Robbins - Skin (Ch. 25) Flashcards by Andrew Herrmann

Child, small tan-red or light brown macules that appear after sun exposure. Fade and darken in seasonal cyclic fashion.

Why more pigmented?

Freckles

More melanin w/in basal keratinocytes

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Large freckle-like spots independent of sun exposure, aggregates of melanosomes

Café au lait spots

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Small, oval, tan-brown macules or patches. Do not darken with sun. Linear melanocyte hyperplasia above basement membrane. Elongated, thinned rete ridges.

Lentigo

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Tan/brown, uniformly pigmented, small macules or papules w/ well-defined, rounded borders.

Genetics? Same as what?

***Genetic difference from melanoma?

Melanocytic nevus (mole)

NRAS/BRAF (Ras pathway) constitutive activation – same as MELANOMA (many)

NO CDKN2A mutation = Permanent growth arrest due to accumulation of p16/INK4a (inhibitor of CDK4, CDK6)

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3 nevi types (w/ histo)

Junctional - nests of round benign cells along D-E junction

Compound - growth of nests/cords w/in dermis

Intradermal - loss of epidermal nests, ONLY dermal nests

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Compound nevus –> small, unpigmented, cords/single cells within the deep dermis that have fusiform contours and grow in fascicles. Loss of TK activity, acquisition of cholinesterase activity.

Malignant?

Neurotization

NO - distinguishing feature from melanoma

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Large, 8 mm, flat brown macules, slightly raised plaques with pebbly surface, or target-like lesions w/ darker raised center. Variable pigmentation, irregular borders. Sun-exposed and sun-hidden areas.

Dysplastic nevi

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Nevi, cellular/nuclear atypia, lentiginous hyperplasia, melanin w/in the dermis, linear fibrosis around the rete ridges

What causes the lentiginous hyperplasia?

Dysplastic nevi (histology)

Fusion of adjacent epidermal nests of cells –> replacement of normal D-E junction

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Irregular, large (12 mm), multi-colored, lesion w/ notched borders. Large cells w/ large irregular nuclei, clumped chromatin at the periphery of the nuclear membrane, prominent eosinophilic nucleoli.

Distinguishing gene mutations from benign counterpart? (2)

Melanoma

(40%) CDKN2A – loss of p16/INK4a = increased melanocytic proliferation due to loss of cell-cycle control

(70%) TERT – reactivation of telomerase

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2 major phases of melanoma growth

Radial growth (horizontal)

Vertical growth (deep)

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The vertical growth phase of melanoma is heralded by the appearance of a _____ and correlates w/ the potential to ____

Nodule

Metastasize

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Unlike benign nevi, melanomas do not show any histologic sign of ____ within the deep invasive part of the dermis

Neurotization

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Melanoma - primary prognostic factor

Metastasize to where?

Breslow thickness (depth)

Regional LNs

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5 things to look for on a suspected melanoma

ABCDEs

Asymmetry
Irregular Borders
Variable Color
Increasing Diameter
Evolution/change (rapid)

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Round pigmented velvety to granular exophytic lesion with rough surface. Sharply demarcated from the adjacent epidermis. Hyperkeratosis at the surface w/ keratin-filled cysts and invaginations.

Genetics?

Many small ones on African American face

Seborrheic keratoses

FGFR3

Dermatosis papulosa nigra

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Rapid appearance of multiple SKs…suspect what?

Why does this happen?

Leser-Trelat sign – GI carcinoma

Stimulation of keratinocytes by TGF-alpha from tumor cells

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Thickened, hyperpigmented skin w/ velvet-like texture in flexural (folds) areas

**2 types (w/ associations)

Acanthosis nigricans

Benign (obesity, DM, puberty)
Paraneoplastic (GI adenocarcinoma)

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Acanthosis nigricans - genetics (familial)

Genetic pathway in DM?

FGFR3 (like in SK)

Insulin –> IGFR1 –> FGFR3 pathway activation

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Small, soft, flesh-colored mass attached to skin by slender stalk. Fibrovascular core covered by squamous epithelium

Other name for these?

Fibroepithelial polyp (skin tag)

Acrochordons

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Fibroepithelial polyps + perifollicular mesenchymal tumors

Birt-Hogg-Dubé syndrome

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Fibroepithelial polyps - become more numerous/prominent during _____

Pregnancy

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Multiple trichilemmomas

Cowden syndrome (PTEN)

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Islands of cells resembling normal epidermal or basal layer cells. Islands fit together like jigsaw puzzle w/in fibrous dermal matrix

Common locations?

