Skin Cancer - A World-Wide Perspective (eBook)

Professor Reinhard Dummer leads a team of ca. 15 practitioners at the Department of Dermatology, University of Zurich Hospital.  He is board certified in dermatology and allergology and clinical immunology. His research includes in particular the immune biology of cutaneous lymphomas, cutaneous melanomas, and epithelial skin cancers, and this research has led to immune interventions in cell cultures and animal models and to translational research. He is the author of more than 300 original articles and is a recognized opinion leader in cutaneous oncology worldwide. Professor Dummer is past president of the International Society for Cutaneous Lymphomas, a board member of the European Association for Dermatological Oncology, and past president for the European Society for Dermatological Research. Mark Pittelkow is a Professor of Dermatology at the Mayo Clinic, Rochester, USA and is board certified by the American Board of Dermatology. His research interests are broad and include cutaneous T-cell lymphoma, cutaneous carcinoma, and especially melanoma. He is a member of the Mayo Clinic Melanoma Study Group. Professor Pittelkow is the author of numerous scientific articles on diverse aspects of dermatology. Professor Keiji Iwatsuki graduated from Hokkaido University School of Medicine and received his PhD from Hamamatsu University School of Medicine, Japan. He is Professor and Chairman of the Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry. His research interests include virus-related lymphomas and autoimmune diseases and he has an impressive publication record.Adele Green is Professor of Epidemiology in the Epithelial Sciences Research Group, School of Translational Medicine, University of Manchester; Deputy Director, Queensland Institute of Medical Research (QIMR), Brisbane, Australia; and Head, Population and Cancer Studies Unit, QIMR. She also holds Professorships at the University of Queensland and Griffith University. In 2004 she was named in the Australian Honours List as a Companion of the Order of Australia. She has served on many Australian research bodies and has also been a chair or member of many committees at the International Agency for Research on Cancer in  Lyon, France. Her main area of interest is cancer epidemiology, with a particular focus on melanoma and other skin cancers.Nagwa M. Elwan is Professor of Dermatology at the Faculty of Medicine, Tanta University, Egypt. She is a member of the Egyptian Society of Dermatology, the American Academy of Dermatology, the American Society of Dermatopathology, the International Society of Dermatopathology, and the International Society for Cutaneous Lymphoma. Professor Elwan is the author of more than 50 research articles on dermatopathology, acne, psoriasis, atopic dermatitis, lymphoma, and leprosy and has been guest speaker at many national and international dermatology meetings.

Skin Cancer - A World-WidePerspective 3
Copyright Page 4
Preface 5
Contents 7
Part 1: Epidemiology 13
1.1: Epidemiology of Basal Cell and Squamous Cell Carcinoma of the Skin 14
1.1.1 Introduction 14
1.1.2 Basal Cell Carcinoma Epidemiology 14
1.1.2.1 Geographic Variation 14
1.1.2.2 Temporal Trends 14
1.1.2.3 Age and Sex Distributions 14
1.1.2.4 Incidence by Anatomical Site 15
1.1.2.5 Repeated Occurrence 15
1.1.3 Squamous Cell Carcinoma Epidemiology 15
1.1.3.1 Geographic Variation 15
1.1.3.2 Temporal Trends 15
1.1.3.3 Age and Sex Distributions 16
1.1.3.4 Incidence by Anatomical Site 16
1.1.3.5 Repeated Occurrence 16
1.1.3.6 Actinic Keratoses 16
1.1.4 Risk Factors for Basal Cell Carcinoma 17
1.1.4.1 Genetic Factors 17
1.1.4.1.1 Patched Mutations and the Sonic Hedgehog Pathway 17
1.1.4.1.2 DNA Repair Defects 17
1.1.4.1.3 Detoxifying Proteins 17
1.1.4.1.4 The p53 Tumor Suppressor Gene 17
1.1.4.2 Solar Radiation 18
1.1.4.2.1 Sunscreen Use 18
1.1.4.3 Dietary Factors 18
1.1.4.4 Other Risk Factors 18
1.1.5 Risk Factors for Squamous Cell Carcinoma 19
1.1.5.1 Genetic Factors 19
1.1.5.2 Solar Radiation 19
1.1.5.2.1 Sunscreen Use 19
1.1.5.3 Human Papilloma Virus 19
1.1.5.4 Dietary Factors 20
1.1.5.5 Other Risk Factors 20
References 20
1.2: Epidemiology of Malignant Melanoma 24
1.2.1 Introduction 24
1.2.2 Patterns of Melanoma Incidence and Mortality 24
1.2.2.1 Geographic Variation 24
1.2.2.2 Temporal Trends 25
1.2.2.2.1 Incidence 25
1.2.2.2.2 Mortality 25
1.2.2.3 Age and Sex Distributions 25
1.2.2.4 Incidence by Anatomical Site 26
1.2.3 Analytical Epidemiology: Risk Factors for Melanoma 26
1.2.3.1 Environmental Factors 26
