Internal Malignancy And The Skin: Paraneoplastic And Cancer Treatment-related Cutaneous Disorders, An Issue Of Dermatologic Clinics (the Clinics: Dermatology)

A wide variety of skin signs have been associated with internal malignancy. Cutaneous manifestations may develop before an internal neoplasm is recognized, and the skin findings can aid in diagnosis. In some cases the skin is infiltrated by malignant cells that represent metastatic or local spread from an internal malignancy. In other cases, the skin lesions are related to the underlying presence of malignancy, but they do not contain malignant cells. This issue of Dermatologic Clinics contains information on topics such as malignancy and cancer treatment-related hair and nail changes, tumor invasion of the skin, radiation therapy toxicity to the skin, and epidermal manifestations of internal malignancy. Cover 1 Preface 2 Cutaneous Manifestations of Internal Malignancies: An Overview 3 Acanthosis nigricans and tripe palms 3 Acquired ichthyosis 5 Pityriasis rotunda 5 Acrokeratosis paraneoplastica 5 Erythema gyratum repens 6 The sign of Leser-TrElat 6 Erythroderma 7 Hypertrichosis lanuginosa acquisita 7 Sweet’s syndrome 7 Dermatomyositis 8 Paraneoplastic pemphigus 9 Necrobiotic xanthogranuloma 9 Multicentric reticulohistiocytosis 10 Amyloidosis 10 Scleromyxedema 10 Scleredema 11 Vasculitis and cryoglobulinemia 11 Hypertrophic osteoarthropathy 11 Necrolytic migratory erythema 12 Carcinoid syndrome 12 Cushing’s syndrome 12 Pruritus 13 Summary 13 References 14 Epidermal Manifestations of Internal Malignancy 18 Malignant acanthosis nigricans, the sign of Leser-TrElat, and tripe palms 18 Malignant acanthosis nigricans 18 History and epidemiology 18 Clinical manifestations 18 Histopathology 19 Associated malignancies 20 Tripe palms 20 History and epidemiology 20 Clinical manifestations 20 Histopathology 21 Associated malignancies 21 The sign of Leser-TrElat 21 History and epidemiology 21 Clinical manifestations 21 Histopathology 22 Associated malignancies 22 Pathogenesis 22 Prognosis 22 Treatment 22 Palmoplantar keratoderma 23 Clinical features and associated malignancies 23 Histopathology 24 Pathogenesis 24 Treatment 24 Bazex syndrome 24 History 24 Epidemiology 25 Clinical manifestations 25 Histopathology 26 Associated malignancies 26 Pathogenesis 26 Treatment 26 Acquired ichthyosis 26 History and epidemiology 26 Clinical manifestations 27 Histopathology 27 Associated malignancies 27 Pathogenesis 27 Treatment 27 References 27 Dermal and Pannicular Manifestations of Internal Malignancy 31 Pathophysiologic considerations 31 Paraneoplastic calcium deposition of the dermis and subcutis 31 Paraneoplastic neutrophilic infiltration of the dermis and subcutis 32 Acute febrile neutrophilic dermatosis (Sweet syndrome) 32 Pyoderma gangrenosum 34 Erythema elevatum diutinum 34 Paraneoplastic fibrocyte disorders of the dermis and subcutis 35 Scleromyxedema 35 Scleredema 36 Paraneoplastic histiocytic infiltrates of the dermis and subcutis 37 Multicentric reticulohistiocytosis (lipoid dermatoarthritis) 37 Necrobiotic xanthogranuloma 37 Normolipemic plane xanthoma 38 Xanthogranuloma 38 Dermal and pannicular paraneoplastic proliferations 38 POEMS syndrome 38 Paraneoplastic urticaria 39 Schnitzler syndrome 39 Paraneoplastic vasculitis and vaso-occlusive disorders 39 Cryoglobulinemias 39 Miscellaneous paraneoplastic disorders of the dermis and subcutis 40 Erythema gyratum repens 40 Pancreatic panniculitis 41 References 41 Cutaneous Vascular Disorders Associated with Internal