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The Cutaneous Lymphoid Proliferations
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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-Sezary) 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 Sezary Syndrome 236 Definition 236 Mycosis fungoides 236 Sezary 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 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 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

About the Author

Cynthia M. Magro MD Professor of Pathology and Laboratory Medicine Department of Pathology, Cornell University Weill Cornell Medicine New York, NY, USA A. Neil Crowson MD Clinical Professor of Dermatology, Pathology, and Surgery Director of Dermatopathology at the University of Oklahoma and Regional Medical Laboratory President of Pathology Laboratory Associates Tulsa, OK, USA Martin C. Mihm MD Clinical Professor of Pathology and Dermatology, Harvard Medical School Director of Melanoma Program, Dermatology, Brigham and Women's Hospital Co-Director of Melanoma Program, Dana-Farber and Brigham and Women's Cancer Center Director, Mihm Cutaneous Pathology Consultative Service Brigham and Women's Hospital Boston, MA, USA

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