1.2.3.1.1 Opposition to the Sunlight Hypothesis 26
1.2.3.1.2 The “Critical Period” Hypothesis for Sun Exposure 27
1.2.3.1.3 Patterns of Exposure 27
1.2.3.1.4 Artificial Sources of Ultraviolet Radiation 28
1.2.3.2 Host Factors for Melanoma 28
1.2.3.3 Genes and Melanoma 28
1.2.3.3.1 High-Risk Genes 28
1.2.3.3.2 Low-Risk Genes 29
1.2.4 Multiple Causal Pathways to Melanoma? 30
1.2.4.1 Variations in Site-Specific Incidence of Melanoma with Age 30
1.2.4.2 Risk Factors for Melanoma at Different Anatomical Sites 30
1.2.4.3 Nevus-Associated Melanomas Differ from Other Melanomas 31
1.2.4.4 Population Heterogeneity in Nevus Burden 31
1.2.4.5 The Hypothesis of Divergent Causal Pathways to Melanoma 31
1.2.4.5.1 Ecological Studies 32
1.2.4.5.2 Risk Factor Studies 32
1.2.4.5.3 Somatic Mutation Studies 32
1.2.5 Conclusions 33
References 33
1.3: Epidemiology of Cutaneous Lymphomas 38
References 42
1.4: Epidemiology of Histocytoses 43
1.4.1 Langerhans Cell Histiocytosis 43
1.4.2 Indeterminate Cell Histiocytosis 43
1.4.3 Sinus Histiocytosis with Massive Lymphadenopathy (Rosai–Dorfman Disease) 43
1.4.4 Juvenile Xanthogranuloma 43
1.4.5 Reticulohistiocytosis 43
References 44
1.5: Epidemiology of Kaposi Sarcoma 45
1.5.1 Endemic African KS 45
1.5.2 Epidemic or AIDS Associated KS 46
1.5.3 Immunosuppression: Associated or Iatrogenic KS 46
1.5.4 Epidemiology of KS Associated Herpes Virus (KSHV) 46
References 46
1.6: Epidemiology of Dermatofibrosarcoma Protuberans 48
References 48
1.7: Epidemiology of Merkel Cell Carcinoma 49
1.7.1 Definition 49
1.7.2 Incidence 49
1.7.3 Sex 49
1.7.4 Age 49
1.7.5 Ethnic Groups 49
1.7.6 Anatomic Site 50
1.7.7 Risk Factors 50
References 50
Part 2: Pathogenesis 51
2.1: Pathogenesis of Nonmelanoma Skin Cancer 52
2.1.1 BCC Pathology 52
2.1.2 SCC Pathology 52
2.1.3 Genetic Aberrations 53
2.1.3.1 p53 and Skin Cancer 53
2.1.3.2 BCCs are Characterized by a Defective SONIC Hedgehog Pathway 53
2.1.3.3 Other Genetic Aberrations in BCCs 54
2.1.3.4 SCCs are Characterized by Multiple Genetic Aberrations 54
2.1.3.4.1 Potential Involvement of Aberrant Signal Transduction Pathways 54
2.1.3.5 Other Genetic Aberrations in SCCs 54
2.1.4 UVA May be Causal for Structural Chromosomal Aberrations 57
2.1.4.1 The Role of Human Papillomavirus (HPV) 57
2.1.5 Conclusions and Further Perspective 58
References 59
2.2: Pathogenesis of Malignant Melanoma 62
2.2.1 Transformation I: Genetic Mutation 62
2.2.2 Transformation II: Gene Expression Changes 64
2.2.3 Molecular Biology of Progression 65
References 68
2.3: Pathogenesis of Primary Cutaneous Lymphomas 72
2.3.1 Primary Cutaneous T-Cell Lymphomas 72
2.3.1.1 Cytogenetic Studies 72
2.3.1.2 Genomic and Epigenetic Abnormalities (Fig. 2.3.1) 73
2.3.1.3 Gene Expression Profiling 73
2.3.1.4 Conclusion 74
2.3.2 Primary Cutaneous B-Cell Lymphomas 74
2.3.3 Primary Cutaneous Marginal Zone Lymphoma 74
2.3.3.1 Cytogenetics 75
2.3.3.2 Genomic and Epigenetic Abnormalities 75
2.3.4 Primary Cutaneous Follicle Centre Lymphoma 75
2.3.4.1 Cytogenetic Studies 75
2.3.4.2 Genomic and Epigenetic Abnormalities 75
2.3.5 Primary Cutaneous Large B-Cell Lymphoma 75
2.3.5.1 Cytogenetics 75
2.3.5.2 Genomic and Epigenetic Abnormalities 76
2.3.5.3 Conclusion 76
References 76
2.4: Pathogenesis of Histiocytoses 80
2.4.1 Langerhans Cell Histiocytosis 80
2.4.2 Indeterminate Cell Histiocytosis 80
2.4.3 Sinus Histiocytosis with Massive Lymphadenopathy (Rosai–Dorfman Disease) 81
2.4.4 Juvenile Xanthogranuloma 81
2.4.5 Reticulohistiocytosis 81
References 81
2.5: Pathogenesis of Kaposi Sarcoma 82
2.5.1 HIV and Kaposi Sarcoma 82
2.5.2 Cytokines and Kaposi Sarcoma 82
2.5.3 Herpes Virus and Kaposi Sarcoma 83
2.5.4 Is Kaposi Sarcoma a True Neoplasm or a Reactive Hyperplasia? [18, 21] 83
References 83
2.6: Pathogenesis of Dermatofibrosarcoma Protuberans 85
References 86
2.7: Pathogenesis of Merkel Cell Carcinoma 87
References 91
Part 3: Disease Entities 93
3.1: Nonmelanoma Skin Cancer: Keratinocytic Tumors 94
3.1.1 Basal Cell Carcinoma 94
3.1.1.1 Definition 94
3.1.1.2 ICD-O Code 94
3.1.1.3 Synonyms 94
3.1.1.4 History 94
3.1.1.5 BCC Epidemiology 94
3.1.1.6 Pathogenesis 95
3.1.1.6.1 P53 96
3.1.1.6.2 PTCH1 and the SHH Pathway 96
3.1.1.7 Clinico-Pathologic Features and Prognosis 96
3.1.1.7.1 Nodular 96
ICD-O 96
Clinical 96
Dermatopathology 97
Prognosis 97
3.1.1.7.2 Superficial BCC 97
ICD-O 97
Clinical 97
Dermatopathology 97
Prognosis 98
3.1.1.7.3 Sclerosing (Morpheaform) 98
ICD-O 98
Clinical 98
Dermatopathology 98
Prognosis 98
3.1.1.7.4 Infiltrative 99
ICD-O 99
Clinical 99
Dermatopathology 99
Prognosis 100
3.1.1.7.5 Micronodular 100
ICD-O 100
Clinical 100
