This study guide was prepared by Fanconi.

·         Macroscopic terms

o        Macule = flat, circumscribed area of different color

o        Papule = elevated solid area less than 5 mm

o        Nodule = elevated solid area greater than 5 mm

o        Plaque = elevated flat-topped lesion greater than 5 mm

o        Vesicle = elevated fluid-filled lesion less than 5 mm

o        Bulla = as above, greaer than 5 mm (blister)

o        Wheal = pruritic, erythematous area (dermal edema)

o        Scale = dry, plate-like excrescence resulting from aberrant cornification

o        Lichenification = thick, rough skin with prominent skin markings (rubbing)

o        Excoriation = linear, traumatic lesion (deep scratch)

o        Onycholysis = loss of nail substance

·         Microscopic terms

o        Hyperkeratosis = stratum corneum thickening, aberrant keratinization

o        Parakeratosis = abnl retention of nuclei in stratum corneum

o        Acanthosis = epidermal hyperplasia

o        Dyskeratosis = abnl keratinization below stratum corneum

o        Acantholysis = loss of connections between keratinocytes

o        Papillomatosis = elongation or widening of dermal papillae

o        Lentiginous = linear pattern of melanocyte proliferation in the epidermal basal cell layer, may be reactive or neoplastic

o        Spongiosis = epidermal intercellular edema

o        Exocytosis = inflammatory cells in epidermis

o        Erosion = focal, incomplete loss of epidermis

o        Ulceration = focal, complete loss of dermis, may include dermis or SQ fat

o        Vacuolization = vacuoles within or adjacent to cells

·         Disorders of Pigmentation and Melanocytes

o        Vitiligo

§         Macules devoid of pigmentation

§         Melanocyte autoantibodies

§         Neurohumoral factors

§         Self-destruction of melanocytes by toxic intermediates of melanin synthesis

§         Loss of melanocytes

§         NOT albinism (where melanocytes are present but nonfunctional)

o        Ephelis

§         1-10 mm pigmented macules

§         Normal melanocyte number

§         Increased pigmentataion in basal keratinocytes

o        Melasma

§         Mask-like zone of facial hyperppigmentation (assoc. with pregnancy)

§         Epidermal type = increased melanin deposition in basal layers

§         Dermal type = pigment incontinence (macrophage phagocytosis of melanin released from epidermis)

o        Lentigo

§         Do not darken with sun exposure (in contrast to freckles)

§         Linear basal hyperpigmentation = melanocyte hyperplasia

§         Elongation, thinning of rete ridges

o        Nevocellular Nevus

§         Congenital or acquired melanocyte neoplasms

§         Well-demarcated, tan to brown in color

§         Derive from basal dendritic cells that have transformed into round-to-oval cells with uniform nuclei

·         Nests along DEJ = junctional nevi

·         Extending into dermis = compound nevi

o        Maturation = become nonpigmented and resemble neural tissue

o        Melanomas show no maturation, in contrast to nevi

·         Loss of epidermal component = dermal nevi

o        Dysplatic nevi = (autosomal dominant, chromosome 1)

§         May evolve into malignancy

§         Larger, greater than 5 mm

§         Pigment variegation on both sun-exposed and non-sun-exposed skin

§         Cytologic and architectural atypia

§         Risk for developing melanoma increased for unaffected skin as well

o        Malignant Melanoma

§         Sun exposure

§         Lightly-pigmented individuals

§         Dysplastic nevus syndrome increases risk

§         Pruritic, irregular variegated lesions

§         Black, brown, red-blue, or gray

§         Radial growth phase

§         Vertical growth phase

§         Molecular genetics

·         CMM1 gene on chromosome 1p36

·         Tumor-suppressor gene p16, mapped to chromosme 9, inhibits CDK4 (thus negatively regulates cell cycle)

·         Cyclin-dependent kinase gene CDK4 on chromosome 12

§         Most important clinical sign of disease is a change in color in a pigmented lesion

