Flow Cytometry of Hematological Malignancies

Flow Cytometry of Hematological Malignancies

Flow cytometric analysis is often integral to the swift and accurate diagnosis of leukemias and lymphomas of the blood, bone marrow, and lymph nodes. However, in the fast-moving and expanding field of clinical hematology, in can be challenging to remain up to speed with the latest biological research and technological innovations. Flow Cytometry of Hematological Malignancies has been designed to provide all those working in hematological oncology with a practical, cutting-edge handbook, featuring clear and fully illustrated guidance on all aspects of cytometry’s role in diagnosis and analysis. This essential second edition includes:

• Explorations of more than 70 antigens
• Full-color illustrations throughout
• New descriptions of recently discovered markers
• WHO classifications of hematological neoplastic diseases
• Helpful tips for result interpretation and analysis

Featuring all this and more, Flow Cytometry of Hematological Malignancies, Second Edition, is an invaluable resource for both trainee and experienced hematologists, hematopathologists, oncologists, and pathologists, as well as medical students and diagnostic lab technicians.Flow Cytometry of Hematological Malignancies bietet eine Vielzahl grafisch aufbereiteter Ergebnisse, die mit der Durchflusszytometrie bei der Untersuchung der häufigsten Erkrankungen gewonnen wurden. Auch weniger bekannte Krankheiten werden vorgestellt.

Das Fachbuch wurde als Referenzwerk zum schnellen Nachschlagen konzipiert. Es ist ein Muss für Kliniker, die hämatologische Erkrankungen diagnostizieren und analysieren, darunter Hämatologen, Hämatopathologen, Onkologen, Pathologen und Mitarbeiter in diagnostischen Labors.

Foreword to the Second Edition xi
by Michael J. Borowitz

Foreword to the First Edition xii
by Maryalice Stetler-Stevenson

Foreword to the First Edition xiii
by Bruno Brando

Preface to the Second Edition xv

Preface to the First Edition xvi

Abbreviations xvii

1 Antigens 1

Clustered (CD) Antigens

CD1 3

CD2 5

CD3 8

CD4 17

CD5 21

CD7 24

CD8 26

CD10 30

CD11b 35

CD11c 38

CD13 40

CD14 44

CD15 46

CD16 49

CD19 52

CD20 55

CD22 59

CD23 61

CD24 64

CD25 66

CD26 67

CD27 69

CD28 70

CD30 71

CD33 73

CD34 77

CD38 79

CD43 81

CD45 82

CD45 Isoforms 87

CD49 90

CD56 93

CD57 96

CD61 97

CD62L 98

CD64 99

CD65 101

CD66c 102

CD71 103

CD79 104

CD81 107

CD103 108

CD117 110

CD123 112

CD138 113

CD200 114

CD305 116

CD307 (IRTA) Antigen Family 117

CD371 118

Non clustered (or primarily known with other names) antigens Bcl‐2 Protein 119

Chemokines and Chemokine Receptors 121

CRLF2 128

Cytotoxic Proteins 129

HLA‐DR 130

Immunoglobulins 132

KIR, CD158 isoforms 136

Myeloperoxidase (MPO) 139

NG2 140

PCA‐1 141

ROR1 141

SLAM Molecules and SLAM‐associated Protein (SAP) 142

SOX11 144

T‐cell Receptor (TCR) 145

Terminal Deoxy‐nucleotidyl‐transferase (TdT) 148

Toll‐like Receptors (TLR) 150

VS38 151

ZAP‐70 152

2 Diseases 155

Myeloproliferative neoplasms 157

Chronic myeloid leukemia (CML) 157

Myeloproliferative neoplasms other than CML 160

Chronic neutrophilic leukemia (CNL) 160

Polycythemia vera (PV) 160

Primary myelofibrosis (PMF) 160

Essential thrombocythemia (ET) 160

Chronic eosinophilic leukemia (CEL) 161

Mastocytosis 162

Acute mast‐cell leukemia (AMCL) 162

Chronic mast‐cell leukemia (CMCL) 163

Myelomastocytic leukemia (MML) 163

Myelodysplastic/myeloproliferative neoplasms 164

Chronic myelomonocytic leukemia (CMML) 164

Other myelodysplastic/myeloproliferative neoplasms and related conditions 167

Juvenile myelomonocytic leukemia (JMML) 167

Atypical CML bcr/abl negative (ACML) 167

RAS‐associated autoimmune leukoproliferative disorder (RALD) 167

Myelodysplastic syndromes 168

Myeloid neoplasms with germline predisposition 171

Acute myeloid leukemias 172

AMLs with recurrent genetic anomalies 173

AMLs with chromosomal anomalies 173

AMLs with gene mutations 180

Relationships between genotype and phenotype in cases of AML not recognized as separate entities in WHO 2017 181

