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1Keratinocytic tumours 9 WHO and TNM classification 10 Introduction 11 Basal cell carcinoma 13 Superficial basal cell carcinoma 15 Nodular basal cell carcinoma 16 Micronodular basal cell carcinoma 16 Infiltrating basal cell carcinoma 17 Fibroepithelial basal cell carcinoma 17 Basal cell carcinoma with adnexal differentiation 18 Basosquamous carcinoma 18 Keratotic basal cell carcinoma 19 Other variants 19 Squamous cell carcinoma 20 Acantholytic squamous cell carcinoma 21 Spindle-cell squamous cell carcinoma 22 Verrucous squamous cell carcinoma 22 Pseudovascular squamous cell carcinoma 23 Adenosquamous carcinoma 24 Bowen disease 26 Bowenoid papulosis 28 Actinic keratosis 30 Arsenical keratosis 32 PUVA keratosis 33 Verrucas 34 Verruca vulgaris 36 Verruca plantaris 37 Verruca plana 38 Acanthomas 39 Epidermolytic acanthoma 39 Warty dyskeratoma 39 Acantholytic acanthoma 40 Lentigo simplex 40 Seborrhoeic keratosis 41 Melanoacanthoma 43 Clear cell acanthoma 43 Large cell acanthoma 44 Keratoacanthoma 44 Lichen planus-like keratosis 47 2 Melanocytic tumours 49 WHO classification 50 TNM classification 51 Malignant melanoma: Introduction 52 Superficial spreading melanoma 66 Nodular melanoma 68 Lentigo maligna 70 Acral-lentiginous melanoma 73 Desmoplastic melanoma and desmoplastic neurotropic melanoma 76 Melanoma arising from blue naevus 79 Melanoma arising in giant congenital naevi 83 Childhood melanoma 84 Naevoid melanoma 86 Persistent melanoma and local metastasis of melanoma 90 Congenital melanocytic naevus 93 Superficial type 93 Proliferative nodules in congenital melanocytic naevi 93 Blue naevi 95 Common blue naevus 95 Mongolian spot 96 Naevus of Ito and naevus of Ota 96 Cellular blue naevus 96 Deep penetrating naevus 98 Combined naevus 100 Melanotic macules 103 Simple lentigo – lentiginous melanocytic naevus 104 Dysplastic naevus 105 Site specific and Meyerson naevi 110 Acral naevus 110 Genital naevus 110 Meyerson naevus 111 Persistent (recurrent) melanocytic naevus 113 Spitz naevus 114 Pigmented spindle cell naevus (Reed) 117 Halo naevus 118 3 Appendageal tumours 121 WHO and TNM classification 122 Introduction 123 Malignant tumours with apocrine and eccrine differentiaton 125 Tubular carcinoma 125 Microcystic adnexal carcinoma 125 Malignant mixed tumour 127 Porocarcinoma 128 Spiradenocarcinoma 130 Hidradenocarcinoma 131 Mucinous carcinoma 131 Digital papillary carcinoma 133 Adenoid cystic carcinoma 134 Apocrine carcinoma 135 Paget disease and extramammary Paget disease 136 Benign tumours with apocrine and eccrine differentiation 139 Hidrocystoma 139 Syringoma 140 Poroma 141 Syringofibroadenoma 142 Hidradenoma 143 Spiradenoma 143 Cylindroma 145 Tubular and tubular papillary adenoma 145 Syringocystadenoma papilliferum 146 Hidradenoma papilliferum 147 Contents Mixed tumour (chondroid syringoma) 147 Malignant tumours with follicular differentiation 149 Pilomatrical carcinoma 149 Proliferating tricholemmal tumour 150 Benign tumours with follicular differentiation 152 Trichoblastoma 152 Pilomatricoma 153 Tricholemmoma 155 Trichofolliculoma 156 Pilar sheath acanthoma 157 Tumour of the follicular infundibulum 158 Fibrofolliculoma / trichodiscoma 158 Tumours with sebaceous differentiation 160 Sebaceous carcinoma 160 Sebaceous adenoma 161 Sebaceoma 162 Cystic sebaceous tumour 163 4 Haematolymphoid tumours 165 WHO / EORTC classification 166 TNM classification 167 Introduction 168 Mycosis fungoides (MF) 169 Pagetoid reticulosis 173 Syringotropic MF 173 Folliculotropic MF 173 Granulomatous MF 174 Sézary syndrome 175 Granulomatous slack skin 178 CD30 T-cell lymphoproliferative disorders 179 Lymphomatoid papulosis (Ly P) 179 Primary cutaneous anaplastic large-cell lymphoma 180 Subcutaneous panniculitis-like T-cell lymphoma 182 Primary cutaneous peripheral T-cell lymphoma, unspecified 