Cutaneous Lymphoid Proliferations

Cynthia M. Magro MDProfessor of Pathology and Laboratory MedicineDepartment of Pathology, Cornell UniversityWeill Cornell MedicineNew York, NY, USAA. Neil Crowson MDClinical Professor of Dermatology, Pathology, and SurgeryDirector of Dermatopathology at the University of Oklahoma and Regional Medical LaboratoryPresident of Pathology Laboratory AssociatesTulsa, OK, USAMartin C. Mihm MDClinical Professor of Pathology and Dermatology, Harvard Medical SchoolDirector of Melanoma Program, Dermatology, Brigham and Women’s HospitalCo-Director of Melanoma Program, Dana-Farber and Brigham and Women’s Cancer CenterDirector, Mihm Cutaneous Pathology Consultative ServiceBrigham and Women’s HospitalBoston, MA, USA

• Acknowledgments, viii1 Introduction to the Classification of Lymphoma 1Kiel Lukes–Collins, and Working Formulation classifications 1WHO, REAL, EORTC, and the Combined WHO/EORTC classifications 2Summary 7References 8Appendix: Definitions of key terms and techniques 92 The Therapy of Cutaneous T Cell Lymphoma 14Benjamin H. Kaffenberger, Mark A. Bechtel, and Pierluigi PorcuIntroduction 14Diagnostic work-up and staging procedures 14CTCL therapies 15Goals of therapy in advanced-stage CTCL 16Extracorporeal photopheresis (ECP) 17Interferons 17Retinoids 17Immunotoxins 18Monoclonal antibodies 18Histone deacetylase inhibitors (HDACi) 19Antibody drug conjugates (ADC) 19Cytotoxic chemotherapy 19Investigational therapies 20TLR agonists and cytokines 20Allogeneic hematopoietic stem cell transplantation (allo-HSCT) 20References 213 Molecular Analysis in Cutaneous Lymphoid Proliferation 23Shabnam Momtahen, Cynthia Magro, and Carl MorrisonIntroduction 23Immunoglobulin and T cell receptor structure 23PCR design for determination of clonality 24Detection of PCR products for clonality 24Evaluation of results 25The value and utility of molecular diagnostics in primary cutaneous lymphomas 26Limitations of clonality assessment by PCR 27Case vignettes 29References 364 Benign Lymphocytic Infiltrates 37Introduction 37Spongiotic and eczematous dermatitis 37Other spongiotic/eczematous tissue reactions 40Other causes of subacute eczematous dermatitis 40Interface dermatitis: cell-poor vacuolar interface dermatitis 42Interface dermatitis: lichenoid pattern 46Diffuse and nodular lymphocytic dermal infiltrates without atypia 51Diffuse and nodular lymphocytic infiltrates associated with autoimmune disease 53References 575 Reactive Lymphomatoid Tissue Reactions Mimicking Cutaneous T and B Cell Lymphoma 59Lymphomatoid drug eruptions 59Molecular profile of lymphomatoid drug eruptions 61Pathogenetic basis of lymphomatoid drug reactions 62Reactive lymphomatoid lesions encountered in lesions of collagen vascular disease 63Angiomatous Variants of Pseudolymphoma 67Case vignettes 69References 866 Precursor Lesions of Cutaneous T Cell Lymphoma 89Cutaneous T cell lymphoid dyscrasia 89Large plaque parapsoriasis 90Hypopigmented interface T cell dyscrasia: a unique indolent T cell dyscrasia 91Pigmented purpuric dermatosis (PPD) 92Pityriasis lichenoides 94Idiopathic erythroderma (pre-Sézary) 96Syringolymphoid hyperplasia with alopecia 96Folliculotropic T cell lymphocytosis/pilotropic T cell dyscrasia 97Idiopathic follicular mucinosis/alopecia mucinosa 98Keratoderma-like T cell dyscrasia 99Atypical lymphocytic lobular panniculitis 100Case vignettes 102References 1327 Marginal Zone Lymphoma and Other Related Post Germinal Center B Cell Lymphoproliferative Disorders of The Skin 134Marginal zone lymphoma 134Blastic marginal zone lymphoma 140Epidermotropic marginal zone lymphoma 140Castleman disease 141Primary cutaneous plasmacytoma 142Case vignettes 145References 1668 Primary Cutaneous Follicle Center Cell Lymphoma 169Clinical features 169Pathology 169Phenotypic profile 171Molecular studies 172Pathogenesis 172Cytogenetics 172Case vignettes 174Additional molecular and cytogenetic study 185References 1869 Primary Cutaneous Diffuse Large B-Cell Lymphoma Including the Leg Type and Precursor B Cell Lymphoblastic Lymphoma 187Primary cutaneous diffuse large B cell lymphoma 187Systemic diffuse large B cell lymphomas with a propensity to involve the skin 197Case vignettes 200Additional light microscopic, phenotypic, molecular, cytogenetic studies 210References 21510 Intravascular Lymphoma 218Clinical features 218Light microscopic findings 219Phenotypic profile 219Molecular and cytogenetic studies 219Pathogenesis 219Differential diagnosis 219Intravascular anaplastic large cell lymphoma 219Benign intravascular proliferations of histiocytes and reactive T cells 220Case vignettes 221References 22411 Cutaneous Mantle Cell Lymphoma 225Clinical features 225Light microscopic findings 225Phenotypic profile 226Molecular studies 227Cytogenetic profile 227Pathogenesis 227Case vignettes 229Additional molecular and cytogenetic studies 233References 23412 Mycosis Fungoides and Sézary Syndrome 236Definition 