WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

WHO classification of tumours of haematopoietic and
lymphoid tissues 10
Introduction to the WHO classification of tumours of
haematopoietic and lymphoid tissues 13
1 Introduction and overview of the classification of the
myeloid neoplasms 15
2 Myeloproliferative neoplasms 29
Chronic myeloid leukaemia, BCR-ABL1-positive 30
Chronic neutrophilic leukaemia 37
Polycythaemia vera 39
Primary myelofibrosis 44
Prefibrotic/early primary myelofibrosis 46
Overt primary myelofibrosis 48
Essential thrombocythaemia 50
Chronic eosinophilic leukaemia, not otherwise specified 54
Myeloproliferative neoplasm, unclassifiable 57
3 Mastocytosis 61
Cutaneous mastocytosis 65
Systemic mastocytosis 66
Mast cell sarcoma 69
4 Myeloid/lymphoid neoplasms with eosinophilia and
gene rearrangement 71
Myeloid/lymphoid neoplasms with PDGFRA rearrangement 73
Myeloid/lymphoid neoplasms with PDGFRB rearrangement 75
Myeloid/lymphoid neoplasms with FGFR1 rearrangement 77
Myeloid/lymphoid neoplasms with PCM1-JAK2 78
5 Myelodysplastic/myeloproliferative neoplasms 81
Chronic myelomonocytic leukaemia 82
Atypical chronic myeloid leukaemia, BCR-ABL1-negative 87
Juvenile myelomonocytic leukaemia 89
Myelodysplastic/myeloproliferative neoplasm with ring
sideroblasts and thrombocytosis 93
Myelodysplastic/myeloproliferative neoplasm, unclassifiable 95
6 Myelodysplastic syndromes 97
Overview 98
Myelodysplastic syndrome with single lineage dysplasia 106
Myelodysplastic syndrome with ring sideroblasts 109
Myelodysplastic syndrome with multilineage dysplasia 111
Myelodysplastic syndrome with excess blasts 113
Myelodysplastic syndrome with excess blasts and
erythroid predominance 114
Myelodysplastic syndrome with excess blasts
and fibrosis 114
Myelodysplastic syndrome with isolated del(5q) 115
Myelodysplastic syndrome, unclassifiable 116
Childhood myelodysplastic syndrome 116
Refractory cytopenia of childhood 117
7 Myeloid neoplasms with germline predisposition 121
Myeloid neoplasms with germline predisposition without a
pre-existing disorder or organ dysfunction 124
Acute myeloid leukaemia with germline
CEBPA mutation 124
Myeloid neoplasms with germline DDX41 mutation 125
Myeloid neoplasms with germline predisposition and
pre-existing platelet disorders 125
Myeloid neoplasms with germline RUNX1 mutation 125
Myeloid neoplasms with germline ANKRD26 mutation 125
Myeloid neoplasms with germline ETV6 mutation 126
Myeloid neoplasms with germline predisposition
associated with other organ dysfunction 126
Myeloid neoplasms with germline GATA2 mutation 126
Myeloid neoplasms with germline predisposition associated
with inherited bone failure syndromes and
telomere biology disorders 128
8 Acute myeloid leukaemia and related precursor
neoplasms 129
Acute myeloid leukaemia with recurrent genetic
abnormalities 130
Introduction 130
Acute myeloid leukaemia with t(8;21)(q22;q22.1);
RUNX1-RUNX1T1 130
Acute myeloid leukaemia with inv(16)(p13.1 q22) or
t(16; 16)(p 13.1 ;q22); CBFB-MYH11 132
Acute promyelocytic leukaemia with PML-RARA 134
Acute myeloid leukaemia with t(9;11)(p21.3;q23.3);
KMT2A-MLLT3 136
Acute myeloid leukaemia with t(6;9)(p23;q34.1);
DEK-NUP214 137
Acute myeloid leukaemia with inv(3)(q21.3q26.2) or
t(3;3)(q21.3;q26.2); GATA2, MECOM 138
Acute myeloid leukaemia (megakaryoblastic) with
t(1;22)(p13.3;q13.1); RBM15-MKL1 139
Acute myeloid leukaemia with BCR-ABL1 140
Acute myeloid leukaemia with gene mutations 141
Acute myeloid leukaemia with mutated NPM1 141
Acute myeloid leukaemia with biallelic
mutation of CEBPA 142
Acute myeloid leukaemia with mutated RUNX1 144
Acute myeloid leukaemia with myelodysplasia-related
changes 150
Therapy-related myeloid neoplasms 153
Acute myeloid leukaemia, not otherwise specified 156
Acute myeloid leukaemia with minimal differentiation 156
Acute myeloid leukaemia without maturation 157
Acute myeloid leukaemia with maturation 158
Acute myelomonocytic leukaemia 159
Acute monoblastic and monocytic leukaemia 160
Pure erythroid leukaemia 161