AMLs with myelodysplasia‐related changes (AML‐MRC) 182

AMLs not otherwise specified 182

AML with minimal differentiation 182

AML without maturation 183

AML with maturation 183

Acute myelomonocytic leukemia (AMMoL) 183

Acute monoblastic and monocytic leukemia (AMoL) 184

Pure erythroid leukemia (PEL) 185

Acute megakaryoblastic leukemia (AMKL) 186

Acute basophilic leukemia (ABL) 188

Myeloid proliferations associated with Down syndrome 188

Transient abnormal myelopoiesis (TAM) 189

AMLs in patients with Down syndrome 189

Blastic plasmacytoid dendritic cell neoplasm (BPDCN/PDCL) 189

Acute leukemias with ambiguous lineage attribution (ALAL) 192

Acute undifferentiated leukemias (AUL) 192

Mixed phenotype acute leukemias (MPAL) 192

Neoplastic diseases of B and T lymphatic precursors 194

B lymphoblastic leukemia/lymphoma, not otherwise specified (B‐ALL/LBLnos) 195

B lymphoblastic leukemia/lymphoma with recurrent genetic anomalies 197

Relationships between genotype and phenotype in cases of B‐ALL not recognized as separate entities in WHO 2017 201

T lymphoblastic leukemia/lymphoma (T‐ALL/LBL) 202

Early T‐cell precursor lymphoblastic leukemia (ETP‐ALL) 205

NK lymphoblastic leukemia/lymphoma (NK‐ALL/LBL) 205

Neoplastic diseases of mature B cells 206

Chronic lymphocytic leukemia/small

lymphocytic lymphoma (B‐CLL/SLL) 206

Familial B‐CLL 215

Richter syndrome 215

Monoclonal B‐cell lymphocytosis (MBL) 216

CLL‐like monoclonal B lymphocytosis 216

Non‐CLL‐like monoclonal B lymphocytosis 216

B‐cell prolymphocytic leukemia (B‐PLL) 216

Lymphoplasmacytic lymphoma (LPL) 218

Heavy chain disease (HCD) 221

γ heavy chain disease 222

μ heavy chain disease 222

α heavy chain disease 222

Hairy cell leukemia (HCL) 222

Hairy cell leukemia, variant (HCL‐v) 226

Hairy cell leukemia, Japanese variant (HCL‐J) 227

Splenic diffuse red pulp lymphoma (SDRPL) 227

Marginal zone lymphomas (MZL) 228

Nodal marginal zone lymphoma (NMZL) 229

Splenic marginal zone lymphoma (SMZL) 230

Extranodal marginal zone lymphoma (EMZL/MALToma) 232

Clonal B‐cell lymphocytosis with MZL‐like phenotype (CBL‐MZ) 233

Follicular lymphoma (FCL) 234

Testicular follicular lymphoma 237

Duodenal type follicular lymphoma 237

Pediatric type follicular lymphoma 237

Primitive cutaneous follicular lymphoma (PCFL) 237

Large B‐cell lymphoma with IRF4 rearrangement 237

Mantle‐cell lymphoma (MCL) 237

Blastic mantle‐cell lymphoma (BMCL) 240

Leukemic non nodal mantle‐cell lymphoma 240

DLBCL not otherwise specified (DLBCLnos) 240

CD5(+) diffuse large cell lymphoma (CD5(+) DLBCL) 243

T‐cell/histiocyte‐rich B‐cell lymphoma (THRLBCL) 243

Primary DLBCL of the CNS (PCNSL) 244

Primary cutaneous DLBCL, “leg type” 244

EBV(+) DLBCLnos 244

DLBCL associated with chronic inflammation (PAL) 245

Fibrin associated DLBCL 245

Lymphomatoid granulomatosis (LYG) 245

Primary mediastinal B‐cell lymphoma (PMBCL) 245

Intravascular large B‐cell lymphoma (IVBCL) 246

ALK‐positive large cell lymphoma (ALK(+) LBCL) 246

Plasmablastic lymphoma (PBL) 247

Primary effusion lymphoma (PEL) 247

HHV8‐associated lymphoproliferative disorders 247

HHV8‐positive DLBCL 248

HHV8‐positive germinotropic lymphoproliferative disorder 248

Burkitt lymphoma (BL) 248

Burkitt leukemia with immature phenotype 250

Burkitt‐like lymphoma with 11q aberrations 251

High‐grade B‐cell lymphoma (HGBL) 251

Plasma cell neoplasms 251

Monoclonal gammopathies of undetermined significance (MGUS) 253

Multiple myeloma (MM) 253

Plasma cell leukemia (PCL) 257

Neoplastic diseases of mature T and NK cells 258

T‐cell prolymphocytic leukemia (T‐PLL) 258

T‐cell large granular lymphocytic leukemia (T‐LGL) 261

Chronic lymphoproliferative disorders of NK cells (CLPD‐NK/CNKL) 263

Aggressive NK‐cell leukemia (ANKL) 266

Adult T‐cell leukemia/lymphoma (ATLL) 266

Extranodal NK/T-cell lymphoma, “nasal type” (ENKTL) 269

Intestinal T‐cell lymphomas (ITCL) 270

Enteropathy‐associated T‐cell lymphoma (EATCL) 270

Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL) 272

Indolent gastro‐intestinal T lymphoproliferative disorder (indolent GI T‐LPD) 273

