Tumors of the Skin PDF

TUMORS OF THE SKIN Dr. H. Reid, DVM, MD [email protected] 1 LEARNING OBJECTIVES LO1: Apply the fundamental principles of skin structure and neoplasia to discuss the pathogenesis, clinical presentation and histopathologic features of benign epithelial tumors of skin 1) Seborrheic Keratosis 2) Acanthosi...

TUMORS OF THE SKIN Dr. H. Reid, DVM, MD [email protected] 1 LEARNING OBJECTIVES LO1: Apply the fundamental principles of skin structure and neoplasia to discuss the pathogenesis, clinical presentation and histopathologic features of benign epithelial tumors of skin 1) Seborrheic Keratosis 2) Acanthosis Nigricans 3) Fibro-epithelial Polyp /Acrochordon /Squamous Papilloma 4) Epithelial Cyst 5) Adnexal (Appendage) Tumors i. Cylindroma (apocrine glands; forehead, scalp) ii. Syringoma (eccrine glands; lower eyelids) iii. Trichoepithelioma (hair follicles, head, neck) 2 LO2: Apply the fundamental principles of skin structure, molecular genetics and neoplasia to compare and contrast the pathogenesis, clinical presentation and histopathologic features of pre-malignant and malignant epidermal tumors. 1) 2) 3) 4) Actinic Keratosis Squamous Cell Carcinoma Keratoacanthoma Basal Cell Carcinoma 3 LO3: Apply the fundamental principles of skin structure and neoplasia to discuss the pathogenesis, clinical presentation and histopathologic features of tumors of the dermis. 1) Benign fibrous histiocytoma (dermatofibroma) 2) Dermatofibrosarcoma protuberans LO4: Apply the fundamental principles of hematology to discuss cutaneous manifestations of tumors of cellular migrants to the skin in terms of clinical presentation, pathogenesis and histopathological features. 1) Mycosis fungoides (cutaneous T-cell lymphoma) 2) Mastocytosis 4 Benign Epithelial Tumors Of Skin 1. Seborrheic Keratosis 2. Acanthosis Nigricans 3. Fibro-epithelial Polyp /Acrochordon /Squamous Papilloma 4. Epithelial Cyst 5. Adnexal (Appendage) Tumors 1. Cylindroma (apocrine glands; forehead, scalp) 2. Syringoma (eccrine glands; lower eyelids) 3. Trichoepithelioma (hair follicles, head, neck) 5 6 Seborrheic Keratosis Common Epidermal Tumors Age Most frequent in middle-agedor older individuals Location Brown stuck-on plaque Numerous on trunk Extremities, head, and neck may also be involved Pathogenesis Mutation in FGFR3 Leser-Trelat sign Large numbers of seborrheic keratosislesions Paraneoplastic syndrome in patientswith carcinomas of GIT -> production of TGF-α by malignant cells Multiple, well-circumscribed, hyperpigmented verrucous plaques with a “stuck-on” appearance 6 GROSS Round, flat, coin-like, waxy plaques Size – Variable (mm to several cm) Color – Uniformly tan todark brown Appearance - Velvety to granular surface Inspection with a hand lens Small, round, pore-like ostia impacted with keratin. MICROSCOPY Exophytic and sharply demarcated from adjacent epidermis Sheets of small cells ~ basal cells of normal epidermis Variable melanin - brown color Exuberant keratin production (hyperkeratosis) at surface Small keratin-filled cysts (horn cysts) and invaginations of keratin into main mass (invagination cysts) 7 Seborrheic Keratosis Well-demarcated coin-like pigmented lesion containing dark keratin-filled surface plugs (inset) Histology - benign basaloid cells associated with prominent keratin-filled "horn"8 cysts, some communicate with surface (pseudo-horn cysts). ACANTHOSIS NIGRICANS Thickened, hyperpigmented skin with a "velvetlike" texture Location – Flexural areas (axillae, skin folds of neck, groin, anogenital regions) Important cutaneous marker of benign and malignant conditions Types – Benign type 80% cases In childhood or during puberty; associated with obesity/endocrine abnormalities (diabetes) – Malignant type In middle-aged and older individuals; in association with underlying cancers, most commonly GIT adenocarcinomas 9 Acanthosis nigricans FGFR3 TGF-α-> GI Carcinomas Type 2 diabetes- IGFR1 10 Acanthosis nigricans Variable hyperplasia with hyperkeratosis and basal cell layer hyperpigmentation 11 Fibroepithelial Polyp Syn.