184 Cutaneous γδ T-cell lymphoma 184 Primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma 185 Primary cutaneous small-medium CD4 T-cell lymphoma 186 Primary cutaneous PTL, unspecified 186 Cutaneous adult T-cell leukaemia / lymphoma 189 Extranodal NK/T-cell lymphoma, nasal-type 191 Hydroa vacciniforme-like cutaneous T-cell lymphoma 192 Cutaneous involvement in primary extracutaneous T-cell lymphoma 193 Systemic anaplastic large cell lymphoma (ALCL) 193 Angioimmunoblastic T-cell lymphoma (AITL) 193 Cutaneous marginal zone B-cell lymphoma 194 Cutaneous follicle centre lymphoma 196 Cutaneous diffuse large B-cell lymphoma 198 Diffuse large B-cell lymphoma, leg-type 198 Diffuse large B-cell lymphoma, other 198 T-cell / histiocyte-rich large B-cell lymphoma 199 Plasmablastic lymphoma 199 Secondary skin involvement by diffuse large B-cell lymphoma 199 Intravascular large B-cell lymphoma 200 Lymphomatoid granulomatosis 202 Cutaneous involvement in primary extracutaneous B-cell lymphoma 204 Mantle cell lymphoma 204 Burkitt lymphoma 205 Chronic lymphocytic leukaemia / small lymphocytic lymphoma 205 Hodgkin lymphoma 207 Blastic NK-cell lymphoma 208 Precursor T-lymphoblastic leukaemia / lymphoma and precursor B-lymphoblastic leukaemia / lymphoma 210 Cutaneous involvement by myeloid leukaemia 211 Lymphoid infiltrates of the skin mimicking lymphoma 212 Parapsoriasis 215 Small plaque parapsoriasis 215 Parapsoriasis – Large patch type, with or without poikiloderma 215 Langerhans cell histiocytosis 217 Indeterminate cell histiocytosis 220 Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman) 221 Juvenile xanthogranuloma 222 Reticulohistiocytosis 224 Mastocytosis 226 5 Soft tissue tumours 229 WHO and TNM classification 230 Introduction 231 Vascular tumours 233 Haemangioma of infancy 233 Cherry haemangioma 233 Sinusoidal haemangioma 234 Hobnail haemangioma 234 Glomeruloid haemangioma 235 Microvenular haemangioma 236 Angiolymphoid hyperplasia with eosinophilia 237 Spindle cell haemangioma 239 Tufted angioma 239 Bacillary angiomatosis 240 Reactive angioendotheliomatosis 241 Verrucous haemangioma 242 Pyogenic granuloma 243 Cavernous haemangioma 243 Angiokeratomas 244 Arteriovenous haemangioma 245 Cutaneous angiosarcoma 246 Lymphatic tumours 247 Lymphangioma circumscriptum 247 Progressive lymphangioma 248 Lymphangiomatosis 249 Smooth and skeletal muscle tumours 250 Smooth muscle hamartoma 250 Pilar leiomyoma 251 Cutaneous leiomyosarcoma 251 Rhabdomyomatous mesenchymal hamartoma 252 Fibrous, fibrohistiocytic and histiocytic tumours 254 Keloid scar 254 Hypertrophic scar 254 Dermatomyofibroma 255 Infantile myofibromatosis 256 Sclerotic fibroma 256 Digital mucous cyst 257 Digital fibrokeratoma 257 Pleomorphic fibroma 258 Giant cell fibroblastoma 258 Dermatofibrosarcoma protuberans 259 Dermatofibroma (fibrous histiocytoma) 261 6 Neural tumours 263 WHO and TNM classification 264 Palisaded, encapsulated neuroma and traumatic neuroma 265 Palisaded encapsulated neuroma 265 Traumatic neuroma 266 Primary malignant peripheral primitive neuroectodermal tumour (PNET) / Extraskeletal Ewing sarcoma (ES) 268 Nerve sheath myxoma / neurothekeoma 270 Merkel cell carcinoma 272 Granular cell tumour 274 7 Inherited tumour syndromes 277 Familial cutaneous melanoma 279 Xeroderma pigmentosum 282 Naevoid basal cell carcinoma (Gorlin) syndrome 285 Cowden syndrome 288 Carney complex 291 Contributors 295 Source of charts and photographs 300 References 301 Subject index 341 CHAPTER 1 Keratinocytic Tumours Keratinocytic tumours are derived from epidermal and adnexal keratinocytes and comprise a large spectrum of lesions rang-ing from benign proliferations (acanthomas) to malignant squa-mous cell carcinomas which occasionally show aggressive growth and even metastatic potential. Milburn PB, Brandsma JL, Goldsman CI, Teplitz ED, Heilman EI (1988).