Dermatopathology 100
Prognosis 100
3.1.1.7.6 Basosquamous (Metatypical) 100
ICD-O 100
Clinical 100
Dermatopathology 101
Prognosis 101
3.1.1.7.7 Infundibulocystic BCC 101
ICD-O 101
Clinical 101
Dermatopathology 101
Prognosis 102
3.1.1.7.8 Fibroepithelioma (Fibroepithelioma of Pinkus) or Fenestrated Trichoblastoma 102
ICD-O 102
Clinical 102
Dermatopathology 102
Prognosis 102
3.1.1.7.9 Basal Cell Carcinoma with Adnexal Differentiation (Sebaceous) 102
ICD-O 102
Clinical 102
Dermatopathology 102
Prognosis 103
3.1.1.7.10 Keratotic Basal Cell Carcinoma 103
ICD-O 103
Clinical 103
Dermatopathology 103
Prognosis 103
3.1.1.8 Other Important Entities 104
3.1.1.8.1 Giant BCC 104
3.1.1.8.2 Pigmented BCC 104
3.1.1.8.3 Metastatic 104
3.1.2 Squamous Cell Carcinoma 105
3.1.2.1 Definition 105
3.1.2.2 ICD-O Code 105
3.1.2.3 Synonyms 105
3.1.2.4 History 105
3.1.2.5 SCC Epidemiology 106
3.1.2.6 Pathogenesis of SCC 107
3.1.2.6.1 RAS 107
3.1.2.6.2 P53 107
3.1.2.6.3 CDK2NA and Chromosome 9q21 107
3.1.2.7 Clinico-Pathologic Features and Prognosis 108
3.1.2.7.1 Invasive Squamous Cell Carcinoma 108
ICD-O 108
Clinical 108
Dermatopathology 108
Prognosis 109
3.1.2.7.2 Acantholytic (Adenoid) Squamous Cell Carcinoma 109
ICD-O 109
Clinical 109
Dermatopathology 109
Prognosis 109
3.1.2.7.3 Spindle-Cell Squamous Cell Carcinoma 110
ICD-O 110
Clinical 110
Dermatopathology 110
Prognosis 111
3.1.2.7.4 Verrucous Squamous Cell Carcinoma 111
ICD-O 111
Clinical 111
Ackerman (Florid Papillomatosis) 111
Epithelioma Cuniculatum 111
Buschke-Löwenstein 111
Cutaneous Verrucous Carcinoma (Papillomatosis Cutis Carcinoids) 112
Dermatopathology 112
Prognosis 113
3.1.2.7.5 Keratoacanthoma 113
ICD-O 113
Clinical 113
Dermatopathology 113
Prognosis 114
3.1.3 Bowen’s Disease 114
3.1.3.1 Definition 114
3.1.3.2 ICD-O Code 114
3.1.3.3 Synonyms 114
3.1.3.4 Clinical Features 114
3.1.3.5 Histopathology 115
3.1.3.6 Prognosis and Predictive Factors 115
3.1.3.7 Bowenoid Papulosis 116
3.1.4 Actinic Keratosis 117
3.1.4.1 Definition 117
3.1.4.2 ICD-O Code 117
3.1.4.3 Synonyms 117
3.1.4.4 Clinical Features 117
3.1.4.4.1 Risk Factors 118
3.1.4.4.2 Diagnostics 118
3.1.4.5 Histopathology 118
3.1.4.6 Prognosis and Predictive Factors 119
3.1.4.6.1 Prognosis 119
3.1.4.6.2 Predictive Factors 119
3.1.4.6.3 Prevention 119
3.1.4.7 Arsenic Keratosis 120
3.1.4.8 PUVA Keratosis 120
References 120
3.2: Non-Melanoma Skin Cancer: Appendageal Tumours 126
3.2.1 Tumours with Apocrine and Eccrine Differentiation 126
3.2.1.1 Malignant Tumours 126
3.2.1.1.1 Tubular Carcinoma 126
3.2.1.1.2 Microcystic Adnexal Carcinoma 127
3.2.1.1.3 Porocarcinoma 128
3.2.1.1.4 Spiradenocarcinoma 129
3.2.1.1.5 Malignant Mixed Tumour 130
3.2.1.1.6 Hidradenocarcinoma 130
3.2.1.1.7 Primary Cutaneous Mucinous Carcinoma 131
3.2.1.1.8 Digital Papillary Carcinoma 131
3.2.1.1.9 Adenoid Cystic Carcinoma 132
3.2.1.1.10 Apocrine Carcinoma 133
3.2.1.1.11 Paget Disease of Breast 133
3.2.1.1.12 Extra-Mammary Paget Disease 135
3.2.1.2 Benign Tumours 136
3.2.1.2.1 Hidrocystoma 136
3.2.1.2.2 Syringoma 136
3.2.1.2.3 Poroma 138
3.2.1.2.4 Syringofibroadenoma 139
3.2.1.2.5 Hidradenoma 140
3.2.1.2.6 Spiradenoma 140
3.2.1.2.7 Cylindroma 141
3.2.1.2.8 Tubular Adenoma and Tubular Papillary Adenoma 142
3.2.1.2.9 Syringocystadenoma Papilliferum 143
3.2.1.2.10 Hidradenoma Papilliferum 144
3.2.1.2.11 Mixed Tumour (Chondroid Syringoma) 144
3.2.2 Tumours with Follicular Differentiation 146
3.2.2.1 Pilomatrical Carcinoma 146
3.2.2.2 Proliferating Tricholemmal Tumour 146
3.2.2.3 Trichoblastoma 149
3.2.2.3.1 Nodular Trichoblastoma 149
3.2.2.3.2 Adamantinoid Trichoblastoma 150
3.2.2.3.3 Retiform Trichoblastoma 151
3.2.2.3.4 Cribriform Type Trichoblastoma (Conventional Trichoepithelioma) 151
3.2.2.3.5 Racemiform Type Trichoblastoma 151
3.2.2.3.6 Columnar Type Trichoblastoma (Desmoplastic Trichoepithelioma) 151
3.2.2.4 Pilomatricoma 152
3.2.2.5 Tricholemmoma 153
3.2.2.6 Trichofolliculoma 155
3.2.2.7 Fibrofolliculoma/Trichodiscoma 156
3.2.3 Tumours with Sebaceous Differentiation 158
3.2.3.1 Sebaceous Carcinoma 158
3.2.3.2 Sebaceous Adenoma 159
3.2.3.3 Sebaceoma 161
3.2.3.4 Cystic Sebaceous Tumour 161
References 162
3.3: Melanocytic Tumors 173
3.3.1 Disease Entities: Malignant Melanoma 173
3.3.1.1 Malignant Melanoma: Introduction 173
3.3.1.1.1 Definition 173
3.3.1.1.2 Clinical Features 173
Major Subtypes 173
Sites of Involvement 173
Age Distribution 173
3.3.1.1.3 Diagnosis 174
ABCD Rule 174
Dermoscopy 174
Histopathology 174
Immunohistochemistry 174
3.3.1.1.4 Staging 175
T Classification 175
N Classification 176
M Classification 177
Stage Grouping 177
3.3.1.1.5 Prognosis 177