Cylindroma

Forehead, scalp

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Multiple, small, tan papules around the lower eyelids

Syringomas

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Proliferation of basaloid cells forming primitive hair follicles

Trichoepithelioma

Lobular proliferation of sebocytes, mature ones w/ frothy or bubbly cytoplasm in the central portion

Sebaceous adenoma

Small (under 1 cm) tan-brown-red-pale lesion w/ rough sand-paper consistency. Hyperkeratosis. Protrudes as a horn from the skin surface. Cause? Risk?

Actinic keratosis Sun damage Squamous cell carcinoma

Cytologic atypia, hyperplasia of basal cells, thinning of epidermis, pink/red cytoplasm of basal cells, intercellular bridges. Blue elastic fibers in superficial dermis. Parakeratosis of stratum corneum. Treatment?

Actinic keratosis Imiquimod

Nodular, ulcerative lesion w/ hyperkeratotic scaling. Atypical nuclei throughout the epidermis. Positive keratin staining. Locally invasive into dermis and regional LNs.

Cutaneous squamous cell carcinoma

**Those susceptible to cutaneous squamous cell carcinoma (6)

- Excessive sunlight - Light skin - Immunosuppressed (HPV 5/8) - Epidermodysplasia verruciformis (HPV) - Arsenic exposure - Xeroderma pigmentosum

Cutaneous SCC - genetics WHEN INDUCED BY SUNLIGHT (actinic keratosis)

P53 mutations

Impaired nucleotide excision repair (can't fix pyrimidine dimers) Increased risk of what?

Xeroderma pigmentosum Squamous cell carcinoma (sun-exposure)

Pearly papules w/ dilated subepidermal BVs (telangiectasias), rolled borders, central crusting or non-healing ulceration. Tumor cells resemble normal basal epidermis. Separation of stroma from mass. Cells at the periphery arranged radially (parallel). What does the 2nd to last sentence describe? What does the last sentence describe?

Basal cell carcinoma Clefts/separation artifacts that differentiate BCC from appendage tumors that have basaloid cells PALISADING cells

BCC - genetics

SHH dysregulation

Multiple BCCs before age 20 + many other tumors ***Genetics? Results?

Nevoid BCC syndrome (Gorlin syndrome) PTCH mutation (SHH pathway activation --> SMO and GLI1 activation)

Young/middle-age woman, small firm tan/brown papule on her leg at spot. Some cells are Factor 13a positive. Rest are well-defined spindle-shaped cells. What else seen on histology? What is often a precedent to this? Cell type? Encapsulated?

Dermatofibroma Downward elongation of hyperpigmented rete ridges (pseudoepitheliomatous hyperplasia) Trauma (abnormal immune response like a keloid) Spindle-shaped cells Non-encapsulated mass in the dermis

Nodule on trunk w/in a firm plaque that my ulcerate. Fibroblasts arranged radially (storiform - swirling). Thinned epidermis. Deep "honeycomb" or "swiss cheese" extension into dermis. **Genetics? Causes what?

Dermatofibrosarcoma protuberans COL1A1: PDGFB translocation - Excessive PDGF-beta, causing excessive collagen deposition

Trunk, exzema-lie scaly red-brown patches, psoriasis-like plaques, and/or necrotic nodules Cell type? Diffuse erythema and scaling of whole body

Mycosis fungoides Clonal CD4+ T cells that home to skin Sezary Syndrome (seeding into blood)

Bandlike aggregates w/in the superficial dermis that invade the epidermis as single cells and small clusters. Cerebriform contour (infolding of nuclear membranes)...cell type? What are clusters called?

Sezary-Lutzner cells (Mycosis Fungoides) Pautrier microabscesses

Child, multiple round/oval red-brown non-scaling papules and plaques. Localized area of dermal edema and erythema when skin is rubbed. KIT activating mutation. Lesions are due to effects of what molecules? (2) From what cells? 2 clinical signs? Genetics?

Urticaria pigmentosa (cutaneous mastocytosis) Histamine, heparin - From MAST CELLS ``` Darier sign (wheal) Dermatographism -- redness when skin rubbed/scraped ``` KIT

Solitary pink to brown nodule, pruritic, blister. Tightly-packed stellate cells in upper to mid-dermis. Tryptase and KIT.

Mastocytoma

Excessive buildup of compacted keratin in stratum corneum w/ loss of normal basket-weave pattern. Little to no inflammation. Dry skin. Cause?

