Dermatopathology Eva Brehmer-Andersson

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Eva Brehmer-Andersson Dermatopathology

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Eva Brehmer-Andersson

Dermatopathology

With 138 Figures in 445 Separate Illustrations and 5 Tables

123

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Eva Brehmer-Andersson Värtavägen 17

115 53 Stockholm Sweden

ISBN-10 3-540- 30245-X Springer-Verlag Berlin Heidelberg NewYork ISBN-13 978-3-540- 30245-2 Springer-Verlag Berlin Heidelberg NewYork

Library of Congress Control Number: 2006920598

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The purpose of this book is to introduce future pathologists and dermatolo- gists to the exciting field of dermatopathology. During the past 40 years dermatopathology has become a big and important topic. There are today many excellent and comprehensive textbooks on the subject, but the overwhelming amount of material and increasing number of this kind of textbook make it difficult to start to discover new fields. I have chosen to focus on relevant pro- cesses in basic pathology and discuss how they work or are supposed to work in both common and unusual skin diseases, which I have been confronted with during a life-long practice in pathology and dermatopathology. I also focus on some controversial concepts prevailing and on the diversity in nomenclature. My expectation is to promote the understanding of pathogenesis in diseases of the skin and arouse an appetite for further and more comprehensive studies, and hopefully even to inspire new fruitful investigations. In this respect, the book will even address those experienced in the specialty.

Eva Brehmer-Andersson March 2006

Preface

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This book is based on experiences acquired at the Departments of Pathology of the University Hospitals in Lund and Umeå, and at the Karolinska Univer- sity Hospital and South Hospital in Stockholm, Sweden. In all these places I have had a close and inspiring collaboration with the respective Departments of Dermatology. I want to heartily thank all staff members who during the years, besides their own routine work, have willingly helped me with important things such as further sections and stainings, and searching for old slides, records and print-outs.

I am deeply indebted to Sven Lindskog, Professor at the Department of Oral Histology, Karolinska Institute, Stockholm, for generously having put his photo laboratory at my disposal, and to Karl Gabor, colleague and photogra- pher, for valuable advice about adaptation of the photographic material.

Acknowledgement

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Contents

1 Requirements for a Good Diagnostic Result

1.1 Sampling Technique . . . 1

1.2 The Consulting Form . . . 1

1.3 Routine Processing . . . 2

1.4 Interpretation of Histopathologic Changes . 2 2 The Dermal Blood Vasculature 2.1 General Architecture of Blood Vessels . . . . 4

2.1.1 Arteries . . . 4

2.1.2 Capillaries . . . 4

2.1.3 Veins . . . 4

2.1.4 The Endothelium . . . 5

2.1.5 Arteriovenous Anastomoses . . . 5

2.2 The Microvasculature of the Skin . . . 5

References . . . 6

3 The Dermal Lymphatic Vasculature 3.1 The Construction of Lymphatic Capillaries . 9 3.2 Lymphatic Capillaries in the Skin . . . 9

3.3 Prelymphatics and Initial Lymphatics (Lymphatic Sinusoids, Blind Tubes) . . . . 10

4 The Immune Response 4.1 Adaptive Immunity . . . 12

4.1.1 B and T Cells . . . 12

4.1.2 The Lymph Node . . . 13

4.1.2.1 The Cortex—the Main Territory for B Cells 13 4.1.2.2 Paracortex or Deep Cortex—the Main Territory for T Cells . . . 14