3.3.1.1.6 Prevention 177
3.3.1.2 Superficial Spreading Melanoma 179
3.3.1.2.1 ICD-O Code 179
3.3.1.2.2 Synonyms 179
3.3.1.2.3 Clinical Features 179
3.3.1.2.4 Histopathology and Immunohistochemistry 179
3.3.1.3 Nodular Melanoma 179
3.3.1.3.1 ICD-O Code 179
3.3.1.3.2 Clinical Features 179
3.3.1.3.3 Histopathology and Immunohistochemistry 180
3.3.1.4 Lentigo Maligna and Lentigo Maligna Melanoma 180
3.3.1.4.1 ICD-O Code 180
3.3.1.4.2 Synonyms 180
3.3.1.4.3 Clinical Features 180
3.3.1.4.4 Histopathology and Immunohistochemistry 180
3.3.1.5 Acral-Lentiginous Melanoma 181
3.3.1.5.1 ICD-O Code 181
3.3.1.5.2 Synonyms 181
3.3.1.5.3 Clinical Features 181
3.3.1.5.4 Histopathology and Immunohistochemistry 182
3.3.1.6 Desmoplastic Melanoma 182
3.3.1.6.1 ICD-O Code 182
3.3.1.6.2 Clinical Features 182
3.3.1.6.3 Histopathology and Immunohistochemistry 182
3.3.1.6.4 Desmoplastic Neurotropic Melanoma 183
3.3.1.7 Melanoma Arising from Blue Naevus 184
3.3.1.7.1 ICD-O Code 184
3.3.1.7.2 Synonyms 184
3.3.1.7.3 Clinical Features 184
3.3.1.7.4 Histopathology and Immunohistochemistry 184
3.3.1.7.5 Prognosis 185
3.3.1.8 Melanoma Arising in a Giant Congenital Naevus 185
3.3.1.8.1 ICD-O Code 185
3.3.1.8.2 Synonyms 185
3.3.1.8.3 Clinical Features 185
3.3.1.8.4 Histopathology and Immunohistochemistry 186
3.3.1.9 Melanoma of Childhood 186
3.3.1.9.1 Clinical Features 186
3.3.1.9.2 Histopathology and Immunohistochemistry 187
3.3.1.10 Naevoid Melanoma 187
3.3.1.10.1 ICD-O Code 187
3.3.1.10.2 Synonyms 187
3.3.1.10.3 Clinical Features 187
3.3.1.10.4 Histopathology and Immunohistochemistry 187
3.3.1.11 Persistent Melanoma and Local Metastasis of Melanoma 188
3.3.1.11.1 Synonyms 188
3.3.1.11.2 Clinical Features 188
3.3.1.11.3 Histopathology and Immunohistochemistry 189
3.3.1.11.4 Rare Manifestations of Metastatic Melanoma 189
3.3.2 Benign Melanocytic Tumors 190
3.3.2.1 Congenital Melanocytic Naevi 190
3.3.2.1.1 Superficial Type 191
3.3.2.1.2 Proliferative Nodules in Congenital Melanocytic Nevi 191
3.3.2.2 Dermal Melanocytic Lesions 192
3.3.2.2.1 Mongolian Spot 192
3.3.2.2.2 Naevus of Ota and Ito 192
3.3.2.3 Blue Naevus 192
3.3.2.3.1 Cellular Blue Naevus 193
3.3.2.4 Combined Naevus 193
3.3.2.5 Melanotic Macule, Simple Lentigo and Lentiginous Naevus 193
3.3.2.6 Dysplastic Naevus 194
3.3.2.7 Site-Specific and Meyerson Naevi 195
3.3.2.7.1 Acral Naevus 195
3.3.2.7.2 Genital Naevus 195
3.3.2.7.3 Meyerson Naevus 195
3.3.2.8 Persistent (Recurrent) Melanocytic Naevus 196
3.3.2.9 Spitz Naevus 196
3.3.2.10 Pigmented Spindle Cell Naevus (Reed) 196
3.3.2.11 Halo Naevus 197
References 197
3.4: Cutaneous Lymphoma, Leukemia and Related Disorders 201
3.4.1 Mature T-Cell and NK-Cell Neoplasms* 201
3.4.1.1 Mycosis Fungoides 201
3.4.1.1.1 Definition 201
3.4.1.1.2 ICD-O Code 201
3.4.1.1.3 Synonyms 201
3.4.1.1.4 Clinical Features 201
3.4.1.1.5 Histopathology 201
3.4.1.1.6 Prognosis and Predictive Factors 202
3.4.1.1.7 Pagetoid Reticulosis (Localized Disease) 204
Definition 204
ICD-O Code 204
Synonyms 204
Clinical Features 204
Histology 204
Immunohistochemistry 205
Prognosis and Predictive Factors 205
3.4.1.1.8 Folliculotropic (Follicular), Syringotropic, Granulomatous Variants 205
Definition 205
ICD-O Code 205
Synonyms 205
Clinical Features and Histopathology 205
Prognosis and Predictive Factors 205
3.4.1.1.9 Granulomatous Slack Skin (GSS) 206
Definition 206
ICD-O Code 206
Synonyms 206
Clinical Features 206
Histopathology 206
Prognosis and Predictive Factors 207
3.4.1.2 Sézary Syndrome (SS) 207
3.4.1.2.1 Definition 207
Sézary Syndrome (SS) 207
3.4.1.2.2 ICD-O Code 207
3.4.1.2.3 Synonyms 207
3.4.1.2.4 Clinical Features 207
3.4.1.2.5 Histopathology 208
3.4.1.2.6 Prognosis and Predictive Factors 209
3.4.1.3 Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders 209
3.4.1.3.1 Lymphomatoid Papulosis (LyP) 209
Definition 209
ICD-O Code 209
Synonyms 209
Clinical Features 209
Histopathology 209
Prognosis and Predictive Factors 210
3.4.1.3.2 Primary Cutaneous Anaplastic Large Cell Lymphoma (ALCL) 211
Definition 211
Synonyms 211
Clinical Features 211
Histopathology 211
Prognosis and Predictive Factors 212
3.4.1.4 Subcutaneous Panniculitis-Like T-Cell Lymphoma (SPTCL) 212
3.4.1.4.1 Definition 212
3.4.1.4.2 ICD-O Code 213
3.4.1.4.3 Synonyms 213
3.4.1.4.4 Clinical Features 213
3.4.1.4.5 Histopathology 213
3.4.1.4.6 Prognosis and Predictive Factors 213
3.4.1.5 Primary Cutaneous Peripheral T-Cell Lymphoma (PTL) 214
3.4.1.5.1 Peripheral T-Cell Lymphoma (PTL), Unspecified 214
Definition 214
Synonyms 214
3.4.1.6 Subtypes of PTL (Provisional) 214
3.4.1.6.1 Primary Cutaneous Aggressive Epidermotropic CD8-Positive Cytotoxic T-Cell Lymphoma 214