236Mycosis fungoides 236Sézary syndrome and erythrodermic mycosis fungoides 243Large cell transformation of mycosis fungoides 251Extracutaneous involvement in mycosis fungoides 254Case vignettes 259References 27113 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 274Introduction 274Lymphomatoid papulosis 274CD8+ lymphomatoid papulosis, including the type D variant 278Type E lymphomatoid papulosis (Case vignette 15) 278Borderline CD30-positive lymphoproliferative disorders (type C LYP) (Case vignette 9) 279Lymphomatoid papulosis with a rearrangement of chromosome 6p25.3 279Cutaneous anaplastic large cell lymphoma 280Small cell ALCL 282Additional unusual histologic variants of anaplastic large cell lymphoma 282Breast-implant-associated anaplastic large cell lymphoma 282Intravascular anaplastic large cell lymphoma 282Sarcomatoid anaplastic large cell lymphoma (Case vignette 14) 283CD30-positive large B cell lymphoma 285Case vignettes 286References 30914 CD4+ Peripheral T Cell Lymphoma, Not Otherwise Specified, Including Primary Cutaneous Cd4+ Small/Medium-Sized Pleomorphic T Cell Lymphoma 312Introduction 312Primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma 312CD30-negative large cell T cell lymphoma 313Cutaneous follicular helper T cell lymphoma 314Overview of overall prognosis of primary cutaneous peripheral T cell lymphoma, unspecified 315Evolution of the nomenclature of primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma 319Case vignettes 320References 33315 Subcutaneous Panniculitis-Like T Cell Lymphoma 334Clinical features 334Morphology 336Phenotype 337Molecular studies 337Differential diagnosis 337Case vignettes 340References 34916 CD8 T Cell Lymphoproliferative Disease of the Skin 351Overview 351Introduction 351Classification of primary CD8+ cutaneous T cell lymphomas 352Histomorphology 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 353CD8 variant of lymphomatoid papulosis and other related CD30-positive T cell lymphoproliferative disorders of CD8 subtype 354Light microscopic findings 354Indolent CD8 positive lymphoid proliferation of the face and other body sites including acral surfaces 355CD8 prolymphocytic leukemia 355CD8 pseudolymphoma related to underlying HIV disease 356Drug-associated CD8+ pseudolymphoma 356Actinic reticuloid as a unique form of CD8+pseudolymphoma 356Case vignettes 357References 37517 Nasal and Related Extranodal Natural Killer Cell/T Cell Lymphomas and Blastic Plasmacytoid Dendritic Cell Neoplasm 377Introduction 377Biology of NK and NK-like T cells 377NK/T-cell lymphoma 379Nasal NK/T cell lymphoma 379Nasal type NK/T cell lymphoma 380Aggressive NK cell lymphoma 380Role of Epstein–Barr virus in the evolution of NK/T cell lymphomas 382Blastic plasmacytoid dendritic cell neoplasm 382CD56-positive γ δ lymphoma involving the subcutaneous fat 383Chronic granular lymphocytosis/large granular cell leukemia 384Natural killer-like CD4+ T cell lymphoma 384EBV-associated NK/T cell lymphomas of the elderly 385Hydroa vaccineforme (HV)-like lymphoma 385Cutaneous intravascular NK T cell lymphoma 386Case vignettes 387References 40118 Primary Cutaneous γ δ T Cell Lymphoma 404Introduction 404Case vignettes 409Additional supplemental figures 411References 41419 Epstein–Barr Virus-Associated Lymphoproliferative Disease 415Introduction 415Hydroa vacciniforme-like EBV-associated T cell lymphoproliferative disease/mosquito bite hypersensitivity 416EBV+ cutaneous B cell lymphoproliferative disorder of the elderly 420EBV-associated mucocutaneous ulcer 421EBV + T cell lymphoproliferative disease of the elderly 421General principles regarding EBV-associated lymphomagenesis 421Pathogenetic link between EBV-associated B cell lymphoma and iatrogenic immune dysregulation related to either methotrexate or cyclosporine 421Case vignettes 423References 43220 Hodgkin Lymphoma of the Skin 435Clinical features 435Subtypes of Hodgkin lymphoma 436References 44721 Chronic Lymphocytic Leukemia of B Cell and T Cell Prolymphocytic Leukemia 449B cell chronic lymphocytic leukemia 449T cell prolymphocytic leukemia 452Case vignettes 455References 47122 Adult T Cell Leukemia/Lymphoma 473Clinical features 473Pathology 474Phenotypic studies 475Pathogenesis 475Infective dermatitis of childhood 476Case vignettes 477References 48423 Angioimmunoblastic Lymphadenopathy/Angioimmunoblastic T Cell Lymphoma 486Clinical features 486Light microscopic findings 487Phenotypic studies 488Molecular studies 488Pathogenesis 489Case vignettes 491References 49724 Lymphomatoid Granulomatosis 499Introduction 499Clinical features 499Histopathology 500Histogenesis 501Clonality studies 501Differential diagnosis 501Treatment 502Case vignette 503References 50625 Cutaneous Infiltrates of Myeloid Derivation 507Introduction 507Leukemia cutis 507Clonal histiocytopathy syndromes 509Histiocytopathy of factor XIIIA perivascular dermal dendritic cell origin 514Case vignettes 517References 537Index 541