4.1.2.3 Medulla—the Area Between the Paracortex and the Hilus . . . 14

4.1.3 The Recirculation of Lymphocytes . . . 14

4.1.4 Immune Response in Non-Lymphoid Tissues . . . 15

4.1.5 Cytokines and Cell Adhesion Molecules . . 15 4.2 Innate Immunity . . . 16

4.2.1 The Complement System . . . 17

4.2.1.1 The Classic Pathway . . . 17

4.2.1.2 The Alternative Pathway . . . 17

4.3 Adverse Reactions of the Immune System . 17 4.3.1 Type I. Immediate Reactions . . . 17

4.3.2 Type II. Cytotoxic Antibody-Dependent Reactions . . . 17

4.3.3 Type III. Reactions due to Circulating Immune Complex Activated by Complement . . . 18

4.3.4 Type IV. Cell-Mediated Hypersensitivity Reactions . . . 18

4.4 The Skin Immune System . . . 18

4.4.1 Lymphocytes in Normal Skin . . . 18

4.4.2 Langerhans Cells . . . 18

4.4.3 Keratinocytes . . . 19

4.5 The Immune Response and Skin Diseases . 19 References . . . 19

5 Cell and Vascular Response to Infection and Injury 5.1 Inflammatory Cells . . . 21

5.1.1 Neutrophils . . . 21

5.1.2 Eosinophils . . . 21

5.1.3 Lymphocytes . . . 21

5.1.4 Plasma Cells . . . 22

5.1.5 Mast Cells . . . 22

5.1.6 Basophils . . . 23

5.1.7 Monocytes/Macrophages . . . 23

5.2 Acute Inflammation . . . 23

5.2.1 Active Phase . . . 23

5.2.2 Healing Without Residue . . . 24

5.2.3 Abscess Formation . . . 25

5.2.4 Healing with Fibrosis and Scar Formation 25 5.2.4.1 Examples . . . 25

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Contents X

5.3 Chronic Inflammation . . . 26

5.3.1 Immune Granulomas . . . 26

5.3.1.1 The Tuberculous Granuloma . . . 27

5.3.1.2 Sarcoidosis . . . 28

5.3.1.2.1 Example . . . 28

5.3.2 Foreign Body Granuloma . . . 28

5.3.3 Relevant Investigations . . . 28

5.4 Angiogenesis . . . 28

5.5 Cell Division . . . 29

6 Cell Death in the Living Body 6.1 Accidental Cell Death . . . 31

6.2 Apoptosis . . . 31

6.2.1 Apoptosis in Embryonic Development . . . 32

6.2.2 Apoptosis in Postnatal Life . . . 33

6.2.4 Apoptosis and the Skin . . . 33

7 Vasculitis 7.1 Category I: Neutrophilic Venular Vasculitis 35 7.1.1 Clinical Appearance . . . 37

7.1.2 Histopathologic Appearance . . . 37

7.1.3 Pathogenesis . . . 37

7.1.4 Examples . . . 38

7.1.5 Variants of Leukocytoclastic Vasculitis . . . 38

7.1.5.1 Henoch-Schönlein Purpura . . . 38

7.1.5.2 Infantile Acute Hemorrhagic Edema of the Skin . . . 39

7.1.5.3 Urticarial Vasculitis . . . 39

7.1.5.4 Recurrent Cutaneous Necrotizing Eosinophilic Vasculitis . . . 40

7.1.5.5 Pustular Vasculitis of the Hands . . . 40

7.1.6 Differential Diagnosis . . . 40

7.2 Category II: Lymphocytic Venular Vasculitis . . . 40

7.2.1 Clinical Appearance . . . 40

7.2.3 Pathogenesis . . . 40

7.2.4 Examples . . . 40

7.3 Category III: Granulomatous Venular Vasculitis . . . 41

7.3.1 Example . . . 42

7.4 Category IV: Neutrophilic Arterial Vasculitis . . . 42

7.4.3 Pathogenesis . . . 43

7.4.4 Examples . . . 43

7.5 Category V: Lymphocytic/Monocytic Arterial Vasculitis . . . 44

7.5.3 Examples . . . 44

7.5.4 Comment . . . 49

7.6 Category VI: Granulomatous Neutrophilic Arterial Vasculitis . . . 49

7.6.3 Examples . . . 50

7.6.4 Comment . . . 50

7.7 Category VII: Mixed Group . . . 50

7.7.1 Erythema Elevatum Diutinum . . . 51

7.7.1.1 Clinical Appearance . . . 53

7.7.1.2 Histopathologic Appearance . . . 53

7.7.1.3 Example . . . 53

7.7.1.4 Comment . . . 53

7.7.2 Granuloma Faciale . . . 55

7.7.2.1 Clinical Appearance . . . 55

7.7.2.2 Histopathologic Appearance . . . 55

7.7.2.3 Pathogenesis . . . 55

7.7.2.4 Example . . . 55

7.7.2.5 Comment . . . 55

7.7.3 Angiolymphoid Hyperplasia with Eosinophilia . . . 55

7.7.3.1 Example . . . 56

7.7.3.2 Comment . . . 57

7.7.4 Bacillary Epithelioid Angiomatosis . . . 57

7.7.4.1 Examples . . . 59

7.7.5 Comment . . . 59

7.8 Nomenclature . . . 61

7.9 Conclusion . . . 62

8 Skin Lesions due to Abnormalities in Blood Components 8.1 The Normal Coagulation/Fibrinolytic Balance in the Coagulation System . . . 65