Ichthyosis Defective desquamation (shedding of outer keratin)

Small to large pruritic edematous plaques that come and fade w/in hours. Collagen bundles are abnormally spaced (edema confined to dermis). Dilated lymphatic channels. Normal epidermis. 3 types (w/ causes and examples)

Urticaria (hives) - IgE (mast cell) dependent - pollens, foods, drugs, etc - Type 1 Hypersensitivity - IgE independent (mast cell) - Opiates, antibiotics curare, contrast media - Direct degranulation - Mast cell independent - Aspirin, C1 inhibitor deficiency (H.A.E.) - Directly increase vascular permeability

Red, vesicular, oozing, very pruritic rash. Edema within the intercellular spaces of the epidermis, separating keratinocytes in the stratum spinosum. Intraepidermal vesicles. What is that edema sentence called?

Acute Eczema Spongiosis -- CLASSIC for acute eczematous dermatitis

Eczematous dermatitis (eczema) -- molecular cause? Describe the path of events

T-cell mediated inflammatory reaction (type 4 hypersensitivity) Hapten taken up by Langerhans cells --> presented to naive CD4 T cells. RE-EXPOSURE --> memory T cells release cytokines and chemokines that cause characteristic inflammation.

How to tell if eczema is caused by contact or ingested substance?

Contact = mononuclear infiltrate w/in superficial dermis Ingested = lymphocytic infiltrate w/ eosinophils around superficial AND deep dermal vessels

Pruritic rash. Multiple erythematous patches of the distal arms and legs, dorsum of hands, palms and soles. Some have pale, vesicular, or eroded centers w/ surrounding erythematous rings. Dx? What is it? Predisposing conditions? (4 groups)

Erythema multiforme Hypersensitivity reaction to infections or drugs Infections = HSV, Mycoplasma, Histo, Coccidio, Typhoid, Leprosy, other Drugs = Sulfa, penicillin, other Cancer = carcinoma, lymphoma Collagen dz = SLE, dermatomyositis, PAN

Erythema multiforme - molecular cause

Skin-homing of CD8+ T cells (central portion) and other cells

Child. Pruritic rash w/ various erythematous patches everywhere. Target lesions. FEVER. Predisposing conditions?

Stevens-Johnson syndrome Same as erythema multiforme

Child. Fever. Extensive rash with diffuse necrosis and sloughing of cutaneous and mucosal epithelial surfaces. Target lesions.

Toxic epidermal necrolysis

Well-demarcated, pink to salmon-colored plaques covered by loosely adherent parakeratotic silver-white scales. Marked epidermal thickening, downward elongation of rete ridges. Little to no stratum granulosum. Thinned epidermis over dermal papillae tips. Dilated tortuous BVs within papillae. Cause? Most common cytokines? (4) Genetics?

Psoriasis Autoimmune Th1, Th17, and CD8+ cells accumulate in epidermis, secrete cytokines and growth factors, causing keratinocyte proliferation. IL-12, IFN-gamma, TNF, IL-17 HLA-C

Koebner phenomenon Seen in what entities? (2)

Local trauma --> psoriatic lesion formation Psoriasis, Lichen Planus

DESCRIBE: - Auspitz sign - Spongiform pustules - Munro microabscesses Disease?

Tiny bleeds when scale is lifted from plaque Small aggregates of neutrophils w/in spongiotic foci of epidermis Small aggregates of neutrophils in parakeratotic stratum corneum PSORIASIS

Red-yellow macules and papules w/ greasy base and scaling and crusting. Dandruff. Fissues behind ears. Mounds of parakeratosis w/ neutrophils and serum at ostia of hair follicles. 2 potential causes?

Seborrheic Dermatitis - Increased sebum production (found in oily locations) - Malassezia infection Both --> inflammation of the epidermis

Itchy, purple, polygonal, planar papules and plaques Characteristic microscopic finding? Classic finding on the plaques

Lichen planus Dense, continuous infiltrate of lymphocytes along the D-E junction (INTERFACE DERMATITIS) -- SAWTOOTH Wickham striae -- white dots or lines (hypergranulosis)

70% of Lichen planus is associated with ___ lesions

Oral -- white, reticulated, or net-like

Oral ulcers that persist for months, followed by cutaneous superficial thin vesicles and bullae that rupture easily, leaving shallow erosions covered in serum and crust Cause? Results in what? Most common type/location of blister?

Pemphigus vulgaris Autoantibodies against DESMOGLEIN 1 and 3, causing disruption of intercellular adhesions and formation of blisters. ACANTHOLYSIS Supra-basal

Tense bullae w/ clear fluid involving erythematous or normal-looking skin. Do not rupture easily, heal without scarring. Basal cell vacuolization. Most common type/location of blister? Molecular cause?

