Dermato-Oncology Study Guide. Essential Text and Review

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Acknowledgments Contents Introduction 1: Cutaneous Metastases Introduction History Pathophysiology Clinical Themes Epidemiology Age Sex Clinical Morphology Primary/Secondary Morphology Color Distribution [10] Associated Symptoms/Signs Noninvasive Testing Work-Up/Investigation Pathologic Examination Technique Histomorphology Ancillary Testing Immunohistochemistry Molecular Testing [49, 51] Laboratory Testing [52–54] Imaging/Procedures [54] Management and Prognosis CMs of Known Primary Tumors Metastasis of Unknown Primary [60] Specific Cutaneous Metastases Melanoma Epidemiology Location [65] Clinical Patterns Histopathology Breast Cancer Epidemiology Location Clinical patterns Lung Cancer Epidemiology [31] Location [81, 83] Clinical Patterns Histopathology Renal Cancer Epidemiology [31] Location Clinical Patterns Histopathology Gastric Cancer Epidemiology [27] Location Clinical Patterns Histopathology Colorectal Cancer Epidemiology Location Clinical Patterns [32, 38, 93] Histopathology SCC of the Upper Aerodigestive Tract Epidemiology Location Clinical Patterns Histopathology Urinary Bladder Cancer (Lower GU) Epidemiology Location Clinical Patterns [8, 32] Histopathology Ovarian Cancer Epidemiology Location Clinical Patterns [32, 99] Histopathology Prostate Cancer Epidemiology Location Clinical Patterns Histopathology Liver Cancer Epidemiology Location [102] Clinical Patterns [32, 102] Histopathology Thyroid Cancer Epidemiology Location [32, 105, 106] Clinical Patterns Histopathology Metastasis of Unknown Primary Site Epidemiology Location Clinical Patterns Histopathology Conclusions References 2: Paraneoplastic Dermatoses and Related Conditions Introduction History [4, 5, 8] Pathophysiology Clinical Themes Epidemiology Age Gender Strength of Association Temporal Association Diagnostic Considerations/Workup Specific Paraneoplastic Dermatoses Obligate (Strong Association) PNDs Tripe Palms (aka Acquired Pachydermatoglyphia and Acanthosis Palmaris) Epidemiology Clinical Features [14, 19] Histopathology Management and Prognosis Bazex Syndrome (aka Acrokeratosis Paraneoplastica) Epidemiology Clinical Features [8, 24] Histopathology [6, 8, 24] Management and Prognosis [24] Paraneoplastic Pemphigus Epidemiology Clinical Features [27] Histopathology [26] Management and Prognosis [24, 28] Erythema Gyratum Repens Epidemiology [24, 33] Clinical Features [24, 33] Histopathology [33] Management and Prognosis Necrolytic Migratory Erythema Epidemiology [7] Clinical Features [4, 24, 35] Histopathology [4, 35] Management and Prognosis [4, 35, 36, 38] Scleromyxedema Epidemiology [7, 13] Clinical Features [13, 14, 39] Histopathology [14, 39–41] Management and Prognosis [13, 14, 39] Hypertrichosis Lanuginosa Acquisita Epidemiology [14, 42, 43] Clinical Features [14, 24, 43] Histopathology Management and Prognosis [14, 43] Necrobiotic Xanthogranuloma Epidemiology Clinical Features [44] Histopathology Management and Prognosis [44–47] Facultative (Moderate, Weak, and Poorly Established Association) PNDs Paraneoplastic Syndromes Caused by Skin Tumors Conclusions References 3: Genodermatoses with Malignant Potential References 4: Systemic Implications of Melanoma Epidemiology Incidence and Mortality Risk Factors Prevention Primary Prevention on an Individual Level Public Health Initiatives Work-up and Evaluation Clinical Skin Examination Biopsy Considerations Adjunctive Diagnostic Tests Management Staging (Tables 4.2 and 4.3) Staging Work-Up Role of Imaging Studies Role of Sentinel Lymph Node Biopsy and Completion Lymph Node