8.2 Disseminated Intravascular Coagulation . . 65

8.2.1 Example . . . 66

8.3 Thrombotic-Thrombocytopenic Purpura/ Hemolytic-Uremic (TTP/HUS) Syndrome 66 8.3.1 Examples . . . 66

8.3.2 Comment . . . 67

8.4 Hypercoagulability of Minor Severity . . . 68

8.4.1 Examples . . . 68

8.4.2 Comment . . . 70

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XI

8.5 Skin Necrosis Induced by Treatment with

Warfarin . . . 70

8.6 Cryoglobulinemia . . . 70

8.6.1 Example . . . 71

8.7 Hereditary Hemoglobinopathies . . . 71

8.7.1 Example . . . 72

9 Arteriosclerosis in the Skin 9.1 Arteriolosclerosis . . . 75

9.1.1 Hyaline Arteriolosclerosis . . . 75

9.1.2 Hyperplastic Arteriolosclerosis . . . 75

9.2 Arteriosclerosis . . . 75

9.3 Examples . . . 75

9.4 Differential Diagnosis . . . 77

10 Thromboangiitis Obliterans 10.1 Clinical Appearance . . . 78

10.2 Histopathologic Appearance . . . 78

10.3 Example . . . 78

11 Angiotropic Lymphoma 11.1 Clinical and Histopathologic Appearances 80 11.2 Examples . . . 80

12 Infections Caused by Common Pyogenic Bacteria 12.1 Streptococcal Infections . . . 83

12.2 Staphylococcal Infections . . . 83

12.2.1 Non-Bullous Impetigo . . . 83

12.2.2 Bullous Impetigo . . . 83

12.3 Anonymous Bacterial Infections . . . 83

12.4 Examples . . . 83

12.4.1 Comment . . . 85

Reference . . . 85

13 Common Fungal Infections 13.1 Dermatophytosis (Ringworm, Tinea) . . . . 86

13.1.4 Examples . . . 91

13.1.5 Comment . . . 92

13.2 Malassezia furfur/Pityrosporum infections 93 13.2.1 Pityriasis (Tinea) Versicolor . . . 93

13.2.1.1 Clinical appearance . . . 93

13.2.1.2 Histopathologic Appearance . . . 93

13.2.2 Pityrosporum folliculitis . . . 93

13.2.2.1 Clinical Appearance . . . 93

13.2.2.2 Histopathologic Appearance and Pathogenesis . . . 93

13.2.3 Systemic Manifestation . . . 94

13.3 Candidiasis . . . 95

13.3.1.1 Skin Lesions . . . 95

13.3.1.2 Oral Lesions . . . 95

13.3.1.3 Mucocutaneous Infection . . . 95

13.3.1.4 Chronic Mucocutaneous Candidiasis . . . . 95

13.3.1.5 Systemic Manifestation . . . 95

13.3.3 Examples . . . 97

13.4 Aspergillosis . . . 97

13.4.3 Examples . . . 97

14 Demodicidosis 14.1 Characteristics of Demodex Mites . . . . 100

14.2 Pathogenesis and Clinical Appearance . . 100

14.3 Example . . . 101

References . . . . 101

15 Infections Caused by Mycobacterium Tuberculosis, M. Bovis, and Atypical Mycobacteria 15.1 Mycobacterium Tuberculosis and M. Bovis Infections in the Skin . . . . 102

