Cutaneous Lymphoid Proliferations

Cynthia M. Magro MD Professor of Pathology and Laboratory Medicine Department of Pathology, Cornell University Weill Medical College New York, USA

A. Neil Crowson MD Professor of Pathology, Departments of Dermatology, Pathology, and Surgery University of Oklahoma, and Regional Medical Laboratory Tulsa, OK, USA

Martin C. Mihm Jr. MD Professor of Pathology Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston, MA, USA

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 gamma delta 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 gamma delta 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