Malignancy 44 Disorders related to vascular dilatation 44 Flushing 44 Carcinoid syndrome 44 Mastocytosis 46 Pheochromocytoma 46 Medullary carcinoma of the thyroid 46 Renal cell carcinoma 47 Pancreatic tumors 47 POEMS syndrome 47 Harlequin syndrome 47 Telangiectasia 47 Primary telangiectasia 47 Secondary telangiectasia 48 Diseases related to vascular inflammation: vasculitis 48 Diseases related to vascular occlusion 49 Thrombophlebitis and thromboembolism 49 Purpura and ecchymoses 51 Cutaneous ischemia 51 References 52 Malignancy and Cancer Treatment-Related Hair and Nail Changes 57 Normal hair physiology 57 Paraneoplastic hair changes 58 Acquired hypertrichosis lanuginosa 58 Alopecia areata 58 Cicatricial alopecia 59 Alopecia neoplastica 59 Cancer treatment-related hair disorders 59 Anagen effluvium 59 Telogen effluvium 60 Chemotherapy-induced hair color changes 60 Chemotherapy-induced hair texture changes 60 Follicular spicules 60 Radiation therapy-induced hair changes 60 Paraneoplastic and cancer treatment-related nail changes 60 Normal nail physiology 60 Paraneoplastic nail changes 61 Acquired digital clubbing 61 Yellow nail syndrome 62 Nonspecific nail changes 62 Nail plate abnormalities 63 Nail bed changes 64 Proximal nail fold changes 64 Summary 64 References 64 Genodermatoses with Cutaneous Tumors and Internal Malignancies 67 Genodermatoses with cutaneous tumors and internal malignancies 68 Group I 68 Nevoid basal cell carcinoma syndrome 68 Cutaneous features 68 Extracutaneous tumors and features 68 Molecular genetics (PTCH gene on chromosome 9q22.3) 69 Familial melanoma 69 Cutaneous features 69 Extracutaneous tumors and features 70 Molecular genetics (CDKN2A gene on chromosomes 9p21) 70 Xeroderma pigmentosum 70 Cutaneous features 70 Extracutaneous tumors and features 71 Molecular genetics (8 XP genes on various chromosomes) 71 Group II 71 Cowden syndrome 71 Cutaneous features 71 Extracutaneous tumors and features 71 Molecular genetics (PTEN/MMAC1 gene on chromosome 10q23) 72 Muir-Torre syndrome 73 Cutaneous features 73 Extracutaneous tumors and features 73 Molecular genetics (MSH2 gene on chromosome 2p22) 73 Gardner syndrome 73 Cutaneous features 74 Extracutaneous tumors and features 74 Molecular genetics (APC gene on chromosome 5q21-q22) 74 Tuberous sclerosis 74 Cutaneous features 75 Extracutaneous tumors and features 76 Molecular genetics (TSC1 and TSC2 genes on chromosomes 9q34 and 16p13.3 respectively) 76 Neurofibromatosis type 1 76 Cutaneous features 76 Extracutaneous tumors and features 77 Molecular genetics (NF1 gene on chromosome 17q11.2) 77 Neurofibromatosis type 2 78 Cutaneous features 78 Extracutaneous tumors and features 78 Molecular genetics (NF2 gene on chromosome 22q12.2) 78 Birt-Hogg-Dube syndrome 79 Cutaneous features 79 Extracutaneous tumors and features 79 Molecular genetics (BHD on chromosome 17p11.2) 79 Hereditary leiomyomatosis and renal cell cancer 79 Cutaneous features 79 Extracutaneous tumors and features 79 Molecular genetics (FH gene at chromosome 1q42.3-43) 79 Summary 80 References 80 Tumor Invasion of the Skin 86 Metastasis 86 Mechanisms of metastasis 86 Anatomic distribution of metastasis 87 Solid organ malignancies that metastasize to the skin 87 Breast cancer 88 En cuirasse metastatic carcinoma 88 Inflammatory metastatic carcinoma 90 Telangiectatic metastatic breast carcinoma 90 Nodular metastatic carcinoma 90 Alopecia neoplastica 90 Breast carcinoma of the inframammary crease 90 Metastatic mammary carcinoma of the eyelid withnbsphistiocytoid histology 91 Paget’s disease 91 