IARC Library Cataloguing in Publication Data Pathology and genetics of skin tumours/ edited by Philip E. Enquiries should be addressed to the Communications Unit, International Agency for Research on Cancer, 69008 Lyon, France, which will provide the latest information on any changes made to the text and plans for new editions. The color of the skin of the palms and soles as a possible clue to the patho-genesis of acral-lentiginous melanoma. Cutaneous bacillary angiomatosis in a patient with chronic lym-phocytic leukemia.

Members of the Working Group are indicated in the List of Contributors on page 295. The authors alone are responsible for the views expressed in this publication. Milde P, Brunner M, Borchard F, Sudhoff T, Burk M, Zumdick M, Goerz G, Ruzicka T (1995).

Asiedua Asante Agnès Meneghel Marlen Grassinger Stephan Rappo Sibylle Söring Nobert Wey Thomas Odin Team Rush 69603 Villeurbanne, France IARCPress International Agency for Research on Cancer (IARC) 69008 Lyon, France This volume was produced in collaboration with the International Academy of Pathology (IAP) European Organization for Research and Treatment of Cancer (EORTC) and the Department of Pathology, University Hospital, Zurich, Switzerland The WHO Classification of Skin Tumours presented in this book reflects the views of a Working Group that convened for an Editorial and Consensus Conference in Lyon, France, September 22-25, 2003. (World Health Organization classification of tumours ; 10) 1. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.

The designations used and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The role of human papillomavirus in the development of pyo-genic granulomas.

Other genes involved in the multistep formation of skin cancer include PTCH and the RAS oncogene.

Keratinocytic tumours are very frequent and, despite their low mortality rate, pose a significant public health problem, The main etiologic factor is solar radiation which causes DNA alterations, including pyrim-idine dimers which during DNA replication may lead to CC: TT mutations in the TP53 tumour suppressor gene. Disseminated warts and evolving squa-mous cell carcinoma in a patient with acquired immunodeficiency syndrome.

Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. 33 4 72 73 85 15 Fax 33 4 72 73 83 02 [email protected] Marketing and Dissemination 1211 Geneva (Switzerland) Tel. Le Boit Günter Burg David Weedon Alain Sarasin IARCPress Lyon, 2006 WHO OMS World Health Organization Classification of Tumours Series Editors Paul Kleihues, M. Ackerman and others have proposed that solar keratoses should be regarded as squamous cell carcinoma de novo and not as pre-malignancies or pre-can-cers that evolve into squamous cell car-cinoma . Malignant and potentially malignant fibroblastic and myofibroblastic tumors. Miettinen M, Holthofer H, Lehto VP, Miettinen A, Virtanen I (1983).

Pathology and Genetics of Tumours of the Nervous System. Actinic keratoses are erythematous, scaling lesions occurring on heavily sun-light exposed areas that increase in prevalence with increasing age in fair skinned people. Michal M, Kerekes Z, Kinkor Z, Ondrias F, Pizinger K (1995).

(Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. These include actinic keratosis and Bowen disease (intraepidermal car-cinoma/squamous cell carcinoma in-situ). Spiradenocylindromas of the skin: tumors with morphological fea-tures of spiradenoma and cylindroma in the same lesion: report of 12 cases. Acquired tufted 325 References angioma in association with a complex cutaneous vascular malformation.

Thus the majority of lesions do not progress to squamous cell carcino-ma . Cellular blue nevus of the scalp infil-trating the underlying bone: case report and review.

Bowen disease demonstrates ker-atinocyte atypia involving the full thick-ness of the epidermis.

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