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Acknowledgments, viii
1 Introduction to the Classification of Lymphoma 1
Kiel Lukes–Collins, and Working Formulation classifications 1
WHO, REAL, EORTC, and the Combined WHO/EORTC classifications 2
Summary 7
References 8
Appendix: Definitions of key terms and techniques 9
2 The Therapy of Cutaneous T Cell Lymphoma 14
Benjamin H. Kaffenberger, Mark A. Bechtel, and Pierluigi Porcu
Introduction 14
Diagnostic work-up and staging procedures 14
CTCL therapies 15
Goals of therapy in advanced-stage CTCL 16
Extracorporeal photopheresis (ECP) 17
Interferons 17
Retinoids 17
Immunotoxins 18
Monoclonal antibodies 18
Histone deacetylase inhibitors (HDACi) 19
Antibody drug conjugates (ADC) 19
Cytotoxic chemotherapy 19
Investigational therapies 20
TLR agonists and cytokines 20
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) 20
References 21
3 Molecular Analysis in Cutaneous Lymphoid Proliferation 23
Shabnam Momtahen, Cynthia Magro, and Carl Morrison
Introduction 23
Immunoglobulin and T cell receptor structure 23
PCR design for determination of clonality 24
Detection of PCR products for clonality 24
Evaluation of results 25
The value and utility of molecular diagnostics in primary cutaneous lymphomas 26
Limitations of clonality assessment by PCR 27
Case vignettes 29
References 36
4 Benign Lymphocytic Infiltrates 37
Introduction 37
Spongiotic and eczematous dermatitis 37
Other spongiotic/eczematous tissue reactions 40
Other causes of subacute eczematous dermatitis 40
Interface dermatitis: cell-poor vacuolar interface dermatitis 42
Interface dermatitis: lichenoid pattern 46
Diffuse and nodular lymphocytic dermal infiltrates without atypia 51
Diffuse and nodular lymphocytic infiltrates associated with autoimmune disease 53
References 57
5 Reactive Lymphomatoid Tissue Reactions Mimicking Cutaneous T and B Cell Lymphoma 59
Lymphomatoid drug eruptions 59
Molecular profile of lymphomatoid drug eruptions 61
Pathogenetic basis of lymphomatoid drug reactions 62
Reactive lymphomatoid lesions encountered in lesions of collagen vascular disease 63
Angiomatous Variants of Pseudolymphoma 67
Case vignettes 69
References 86
6 Precursor Lesions of Cutaneous T Cell Lymphoma 89
Cutaneous T cell lymphoid dyscrasia 89
Large plaque parapsoriasis 90
Hypopigmented interface T cell dyscrasia: a unique indolent T cell dyscrasia 91
Pigmented purpuric dermatosis (PPD) 92
Pityriasis lichenoides 94
Idiopathic erythroderma (pre-Sézary) 96
Syringolymphoid hyperplasia with alopecia 96
Folliculotropic T cell lymphocytosis/pilotropic T cell dyscrasia 97
Idiopathic follicular mucinosis/alopecia mucinosa 98
Keratoderma-like T cell dyscrasia 99
Atypical lymphocytic lobular panniculitis 100
Case vignettes 102
References 132
7 Marginal Zone Lymphoma and Other Related Post Germinal Center B Cell Lymphoproliferative Disorders of The Skin 134
Marginal zone lymphoma 134
Blastic marginal zone lymphoma 140
Epidermotropic marginal zone lymphoma 140
Castleman disease 141
Primary cutaneous plasmacytoma 142
Case vignettes 145
References 166
8 Primary Cutaneous Follicle Center Cell Lymphoma 169
Clinical features 169
Pathology 169
Phenotypic profile 171
Molecular studies 172
Pathogenesis 172
Cytogenetics 172
Case vignettes 174
Additional molecular and cytogenetic study 185
References 186
9 Primary Cutaneous Diffuse Large B-Cell Lymphoma Including the Leg Type and Precursor B Cell Lymphoblastic Lymphoma 187
Primary cutaneous diffuse large B cell lymphoma 187
Systemic diffuse large B cell lymphomas with a propensity to involve the skin 197
Case vignettes 200
Additional light microscopic, phenotypic, molecular, cytogenetic studies 210
References 215
10 Intravascular Lymphoma 218
Clinical features 218
Light microscopic findings 219
Phenotypic profile 219
Molecular and cytogenetic studies 219
Pathogenesis 219
Differential diagnosis 219
Intravascular anaplastic large cell lymphoma 219
Benign intravascular proliferations of histiocytes and reactive T cells 220
Case vignettes 221
References 224
11 Cutaneous Mantle Cell Lymphoma 225
Clinical features 225
Light microscopic findings 225
Phenotypic profile 226
Molecular studies 227
Cytogenetic profile 227
Pathogenesis 227
Case vignettes 229
Additional molecular and cytogenetic studies 233
References 234
12 Mycosis Fungoides and Sézary Syndrome 236
Definition 236
Mycosis fungoides 236
Sézary syndrome and erythrodermic mycosis fungoides 243
Large cell transformation of mycosis fungoides 251
Extracutaneous involvement in mycosis fungoides 254
Case vignettes 259
References 271
13 CD30-Positive Lymphoproliferative Disorders Including Lymphomatoid Papulosis, Borderline CD30-Positive Lymphoproliferative Disease, Anaplastic Large Cell Lymphoma, and T-Cell-Rich CD30-Positive Large B Cell Lymphoma 274
Introduction 274
Lymphomatoid papulosis 274
CD8+ lymphomatoid papulosis, including the type D variant 278