- Acrochordon, Squamous Papilloma, Skin Tag Common cutaneous lesion, often an incidental finding in middleaged/older individuals, located in neck, trunk, face and inter-triginous areas. Clinical course: Associated with diabetes, obesity, intestinal polyposis; more numerous or prominent during pregnancy 12 Fibroepithelial Polyp ctd. Gross- Soft, fleshcolored, bag-like tumor attached to skin by slender stalk M/E- Fibro-vascular cores covered by benign squamous epithelium 13 Epithelial Cyst aka: Follicular inclusion cyst or Wen Invagination and cystic expansion of epidermis or a hair follicle Cysts are filled with keratin and lipidcontaining debris from sebaceous secretions Dermal or subcutaneous, wellcircumscribed, firm, mobile nodules Histological types – Epidermal inclusion cyst (simple cyst with keratin) – Pilar or trichilemmal cysts – Dermoid cyst – Steatocystoma simplex (Sebaceous cyst with keratin 17 gene mutation) 14 Adnexal (appendage) tumors Neoplasms arising from or differentiating toward cutaneous appendages Flesh-colored solitary or multiple papules and nodules Syringoma – Lesions with eccrine differentiation – Multiple, small, tan papules near lower eyelids/upper cheek – Micro: Small ducts ~ intra-epidermal portion of eccrine sweat ducts 15 Cylindroma Appendage tumor with ductal (apocrine or eccrine) differentiation Location- Forehead and scalp Gross- Coalescence of nodules - hat-like growth (Turban tumor) Microscopy Islands of cells resembling normal epidermal or adnexal basal cell layer (basaloid cells) surrounded by hyalinized, thickened basement membrane zone A. Cylindroma or turban tumor. B.Cylindroma with irregularly shaped aggrega16tions of basaloid cells arranged in a “jigsaw puzzle” pattern. Sebaceous Adenoma Associated with internal malignancy in Muir-Torre syndrome Subset of hereditary non-polyposis colorectal carcinoma syndrome Associated with germline deficits in DNA mismatch repair proteins. Micro: ✓ Lobular proliferation of sebocytes ✓ Frothy or bubbly cytoplasm due to lipid vesicle content Sebaceous adenoma: Inset demonstrates sebaceous differentiation17 Pilomatricoma Trichoepithelioma Apocrine carcinoma ▪Show follicular differentiation ▪Proliferation of basaloid ▪Shows ductal differentiation ▪Mutations in CTNNB1, gene encoding β-catenin ▪Composed of basaloid cells that show trichilemmal or hairlike differentiation cells that forms primitive structures resembling hair follicles with prominent decapitation secretion like that seen in the normal apocrine gland – hint of malignancy 18 Premalignant & Malignant Epidermal Tumors 1. Actinic Keratosis 2. Squamous Cell Carcinoma 3. Keratoacanthoma 4. Basal Cell Carcinoma 19 ACTINIC KERATOSIS aka Solar elastosis -Usually occur in sun-damaged skin and exhibit hyperkeratosis Location ✓ Sun-exposed sites (face, arms, dorsum of hands)- most frequent ✓ Lips - similar lesions (termed actinic cheilitis) “Sand-paper like” plaques Associated risk factors ✓ High incidence in lightly pigmented individuals ✓ Exposure to ionizing radiation, industrial hydrocarbons and arsenicals Gross: Usually, < 1 cm in diameter Tan-brown, red, skin-colored; rough, sandpaperlike consistency Some lesions produce so much keratin -"cutaneous horn" 2 0 Excessive scale formation has produced a "cutaneous horn.