Acute megakaryoblastic leukaemia 162
Acute basophilic leukaemia 164
Acute panmyelosis with myelofibrosis 165
Myeloid sarcoma 167
Myeloid proliferations associated with Down syndrome
Transient abnormal myelopoiesis associated with
Down syndrome
Myeloid leukaemia associated with Down syndrome
169
169
170
9 Blastic plasmacytoid dendritic cell neoplasm 173
10 Acute leukaemias of ambiguous lineage 179
Acute undifferentiated leukaemia 182
Mixed-phenotype acute leukaemia with
t(9;22)(q34.1 ;q11.2); BCR-ABL1 182
Mixed-phenotype acute leukaemia with t(v;11q23.3);
KMT2A-re arranged 183
Mixed-phenotype acute leukaemia, B/myeloid,
not otherwise specified 184
Mixed-phenotype acute leukaemia, T/myeloid,
not otherwise specified 185
Mixed-phenotype acute leukaemia, not otherwise specified,
rare types 186
Acute leukaemias of ambiguous lineage,
not otherwise specified 187
11 Introduction and overview of the classification of the
lymphoid neoplasms 189
12 Precursor lymphoid neoplasms 199
B-lymphoblastic leukaemia/lymphoma,
not otherwise specified 200
B-lymphoblastic leukaemia/lymphoma with recurrent
genetic abnormalities 203
B-lymphoblastic leukaemia/lymphoma with
t(9;22)(q34.1 ;q11.2); BCR-ABL 1 203
B-lymphoblastic leukaemia/lymphoma with
t(v;11q23.3); K7W724-rearranged 203
B-lymphoblastic leukaemia/lymphoma with
t(12;21)(p13.2;q22.1); ETV6-RUNX1 204
B-lymphoblastic leukaemia/lymphoma with hyperdiploidy 205
B-lymphoblastic leukaemia/lymphoma with hypodiploidy 206
B-lymphoblastic leukaemia/lymphoma with
t(5; 14)(q31.1 ;q32.1); IGH//L3 206
B-lymphoblastic leukaemia/lymphoma with
t(1 ;19)(q23;p13.3); TCF3-PBX1 207
B-lymphoblastic leukaemia/lymphoma, BCR-ABL1-like 208
B-lymphoblastic leukaemia/lymphoma with iAMP21 208
T-lymphoblastic leukaemia/lymphoma
Early T-cell precursor lymphoblastic leukaemia
209
212
NK-lymphoblastic leukaemia/lymphoma 213
13 Mature B-cell neoplasms 215
Chronic lymphocytic leukaemia/
small lymphocytic lymphoma 216
Monoclonal B-cell lymphocytosis 220
B-cell prolymphocytic leukaemia 222
Splenic marginal zone lymphoma 223
Hairy cell leukaemia 226
Splenic B-cell lymphoma/leukaemia, unclassifiable 229
Splenic diffuse red pulp small B-cell lymphoma 229
Hairy cell leukaemia variant 230
Lymphoplasmacytic lymphoma 232
IgM Monoclonal gammopathy of undetermined significance 236
Heavy chain diseases 237
Mu heavy chain disease 237
Gamma heavy chain disease 238
Alpha heavy chain disease 240
Plasma cell neoplasms 241
Non-IgM monoclonal gammopathy of undetermined
significance 241
Plasma cell myeloma 243
Plasma cell myeloma variants 249
Smouldering (asymptomatic) plasma cell myeloma 249
Non-secretory myeloma 250
Plasma cell leukaemia 250
Plasmacytoma 250
Solitary plasmacytoma of bone 250
Extraosseous plasmacytoma 251
Monoclonal immunoglobulin deposition diseases 254
Primary amyloidosis 254
Light chain and heavy chain deposition diseases 255
Plasma cell neoplasms with associated
paraneoplastic syndrome 256
POEMS syndrome 256
TEMPI syndrome 257
Extranodal marginal zone lymphoma of mucosa-associated
lymphoid tissue (MALT lymphoma) 259
Nodal marginal zone lymphoma 263
Paediatric nodal marginal zone lymphoma 264
Follicular lymphoma 266
Testicular follicular lymphoma 268
In situ follicular neoplasia 274
Duodenal-type follicular lymphoma 276
Paediatric-type follicular lymphoma 278
Large B-cell lymphoma with IRF4 rearrangement 280
Primary cutaneous follicle centre lymphoma 282
Mantle cell lymphoma 285
Leukaemic non-nodal mantle cell lymphoma 290
In situ mantle cell neoplasia 290
Diffuse large B-cell lymphoma (DLBCL), NOS 291
T-cell/histiocyte-rich large B-cell lymphoma 298
Primary diffuse large B-cell lymphoma of the CNS 300
Primary cutaneous diffuse large B-cell lymphoma, leg type 303
EBV-positive diffuse large B-cell lymphoma, NOS 304
EBV-positive mucocutaneous ulcer 307
Diffuse large B-cell lymphoma associated with
chronic inflammation 309
Fibrin-associated diffuse large B-cell lymphoma 311
Lymphomatoid granulomatosis 312
Primary mediastinal (thymic) large B-cell lymphoma 314