·         Benign Epithelial Tumors

o        Seborrheic Keratoses

§         Paraneoplastic syndrome (sign of Leser-Trelat) = tumor elaboration of growth factors (e.g., TGF-a)

§         Uniform, tan-brown, velvety or granular plaques

§         Keratin-filled plugs

§         Hyperkeratosis and keratin-filled horn cysts

§         Grow downward when associated with a hair follicle (inverted follicular keratosis)

o        Acanthosis Nigricans

§         Thickened, hyperpigmented zones in flexural areas

§         Benign (80%), autosomal dominant or associated with obesity or endocrine disorders

§         Malignant = assoc. with occult adenocarcinoma

§         Hyperkeratosis

§         Prominent rete ridges

§         Basal hyperpigmentation

o        Fibroepithelial Polyp

§         Skin tag

§         Stalk, fibrovascular core

§         Pregnancy, diabetes, or intestinal polyposis

o        Epithelial Cyst (Wen)

§         Epidermal inclusion cyst = wall looks like normal epidermis

§         Trichilemmal cyst = no granular cell layer

§         Dermoid cyst = multiple appendages

§         Steatocystoma multiplex = wall resembles sebaceous gland ductal epith.

o        Keratoacanthoma

§         Spontaneously-resolving, rapidly-growing lesion on sun-exposed skin in white people > 50 years of age.

§         Detectable p53 oncoprotein (may be a form of SCC that regresses)

o        Adnexal (Appendage) Tumors

§         Cylindromas = scalp, forehead, apocrine, turban tumors with basaloid cells

§         Syringomas = tan papules on lower eyelids, eccrine differentiation

§         Trichoepitheliomas= flesh-colored papules on face, scalp, neck, trunk

§         Hidradenoma papilliferum = face, scalp, apocrine

·         Premalignant and Malignant Epidermal Tumors

o        Actinic Keratosis

§         Chronic sun exposure, radiation, hydrocarbons, arsenicals

§         Malignant transformation possible

§         Hyperkeratosis with a rough consistency

§         Cytologic atypia in lower dermis

§         Basal cell hyperplasia and dyskeratosis

§         Dermis = solar elastosis (thickened, blue-gray elastic fibers from aberrant synthesis by sun-damaged fibroblasts)

o        Squamous Cell Carcinoma

§         Most common tumor of sun-exposed skin of older people

§         Men > women, except lower leg lesions

§         UVR is greatest predisposing factor

·         Damages DNA

·         Immunosuppression = injuring antigen-presenting cells and augmenting development of suppressor T cells

§         Immunosuppression, xeroderma pigmentosum, and HPV-36 may increase risk

§         In situ = wall-demarcated, red, scaling plaques.

§         Invasive lesions are nodular, prone to ulceration

§         Mucosal involvement = leukoplakia

§         Full-thickness epidermal atypia (AK has only basal atypia)

o        Basal Cell Carcinoma

§         Common, slow-growing tumors of sun-exposed skin

§         Immunosuppresion and xeroderma pigmentosum increased incidence

§         Basal cell nevus syndrome = bone, CNS, eye, reproductive organ abnormalities, mutations in PTC tumor-suppressor gene

§         Uniform, monotonous basal cell proliferation

o        Merkel Cell Tumor

§         Neural crest derivative

§         Small, round, malignant cells

§         Looks like small cell CA of lung

·         Tumors of the Dermis

o        Benign Fibrous Histiocytoma

§         Neoplasms of dermal fibroblasts and histiocytes

§         Lesions on legs of young to middle-aged women

§         Antecedent trauma

§         Most common form is dermatofibroma

§         One variant is sclerosing hemagioma

o        Dermatofibrosarcoma Protuberans

§         Slow-growing fibrosarcoma

§         Locally aggressive, rarely metastasizes

§         Radially-oriented (storiform) fibroblasts

§         Numerous mitoses

o        Xanthoma

§         Not true neoplasms, are focal accumulations of foamy histiocytes

§         Hyperlipidemia, lymphoproliferative disorder

·         Eruptive = showers of yellow papules that wax and wane with plasma triglyceride and lipid levels