Definition 214
Root 214
Clinical Features 214
Histopathology 214
Prognosis and Predictive Factors 214
3.4.1.6.2 Primary Cutaneous Gamma/Delta-Positive T-Cell Lymphoma (CGD-TCL) 214
Definition 214
Root 215
Synonyms 215
Clinical Features 215
Histopathology 215
Prognosis and Predictive Factors 215
3.4.1.6.3 Primary Cutaneous Small/Medium CD4+ T-Cell Lymphoma 215
Definition 215
Synonyms 215
Clinical Features 215
Histopathology 215
Prognosis and Predictive Factors 215
3.4.1.7 Extranodal NK/T-Cell Lymphoma, Nasal Type 215
3.4.1.7.1 Hydroa Vacciniformia-Like Lymphoma (Variant) (HVLL) 215
Definition 215
ICD-O Code 216
Synonyms 216
Clinical Features 216
Histopathology 216
Prognosis and Predictive Factors 216
3.4.1.8 Adult T-Cell Leukemia/Lymphoma (ATLL) 216
3.4.1.8.1 Definition 216
3.4.1.8.2 ICD-O Code 216
3.4.1.8.3 Synonyms 216
3.4.1.8.4 Clinical Features 216
3.4.1.8.5 Histopathology 217
3.4.1.8.6 Prognosis and Predictive Factors 217
3.4.1.9 Angioimmunoblastic T-Cell-Lymphoma (AITL) 217
3.4.1.9.1 Definition 217
3.4.1.9.2 ICD-O Code 217
3.4.1.9.3 Synonyms 217
3.4.1.9.4 Clinical Features 217
3.4.1.9.5 Histopathology 217
3.4.1.9.6 Prognosis and Predictive Factors 217
3.4.2 Mature Cutaneous B-Cell Neoplasms (CBCL)* 218
3.4.2.1 Extranodal Marginal Zone Lymphoma of the “Mucosa Associated Lymphoid Tissue” (MALT-Lymphoma) 218
3.4.2.1.1 Definition 218
3.4.2.1.2 ICD-O Code 218
3.4.2.1.3 Synonyms 218
3.4.2.1.4 Clinical Features 218
3.4.2.1.5 Histopathology 218
3.4.2.1.6 Prognosis and Predictive Factors 219
3.4.2.2 Primary Cutaneous Follicle Center Lymphoma (FCL) 219
3.4.2.2.1 Definition 219
3.4.2.2.2 ICD-O Code 219
3.4.2.2.3 Synonyms 219
3.4.2.2.4 Clinical Features 219
3.4.2.2.5 Histopathology 219
3.4.2.2.6 Prognosis and Predictive Factors 220
3.4.2.3 Primary Cutaneous Diffuse Large B-Cell Lymphoma (DLBCL) 220
3.4.2.3.1 Definition 220
3.4.2.3.2 ICD-O Code 220
3.4.2.3.3 Synonyms 221
3.4.2.3.4 Clinical Features 221
3.4.2.3.5 Histopathology 221
3.4.2.3.6 Prognosis and Predictive Factors 221
3.4.2.4 Intravascular Large B-Cell Lymphoma (IV-LBL) 221
3.4.2.4.1 Definition 221
3.4.2.4.2 ICD-O Code 221
3.4.2.4.3 Synonyms 221
3.4.2.4.4 Clinical Features 221
3.4.2.4.5 Histopathology 223
3.4.2.4.6 Prognosis and Predictive Factors 223
3.4.2.5 Lymphomatoid Granulomatosis (LYG) 223
3.4.2.5.1 Definition 223
3.4.2.5.2 ICD-O Code 223
3.4.2.5.3 Synonyms 223
3.4.2.5.4 Clinical Features 223
3.4.2.5.5 Histopathology 223
3.4.2.5.6 Prognosis and Predictive Factors 223
3.4.2.6 B-Cell Chronic Lymphocytic Leukemia (B-CLL) 223
3.4.2.6.1 Definition 223
3.4.2.6.2 ICD-O Code 224
3.4.2.6.3 Synonyms 224
3.4.2.6.4 Clinical Features 224
3.4.2.6.5 Histopathology 224
3.4.2.6.6 Prognosis and Predictive Factors 224
3.4.2.7 Mantle Cell Lymphoma (MCL) 224
3.4.2.7.1 Definition 224
3.4.2.7.2 ICD-O Code 225
3.4.2.7.3 Synonyms 225
3.4.2.7.4 Clinical Features 225
3.4.2.7.5 Histopathology 225
3.4.2.7.6 Prognosis and Predictive Factors 225
3.4.2.8 Burkitt Lymphoma (BL) 225
3.4.2.8.1 Definition 225
3.4.2.8.2 ICD-O Code 225
3.4.2.8.3 Synonyms 225
3.4.2.8.4 Clinical Features 225
3.4.2.8.5 Histopathology 225
3.4.2.8.6 Prognosis and Predictive Factors 225
3.4.3 Immature Hematopoietic Malignancies 226
3.4.3.1 Blasti Plasmacytoid Dendritic Cell Neoplasm 226
3.4.3.1.1 Definition 226
3.4.3.1.2 ICD-O Code 226
3.4.3.1.3 Synonyms 226
3.4.3.1.4 Clinical Features 226
3.4.3.1.5 Histopathology and Immunophenotype 227
3.4.3.1.6 Prognosis and Predictive Factors 227
3.4.3.2 Precursor Lymphoblastic Leukemia/Lymphoma 228
3.4.3.2.1 Definition 228
3.4.3.2.2 ICD-O Code 228
3.4.3.2.3 Precursor T-Cell Lymphoblastic Leukemia/Lymphoblastic Lymphoma (T-ALL/T-LBL) 228
3.4.3.2.4 Precursor B-Cell Lymphoblastic Leukemia/Lymphoblastic Lymphoma (B-ALL/B-LBL) 228
3.4.3.2.5 Skin Manifestations and Histopathology of Precursor Lymphoblastic Leukemia/Lymphoma 228
3.4.3.2.6 Immunophentype of Precursor Lymphoblastic Leukemia/Lymphoma 229
3.4.3.3 Myeloid and Monocytic Leukemias 229
References 230
3.5: Histiocytoses 236
Sec39_19 236
3.5.1 Introduction 236
3.5.1.1 Langerhans Cell Histiocytosis 236
3.5.1.1.1 Definition 236
3.5.1.1.2 Etiology 237
3.5.1.1.3 Clinical Manifestations 237
3.5.1.1.4 Histopathology 237
3.5.1.1.5 Differential Diagnosis 237
3.5.1.1.6 Therapy and Prognosis 238
3.5.1.2 Indeterminate Cell Histiocytosis 238
3.5.1.2.1 Definition 238
3.5.1.2.2 Etiology 238
3.5.1.2.3 Clinical Features 238
3.5.1.2.4 Histopathology 239
3.5.1.2.5 Differential Diagnosis 239
3.5.1.2.6 Treatment and Prognosis 239
3.5.1.3 Sinus Histiocytosis With Massive Lymphadenopathy (Rosai–Dorfman Disease) 239