Dissection Adjunctive Molecular Testing for Prognosis Treatment Surgical Treatment Medical Therapies for Systemic Melanoma Immune Checkpoint Inhibitors (Immunotherapy) Targeted Antitumor Therapy Conclusions References 5: Surgical Approach to Cutaneous Malignancy with Systemic Implications Surgical Issues of Systemic Malignancy Introduction Diagnostic and Procedural Considerations in Dermatooncology Introduction [1–3] Shave Biopsy [1–3, 9] Saucerization Biopsy [1–3, 7, 9] Punch Biopsy [1–3, 9] Incisional Biopsy [1–3] Excisional Biopsy [1–3] Wide Local Excision [1–3] Mohs Micrographic Surgery (MMS) [1–3] Fine Needle Aspiration (FNA) [4–6] Core Needle Biopsy (CNB) [4–6] Surgical Management of Cutaneous Malignancies with High Rate of Systemic Spread Melanoma [10–24] High Risk Non-melanoma Skin Cancer [25–34] Cutaneous Squamous Cell Carcinoma (cSCC) Basal Cell Carcinoma Merkel Cell Carcinoma (MCC) [35–39] Dermatofibrosarcoma Protuberans [40–43] Vascular Neoplasms (Angiosarcoma) [44, 45] Adnexal Malignant Tumors Malignant Sebaceous Tumors Sebaceous Carcinoma [47–49] Malignant Apocrine Tumors Extramammary Paget’s Disease (EMPD) [50, 51] Malignant Eccrine Tumors Aggressive Digital Papillary Adenocarcinoma (ADPA) [52–55] Eccrine Porocarcinoma (EPC) [56–58] General Surgical Considerations in Patients with Systemic Malignancy Immunosuppression [59–65, 68–70] Autoimmune Cytopenias and CLL [66, 67] References 6: Malignancy Risks of Dermatologic Therapies Introduction Definitions Interpreting Data on Rare Adverse Events Issues with Interpreting Malignancy Risk Data in Dermatology Patients Importance of Long-Term Follow-Up and Continual Monitoring Malignancy Risk of Traditional Systemic Agents (Table 6.1) Immunosuppressant Medications Retinoids Small Molecule Inhibitors Antibiotic Malignancy Risk of Phototherapy Malignancy Risk of Biologics (Table 6.2) TNF Inhibitors IL-12/23 Inhibitor IL-17 Inhibitors IL-23 Inhibitors IL-4/13 Inhibitor CD20 Inhibitor Anti-IgE IVIG Malignancy Risk Analysis in Immunosuppressed Patients Transplant Patients HIV Patients References 7: Infection, Skin, and Systemic Malignancy Introduction Cutaneous Infections in the Setting of Malignancies Risk Factors for SSTIs in Patients with Systemic Malignancy [1] Specific Risk Populations Bacterial Infections Cellulitis/Erysipelas Bacterial Folliculitis Furuncle, Carbuncle, Abscess Ecthyma Gangrenosum Atypical Mycobacterial Infections Viral Infections Herpes Simplex Virus 1 and 2 (HSV1/HSV2) Varicella Zoster Virus (VZV) Verruca Vulgaris Cytomegalovirus (CMV) Oral Hairy Leukoplakia Trichodysplasia Spinulosa (Viral Associated Trichodyplasia) Fungal Infections Dermatophyte Infections Candidiasis Opportunistic Fungal Infections Cryptococcosis (Cryptococcus neoformans) Fungal Sinusitis with Cutaneous Extension Cutaneous Disseminated Fungal Disease Cutaneous Infections Associated with Specific Cancer Therapeutics Taxanes (Docetaxel, Paclitaxel), Antimetabolites (Capecitabine), Topoisomerase II Inhibitors (Etoposide, Teniposide, Amsacrine) Epidermal Growth Factor Receptor (EGFR) Inhibitors MEK Inhibitors, mTOR Inhibitors Infections Associated with Cutaneous Malignancies Squamous Cell Carcinoma (SCC) Epstein-Barr Virus (EBV) Human Herpes Virus 8 (HHV8) Polyomavirus References 8: Dermatologic Adverse Effects of Anticancer Therapy I: General Principles Introduction General Principles of Management General Principles for Steroid Therapy Introduction Topical Steroids Systemic Corticosteroids Management of Alopecia Management of Xerosis Introduction Emollients Additional Strategies Fissure Care Management of Pruritus Management of Edema Management of Mucositis Management