·         Tuberous = especially around knees and elbows

·         Tendinous = over Achilles tendon or finger extensor tendon

·         Plane = in palmar creases, may be assoc. with primary biliary cirrhosis

·         Xanthelasma = eyelids

o        Dermal vascular tumors

§         Hemangiomas (most common)

§         Malignant vascular tumors

§         Kaposi sarcoma

§         Bacillary angiomatosis

·         Tumors of Cellular Immigrants to the Skin

o        Histiocytosis X

§         Scaling erythematous plaques resemble seborrheic dermatitis

§         Eosinophils, mononuclear cells

§         Birbeck granules, CD1 antigens confirm derivation from Langerhans cells

o        Mycosis Fungoides

§         Cutaneous T-cell lymphoma

§         Sezary-Lutzner cells = malignant CD4+ cell with a cerebriform nucleus

o        Mastocytosis

§         Family of rare disorders, cutaneous and visceral mast cell proliferation

§         Pruritis, flushing, rhinorrhea, dermal edema and erythema

§         Wheal, Darier sign = it turns red

·         Urticaria pigmentosa = 50% of all cases, favorable prognosis

·         Systemic mastocytosis = adults, poorer prognosis

o        Point mutations of C-kit protooncogene, activation of KIT tyrosine kinase that directs mast cell growth and proliferation

o        Ichthyosis

§         Disorder of epidermal maturation

§         Hyperkeratosis resembling fish scales

§         Increased cell-cell adhesion resulting in abnormal desquamation

§         Compacted stratum corneum, minimal inflammation

·         Acute Inflammatory Dermatoses

o        Urticaria (Hives)

§         Focal mast cell degranulation

§         Histamine-mediated dermal pruritis, edema, and wheal

§         Angioedema is related, dermal and subQ fat edema

§         No evidence if increased mast cell numbers

§         IgE-independent = degranulation with inhibition of prostaglandin synthesis (aspirin)

§         Persistent urticaria = can’t clear antigen, collagen vascular disorders, Hodgkin dz

o        Acute Eczematous Dermatitis

§         May be a delayed-type inflammatory response

§         Pruritic, red, papulovesicular, blustered, oozing, crusting

§         Impetiginization = bacterial superinfection

o        Erythema Multiforme

§         Uncommon, self-limited hypersensitivity response to certain drugs, infections, or systemic disorders

§         CD8+ cytotoxicity

§         Target lesions, symmetric involvement of extremities

o        Stevens-Johnson Syndrome

§         Hemorrhagic crusting of mucosa

o        Toxic Epidermal Necrolysis

§         Clinically analogous to extensive third-degree burns

·         Chronic Inflammatory Dermatoses

o        Psoriasis

§         1-2% all people, can develop at any age

§         Elbows, knees, scalp, lumbosacral areas, glans penis

§         Total body scaling = erythroderma

§         Pathology

·         Stratum granulosum is thinned or absent

·         Extensive parakeratotic scale

·         Auspitz sign = mini bleeds when scale is removed

·         Munro’s microabscesses

·         Nail pitting, onycholysis

§         Koebner phenomenon = develop at sites of trauma

·         Damage to stratum corneum unmasks antigens, C’ activation

§         Can be associated with other diseases

o        Lichen Planus

§         Self-limited disease of 1-2 years

§         Oral lesions occasionally become malignant

§         Prutitic, purple, polygonal papules

§         Highlighted by Wickham striae

§         Basal layer degeneration, rete saw-toothing, acanthosis

§         Necrotic basal cells sloughed into dermis, forming Civatte bodies

o        Lupus Erythematosus

§         DLE patients rarely progress to SLE

§         1/3 of SLE patients will develop DLE

§         Discoid erythematous scaling plaques, worsened with sun exposure

§         DEJ, perivascular, and periappendiceal lymphocytic infiltration

§         Infiltration of fat = lupus profundus

§         Lupus band test = granular band of Ig and C’ along DEJ and dermal-follicular jn

