 PB film in large cell variant of Sézary syndrome. Both cells have ...

Fig. 7.67 PB film in small cell variant of Sézary syndrome. The nuclei show ...

Fig. 7.68 Ultrastructural examination in Sézary syndrome showing the charact...

Fig. 7.69 Clinical photograph showing plaque and tumour lesions of mycosis f...

Fig. 7.70 PB film from a patient with hepatosplenic lymphoma in leukaemic ph...

Fig. 7.71 Trephine biopsy section from a patient with hepatosplenic lymphoma...

Fig. 7.72 PB film in T‐lineage lymphoma. MGG ×100.

Fig. 7.73 PB in angioimmunoblastic T‐cell lymphoma showing medium to large l...

Fig. 7.74 PB in anaplastic large cell lymphoma. The lymphoma cells are very ...

Fig. 7.75 BM aspirate in anaplastic large cell lymphoma. The lymphoma cell (...

Chapter 8

Fig. 8.1 Bone marrow (BM) film of B‐lineage acute lymphoblastic leukaemia (B...

Fig. 8.2 Peripheral blood (PB) film from a case of B‐ALL showing FAB L2 cyto...

Fig. 8.3 Flow chart illustrating diagnostic pathways in acute leukaemia when...

Fig. 8.4 Periodic acid‐Schiff (PAS) stain of the bone marrow of a patient wi...

Fig. 8.5 Acid phosphatase stain of the peripheral blood of a patient with T‐...

Fig. 8.6 BM aspirate film showing infiltration by neuroblastoma. Although th...

Fig. 8.7 BM aspirate showing infiltration by rhabdomyosarcoma. (a) The neopl...

Fig. 8.8 PB film, Burkitt lymphoma, showing strong cytoplasmic basophilia an...

Fig. 8.9 Clinical photograph of a child with endemic Burkitt lymphoma.

Guide

Cover Page

Table of Contents

Title Page

Copyright Page

Preface

Acknowledgements

Commonly Used Abbreviations

Begin Reading

Index

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Leukaemia Diagnosis

Barbara J. Bain MB BS, FRACP, FRCPath

Professor of Diagnostic Haematology

St Mary’s Hospital Campus

Imperial College London Faculty of Medicine and

Honorary Consultant Haematologist

St Mary’s Hospital

London, UK

Mike Leach MB ChB, FRCP, FRCPath

Consultant Haematologist and Honorary Senior Lecturer

Haematology Laboratories and West of Scotland Cancer Centre

Gartnavel General Hospital

Glasgow, UK

Sixth Edition

This edition first published 2024© 2024 John Wiley & Sons Ltd

Edition History1st edition: 1990 by Gower Medical Publishing. Reprinted 1993 by Wolfe Publishing2nd edition: 1999 by Blackwell Science3rd edition: 2008 by Wiley‐Blackwell4th edition: 2010 by Wiley‐Blackwell5th edition: 2017 by Wiley‐Blackwell

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 law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

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Limit of Liability/Disclaimer of WarrantyThe 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 scientific method, diagnosis, or treatment by physicians for any particular patient. 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. While the publisher and authors have used their best efforts in preparing this work, they 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 merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

Library of Congress Cataloging‐in‐Publication Data Applied for:

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Cover Design: WileyCover Images: Courtesy of Mike Leach

Preface

Leukaemias are a very heterogeneous group of diseases, which differ from each other in aetiology, pathogenesis, prognosis and responsiveness to treatment. Accurate diagnosis and classification are necessary for the identification of specific biological entities and underpin scientific advances in this field. The detailed characterisation of haematological neoplasms is also essential for the optimal management of individual patients. Many systems for the classification of leukaemia have been proposed. Between 1976 and 1999, a collaborative group of French, American and British haematologists (the FAB group) proposed a number of classifications, which became widely accepted throughout the world. In 2001, a quarter of a century after the first FAB proposals, a World Health Organization (WHO) expert group proposed an updated system for the classification of leukaemia and lymphoma incorporating clinical features, haematological and histological features, immunophenotyping and the results of cytogenetic and, to a lesser extent, molecular genetic analysis. In 2008 and 2016 further updating of the WHO classification incorporated new knowledge and gave a greater importance to molecular genetic features. In 2022 the WHO classification was updated again, by both a WHO‐appointed group and an independent International Consensus group. Both these classifications have been incorporated in the 6th edition of Leukaemia Diagnosis.