3.5.1.3.1 Definition 239
3.5.1.3.2 Etiology 239
3.5.1.3.3 Clinical Features 239
3.5.1.3.4 Histopathology 239
3.5.1.3.5 Differential Diagnosis 239
3.5.1.3.6 Treatment and Prognosis 240
3.5.1.4 Juvenile Xanthogranuloma 240
3.5.1.4.1 Variants 240
3.5.1.4.2 Definition 240
3.5.1.4.3 Etiology 240
3.5.1.4.4 Clinical Features 241
3.5.1.4.5 Histopathology 242
3.5.1.4.6 Differential Diagnosis 242
3.5.1.4.7 Treatment and Prognosis 242
3.5.1.5 Reticulohistiocytosis 242
3.5.1.5.1 Definition 242
3.5.1.5.2 Variant 242
3.5.1.5.3 Etiology 242
3.5.1.5.4 Clinical Features 242
3.5.1.5.5 Histopathology 242
3.5.1.5.6 Differential Diagnosis 242
3.5.1.5.7 Treatments and Prognosis 242
References 243
3.6: Mastocytosis, Vascular, Muscular and Fibrohistiocytic Tumors 244
3.6.1 Mastocytosis 244
3.6.1.1 Definition 244
3.6.1.2 Molecular Abnormality 244
3.6.1.3 Clinical Examination 245
3.6.1.4 Cutaneous Mastocytosis 245
3.6.1.4.1 Urticaria Pigmentosa 245
3.6.1.4.2 Diffuse Cutaneous Mastocytosis 245
3.6.1.4.3 Mastocytoma 245
3.6.1.5 Indolent Systemic Mastocytosis 245
3.6.1.6 Aggressive Systemic Mastocytosis 246
3.6.1.7 Systemic Mastocytosis with an Associated Clonal Hematologic Non-Mast Cell Lineage Disease 246
3.6.1.8 Mast Cell Leukemia 246
3.6.2 Disease Entities of Kaposi Sarcoma 246
3.6.2.1 Clinical Features 246
3.6.2.2 Cutaneous KS 246
3.6.2.3 Clinical Variants of Cutaneous KS 246
3.6.2.4 Extracutaneous KS 247
3.6.2.5 Staging of KS 247
3.6.2.6 Histopathology of KS 247
3.6.2.7 Prognosis 248
3.6.3 Hemangiomas of Infancy 248
3.6.3.1 Hemangiomas of Infancy 248
3.6.3.2 Clinical Features 248
3.6.3.3 Classification 249
3.6.3.4 Histopathology 249
3.6.3.5 Prognosis and Management 250
3.6.4 Disease Entities of Cherry Hemangioma 250
3.6.4.1 Histopathology 250
3.6.5 Disease Entities of Sinusoidal Hemangioma 251
3.6.5.1 Histopathology 251
3.6.6 Disease Entities of Glomeruloid Hemangioma 251
3.6.6.1 Histopathology 251
3.6.7 Hobnail Hemangioma (Targetoid Hemosiderotic Hemangioma) 252
3.6.7.1 Clinical Features 252
3.6.7.2 Histopathologic Features 252
3.6.7.3 Treatment 252
3.6.8 Microvenular Hemangioma 253
3.6.8.1 Clinical Features 253
3.6.8.2 Histopathologic Features 253
3.6.8.3 Treatment 254
3.6.9 Angiolymphoid Hyperplasia with Eosinophilia 254
3.6.9.1 Clinical Features 254
3.6.9.2 Histopathologic Features 255
3.6.9.3 Treatment 256
3.6.10 Spindle-Cell Hemangioma 256
3.6.10.1 Clinical Features 256
3.6.10.2 Histopathologic Features 257
3.6.10.3 Treatment 257
3.6.11 Tufted Angioma 258
3.6.11.1 Clinical Features 258
3.6.11.2 Histopathologic Features 258
3.6.11.3 Treatment 258
3.6.12 Disease Entities of Arteriovenous Hemangioma 259
3.6.12.1 Histopahtology of Arteriovenous Hemangioma 259
3.6.13 Disease Entities of Cutaneous Angiosarcoma 259
3.6.13.1 Definition 259
3.6.13.2 Epidemiology 259
3.6.13.3 Etiopathogenesis 259
3.6.13.4 Clinical Appearance 260
3.6.13.5 Histopathology 260
3.6.13.6 Differential Diagnosis 260
3.6.13.7 Clinical Course and Prognosis 260
3.6.14 Lymphatic Tumors 261
3.6.14.1 Lymphangioma Circumscriptum 261
3.6.14.2 Progressive Lymphangioma 261
3.6.15 Smooth and Skeletal Muscle Tumors 262
3.6.15.1 Disease Entities of Pilar Leiomyoma 262
3.6.15.1.1 Histopathology 262
3.6.16 Smooth and Skeletal Muscle Tumors 263
3.6.16.1 Cutaneous Leiomyosarcoma 263
3.6.17 Fibrous, Fibrohistiocytic, and Histiocytic Tumors 264
3.6.17.1 Dermatomyofibroma 264
3.6.17.1.1 Definition 264
3.6.17.1.2 Clinical Features 264
3.6.17.1.3 Histopathology 264
3.6.17.1.4 Pathogenesis and Genetic Features 265
3.6.17.1.5 Therapy 265
3.6.17.1.6 Prognosis 265
3.6.17.2 Infantile Myofibromatosis 265
3.6.17.2.1 Definition 265
3.6.17.2.2 Clinical Features 265
3.6.17.2.3 Histopathology 265
3.6.17.2.4 Pathogenesis and Genetic Features 265
3.6.17.2.5 Therapy 265
3.6.17.2.6 Prognosis 265
3.6.17.3 Sclerotic Fibroma 266
3.6.17.3.1 Definition 266
3.6.17.3.2 Clinical Features 266
3.6.17.3.3 Histopathology 266
3.6.17.3.4 Pathogenesis and Genetic Features 266
3.6.17.3.5 Therapy 266
3.6.17.3.6 Prognosis 266
3.6.17.4 Pleomorphic Fibroma 266
3.6.17.4.1 Definition 266
3.6.17.4.2 Clinical Features 266
3.6.17.4.3 Histopathology 266
3.6.17.4.4 Pathogenesis and Genetic Features 266
3.6.17.4.5 Therapy 266
3.6.17.4.6 Prognosis 267
3.6.17.5 Dermatofibrosarcoma Protuberans 267
3.6.17.5.1 Definition 267
3.6.17.5.2 Clinical Features 267
3.6.17.5.3 Histopathology 267
3.6.17.5.4 Differential Diagnoses 267
3.6.17.5.5 Pathogenesis and Genetic Features 267
3.6.17.5.6 Therapy 267
3.6.17.5.7 Prognosis 268
3.6.17.6 Dermatofibroma (Fibrous Histiocytoma) 268
3.6.17.6.1 Definition 268
3.6.17.6.2 Clinical Features 269