Hepatosplenic T‐cell lymphoma (HSTCL) 273

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) 275

Mycosis fungoides (MF) 275

Sezary syndrome (SS) 277

Primary cutaneous CD30(+) lymphoproliferative disorders 279

Lymphomatoid papulosis (LyP) 279

Primary cutaneous anaplastic T‐cell lymphoma (pcALCL) 279

Primary cutaneous peripheral T‐cell lymphoma (PTCL) 280

Primary cutaneous TCRγδ(+) T‐cell lymphoma (PCGD‐TCL) 280

Primary cutaneous CD8(+) aggressive epidermotropic cytotoxic T‐cell lymphoma (PCAETL) 280

Primary cutaneous acral CD8(+) T‐cell lymphoma (PCATCL) 280

Primary cutaneous lymphoma of the medium/small CD4(+) T cells (PCSM‐TCL) 281

Peripheral T‐cell lymphoma, not otherwise specified (PTCLnos) 281

Nodal lymphomas of follicular T‐helper derivation 283

Angioimmunoblastic T‐cell lymphoma (AITL) 283

Follicular T‐cell lymphoma (FTCL) 285

Nodal PTCL with follicular T‐helper phenotype 285

Anaplastic large cell lymphoma ALK(+) (ALCL ALK(+)) 285

Anaplastic large cell lymphoma ALK(‐) (ALCL ALK(‐)) 288

Breast implant–associated anaplastic large cell lymphoma (biaALCL) 288

Hodgkin lymphomas 289

Classic Hodgkin lymphoma (CHL) 289

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) 290

Neoplastic diseases of histiocytic and dendritic cells 291

Histiocytic sarcoma (HS) 292

Langerhans cell histiocytosis (LCH) 292

Indeterminate dendritic cell tumor (IDCT) 292

Interdigitating dendritic cell sarcoma (IDCS) 292

Follicular dendritic cell sarcoma (FDCS) 292

Erdheim–Chester disease (EDC) 292

3 Appendix 293

Acute leukemias not recognized by the 2017 WHO classification 294

Acute leukemia of myeloid/NK precursors (M/NK‐AL) 294

Acute leukemia of myeloid dendritic cells (MDCL) 294

Acute leukemia of Langerhans cells 294

Composite lymphomas 294

Hypereosinophilic syndrome (HES), lymphocyte variant 295

Indolent T lymphoblastic proliferations (iT‐LBP) 295

Polyclonal lymphocytoses of B lymphocytes 298

Persistent polyclonal B‐cell lymphocytosis (PPBL) 298

Persistent polyclonal CD5(+) B‐cell lymphocytosis 298

Persistent polyclonal B‐cell lymphocytosis, Japanese (hairy) variant 298

Polyclonal plasmacytoses 299

Small round (blue) cell tumors (SR(B)CT) 300

References 301

Index 429

About the author

Claudio Ortolani is an expert in the area of diagnosis of hematological malig­­nancies. Now retired, Dr Ortolani was Consultant in the Department of Clinical Pathology at Venice General Hospital, Venice, Italy. He is one of the founding members of the Italian Society for Cytometric Cell Analysis (ISCCA), of whose board he is currently a member. He has taught and lectured internationally on how to use flow cytometry to aid in diagnosing hematological diseases.

Flow cytometric analysis is often integral to the swift and accurate diagnosis of leukemias and lymphomas of the blood, bone marrow, and lymph nodes. However, in the fast-moving and expanding field of clinical hematology, in can be challenging to remain up to speed with the latest biological research and technological innovations. Flow Cytometry of Hematological Malignancies has been designed to provide all those working in hematological oncology with a practical, cutting-edge handbook, featuring clear and fully illustrated guidance on all aspects of cytometry’s role in diagnosis and analysis. This essential second edition includes:

• Explorations of more than 70 antigens
• Full-color illustrations throughout
• New descriptions of recently discovered markers
• WHO classifications of hematological neoplastic diseases
• Helpful tips for result interpretation and analysis

Featuring all this and more, Flow Cytometry of Hematological Malignancies, Second Edition, is an invaluable resource for both trainee and experienced hematologists, hematopathologists, oncologists, and pathologists, as well as medical students and diagnostic lab technicians.