In this book we have sought to illustrate and explain how these many laboratory techniques are used for the diagnosis and classification of leukaemia and related disorders. We have sought to discuss diagnosis and classification in a way that will be helpful to trainee haematologists and to laboratory scientists in haematology and related disciplines. However, we have also tried to provide a useful reference source and teaching aid for those who already have expertise in this field. In addition, we hope that cytogeneticists and molecular geneticists will find that this book enhances their understanding of the relationship of their disciplines to the diagnosis, classification and monitoring of leukaemia and related disorders.

As the diagnosis and classification of leukaemia comes to rely increasingly on sophisticated and expensive investigations there is a risk that some countries will be left behind. A previous appendix became a chapter in the 5th edition, dealing with the diagnosis of leukaemia in under‐resourced laboratories. This may seem presumptuous from haematologists with no recent experience of working in a developing country but we thought that it was important to consider it.

Since photographs have been taken using many different microscopes and exact magnifications differ slightly, magnifications of photomicrographs in this edition are given as the microscope objective used.

Acknowledgements

We should like to record our gratitude to two founder members of the FAB group, the late Professor David Galton and the late Professor Daniel Catovsky, who laid the foundations for this work. Professor Galton read the entire manuscript of the first edition and, by debating many difficult points, gave the benefit of his wisdom and experience. Professor Catovsky also discussed problem areas and permitted photography of blood and bone marrow films from many of his patients. Our thanks are also due to the considerable number of friends and colleagues from five continents who helped by lending material for photography or supplying photographs; they are individually acknowledged in the relevant figure legends.

Barbara J. Bain and Mike Leach, 2023

Commonly Used Abbreviations

Specific cytogenetic abbreviations are shown in Table 2.10.

aCML

atypical chronic myeloid leukaemia

AIDS

acquired immune deficiency syndrome

AIHA

autoimmune haemolytic anaemia

ALAL

acute leukaemia of ambiguous lineage

ALIP

abnormal localisation of immature precursors

ALL

acute lymphoblastic leukaemia

AML

acute myeloid leukaemia

AML‐MR

myelodysplasia‐related AML

AML‐MRC

AML with myelodysplasia‐related changes

ANAE

α‐naphthyl acetate esterase

ANBE

α‐naphthyl butyrate esterase

APAAP

alkaline phosphatase–anti‐alkaline phosphatase (technique)

APC

allophycocyanin (a fluorochrome)

APL

acute promyelocytic leukaemia

ATLL

adult T‐cell leukaemia/lymphoma

ATRA

all‐

trans

‐retinoic acid

AUL

acute undifferentiated leukaemia

B‐ALL

B‐lineage acute lymphoblastic leukaemia

B‐ALL/LBL

B lymphoblastic leukaemia/lymphoma

BCSH

British Committee for Standards in Haematology

BFU‐E

burst‐forming unit – erythroid

BM

bone marrow

c

cytoplasmic or, in cytogenetic terminology, constitutional

CAE

naphthol AS‐D chloroacetate esterase, chloroacetate esterase (cytochemical stain)