15.1.1 Primary Inoculation (Primary Complex, Tuberculous Chancre) . . . 102

15.1.2 Tuberculosis Verrucosa Cutis . . . 102

15.1.3 Lupus Vulgaris . . . 103

15.1.3.2 Histopathologic Appearance . . . . 103

15.1.3.3 Examples . . . . 103

15.1.4 Other Types of Skin Lesions due to Spreading from Internal Organs . . . . 103

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Contents XII

15.2 Infections in the Skin Caused by Atypical

Mycobacteria . . . 105

15.2.1 Infection with M. Avium–Intracellulare Complex . . . 105

15.2.2 Infection with M. Malmoense . . . 105

15.2.3 Infection with M. Marinum . . . 105

15.2.4 Infection with M. Fortuitum–Chelonae Complex . . . 106

15.2.5 Examples . . . . 106

15.3 Comment . . . 107

References . . . . 108

16 Leprosy 16.1 Pathogenesis . . . . 110

16.2 Primary Neuritic Leprosy . . . 110

16.3 Cutaneous Leprosy . . . 110

16.3.1 Indeterminate Leprosy . . . 110

16.3.2 Tuberculoid Leprosy . . . 110

16.3.3 Borderline Leprosy . . . 111

16.3.4 Lepromatous Leprosy . . . . 111

16.3.5 Example . . . 111

16.3.5.1 Comment . . . 112

16.3.6 Reactions in Leprosy . . . 112

16.3.6.1 Type I . . . . 113

16.3.6.2 Type II (Erythema Nodosum Leprosorum) . . . 113

16.3.7 The Paucibacillary and Multibacillary Groups . . . 113

16.3.8 Classification According to Ridley . . . . 113

References . . . . 113

17 Syphilis 17.1 Primary Syphilis . . . 114

17.1.2 Histopathologic Appearance . . . . 114

17.1.3 Examples . . . . 115

17.2 Secondary Syphilis . . . 115

17.2.1.1 Macular Syphilid . . . 116

17.2.1.2 Papular Syphilid . . . . 116

17.2.3 Examples . . . . 116

17.3 Late Benign Syphilis (Tertiary Syphilis) in the Skin . . . . 119

17.3.3 Example . . . 119

17.4 Comment . . . 119

References . . . . 121

18 Lyme Borreliosis 18.1 Pathogenesis . . . . 122

18.2 Erythema Migrans . . . 122

18.2.3.1 Comment . . . 123

18.3 Borrelial Lymphocytoma . . . . 123

18.4 Acrodermatitis Chronica Atrophicans . . 126

18.4.2.1 Comment . . . 131

18.5 Methods to Prove the Presence of Spirochetes in Borrelial Skin Lesions . . . 132

References . . . . 132

19 Leishmaniasis 19.1 Pathogenesis . . . . 134

19.2 Cutaneous Leishmaniasis . . . 134

19.2.3 Example . . . 134

19.2.3.1 Comment . . . 135

References . . . . 135

20 Herpes Simplex, Herpes Zoster/Varicella, and Cytomegalovirus Infections 20.1 Herpes Simplex and Herpes Zoster/Varicella Virus Infections . . . . 136

20.1.1 Clinical Appearance and Pathogenesis . . 136

20.1.3 Examples . . . . 138

20.1.4 Comment . . . 142

20.1.5.1 Comment . . . 143

20.2 Cytomegalovirus Infection . . . . 143

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XIII

20.2.1 Pathogenesis and Clinical Appearance . . 143

20.2.3 Example . . . 144

References . . . . 146

21 Langerhans Cell Histiocytosis in Skin and Mucous Membranes 21.1 Clinical Appearance . . . 147

21.2 Histopathologic Appearance . . . . 147

21.3 Examples . . . . 149

21.4 Comment . . . 151

21.5 Pathogenesis . . . . 153

References . . . . 153

22 Dermatitis (Eczema) 22.1 Clinical Appearance . . . 155

22.1.1 Allergic Contact Dermatitis . . . 155

22.1.2 Irritant Contact Dermatitis . . . 155

22.1.3 Atopic Dermatitis . . . . 155

22.1.4 Nummular Dermatitis . . . 156

22.1.5 Seborrheic Dermatitis . . . 156

22.1.6 Stasis Dermatitis . . . 156

22.1.7 Allergic Contact Stomatitis . . . 156

22.2.1 Acute Dermatitis . . . 156

22.2.2. Subacute Dermatitis . . . 158

22.2.3 Chronic Dermatitis . . . . 158

22.3 Examples . . . . 158

22.5 Erythroderma (Exfoliative Dermatitis) . . 160

22.5.3 Example . . . 161

22.5.3.1 Comment . . . 162

References . . . . 162

23 Psoriasis 23.1 Clinical Appearance . . . 163

23.1.1 Psoriasis Vulgaris . . . 163

23.1.2 Psoriasis Guttata . . . 163

23.1.3 Psoriasis Pustulosa . . . 163

23.1.4 Psoriatic Erythroderma . . . 163

23.3 Pathogenesis . . . . 164

23.4 Examples . . . . 164

23.4.1 Comment . . . 167

References . . . . 169

24 Lichen Planus and Lichen Nitidus 24.1 Lichen Planus . . . 170

24.1.3 Pathogenesis . . . . 173

24.2 Lichen Nitidus . . . . 174

24.2.3 Pathogenesis . . . . 174

24.2.4 Example . . . 174

References . . . . 174

25 Autoimmune Vesicular, Bullous, and Pustular Dermatoses 25.1 The Pemphigus Group . . . 176

25.1.1 Pemphigus Vulgaris . . . . 177

25.1.1.3 Pemphigus Vegetans of Neumann Type . 178 25.1.1.4 Pemphigus Vegetans of Hallopeau Type . 178 25.1.2 Pemphigus Foliaceus . . . 178