3.6.17.6.3 Histopathology 269
3.6.17.6.4 Differential Diagnoses 270
3.6.17.6.5 Pathogenesis and Genetic Features 270
3.6.17.6.6 Therapy 271
3.6.17.6.7 Prognosis 271
3.6.17.7 Giant Cell Fibroblastoma 271
3.6.17.7.1 Definition 271
3.6.17.7.2 Clinical Features 271
3.6.17.7.3 Histopathology 271
3.6.17.7.4 Pathogenesis and Genetic Features 271
3.6.17.7.5 Therapy 272
3.6.17.7.6 Prognosis 272
References 272
3.7: Neural Tumors 281
3.7.1 Merkel Cell Carcinoma 281
3.7.1.1 Clinical Features 281
3.7.1.2 Histopathology 281
3.7.1.3 Staging 283
3.7.2 Granular Cell Tumor 284
References 286
Part 4: Therapy 288
4.1: Non-Melanoma Skin Cancer 289
4.1.1 Surgery 289
4.1.1.1 Indication 289
4.1.1.2 Technique 290
4.1.1.2.1 Standard Excision 290
4.1.1.2.2 Micrographically Controlled Surgery 290
4.1.1.2.3 Reconstruction 291
4.1.1.2.4 Metastasizing Non-Melanoma Skin Cancer 291
4.1.1.2.5 Ablative Methods 291
4.1.1.3 Outcome 291
4.1.2 Phototherapy, Laser and Radiation: Phototherapie 292
4.1.2.1 Indication 292
4.1.2.2 Technique 293
4.1.2.2.1 Preparation 293
4.1.2.2.2 Application 293
4.1.2.2.3 Light Sources 293
4.1.2.2.4 Repetition, Precautions, and Adverse Events 293
4.1.2.3 Outcome 293
4.1.3 Phototherapy, Laser and Radiation: Radiation 295
4.1.3.1 Indication and Outcome 295
4.1.3.2 Technique 296
4.1.4 Phototherapy, Laser and Radiation: Lasers for Non-Melanoma Skin Cancer 297
4.1.4.1 Indications 297
4.1.4.2 Technique 298
4.1.4.3 Outcome 298
4.1.5 Drug Therapy for Non-Melanoma Skin Cancer 299
4.1.5.1 Topical Therapy 299
4.1.5.1.1 5-Fluorouracil 299
Indications and Dosages 299
Side Effects and Limitations 299
4.1.5.1.2 Diclofenac-Sodium 299
Indications and Dosage 299
Side Effects and Limitations 300
4.1.5.1.3 Topical Retinoids 300
Indications and Dosage 300
Side Effects and Limitations 300
4.1.5.2 Topical Immunotherapy 300
4.1.5.2.1 Imiquimod 300
Indications and Dosage 300
Side Effects and Limitations 301
4.1.5.3 Systemic Therapy 301
4.1.5.3.1 Interferons 301
Indications and Dosage 301
Side Effects and Limitations 302
References 302
4.2: Melanoma 306
4.2.1 Surgery 306
4.2.1.1 Indications 306
4.2.1.1.1 Primary Excision 306
4.2.1.1.2 Wide Excision 306
4.2.1.1.3 Sentinel Lymph Node Biopsy 306
4.2.1.1.4 Completion Lymph Node Dissection 307
4.2.1.1.5 Systemic Metastases 307
4.2.1.2 Technique 308
4.2.1.2.1 Primary Excision 308
4.2.1.2.2 Wide Excision 308
4.2.1.2.3 Sentinel Lymph Node Biopsy 308
4.2.1.2.4 Completion Lymph Node Dissection 309
4.2.1.2.5 Therapeutic Lymph Node Dissection 309
4.2.1.3 Outcome 309
4.2.2 Radiation 310
4.2.2.1 Radiation Therapy 310
4.2.2.2 Indication 310
4.2.2.2.1 Adjuvant Radiotherapy of the Primary Tumor 310
4.2.2.2.2 Primary Radiotherapy in Lentigo Maligna/Melanoma 310
4.2.2.2.3 Adjuvant Radiation Therapy Following Lymph Node Dissection 310
4.2.2.2.4 Radiation Therapy in Metastases 311
4.2.2.3 Technique 311
4.2.2.4 Outcome 312
4.2.2.4.1 Adjuvant Radiotherapy of the Primary Tumor 312
4.2.2.4.2 Adjuvant Radiation Therapy Following Lymph Node Dissection 314
4.2.2.4.3 Hyperthermia 314
4.2.2.4.4 Radiation Therapy in Metastases 314
Brain Metastases 315
4.2.3 Drug Therapy 315
4.2.3.1 Topical Treatment 315
4.2.3.1.1 Indication 315
4.2.3.1.2 Technique and Outcome 315
4.2.3.2 Topical Immunotherapy 316
4.2.3.2.1 Indication 316
4.2.3.2.2 Technique and Outcome 316
Intratumoral Treatment with Interleukin-2 316
Topical Treatment with Imiquimod 316
2-4 Dinitrochlorobenzene 316
Emerging Therapies 316
4.2.3.3 Systemic Therapy 317
4.2.3.3.1 Indication 317
Adjuvant Therapy 317
Treatment of Metastatic Melanoma 317
4.2.3.3.2 Outcome 317
Adjuvant Therapy 317
Interferon-a 317
Vaccines 318
Treatment of Metastatic Melanoma 320
Chemotherapy 320
Special Case: Metastatic Uveal Melanoma 321
Cytokine Therapy 321
Biochemotherapy 321
Emerging Therapies 323
Oblimersen 323
Elesclomol 323
Sorafenib 323
Cytotoxic T-Lymphocyte-Associated Antigen 4 Blockade 323
Other Treatments in the Early Stages of Development 324
4.2.3.4 Conclusion 324
4.2.4 Adjuvant Immunotherapy in Melanoma: Pegylated Interferons: A New Perspective 325
4.2.4.1 Interferons Type I and II and Their Receptors: Overview 325
4.2.4.1.1 Types of Interferons 325
4.2.4.2 Interferon Biomarkers and Resistance 327
4.2.4.2.1 Interferon-Induced Autoimmunity 327
4.2.4.3 Pegylation 328
4.2.4.3.1 Pegylated IFNa-2b (Pegintron) 328
4.2.4.3.2 Pegylated IFNa-2a (Pegasus) 328
4.2.4.3.3 Pegylated Interferon in the Adjuvant Setting 328
4.2.4.3.4 Pegylated Interferon in Palliative Disease (Stage IV Melanoma) 329
Pegylated Interferon as Monotherapy in Stage IV 329
Pegylated Interferon in Combination with Chemotherapy 329