Bullous pemphigoid Sub-epidermal (hence why it's not breakable) Anti-hemidesmosome (BPAG) autoantibodies

Bilateral, symmetric, grouped urticaria and vesicles, VERY pruritic. Sub-epidermal blisters. Microabscesses at tips of dermal papillae. Common association? Molecular cause?

Dermatitis Herpetiformis Celiac disease (males) IgA antibodies cross-react with reticulin, causing release of epidermal BM from dermis

How will immunofluorescence look for dermatitis herpetiformis?

Localized IgA deposits at the tips of the dermal papillae

Baby born with (or soon develops) sub-epidermal blisters that become erosions in flexural creases or elsewhere. Dx class? 3 types (w/ mutations and locations)

Epidermolysis bullosa - Simplex (keratin 5 or 14) - Basal layer - Junctional (laminin) - Lamina lucida - Dystrophic (COL7A1 - type 7) - Lamina densa

Urticaria and vesicles w/ scarring, exacerbated by sunlight. Sub-epidermal vesicles, thickened dermal vessel walls w/ protein deposition

Porphyria - cutaneous manifestation

Teenager, erythematous papules, nodules, and pustules. Follicular papules w/ and w/o a central black keratin plug. What are those follicular papules called? 3 causes

Acne vulgaris Open and closed comedones - Keratinization plugs sebum outflow - Hypertrophy of sebaceous glands in puberty - Propionibacterium acnes (convert sebum lipids to pro-inflammatory fatty acids)

Episodes of flushing, followed by persistent erythema and telangiectasia, followed by formation of pustules and papules. Finally, thickening of nasal skin by confluent papules/follicles. Cause?

Rosacea High level of CATHELICIDIN, activation of TLR2, up-regulation of kallikrein 5

Rosacea - characteristic morphology

Perifollicular infiltrate of lymphocytes surrounded by dermal edema and telangiectasia

Painful, erythematous plaques and nodules that are easily palpable. Fever and malaise. Connective tissue septae are widened, then inflammation causes septal fibrosis Causes? What is it?

Erythema nodosum ``` Infections = Group A strep, TB Drugs = sulfas, OCPs Sarcoidosis IBD Malignant neoplasms ``` Delayed hypersensitivity to microbial or drug antigens

Erythematous, slightly tender nodule that ulcerates. Granulomatous inflammation and caseous necrosis w/in fat lobules. Necrotizing vasculitis of deep vessels of skin.

Erythema induratum

Relapses of fever and erythematous plaques or nodules on lower extremities w/ aggregates of foamy macrophages and other inflammation. A type of ____. Like what other diseases?

Weber-Christian disease

Gray-white to tan flat/convex small papules w/ rough pebble-like surface on dorsal surfaces and periungual areas Cause?

Verruca vulgaris HPV -- squamous proliferation

Undulant epidermal hyperplasia, cytoplasmic vacuolization, perinuclear halos, condensed granules and jagged eosinophilic cytoplasmic keratin aggregates

Koilocytosis -- Verruca (warts)

Brick or box-shaped dsDNA virus w/ envelope, replicates in the cytoplasm, and has dumbbell-shaped DNA core Disease?

Poxvirus Molluscum contagiosum

Firm, pruritic, pink to skin-colored umbilicated papules.

Molluscum contagiosum

Large ellipsoid, homogenous, cytoplasmic influsions in cells of stratum corneum and granulosum.

Molluscum bodies

Erythematous macule and multiple small pustules. Shallow erosions, drying serum, honey crust. Molecular feature? Cause? What does it do?

Impetigo Neutrophil accumulations beneath the stratum corneum Staph. aureus -- toxin cleaves desmoglein 1, causing loss of upper epidermal cell-cell adhesion, and thus blistering

Children, scalp, hairless patches of skin w/ mild erythema, crust formation, and scaling

Tinea capitis

Children, body, expanding round, slightly erythematous plaque w/ elevated scaling border.

Tinea corporis

Obese men, moist, red patches w/ raised scaly borders in the inguinal areas

Tinea cruris

Diffuse erythema and scaling in web spaces of feet. Discoloration, thickening, and deformity of toe nails

Tinea pedis + onychomycosis

Upper trunk, groups of macules of various size and color w/ fine peripheral scale. Cause?

Tinea versicolor Malassezia furfur (yeast)

Bright pink to red PAS+ organisms w/in the anucleate cornified layer of skin, hair, or nails

Dermatophytes (tineas)

Robbins - Skin (Ch. 25) Flashcards

(80 cards)