Melanoma 91 Lung cancer 91 Colorectal carcinoma 91 Squamous cell carcinoma of the oral cavity 92 Renal cell carcinoma 92 Carcinoma of the ovary 92 Esophageal cancer 92 Gastric adenocarcinoma 92 Carcinoma of the genitourinary systems 92 Hematologic malignancies that metastasize to the skin 93 Leukemia cutis 93 Lymphoma cutis 93 Malignancies that directly extend to the skin 94 Paget’s disease of the breast 94 Epidemiology 94 Clinical presentation 94 Pathogenesis 95 Diagnosis 95 Histology 95 Treatment 95 Extramammary Paget’s disease 96 Epidemiology 96 Clinical presentation 96 Pathogenesis 96 Diagnosis 96 Histology 96 Treatment 97 Summary 97 References 97 Cutaneous Reactions to Chemotherapy: Commonly Seen, Less Described, Little Understood 100 Alopecia 100 Acral erythema 102 Neutrophilic eccrine hidradenitis 103 Epidermal dysmaturation 103 Eccrine squamous syringometaplasia 104 Hyperpigmentation 104 Chemotherapy and radiation recall and sensitivity reactions 106 Phototoxic dermatitis 107 Inflammation of actinic keratoses 107 Extravasation 107 Irritants 107 Vesicants 108 Hypersensitivity 109 Hydroxyurea dermopathy 111 Targeted therapy 111 Nail dystrophy 112 Summary 112 References 113 Cutaneous Reactions Related to Systemic Immunomodulators and Targeted Therapeutics 117 Epidermal growth factor receptor pathway inhibitors 117 Introduction 117 Epidermal growth factor receptor in skin 119 The ‘‘novel’’ epidermal growth factor receptor inhibitor-induced rash 119 Correlation between rash and response/survival 122 Dose-to-rash strategy 122 Histologic assessment 123 Atypical epidermal growth factor receptor inhibitor-associated rashes 123 Issues with assessing rash 123 Management of rash-active 131 Management of rash-preventive 136 When to refer to a dermatologist? 136 Other epidermal growth factor receptor inhibitor cutaneous adverse events 136 Epidermal growth factor receptor inhibitor rash-related issues: future directions 138 Non-epidermal growth factor receptor multikinase inhibitors 138 Sunitinib 139 Sorafenib (Bay 439006) 139 Novel multikinase inhibitor toxicity: subungual splinter hemorrhages 142 Combinations of multikinase inhibitors 143 BCR-ABL tyrosine kinase inhibitors 143 Imatinib 143 Dasatinib 144 Proteosome inhibitors 144 Immunomodulatory drugs 145 Immunosuppressant macrolides: m-TOR inhibitors 148 Do vascular endothelial growth factor inhibitors cause the novel follicular rash? Bevacizumab case report 148 Summary 148 References 148 Radiation Therapy Toxicity to the Skin 156 Histology of the skin 156 History and evolution of radiation therapy in the care of the cancer patient 157 Radiation biology 157 Response of the skin to radiation therapy 159 Process improvements in radiation therapy support improved patient outcome 160 Drug-radiography interactions 162 Secondary cutaneous malignancies as a consequence of cancer management 163 Skin care for the radiation therapy patient 164 Summary 165 References 165 Cover......Page 1 Preface......Page 2 Acanthosis nigricans and tripe palms......Page 3 Acrokeratosis paraneoplastica......Page 5 The sign of Leser-TrElat......Page 6 Sweet’s syndrome......Page 7 Dermatomyositis......Page 8 Necrobiotic xanthogranuloma......Page 9 Scleromyxedema......Page 10 Hypertrophic osteoarthropathy......Page 11 Cushing’s syndrome......Page 12 Summary......Page 13 References......Page 14 Clinical manifestations......Page 18 Histopathology......Page 19 Clinical manifestations......Page 20 Clinical manifestations......Page 21 Treatment......Page 22 Clinical features and associated