of Photosensitivity Introduction Management Management of Nail Changes Introduction Natural Course of Nail Changes Management Management of Extravasation Reactions [7] Introduction References 9: Dermatologic Adverse Effects of Anticancer Therapy II: Cytotoxic Agents Cytotoxic Therapies Platinum Agents (Table 9.1) Dermatologic Adverse Effects Clinical Summary Platinum Agent Infusion Reactions Platinum Agent Extravasation Reactions Alkylating Agents Agents Mechlorethamine (Systemic) Indications Dermatologic Adverse Effects Clinical Summary Mechlorethamine Extravasation Reactions Dermatologic Adverse Effects Clinical Summary Cyclophosphamide- and Ifosfamide-induced Alopecia Cyclophosphamide and Ifosfamide Induced Pigmentary Changes Clinical Summary Chlorambucil Indications Dermatologic Adverse Effects Clinical Summary Bendamustine Indications Dermatologic Adverse Effects Clinical Summary Thiotepa Indications Dermatologic Adverse Effects Clinical Summary Thiotepa-induced Erythema, Desquamation, and Hyperpigmentation [28] Mitomycin C Indications Dermatologic Adverse Effects Clinical Summary Mitomycin C Extravasation Reactions Mitomycin C-induced Diffuse Erythema and Exfoliative Dermatitis [36, 37] Topical Mitomycin C-induced Allergic Reaction [35] Busulfan Indications Dermatologic Adverse Effects Clinical Summary Hyperpigmentation from Busulfan Therapy (“Busulfan Tan”) [41–43] Carmustine (Systemic) Indications Dermatologic Adverse Effects Clinical Summary Streptozocin Indications Dermatologic Adverse Effects Clinical Summary Lomustine Indications Dermatologic Adverse Effects Clinical Summary Procarbazine Indications Dermatologic Adverse Effects Clinical Summary Procarbazine-induced Hypersensitivity Reaction Dacarbazine Indications Dermatologic Adverse Effects Clinical Summary Dacarbazine Extravasation Reactions Dacarbazine-induced Hypersensitivity Reactions Dacarbazine-induced Phototoxic Reactions Temozolomide Indications Dermatologic Adverse Effects Clinical Summary Hydroxyurea Indications Dermatologic Adverse Effects Clinical Summary Hydroxyurea-induced Hyperpigmentation Hydroxyurea-induced Cutaneous Ulcerations Hydroxyurea-induced Dermatomyositis-Like Skin Changes Hydroxyurea-induced Non-melanoma Skin Cancers Antimetabolites Agents Methotrexate Indications Dermatologic Adverse Effects Clinical Summary Hand-Foot Syndrome (Palmar-plantar Erythrodysesthesia) Mucocutaneous Ulceration [66, 67] Radiation Recall Dermatitis Pemetrexed Indications Dermatologic Adverse Effects Clinical Summary Maculopapular Rash Radiation Recall Dermatitis [68, 69] Edema [70] Capecitabine Indications Dermatologic Adverse Effects Clinical Summary Hand-Foot Syndrome (HFS) Fingerprint Loss Cytarabine Indications Dermatologic Adverse Effects Clinical Summary Neutrophilic Eccrine Hidradenitis Gemcitabine Indications Dermatologic Adverse Effects Clinical Summary Drug-induced Linear IgA Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Mercaptopurine Indications Dermatologic Adverse Effects Clinical Summary Thioguanine Indications Dermatologic Adverse Effects Clinical Summary Fludarabine Indications Dermatologic Adverse Effects Clinical Summary Transfusion-Associated Graft Versus Host Disease [71] Cladribine Indications Dermatologic Adverse Effects Clinical Summary Clofarabine Indications Dermatologic Adverse Effects Clinical Summary Nelarabine Indications Dermatologic Adverse Effects Clinical Summary Trifluridine/Tipiracil Indications Dermatologic Adverse Effects Clinical Summary Topoisomerase-Interacting Agents Agents Irinotecan Indications Dermatologic Adverse Effects Clinical Summary Topotecan Indications Dermatologic Adverse Effects