25.1.2.3 Pemphigus Erythematosus . . . . 179

25.1.2.4 Pemphigus Herpetiformis . . . 179

25.1.3 Pathogenesis . . . . 179

25.1.4 Examples . . . . 181

25.1.5.1 Familial Benign Pemphigus (Haily-Haily Disease) . . . 183

25.1.5.2 Keratosis Follicularis (Darier Disease) . . 185

25.1.5.3 Transient Acantholytic Dermatosis (Grover Disease) . . . 185

25.1.5.4 Examples . . . . 187

25.2 Intraepidermal IgA Pustulosis (IgA Pemphigus) . . . 189

25.2.3 Pathogenesis . . . . 190

25.2.4 Example . . . 190

25.2.6 Comment . . . 190

25.3 Paraneoplastic Pemphigus . . . 190

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Contents XIV

25.3.3 Pathogenesis . . . . 191

25.3.4 Examples . . . . 192

25.3.5 Comment . . . 192

25.4 Autoimmune Subepidermal Vesicular and Bullous Dermatoses . . . . 194

25.4.1 Bullous Pemphigoid . . . 194

25.4.1.3 Pathogenesis . . . . 195

25.4.1.4 Differential Diagnosis . . . 195

25.4.2 Dermatitis Herpetiformis . . . 195

25.4.2.3 Pathogenesis . . . . 195

25.4.3 Linear IgA Dermatosis . . . 195

25.4.4 Cicatricial Pemphigoid . . . . 197

25.4.5 Acquired Porphyria Cutanea Tarda (Sporadic or Type I) . . . 197

References . . . . 197

26 Recurrent Vesicular Eruptions 26.1 Erythema Multiforme . . . 199

26.1.3 Pathogenesis . . . . 201

26.1.4 Examples . . . . 201

26.1.5 Comment . . . 201

26.2 Eosinophilic Cellulitis . . . 202

26.2.3 Pathogenesis . . . . 202

26.2.4 Example . . . 204

26.3 Pityriasis Lichenoides et Varioliformis Acuta . . . . 204

26.3.3 Pathogenesis . . . . 205

26.3.4 Examples . . . . 205

26.3.5 Comment . . . 207

References . . . . 208

27 Profiles of the Epidermal/ Dermal Area in some Vesicular/ Bullous Dermatoses 27.1 Vesicular/Bullous Dermatitis (Eczema) . 210 27.2 Necrolytic Migratory Erythema . . . . 210

