Robbins - Skin (Ch. 25) Flashcards Preview

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Flashcards in Robbins - Skin (Ch. 25) Deck (80)
1

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

2

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

Café au lait spots

3

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

Lentigo

4

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)

5

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

6

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

7

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

8

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

9

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

10

2 major phases of melanoma growth

Radial growth (horizontal)

Vertical growth (deep)

11

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

Nodule

Metastasize

12

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

Neurotization

13

Melanoma - primary prognostic factor

Metastasize to where?

Breslow thickness (depth)


Regional LNs

14

5 things to look for on a suspected melanoma

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

15

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

16

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

17

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

**2 types (w/ associations)

Acanthosis nigricans

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

18

Acanthosis nigricans - genetics (familial)

Genetic pathway in DM?

FGFR3 (like in SK)

Insulin --> IGFR1 --> FGFR3 pathway activation

19

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

20

Fibroepithelial polyps + perifollicular mesenchymal tumors

Birt-Hogg-Dubé syndrome

21

Fibroepithelial polyps - become more numerous/prominent during _____

Pregnancy

22

Multiple trichilemmomas

Cowden syndrome (PTEN)

23

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

24

Multiple, small, tan papules around the lower eyelids

Syringomas

25

Proliferation of basaloid cells forming primitive hair follicles

Trichoepithelioma

26

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

Sebaceous adenoma

27

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

28

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

29

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

30

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

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

31

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

P53 mutations

32

Impaired nucleotide excision repair (can't fix pyrimidine dimers)

Increased risk of what?

Xeroderma pigmentosum

Squamous cell carcinoma (sun-exposure)

33

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

34

BCC - genetics

SHH dysregulation

35

Multiple BCCs before age 20 + many other tumors

***Genetics? Results?

Nevoid BCC syndrome (Gorlin syndrome)

PTCH mutation (SHH pathway activation --> SMO and GLI1 activation)

36

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

37

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

38

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)

39

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

40

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

41

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

Mastocytoma

42

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)

43

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

44

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

45

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.

46

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

47

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

48

Erythema multiforme - molecular cause

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

49

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

Predisposing conditions?

Stevens-Johnson syndrome

Same as erythema multiforme

50

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

Toxic epidermal necrolysis

51

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

52

Koebner phenomenon


Seen in what entities? (2)

Local trauma --> psoriatic lesion formation

Psoriasis, Lichen Planus

53

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

54

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

55

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)

56

70% of Lichen planus is associated with ___ lesions

Oral -- white, reticulated, or net-like

57

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

58

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

59

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

60

How will immunofluorescence look for dermatitis herpetiformis?

Localized IgA deposits at the tips of the dermal papillae

61

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

62

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

Porphyria - cutaneous manifestation

63

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)

64

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

65

Rosacea - characteristic morphology

Perifollicular infiltrate of lymphocytes surrounded by dermal edema and telangiectasia

66

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

67

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

Erythema induratum

68

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

69

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

70

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

Koilocytosis -- Verruca (warts)

71

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

Disease?

Poxvirus

Molluscum contagiosum

72

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

Molluscum contagiosum

73

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

Molluscum bodies

74

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

75

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

Tinea capitis

76

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

Tinea corporis

77

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

Tinea cruris

78

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

Tinea pedis + onychomycosis

79

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

Cause?

Tinea versicolor

Malassezia furfur (yeast)

80

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

Dermatophytes (tineas)