CAR

chimaeric antigen receptor

CBF

core binding factor

CCMUS

clonal monocytosis of undetermined significance with cytopenia

CCUS

clonal cytopenia of undetermined significance

CD

cluster of differentiation

CEL

chronic eosinophilic leukaemia

CFU‐E

colony‐forming unit – erythroid

CFU‐GM

colony‐forming unit – granulocyte, macrophage

CFU‐Meg

colony‐forming unit – megakaryocyte

CGH

comparative genomic hybridisation

CHIP

clonal haematopoiesis of indeterminate potential

cIg

cytoplasmic immunoglobulin

CLL

chronic lymphocytic leukaemia

CLL/PL

chronic lymphocytic leukaemia, mixed cell type with prolymphocytoid cells

CML

chronic myeloid leukaemia

CMML

chronic myelomonocytic leukaemia

CMUS

clonal monocytosis of undetermined significance

CNL

chronic neutrophilic leukaemia

CNS

central nervous system

CT

computed tomography

DIC

disseminated intravascular coagulation

DLBCL

diffuse large B‐cell lymphoma

DNA

deoxyribonucleic acid

EBER

EBV early RNA

EBV

Epstein–Barr virus

ECOG

Eastern Cooperative Oncology Group

EDTA

ethylenediamine tetra‐acetic acid

EGIL

European Group for the Immunological Characterization of Leukemias

EMA

epithelial membrane antigen

ERFC

E‐rosette‐forming cells

ETP‐ALL

early T precursor lymphoblastic leukaemia/lymphoma

FAB

French–American–British

FDG‐PET

18

F‐fluorodeoxyglucose positron emission tomography

FISH

fluorescence

in situ

hybridisation

FITC

fluorescein isothiocyanate (a fluorochrome)

FLIPI

Follicular Lymphoma International Prognostic Index

FSC

forward scatter of light (flow cytometry term)

G‐CSF

granulocyte colony‐stimulating factor

GM‐CSF

granulocyte–macrophage colony‐stimulating factor

G6PD

glucose‐6‐phosphate dehydrogenase

H&E

haematoxylin and eosin (stain)

Hb

haemoglobin concentration

HCL

hairy cell leukaemia

HES

hypereosinophilic syndrome

HIV

human immunodeficiency virus

HLA‐DR

human leucocyte antigen DR

HTLV‐1

human T‐cell lymphotropic virus 1

ICC

International Consensus Classification

ICUS

idiopathic cytopenia of undetermined significance

IDUS

idiopathic dysplasia of uncertain significance

Ig

immunoglobulin

IGH

immunoglobulin heavy chain locus

IGHV

immunoglobulin heavy chain variable region genes

IL

interleukin

IPSS

International Prognostic Scoring System

IPSS‐R

International Prognostic Scoring System, Revised

ITD

internal tandem duplication

IWGM‐MDS

International Working Group on Morphology of MDS

JMML

juvenile myelomonocytic leukaemia

KIR

killer inhibitory receptor

L1–L3

categories of acute lymphoblastic leukaemia in the FAB classification

LDH

lactate dehydrogenase

LEF1

lymphoid enhancer‐binding factor 1

LGL

large granular lymphocyte/s

M : E

myeloid : erythroid

M0–M7

categories of acute myeloid leukaemia in the FAB classification

m‐BCR

minor breakpoint cluster region

M‐BCR

major breakpoint cluster region

M‐FISH

multiplex fluorescence

in situ

hybridisation

MAC

morphology–antibody–chromosomes (technique)

MALT

mucosa‐associated lymphoid tissue

McAb

monoclonal antibody/ies

MCV

mean cell volume

MDS

myelodysplastic neoplasm/syndrome/s

MDS‐LB

MDS with low blasts

MDS‐LB‐MLD

MDS‐LB and multilineage dysplasia

MDS‐LB‐SLD

MDS‐LB and single lineage dysplasia

MDS/MPN

myelodysplastic/myeloproliferative neoplasm/s

MDS/MPN‐N

MDS/MPN with neutrophilia

MDS‐U

myelodysplastic syndrome, unclassifiable

MGG

May–Grünwald–Giemsa (stain)

MIC

Morphology, Immunophenotype, Cytogenetics

MIC‐M

Morphology, Immunophenotype, Cytogenetics, Molecular genetics

MLD

multilineage dysplasia

MN‐pCT

myeloid neoplasm post cytotoxic therapy

MPAL

mixed phenotype acute leukaemia

MPN

myeloproliferative neoplasm/s

MPO

myeloperoxidase

MRC

Medical Research Council

MRD

measureable residual disease (previously minimal residual disease)

MRI

magnetic resonance imaging

mRNA

messenger RNA

NAP

neutrophil alkaline phosphatase

NASA

naphthol AS acetate esterase (cytochemical stain)

NASDA

naphthol AS‐D acetate esterase (cytochemical stain)

NGS

next generation sequencing

NHL

non‐Hodgkin lymphoma/s

NK

natural killer

NOS

not otherwise specified

NRBC

nucleated red blood cells

NSE

non‐specific esterase (cytochemical stain)