Clinical Summary Dermatologic Adverse Effects Clinical Summary Extravasation Reactions Actinomycin D (Dactinomycin) Indications Dermatologic Adverse Effects Clinical Summary Dermatologic Adverse Effects Clinical Summary Mitoxantrone Indications Dermatologic Adverse Effects Clinical Summary Antimicrotubule Agents Agents Dermatologic Adverse Effects Clinical Summary Taxane-induced Hypersensitivity Reactions Taxane Extravasation Reactions Periarticular Thenar Erythema and Onycholysis (PATEO) Taxane-induced Nail Changes Clinical Summary Extravasation Reactions Eribulin Indications Dermatologic Adverse Effects Clinical Summary Ixabepilone Indications Dermatologic Adverse Effects Clinical Summary Demethylating Agents, Arsenicals, and Retinoids Agents Demethylating Agents Azacitidine Indications Dermatologic Adverse Effects [93] Clinical Summary Decitabine Indications Dermatologic Adverse Effects Clinical Summary Arsenic Trioxide Indications Dermatologic Adverse Effects Clinical Summary Bexarotene Indications Dermatologic Adverse Effects Clinical Summary Tretinoin (All-trans Retinoid Acid, ATRA) Indications Dermatologic Adverse Effects Clinical Summary ATRA-induced Scrotal Ulcerations References 10: Dermatologic Adverse Effects of Anticancer Therapy III: Targeted and Immunotherapies Targeted Therapies ALK Inhibitors (Table 10.1) Agents Main Indication Clinical Summary Epidermal Growth Factor Receptor Inhibitors (EGFR Inhibitors) (Table 10.2) Dermatologic Adverse Effects Clinical Summary EGFR Inhibitor-Induced Acneiform Rash EGFR Inhibitor-Induced Hair Changes EGFR Inhibitor-Induced Paronychia CDK 4/6 Inhibitors [4] (Table 10.3) Agents Main Indication Clinical Summary Poly (ADP-Ribose) Polymerase (PARP) Inhibitors (Table 10.4) Agents Indications Clinical Summary BRAF Inhibitors (Table 10.5) Agents Dermatologic Adverse Effects Clinical Summary BRAF Inhibitor-Induced Verrucal Keratoses BRAF Inhibitor-Induced Cutaneous SCCs and KAs BRAF Inhibitor-Induced Melanocytic Lesions [14] MEK Inhibitors (Table 10.6) Agents Dermatologic Adverse Effects Clinical Summary MEK Inhibitor-Induced Acneiform Rash [15] Histone Deacetylase Inhibitors Agents Vorinostat Indications Dermatologic Adverse Effects Clinical Summary Romidepsin Indications Dermatologic Adverse Effects Clinical Summary Proteasome Inhibitors Agents Bortezomib Indications Dermatologic Adverse Effects Clinical Summary Carfilzomib Indications Dermatologic Adverse Effects Clinical Summary Ixazomib Indications Dermatologic Adverse Effects Clinical Summary Hedgehog Pathway Inhibitors (SMO Inhibitors) (Table 10.7) Clinical Summary Phosphatidylinositol 3-Kinase (PI3K) Inhibitors (Table 10.8) Agents Idelalisib Dermatologic Adverse Effects Clinical Summary Copanlisib Dermatologic Adverse Effects [43] Clinical Summary Duvelisib Dermatologic Adverse Effects [44, 45] Clinical Summary Other Small Molecule Inhibitors (Table 10.9) Imatinib Dermatologic Adverse Effects Clinical Summary Imatinib-Induced Edema Imatinib-Induced Maculopapular Rash Imatinib-Induced Pigmentation Changes Imatinib-Induced Lichenoid Dermatitis [40, 47] Nilotinib Dermatologic Adverse Effects Clinical Summary Dasatinib Dermatologic Adverse Effects Clinical Summary Dasatinib-Induced Panniculitis [48] Ponatinib Dermatologic Adverse Effects Clinical Summary Ponatinib-Induced Pityriasis Rubra Pilaris-Like Eruption [50, 52] Bosutinib Dermatologic Adverse Effects Clinical Summary Sorafenib Dermatologic Adverse Effects [53] Clinical Summary Hand-Foot Skin Reaction (HFSR) Sorafenib-Induced Facial Erythema Sorafenib-Induced Splinter Hemorrhages Sorafenib-Induced Keratoacanthomas and Nonmelanoma Skin Cancers Sunitinib