Type E lymphomatoid papulosis (Case vignette 15) 278
Borderline CD30-positive lymphoproliferative disorders (type C LYP) (Case vignette 9) 279
Lymphomatoid papulosis with a rearrangement of chromosome 6p25.3 279
Cutaneous anaplastic large cell lymphoma 280
Small cell ALCL 282
Additional unusual histologic variants of anaplastic large cell lymphoma 282
Breast-implant-associated anaplastic large cell lymphoma 282
Intravascular anaplastic large cell lymphoma 282
Sarcomatoid anaplastic large cell lymphoma (Case vignette 14) 283
CD30-positive large B cell lymphoma 285
Case vignettes 286
References 309
14 CD4+ Peripheral T Cell Lymphoma, Not Otherwise Specified, Including Primary Cutaneous Cd4+ Small/Medium-Sized Pleomorphic T Cell Lymphoma 312
Introduction 312
Primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma 312
CD30-negative large cell T cell lymphoma 313
Cutaneous follicular helper T cell lymphoma 314
Overview of overall prognosis of primary cutaneous peripheral T cell lymphoma, unspecified 315
Evolution of the nomenclature of primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma 319
Case vignettes 320
References 333
15 Subcutaneous Panniculitis-Like T Cell Lymphoma 334
Clinical features 334
Morphology 336
Phenotype 337
Molecular studies 337
Differential diagnosis 337
Case vignettes 340
References 349
16 CD8 T Cell Lymphoproliferative Disease of the Skin 351
Overview 351
Introduction 351
Classification of primary CD8+ cutaneous T cell lymphomas 352
Histomorphology of primary cutaneous CD8+ T cell lymphoma: primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma, and CD8+ variants of peripheral T cell lymphoma, NOS, including primary cutaneous CD8+ granulomatous T cell lymphoma 353
CD8 variant of lymphomatoid papulosis and other related CD30-positive T cell lymphoproliferative disorders of CD8 subtype 354
Light microscopic findings 354
Indolent CD8 positive lymphoid proliferation of the face and other body sites including acral surfaces 355
CD8 prolymphocytic leukemia 355
CD8 pseudolymphoma related to underlying HIV disease 356
Drug-associated CD8+ pseudolymphoma 356
Actinic reticuloid as a unique form of CD8+pseudolymphoma 356
Case vignettes 357
References 375
17 Nasal and Related Extranodal Natural Killer Cell/T Cell Lymphomas and Blastic Plasmacytoid Dendritic Cell Neoplasm 377
Introduction 377
Biology of NK and NK-like T cells 377
NK/T-cell lymphoma 379
Nasal NK/T cell lymphoma 379
Nasal type NK/T cell lymphoma 380
Aggressive NK cell lymphoma 380
Role of Epstein–Barr virus in the evolution of NK/T cell lymphomas 382
Blastic plasmacytoid dendritic cell neoplasm 382
CD56-positive γ δ lymphoma involving the subcutaneous fat 383
Chronic granular lymphocytosis/large granular cell leukemia 384
Natural killer-like CD4+ T cell lymphoma 384
EBV-associated NK/T cell lymphomas of the elderly 385
Hydroa vaccineforme (HV)-like lymphoma 385
Cutaneous intravascular NK T cell lymphoma 386
Case vignettes 387
References 401
18 Primary Cutaneous γ δ T Cell Lymphoma 404
Introduction 404
Case vignettes 409
Additional supplemental figures 411
References 414
19 Epstein–Barr Virus-Associated Lymphoproliferative Disease 415
Introduction 415
Hydroa vacciniforme-like EBV-associated T cell lymphoproliferative disease/mosquito bite hypersensitivity 416
EBV+ cutaneous B cell lymphoproliferative disorder of the elderly 420
EBV-associated mucocutaneous ulcer 421
EBV + T cell lymphoproliferative disease of the elderly 421
General principles regarding EBV-associated lymphomagenesis 421
Pathogenetic link between EBV-associated B cell lymphoma and iatrogenic immune dysregulation related to either methotrexate or cyclosporine 421
Case vignettes 423
References 432
20 Hodgkin Lymphoma of the Skin 435
Clinical features 435
Subtypes of Hodgkin lymphoma 436
References 447
21 Chronic Lymphocytic Leukemia of B Cell and T Cell Prolymphocytic Leukemia 449
B cell chronic lymphocytic leukemia 449
T cell prolymphocytic leukemia 452
Case vignettes 455
References 471
22 Adult T Cell Leukemia/Lymphoma 473
Clinical features 473
Pathology 474
Phenotypic studies 475
Pathogenesis 475
Infective dermatitis of childhood 476
Case vignettes 477
References 484
23 Angioimmunoblastic Lymphadenopathy/Angioimmunoblastic T Cell Lymphoma 486
Clinical features 486
Light microscopic findings 487
Phenotypic studies 488
Molecular studies 488
Pathogenesis 489
Case vignettes 491
References 497
24 Lymphomatoid Granulomatosis 499
Introduction 499
Clinical features 499
Histopathology 500
Histogenesis 501
Clonality studies 501
Differential diagnosis 501
Treatment 502
Case vignette 503
References 506
25 Cutaneous Infiltrates of Myeloid Derivation 507
Introduction 507
Leukemia cutis 507
Clonal histiocytopathy syndromes 509
Histiocytopathy of factor XIIIA perivascular dermal dendritic cell origin 514
Case vignettes 517
References 537
Index 541