27.2.1 Example . . . 212

27.3 Vesicular/Bullous Eruption in Systemic Lupus Erythematosus and Dermatomyositis . . 212

27.3.1 Examples . . . . 212

27.4 Lichen Sclerosus et Atrophicus . . . 212

27.4.1 Example . . . 213

27.5 Bullous Pemphigoid . . . 213

27.5.1 Example . . . 213

27.6 Comment . . . 213

References . . . . 213

28 Skin Lesions Due to Drugs 28.1 Acute Allergic Urticaria/Angioedema . . 215

28.1.3 Pathogenesis . . . . 216

28.1.4 Examples . . . . 216

28.2 Maculopapular Eruptions . . . 216

28.2.3 Pathogenesis . . . . 217

28.3 Fixed Drug Eruptions . . . 217

28.3.3 Pathogenesis . . . . 217

28.3.4 Examples . . . . 217

28.4 Toxic Epidermal Necrolysis and Stevens- Johnson Syndrome . . . 218

28.4.3 Pathogenesis . . . . 220

28.4.4 Examples . . . . 220

28.4.4.1 Comment . . . 220

28.5 Acute Generalized Exanthematous Pustulosis . . . 221

28.5.3 Pathogenesis . . . . 222

28.6 Bullous Skin Lesions due to Photosensitivity Reactions . . . . 223

28.6.1 Example . . . 223

28.7 Interstitial Granulomatous Drug Reaction 224 28.7.1 Clinical Appearance . . . 224

28.7.3 Pathogenesis . . . . 224

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XV

28.8 Skin Lesions Provoked by Penicillamine . 224 28.8.1 Nonallergic Degenerative Lesions Induced by

Penicillamine . . . 224

28.8.1.3 Example . . . 225

28.8.1.4 Differential Diagnosis . . . 225

28.8.2 Allergic Skin Reactions Provoked by Penicillamine . . . 225

28.9 Bullous Skin Lesions in Acute Drug Intoxication and Coma . . . . 225

28.9.3 Example . . . 225

28.9.3.1 Comment . . . 228

28.9.4 Pathogenesis . . . . 228

References . . . . 229

29 Artifacts 29.1 Friction Blisters and Scratch Marks . . . . 231

29.1.3 Pathogenesis . . . . 231

29.1.4 Examples . . . . 231

29.2 Decubitus Ulcers . . . 234

29.3 Hematidrosis . . . 234

29.3.3 Example . . . 234

29.4 Burns . . . . 234

29.4.1 Accidental and Self-Inflicted Burns . . . . 234

29.4.2 Late Therapeutic Radiation Dermatitis . . 235

29.4.3 Phytophotodermatitis . . . 235

29.4.4 Examples . . . . 236

29.5 Morsicatio Mucosae Oris . . . 238

29.5.3 Examples . . . . 238

29.5.4 Comment . . . 238

29.6 Amalgam Tattoo . . . 240

29.6.3 Example . . . 241

29.7 Chemical Burns in the Oral Mucosa . . . 241

29.7.1 Examples . . . . 243

References . . . . 243

30 Glossary References . . . . 250

Subject Index . . . 251

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ACA Acrodermatitis chronica atrophicans AGEP Acute generalized

exanthematous pustulosis AIDS Acquired immunodeficiency

syndrome

ALHE Angiolymphoid hyperplasia with eosinophilia

B cells B lymphocytes

BEA Bacillary epithelioid angiomatosis

C Complement

CAMs Cell adhesion molecules c-ANCA Antineutrophilic

cytoplasmic antibodies

CD Common differentiation (antigen) CD3 Molecular complex in T cells CD4 Helper T cells

CD8 Suppressor T cells CMV Cytomegalovirus CSHRH Congenital self-healing

reticulohistiocytosis DIC Disseminated intravascular

coagulation

DNA Deoxyribonucleic acid EBV Epstein-Barr virus

ECP Eosinophilic cationic protein EDN Eosinophilic derived neurotoxin EED Erythema elevatum diutinum ELAM Endothelial leukocyte

adhesion molecule EM Erythema multiforme

EORTC European Organization for Research and Treatment of Cancer

ESR Erythrocyte sedimentation rate FBGC Foreign body giant cell GM-CSF Granulocyte-macrophage

colony-stimulating factor H&E Hematoxylin-eosin HCMV Human cytomegalovirus HIV Human immunodeficiency virus HL Hairy leukoplakia

HLA Human leukocyte antigen HPV Human papilloma virus HSV Herpes simplex virus

ICAM Intercellular adhesion molecule IFN Interferon

IgA Immunoglobulin A IgD Immunoglobulin D IgE Immunoglobulin E IgG Immunoglobulin G

IgM Immunoglobulin M

IL Interleukin

kDa kiloDalton

LCH Langerhans cell histiocytosis LFA Leukocyte function antigen LGC Langhans giant cell LPS Lipopolysaccharide

MAC Macrophage activation antigen MBP Major basic protein

MHC Major histocompatibility complex NK Natural killer (cells)

PAS Periodic-acid-Schiff

PLC Pityriasis lichenoides chronica PLEVA Pityriasis lichenoides et

varioliformis acuta PSR Polymerase chain reaction RNA Ribonucleic acid

S-100 Protein expressed on Langerhans cells

SJ Stevens-Johnson (syndrome) SLE Systemic lupus erythematosus T cells T lymphocytes

TCR T-cell receptor region TEN Toxic epidermal necrolysis TGF Transforming growth factor TNF Tumor necrosis factor t-PA Tissue plasminogen activator t-PAI Inhibitor of t-PA

TTP/HUS Thrombotic-thrombocytopenic purpura /hemolytic-

uremic syndrome

VCAM Vascular cell adhesion molecule VEGF Vascular endothelial growth factor

vG van Gieson

VLA Very late activation (integrins) vWF von Willebrand factor VZV Varicella/herpes zoster virus

Abbreviations

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XVIII

Magnification

Magnification [= the objective × the factor of the microscope × a factor of the magnification device (depending on the distance used)] is mentioned in legends only when considered of special interest (i.e., to make it possible to compare the size of different vessels as in Figs. 2.3 and 9.2 and to give an idea of the size of microorganisms and other small particles as in Figs. 19.1 and 29.7. Indications of size and staining only at the end of the legends include all micrographs in the figure.