Dermatologic Adverse Effects Clinical Summary Sunitinib-Induced Hair Depigmentation Sunitinib-Induced Yellow Skin Discoloration Axitinib Dermatologic Adverse Effects Clinical Summary Regorafenib Dermatologic Adverse Effects Clinical Summary Pazopanib Dermatologic Adverse Effects Clinical Summary Vandetanib Dermatologic Adverse Effects Clinical Summary Cabozantinib Dermatologic Adverse Effects Clinical Summary Everolimus Dermatologic Adverse Effects Clinical Summary Temsirolimus Dermatologic Adverse Effects [84] Clinical Summary Ibrutinib Dermatologic Adverse Effects [88] Clinical Summary Ibrutinib-Induced Petechiae and Purpura Ibrutinib-Induced Panniculitis Acalabrutinib Dermatologic Adverse Effects Clinical Summary Lenvatinib Dermatologic Adverse Effects [94] Clinical Summary Midostaurin Dermatologic Adverse Effects Clinical Summary Alectinib Dermatologic Adverse Effects [94] Clinical Summary Enasidenib Dermatologic Adverse Effects Clinical Summary Immunotherapy Antibodies Against CTLA-4, PD-1, and PD-L1 Agents Anti-CTLA-4 Antibodies Agents Indications Dermatologic Adverse Effects Clinical Summary Ipilimumab-Induced Vitiligo-Like Melanoma-Associated Depigmentation [105, 106] Anti-PD-1 and Anti-PD-L1 Antibodies (Tables 10.10 and 10.11) Dermatologic Adverse Effects Clinical Summary Anti-PD-1-Induced Lichenoid Dermatitis [122, 123] Anti-PD-1-Induced Autoimmune Blistering Dermatitis [47, 108] Clinical Summary References 11: Dermatologic Adverse Effects of Anticancer Therapy IV: Endocrine, Biologic, Radiation and Other Therapies Endocrine Therapy (Table 11.1) Agents Selective Estrogen Receptor Modulators (SERMs) Agents Dermatologic Adverse Effects [1] Clinical Summary SERM-Induced Hot Flashes Aromatase Inhibitors Agents Dermatologic Adverse Effects Clinical Summary Fulvestrant Dermatologic Adverse Effects Clinical Summary Leuprolide Dermatologic Adverse Effects Clinical Summary Antiandrogens Agents Dermatologic Adverse Effects Clinical Summary Fluoxymesterone Dermatologic Adverse Effects Clinical Summary Estradiol Dermatologic Adverse Effects Clinical Summary Somatostatin Analogs Agents Dermatologic Adverse Effects Clinical Summary Megestrol Acetate Dermatologic Adverse Effects Clinical Summary Medroxyprogesterone Acetate Dermatologic Adverse Effects Clinical Summary Pamidronate Disodium Dermatologic Adverse Effects Clinical Summary Zoledronic Acid Dermatologic Adverse Effects Clinical Summary Goserelin Dermatologic Adverse Effects Clinical Summary Degarelix Dermatologic Adverse Effects Clinical Summary Biotherapy Agents Dermatologic Adverse Effects [62, 63] Clinical Summary Interferon Alfa-2b-Related Psoriasis Interleukin-2 (IL-2, Aldesleukin) Indications Dermatologic Adverse Effects Clinical Summary Radiation Therapy Radiopharmaceuticals Agents Lutetium Lu-177 Dotatate Main Indication Dermatologic Adverse Effects [96] Clinical Summary Radium Ra-223 Dichloride Main Indication Dermatologic Adverse Effects Clinical Summary Radiation Dermatitis Acute Radiation Dermatitis [100, 101] Chronic Radiation Dermatitis [100, 102] Radiation Recall Dermatitis [103] Clinical Summary Stem Cell Transplantation Acute Graft Versus Host Disease [104–106] Chronic Graft Versus Host Disease [106, 107] Clinical Summary Other Anticancer Therapies (Table 11.4) Venetoclax [108, 109] Dermatologic Adverse Effects Clinical Summary Omacetaxine Mepesuccinate [110] Dermatologic Adverse Effects Clinical Summary Panobinostat Dermatologic Adverse Effects Clinical Summary Plerixafor [111] Dermatologic Adverse Effects Clinical Summary Pomalidomide Dermatologic Adverse Effects Clinical Summary Axicabtagene Ciloleucel [112] Dermatologic Adverse Effects