PAS

periodic acid–Schiff (cytochemical stain)

PB

peripheral blood

PcAb

polyclonal antibody/ies

PCR

polymerase chain reaction

PE

phycoerythrin (a fluorochrome)

PerCP

peridinin–chlorophyll protein complex (a fluorochrome)

Ph

Philadelphia (chromosome)

PLL

prolymphocytic leukaemia

PMF

primary myelofibrosis

PPO

platelet peroxidase

PTD

partial tandem duplication

PV

polycythaemia vera

RA

refractory anaemia

RAEB

refractory anaemia with excess of blasts

RAEB‐T

refractory anaemia with excess of blasts in transformation

RARS

refractory anaemia with ring sideroblasts

RCMD

refractory cytopenia with multilineage dysplasia

RCUD

refractory cytopenia with unilineage dysplasia

RNA

ribonucleic acid

RQ‐PCR

real‐time quantitative polymerase chain reaction

RS

ring sideroblasts

RT‐PCR

reverse transcriptase polymerase chain reaction

SARS‐CoV‐2

severe adult respiratory syndrome coronavirus 2

SBB

Sudan black B

SKY

spectral karyotyping

SLD

single lineage dysplasia

SLVL

splenic lymphoma with villous lymphocytes

SmIg

surface membrane immunoglobulin

SMZL

splenic marginal zone lymphoma

SNP

single nucleotide polymorphism

SSC

side scatter of light (flow cytometry term)

T‐ALL/LBL

T lymphoblastic leukaemia/lymphoma

t‐AML

therapy‐related acute myeloid leukaemia

t‐MDS

therapy‐related myelodysplastic syndrome

TAM

transient abnormal myelopoiesis

TCR

T‐cell receptor

TdT

terminal deoxynucleotidyl transferase

TKD

tyrosine kinase domain

TKI

tyrosine kinase inhibitor

TRAP

tartrate‐resistant acid phosphatase

VAF

variant allele frequency

VEXAS

vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic (syndrome)

WBC

white cell count

WHO

World Health Organization

WPPS

WHO classification‐based Prognostic Scoring System

ZAP70

zeta‐associated protein 70

1The Nature of Leukaemia, Cytology, Cytochemistry and the Morphological Classification of Acute Leukaemia

CHAPTER MENU

The nature of leukaemia

The aetiology of leukaemia

The importance of classification

The nature and classification of acute leukaemia

The nature and classification of the myelodysplastic syndromes

The nature and classification of chronic myeloid leukaemias and myelodysplastic/myeloproliferative neoplasms

The nature and classification of lymphoid neoplasms

Defining a blast cell, a promyelocyte and a promonocyte

The FAB classification of acute leukaemia

Diagnosing acute leukaemia

Distinguishing between acute myeloid and acute lymphoblastic leukaemias

Defining remission

The incidence of acute leukaemia

The FAB categories and other morphological categories of acute myeloid leukaemia

Acute myeloid leukaemia with minimal evidence of myeloid differentiation: M0 acute myeloid leukaemia

Acute myeloid leukaemia without maturation: M1 acute myeloid leukaemia

Acute myeloid leukaemia with maturation: M2 acute myeloid leukaemia

Acute hypergranular promyelocytic leukaemia: M3 acute myeloid leukaemia

The variant form of acute promyelocytic leukaemia: M3 variant acute myeloid leukaemia

Acute myelomonocytic leukaemia: M4 acute myeloid leukaemia

Acute monocytic/monoblastic leukaemia: M5 acute myeloid leukaemia

Acute myeloid leukaemia with predominant erythroid differentiation: M6 acute myeloid leukaemia

Acute megakaryoblastic leukaemia: M7 acute myeloid leukaemia

Acute eosinophilic leukaemia

Acute basophilic leukaemia

Acute mast cell leukaemia

Langerhans cell leukaemia

Hypoplastic or hypocellular acute myeloid leukaemia

Clinical correlates of FAB categories of acute myeloid leukaemia

The FAB classification of acute lymphoblastic leukaemia

‘Acute lymphoblastic leukaemia’ of L3 subtype

Automated full blood counts in acute leukaemia

References

The nature of leukaemia