Side Effects of PegIFNs 330
4.2.4.4 Summary and Conclusions 331
References 331
4.3: Cutaneous Lymphoma 341
4.3.1 Surgery 341
4.3.2 Phototherapy and Radiation 341
4.3.2.1 Indication 341
4.3.2.2 Technique 341
4.3.2.2.1 PUVA Therapy 341
4.3.2.3 Outcome 342
4.3.3 Radiation Indication 342
4.3.3.1 Indication 342
4.3.3.2 Technique 342
4.3.3.3 Outcome 342
4.3.4 Topical Therapy (CTCL) 342
4.3.4.1 Indication 342
4.3.5 Technique 342
4.3.5.1 Topical Corticosteroids 342
4.3.5.2 Topical HN2 343
4.3.5.3 Topical BCNU 343
4.3.5.4 Topical Bexarotene 343
4.3.6 Outcome 343
4.3.6.1 Topical Corticosteroids 343
4.3.6.2 Topical HN2 343
4.3.6.3 Topical BCNU 344
4.3.6.4 Topical Bexarotene 344
4.3.7 Experimental Topical Therapies for CTCL 344
4.3.7.1 Topical Tazarotene 344
4.3.7.2 Topical Imiquimod 345
4.3.7.3 Topical Methotrexate 345
4.3.7.4 Topical Romidepsin 345
4.3.8 Topical Therapy (CBCL) 345
4.3.8.1 Indication 345
4.3.8.2 Technique 345
4.3.8.2.1 Intralesional Corticosteroids 345
4.3.8.2.2 Intralesional Interferone a2a 345
4.3.8.2.3 Topical BCNU 345
4.3.8.2.4 Topical Imiquimod 346
4.3.8.2.5 Rituximab 346
4.3.9 Experimental Topical Therapies for CBCL 346
4.3.9.1 Adeno Interferon-Gamma 346
4.3.10 Systemic Therapy 346
4.3.10.1 Indication 346
4.3.11 Technique and Outcome 346
4.3.11.1 Therapy of CTCL 346
4.3.11.1.1 Mycosis Fungoides, Follicular Mucinosis, and Pagetoid Reticulosis 346
4.3.11.1.2 Lymphomatoid Papulosis and Large Cell CD30+ CTCL 347
4.3.11.1.3 Sézary Syndrome 347
4.3.12 Therapy of CBCL 349
4.3.12.1 Low-Grade Primary Cutaneous B-Cell Lymphoma (Follicular Lymphoma, Marginal Zone Lymphoma) 349
4.3.12.2 Large Cell B-Cell Lymphoma 349
4.3.13 Therapy of Non-CD4+/CD56+ Hematodermic Neoplasm 350
References 350
4.4: Other Therapies 353
4.4.1 Histiocytoses 353
4.4.1.1 Langerhans Histiocytosis 353
4.4.1.1.1 Solitary LCH or Single-System Involvement 353
4.4.1.1.2 LCH with Multisystem Involvement 353
4.4.1.2 Non-Langerhans Cell Histiocytosis 353
4.4.1.2.1 Juvenile Xanthogranuloma 353
4.4.1.2.2 Systemic and Progressive Forms of XG Family 354
4.4.1.3 Multicentric Reticulohistiocytosis (MCRH) 355
4.4.1.4 Rosai–Dorfman Disease 355
4.4.2 Mastocytosis 356
4.4.2.1 Cutaneous Involvement 356
4.4.2.2 Mediator-Related Symptoms 356
4.4.2.3 Systemic Mastocytosis 356
4.4.2.4 Molecularly Targeted Drugs 356
4.4.3 Therapy of Cutaneous Angiosarcoma 357
4.4.3.1 Surgery 357
4.4.3.2 Radiotherapy 357
4.4.3.3 Chemotherapy 357
4.4.3.4 Immunotherapy 358
4.4.4 Therapy of Kaposi Sarcoma 358
4.4.4.1 Local Therapy of KS 358
4.4.4.1.1 Surgical Excision 358
4.4.4.1.2 Cryotherapy 358
4.4.4.1.3 Laser Therapy 358
4.4.4.1.4 Radiotherapy 358
4.4.4.1.5 Intralesional Chemotherapy 359
4.4.4.1.6 Local Immunotherapy 359
Topical Imiquimod 5% Cream 359
Intralesional Interferon-Alfa (INF- a) 359
Intralesional Tumor Necrosis Factor- Alfa (TNF- a) 359
Topical Retinoids 359
4.4.4.2 Systemic Therapy of KS 359
4.4.4.2.1 Systemic Chemotherapy 359
4.4.4.2.2 Systemic Immunotherapy 360
4.4.4.2.3 Antiangiogenic Therapy 360
4.4.4.2.4 Anti-HHV-8 Drugs 360
4.4.4.2.5 Highly Active Antiretroviral Therapy (HAART) 360
4.4.4.2.6 Systemic Retinoids 360
4.4.5 Treatment of Dermatofibrosarcoma Protuberans 361
4.4.5.1 Surgical Therapy 361
4.4.5.2 Targeted Molecular Therapy 361
4.4.5.3 Other Therapeutic Possibilities 362
4.4.6 Merkel Cell Carcinoma – Therapy 363
References 364
Part 5: Diagnostics 368
5.1: Dermoscopy 369
5.1.1 Introduction 369
5.1.2 Physical Aspects 369
5.1.3 Instrumentation for Dermoscopy 369
5.1.4 Dermoscopic Criteria 369
5.1.5 Colors 369
5.1.6 Dermoscopic Structures 369
5.1.6.1 Pigment Network 369
5.1.6.2 Dots 370
5.1.6.3 Globules 370
5.1.6.4 Branched Streaks 370
5.1.6.5 Radial Streaming 370
5.1.7 Pseudopods 370
5.1.7.1 Streaks 370
5.1.7.2 Structureless Areas 371
5.1.7.3 Blotches 371
5.1.7.4 Regression Pattern 371
5.1.7.5 Blue–White Veil 371
5.1.7.6 Vascular Pattern 371
5.1.7.7 Milia-Like Cysts 371
5.1.7.8 Comedo-Like Openings (Crypts, Pseudofollicular Openings) 372
5.1.7.9 Fissures and Ridges 372
5.1.7.10 Fingerprint-Like Structures 372
5.1.7.11 Moth-Eaten Border 372
5.1.7.12 Leaf-Like Areas 372
5.1.7.13 Spoke-Wheel-Like Structures 372
5.1.7.14 Large Blue–Gray Ovoid Nests 372
5.1.7.15 Multiple Blue–Gray Globules 372
5.1.8 Differential Diagnosis of Pigmented Lesions of the Skin 373
References 374
5.2: PET and PET/CT of Malignant Melanoma 375
5.2.1 Staging of Malignant Melanoma 376
5.2.2 Whole-Body PET and PET/CT Imaging with FDG 376
5.2.2.1 FDG PET and Prognosis 383
5.2.2.2 Treatment Response Evaluation 383
5.2.2.3 Effectiveness of Whole-Body FDG PET 384
5.2.3 Summary 384
References 385
Index 387