“ Actinic keratosis consist of hyperkeratotic erythematous papules and patches on sun-exposed skin. They arise in middle-aged to older adults and have some potential for malignant transformation 21 Micro: Stratum corneum - Thickened with parakeratosis Lowermost layers of epidermis - Cytologic atypia Hyperplasia of basal cells or atrophy --- thinning of epidermis. Atypical basal cells show dyskeratosis (pink or reddish cytoplasm) Intercellular bridges present (in contrast to basal cell carcinoma in which they are not visible) Focal parakeratosis Cytological atypia of basal keratinocytes Progression to fullthickness nuclear atypia, heralds the development of early squamous cell carcinoma in situ. 22 Actinic keratosis Superficial dermis Thickened, blue-gray elastic fibers (elastosis) AKA Solar elastosis Abnormal elastic fiber synthesis by sun-damaged fibroblasts 1. Solar elastosis pale blue colored area beneath the epidermis. 2. Epithelial dysplasia Prognosis: May progress to Squamous cells carcinoma. 23 Actinic keratosis Progression to full-thickness nuclear atypia, with or without presence of superficial epidermal maturation, heralds the development of squamous cell carcinoma in situ Basal cell layer atypia (dysplasia) is associated with marked hyperkeratosis and parakeratosis 24 Squamous Cell Carcinoma (SCC) 2nd most common tumor – On sun-exposed sites in older people, exceeded only by basal cell carcinoma. Clinical course – Invasive SCC’s discovered while small and resectable – 40 yrs. Location: Truncal areas; may spread to extremities, face, and scalp Gross – Scaly, red-brown patches; raised, scaling plaques, fungating nodules – Plaques and nodules may ulcerate – Eczema-like lesions typify early stages of disease – Multiple, large (>10 cm in diam.), nodules (systemic spread) Sezary Syndrome - Seeding of blood by malignant CD4+ cells – Diffuse erythema and scaling of entire body surface (erythroderma) 46 Cutaneous T-cell lymphoma A, Several erythematous plaques with scaling and ulceration are evident. B, Microscopically, there is an infiltrate of atypical lymphocytes that accumulates 47 beneath and invades the epidermis. Mycosis fungoides 48 Mastocytosis Spectrum of rare disorders characterized by increased numbers of mast cells in skin or other organs Urticaria pigmentosa: – Localized cutaneous form - affects children – Lesions are multiple and widely distributed – Round to oval, red-brown, non-scaling papules and small plaques Solitary mastocytomas: – Pink to tan-brown nodules – May be pruritic or show blister formation Systemic mastocytosis: – Systemic disease usually affects adults (poor prognosis) – Skin lesions similar to those of urticaria pigmentosa – Mast cell infiltration of bone marrow, liver, spleen, and lymph nodes 49 Mastocytosis Clinical presentations due to mast cell degranulation and mediators: Darier sign – Wheal that occurs when lesion skin is rubbed Dermatographism - Dermal edema (hive) that occurs in normal skin when stroked (pointed instrument) Systemic disease – Pruritus and flushing triggered by certain foods, temperature changes, alcohol, drugs (morphine, codeine, aspirin) – Watery nasal discharge (rhinorrhea) – GI or nasal bleeding – Bone pain (osteoblastic and osteoclastic involvement) 50 MASTOCYTOMA Mast cell granules contain histamine, heparin, platelet-activating factor and other substances. As they release histamine, they are associated with allergic reactions Manipulation of the tumor may result in redness and swelling from release of mast cell granules, also known as Darier's sign, and prolonged local hemorrhage. In rare cases, a highly malignant tumor is present, and signs may include loss of appetite, vomiting, diarrhea and anemia. Release of a large amount of histamine at one time can result in ulceration of the stomach and duodenum (present in up to 25 percent of cases) or disseminated intravascular coagulation (DIC) 51 Cytology, Giemsa Mastocytosis A: Solitary mastocytoma in a 1-year-old child. B: By histology, numerous ovoid cells with uniform, centrally located nuclei are observed in the dermis. 51 C: Giemsa or T. blue staining reveals purple “metachromatic” granules within the cytoplasm of the mast cells. 53