Intravascular large B-cell lymphoma 317
ALK-positive large B-cell lymphoma 319
Plasmablastic lymphoma 321
Primary effusion lymphoma 323
HHV8-associated lymphoproliferative disorders 325
Multicentric Castleman disease 325
HHV8-positive diffuse large B-cell lymphoma, NOS 327
HHV8-positive germinotropic lymphoproliferative disorder 328
Burkitt lymphoma 330
Burkitt-like lymphoma with 11 q aberration 334
High-grade B-cell lymphoma 335
High-grade B-cell lymphoma with MYC and BCL2
and/or BCL6 rearrangements 335
High-grade B-cell lymphoma, NOS 340
B-cell lymphoma, unclassifiable, with features intermediate
between DLBCL and classic Hodgkin lymphoma 342
14 Mature T- and NK-cell neoplasms 345
T-cell prolymphocytic leukaemia 346
T-cell large granular lymphocytic leukaemia 348
Chronic lymphoproliferative disorder of NK cells 351
Aggressive NK-cell leukaemia 353
EBV-positive T-cell and NK-cell lymphoproliferative
diseases of childhood 355
Systemic EBV+ T-cell lymphoma of childhood
Chronic active EBV infection of T- and
NK-cell type, systemic form
Hydroa vacciniforme-like lymphoproliferative disorder
Severe mosquito bite allergy
355
358
360
362
Adult T-cell leukaemia/lymphoma 363
Extranodal NK/T-cell lymphoma, nasal type 368
Intestinal T-cell lymphoma 372
Enteropathy-associated T-cell lymphoma 372
Monomorphic epitheliotropic intestinal T-cell lymphoma 377
Intestinal T-cell lymphoma, NOS 378
Indolent T-cell lymphoproliferative disorder of the
gastrointestinal tract 379
Hepatosplenic T-cell lymphoma 381
Subcutaneous panniculitis-like T-cell lymphoma 383
Mycosis fungoides 385
Sezary syndrome 390
Primary cutaneous CD30-positive T-cell
lymphoproliferative disorders 392
Lymphomatoid papulosis 392
Primary cutaneous anaplastic large cell lymphoma 395
Primary cutaneous peripheral T-cell lymphomas,
rare subtypes 397
Introduction 397
Primary cutaneous gamma delta T-cell lymphoma 397
Primary cutaneous CD8-positive aggressive
epidermotropic cytotoxic T-cell lymphoma 399
Primary cutaneous acral CD8-positive T-cell lymphoma
Primary cutaneous CD4+ small/medium T-cell
400
lymphoproliferative disorder 401
Peripheral T-cell lymphoma, NOS 403
Angioimmunoblastic T-cell lymphoma and other nodal
lymphomas of T follicular helper (TFH) cell origin 407
Angioimmunoblastic T-cell lymphoma 408
Follicular T-cell lymphoma
Nodal peripheral T-cell lymphoma with
411
TFH phenotype 412
Anaplastic large cell lymphoma, ALK-positive 413
Anaplastic large cell lymphoma, ALK-negative 418
Breast implant-associated anaplastic large cell lymphoma 421
15 Hodgkin lymphomas 423
Introduction 424
Nodular lymphocyte predominant Hodgkin lymphoma 431
Classic Hodgkin lymphoma 435
Nodular sclerosis classic Hodgkin lymphoma 435
Lymphocyte-rich classic Hodgkin lymphoma 438
Mixed-cellularity classic Hodgkin lymphoma 440
Lymphocyte depleted classic Hodgkin lymphoma 441
16 Immunodeficiency-associated lymphoproliferative
disorders 443
Lymphoproliferative diseases associated with primary
immune disorders 444
Lymphomas associated with HIV infection 449
Post-transplant lymphoproliferative disorders (PTLD) 453
Non-destructive PTLD 456
Polymorphic PTLD 457
Monomorphic PTLD (B- and T/NK-cell types) 459
Monomorphic B-cell PTLD 459
Monomorphic T/NK-cell PTLD 461
Classic Hodgkin lymphoma PTLD 462
Other iatrogenic immunodeficiency-associated
lymphoproliferative disorders 462
17 Histiocytic and dendritic cell neoplasms 465
Introduction 466
Histiocytic sarcoma 468
Tumours derived from Langerhans cells 470
Langerhans cell histiocytosis 470
Langerhans cell sarcoma 473
Indeterminate dendritic cell tumour 474
Interdigitating dendritic cell sarcoma 475
Follicular dendritic cell sarcoma 476
Inflammatory pseudotumour-like follicular/fibroblastic
dendritic cell sarcoma 478
Fibroblastic reticular cell tumour 479
Disseminated juvenile xanthogranuloma 480
Erdheim-Chester disease 481
Contributors 484
Declaration of interests 493
Clinical Advisory Committees 494
IARC/WHO Commitee for ICD-O 496
Sources of figures and tables 497
References 504
Subject index 577
List of abbreviations 586