Robbins - Skin (Ch. 25) Flashcards
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
Large freckle-like spots independent of sun exposure, aggregates of melanosomes
Café au lait spots
Small, oval, tan-brown macules or patches. Do not darken with sun. Linear melanocyte hyperplasia above basement membrane. Elongated, thinned rete ridges.
Lentigo
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)
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
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
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
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
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
2 major phases of melanoma growth
Radial growth (horizontal)
Vertical growth (deep)
The vertical growth phase of melanoma is heralded by the appearance of a _____ and correlates w/ the potential to ____
Nodule
Metastasize
Unlike benign nevi, melanomas do not show any histologic sign of ____ within the deep invasive part of the dermis
Neurotization
Melanoma - primary prognostic factor
Metastasize to where?
Breslow thickness (depth)
Regional LNs
5 things to look for on a suspected melanoma
ABCDEs
- Asymmetry
- Irregular Borders
- Variable Color
- Increasing Diameter
- Evolution/change (rapid)
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
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
Thickened, hyperpigmented skin w/ velvet-like texture in flexural (folds) areas
**2 types (w/ associations)
Acanthosis nigricans
- Benign (obesity, DM, puberty)
- Paraneoplastic (GI adenocarcinoma)
Acanthosis nigricans - genetics (familial)
Genetic pathway in DM?
FGFR3 (like in SK)
Insulin –> IGFR1 –> FGFR3 pathway activation
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
Fibroepithelial polyps + perifollicular mesenchymal tumors
Birt-Hogg-Dubé syndrome
Fibroepithelial polyps - become more numerous/prominent during _____
Pregnancy
Multiple trichilemmomas
Cowden syndrome (PTEN)
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
Multiple, small, tan papules around the lower eyelids
Syringomas
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)