·         Blistering (Bullous) Diseases

o        Pemphigus

§         Rare autoimmune disorder

§         Abs to keratinocytes intercellular cement (desmoglein 3)

§         4 variants

·         Pemphigus vulgaris

o        80%, scalp, face… easily ruptured

o        Fatal if untreated

·         Pemphigus vegetans

o        Large moist plaques studded with pustules

·         Pemphigus foliaceus

o        More benign form (only stratum granulosum involved)

o        Epidemically occurring in South America

o        Bullae are very superficial

·         Pemphigus erythematosus

o        Involving malar region

§         Microscopically, acantholysis

§         Suprabasal split, leaving a row of tombstones

§         Immunofluorescence “outlines” each keratinocyte

o        Bullous Pemphigoid

§         Relatively common autoimmune disorder

§         Elderly

§         Abs to hemidesmosome proteins

§         Tense bullae, blisters do not rupture as easily

§         Subepidermal non-acantholytic blister with linear immuno staining along DEJ

o        Dermatitis Herpetiformis

§         Assoc. with celiac disease, responds to a gluten-free diet

§         Gliadin antibodies cross-react with reticulin

§         Granular IgA deposits at dermal papillae tips

·         Non-Inflammatory Blistering Diseases

o        Epidermolysis Bullosa

§         Group of pathogenetically unrelated disorders

§         Neonatal blistering at sites of trauma

§         Junctional = blistering at lamina lucida in normal skin

§         Dystrophic = blistering beneath lamina densa, defective anchoring fibrils

§         Simplex = epidermal basal cell degeneration

o        Porphyria

§         Urticaria and vesicles exacerbated by sun exposure

·         Disorders of Epidermal Appendages

o        Acne Vulgaris

§         P. acnes lipase degradation of sebaceous oils to form irritating fatty acids

§         Noninflammatory = open and closed comedones

§         Inflammatory = pustules, nodules, papules

§         Expanding masses of lipid and keratin at midportion of hair follicle

o        Erythema Nodosum

§         Pannuculitis = inflammation of subQ fat

§         Connective tissue septal widening without vasculitis

o        Erythema Induratum

§         Uncommon, inflammation and necrosis of fat lobules

§         Necrotizing vasculitis

·         Infection and Infestation

o        Verrucae (Warts)

§         Spread by direct contact with papillomaviruses

§         HPV 6, 11, 16 = anogenital warts

§         HPV 16 = anogenital wart dysplasia and SCC

§         Subtypes

·         Verruca vulgaris = most common, on dorsum of hand

·         Verruca plana = flat warts

·         Verruca plantaris = on soles of feet

·         Condyloma accuminatum = cauliflower-like venereal warts

§         Microscopically, keratinocytes perinuclear vacuolization (koilocytosis)

o        Molluscum Contagiosum

§         Poxvirus

§         Pruritic, pink, umbilicated papules

§         Trunk, anogenital regions

§         Cheesy material containing molluscum bodies can be expressed from it

o        Impetigo

§         Strep or staph infection of skin in children or sick adults

§         Face, hands

§         Erythematous macule, shallow erosion with a honey-colored crust

§         Subcorneal pustules that rupture, necrotic debris

o        Superficial Fungal Infections

§         Dermatophytes are fungi that grow in soil and on animals

§         Confined to nonviable stratum corneum

§         Tinea capitis, barbae, corporis, cruris, pedis, versicolor, onychomycosis

§         Mild eczematous dermatitis

o        Arthropod-Associated Lesions

§         Scabies

·         Female mite burrows beneath stratum corneum

·         Linear furrows on interdigital skin, palms, wrists

§         Pediculosis

·         Head, body, or crab louse

·         Attach to hair shafts

·         Wedge-shaped dermal perivascular lymphohistiocytic infiltrate

·         Epidermal necrosis with birefringent insect mouth parts