malignancies......Page 23 History......Page 24 Clinical manifestations......Page 25 History and epidemiology......Page 26 References......Page 27 Paraneoplastic calcium deposition of the dermis and subcutis......Page 31 Acute febrile neutrophilic dermatosis (Sweet syndrome)......Page 32 Erythema elevatum diutinum......Page 34 Scleromyxedema......Page 35 Scleredema......Page 36 Necrobiotic xanthogranuloma......Page 37 POEMS syndrome......Page 38 Cryoglobulinemias......Page 39 Erythema gyratum repens......Page 40 References......Page 41 Carcinoid syndrome......Page 44 Medullary carcinoma of the thyroid......Page 46 Primary telangiectasia......Page 47 Diseases related to vascular inflammation: vasculitis......Page 48 Thrombophlebitis and thromboembolism......Page 49 Cutaneous ischemia......Page 51 References......Page 52 Normal hair physiology......Page 57 Alopecia areata......Page 58 Anagen effluvium......Page 59 Normal nail physiology......Page 60 Acquired digital clubbing......Page 61 Nonspecific nail changes......Page 62 Nail plate abnormalities......Page 63 References......Page 64 Genodermatoses with Cutaneous Tumors and Internal Malignancies......Page 67 Extracutaneous tumors and features......Page 68 Cutaneous features......Page 69 Cutaneous features......Page 70 Extracutaneous tumors and features......Page 71 Molecular genetics (PTEN/MMAC1 gene on chromosome 10q23)......Page 72 Gardner syndrome......Page 73 Tuberous sclerosis......Page 74 Cutaneous features......Page 75 Cutaneous features......Page 76 Molecular genetics (NF1 gene on chromosome 17q11.2)......Page 77 Molecular genetics (NF2 gene on chromosome 22q12.2)......Page 78 Molecular genetics (FH gene at chromosome 1q42.3-43)......Page 79 References......Page 80 Mechanisms of metastasis......Page 86 Solid organ malignancies that metastasize to the skin......Page 87 En cuirasse metastatic carcinoma......Page 88 Breast carcinoma of the inframammary crease......Page 90 Colorectal carcinoma......Page 91 Carcinoma of the genitourinary systems......Page 92 Lymphoma cutis......Page 93 Clinical presentation......Page 94 Treatment......Page 95 Histology......Page 96 References......Page 97 Alopecia......Page 100 Acral erythema......Page 102 Epidermal dysmaturation......Page 103 Hyperpigmentation......Page 104 Chemotherapy and radiation recall and sensitivity reactions......Page 106 Irritants......Page 107 Vesicants......Page 108 Hypersensitivity......Page 109 Targeted therapy......Page 111 Summary......Page 112 References......Page 113 Introduction......Page 117 The ‘‘novel’’ epidermal growth factor receptor inhibitor-induced rash......Page 119 Dose-to-rash strategy......Page 122 Issues with assessing rash......Page 123 Management of rash-active......Page 131 Other epidermal growth factor receptor inhibitor cutaneous adverse events......Page 136 Non-epidermal growth factor receptor multikinase inhibitors......Page 138 Sorafenib (Bay 439006)......Page 139 Novel multikinase inhibitor toxicity: subungual splinter hemorrhages......Page 142 Imatinib......Page 143 Proteosome inhibitors......Page 144 Immunomodulatory drugs......Page 145 References......Page 148 Histology of the skin......Page 156 Radiation biology......Page 157 Response of the skin to radiation therapy......Page 159 Process improvements in radiation therapy support improved patient outcome......Page 160 Drug-radiography interactions......Page 162 Secondary cutaneous malignancies as a consequence of cancer management......Page 163 Skin care for the radiation therapy patient......Page 164 References......Page 165