Clinical Summary Belinostat Dermatologic Adverse Effects Clinical Summary Pralatrexate [113] Dermatologic Adverse Effects Clinical Summary Eltrombopag [109, 114] Dermatologic Adverse Effects Clinical Summary Alternating Electric Field Therapy (Tumor Treating Fields) [115] Indications Dermatologic Adverse Effects Clinical Summary CAR-T- Tisagenlecleucel [116] Indications Dermatologic adverse effects Clinical summary Immunostimulant—Sipuleucel-T [117] Indications Dermatologic Adverse Effects Clinical Summary Transcription factor interference—Trabectedin [118] Indications Dermatologic adverse effects Clinical summary Talimogene Laherparepvec (Oncolytic Herpes Virus) [119] Indications Dermatologic Adverse Effects Clinical Summary Other Chemotherapy Medications l-Asparaginase Indications Dermatologic Adverse Effects Clinical Summary Pegaspargase [121] Indications Dermatologic Adverse Effects Clinical Summary Bleomycin Indications Dermatologic Adverse Effects Clinical Summary Bleomycin-induced Flagellate Dermatitis Thalidomide Indications Dermatologic Adverse Effects Clinical summary Lenalidomide [109, 123] Indications Dermatologic Adverse Effects Clinical Summary Other Hematologic Agents (Tables 11.5 and 11.6) Clinical Summary Clinical Summary Granulocyte–Macrophage Colony-Stimulating Factors—Sargramostim Indications Dermatologic Adverse Effects Clinical Summary Thrombopoietic Growth Factor—Oprelvekin (Interleukin 11) Indications Dermatologic Adverse Effects Clinical Summary Topical Anticancer Therapies Agents Clinical Summary Clinical Summary Clinical Summary References 12: Complementary and Alternative Medicine and Dermatooncology Introduction Agents with Evidence to Avoid Escharotics Background Mechanisms and Effects Conclusions CAM with Possible Skin Cancer Treatment Benefit Gossypin Background Mechanisms and Effects Conclusions BEC (Curaderm) Background Mechanisms and Effects Conclusions Ingenol Mebutate Background Mechanisms and Effects Conclusions Taxus brevifolia Background Mechanisms and Effects Conclusions Hypericum perforatum Background Mechanisms and Effects Conclusions Curcumin Background Mechanisms and Effects Conclusions Coenzyme Q10 Background Mechanisms and Effects Conclusions CAM that May Offer Skin Cancer Preventative Benefits Coffee Plant Extract Background Mechanisms and Effects Conclusions Camellia sinensis Background Mechanisms and Effects Conclusions Beta Carotene Background Mechanisms and Effects Conclusions Genistein Background Mechanisms and Effects Conclusions Proanthocyanidin Background Mechanisms and Effects Conclusions Lycopene Background Mechanisms and Effects Conclusions Silymarin Background Mechanisms and Effects Conclusions Plant Oils Background Mechanisms and Effects Conclusions Niacinamide Background Mechanisms and Effects Conclusions Polypodium leucotomos Background Mechanisms and Effects Conclusions Cutaneous Oncology Issues Hand-Foot Syndrome and Henna Background Mechanisms and Effects Conclusions Pruritus Topical Hydrogels and Bleach Background Mechanisms and Effects Conclusions Systemic Antipruritic and Anti-pain Medications Mirtazapine Background Mechanisms and Effects Conclusions Doxepin Background Mechanisms and Effects Conclusions Aprepitant Background Mechanisms and Effects Conclusions Butorphanol Background Mechanisms and Effects Conclusions Acupressure Background Mechanisms and Effects Conclusions Acupuncture Background Mechanisms and Effects Conclusions Quercetin Background Mechanisms and Effects Conclusions N-Acetyl Cysteine (NAC) Background Mechanisms and Effects Conclusions Impatiens balsamina Background Mechanisms and Effects Conclusions Conclusions References