Skin functions
squamous epithelial cells: synthesize cytokines
melanocytes: produce melanin, protect from UV
dendritic cells: Langerhans cells to present antigens
lymphocytes
neural end organs, axonal processes
o
merkel cells: neuroendocrine function or
mechanoreceptors
adnexal components
o
sweat glands: guard from body temp changes
o
hair follicles: harbor epithelial stem cells
Macroscopic terms
excoriation
traumatic lesion breaking the epidermis
cause raw linear area (deep scratch)
self induced
lichenification
thickened rough skin
prominent skin markings
from repeated rubbing
macule
circumscribed lesion, <5mm
flatness
coloration
patch is >5mm
oncholysis
separation of nail plate from nail bed
papule
elevated dome-shaped or flat-topped lesion
<5mm across
nodule is >5mm
plaque
elevated flat-topped lesion
>5mm across
may be caused by coalescent papules
pustule
discrete pus-filled raised lesion
scale
dry, horny, platelike excrescence
usually from imperfect cornification
vesicle
fluid-filled raised lesion <5mm across
bulla >5mm
blister is common term for both
wheal
itchy, transient, elevated lesion
variable blanching and erythema
from dermal edema
Microscopic terms
acantholysis: loss of intercellular cohesion between
keratinocytes
acanthosis: diffuse epidermal hyperplasia
dyskeratosis: abnoromal, premature keratinization in cells;
below stratum granulosum
erosion: discontinuity of skin showing incomplete loss of
epidermis
exocytosis: infiltration of epidermis by inflammatory cells
hydropic swelling: ballooning; intracellular edema of
keratinocytes; often in viral infections
hypergranulosis:D hyperplasia of stratum granulosum; often
from intense rubbing
hyperkeratosis: thickening of stratum corneum; often with
keratin abnormality
lentinginous: linear pattern of melanocyte proliferation within
epidermal basal cell layer
papillomatosis: surface elevation caused by hyperplasia &
enlargement of contiguous dermal papillae
-
parakeratosis: keratinization with retained nuclei in stratum
corneum; normal on mucous membranes
spongiosis: intercellular edema of epidermis
ulceration: discontinuity of skin; complete loss of epidermis
revealing dermis or subcutis
vacuolization: formation of vacuoles within or adjacent to cells;
often refers to basal cell-BM zone area
Disorders of pigmentation and melanocytes
freckle (ephelis)
MC pigmented lesion in childhood
darken in cyclic fashion
no change in # of melanocytes but degree of pigmentation
lentigo
benign localized hyperplasia of melanocytes
don’t darken w/ sun
melanocytic nevus (pigmented nevus, mole)
junctional nevi  compound nevi  intradermal nevi
maturation: deepest part resemble neural tissue
o
melanomas do not show maturation
mutations in BRAF or NRAF  malignant melanoma stopped by
p16/INK4a
dysplastic nevi
precursors of melanoma
most are stable
markers of increased melanoma risk
larger, pebbly, variably pigmented, irregular borders, acquired
rather than congenital
melanoma
radial growth (horizontal)
o
lack ability to metastasize
o
lentigo maligna: indolent lesion on face of older men;
stays radial for long time
o
superficial spreading: MC type of melanoma; sunexposure related
o
acral/mucosal lentiginous: unrelated to sun exposure
vertical growth
o
can invade
o
nodule that correlates with clone of cells with
metastatic potential
inherited genes + sun exposure
ABCs of melanoma: asymmetry, irregular borders, color changes
good prognosis:
o
tumor depth (Breslow thickness) <1.7 mm
o
few mitoses
o
no tumor regression
o
brisk response of tumor infiltrating lymphocytes
o
female gender
o
on extremities
predisposing factors:
o
severe sunburn early in life
o
mutations that diminish RB proteins common
Benign epithelial tumors
seborrheic keratosis
old people
trunk
pore-like ostia impacted w/ keratin
activating mutation of FGFR3
Leser-Trelat sign: paraneoplastic syndrome when tumor cells of GI
product FGFa
dermatosis papulosa nigra: multiple small lesions on face
acanthosis nigricans
velvet-like thickening
benign type: puberty, AD, DM or pituitary/pineal tumors
malignant type: older people, underlying GI adenocarcinoma
fibroepithelial polyp
skin tag
-
Birt-Hogg Dube syndrome = tumrors of perifollicular mesenchyme
in hairbulb
epithelial cyst (wen)
filled with keratin or lipids from sebaceous secretions
epidermal inclusion: resembles normal epidermis
pilar/trichilemmal: resemble follicular epithelium
dermoid: multiple appendages (hair follicles) budding outward
from its wall
steatocystoma simplex: resembles sebaceous gland duct
steatocystoma multiplex: heritable, missense mutations keratin
17, pachyonychia congenital type 2
adnexal (appendage) tumors
associated with many diseases
multiple trichilemmomas: Cowden syndrome, mutation in
suppressor PTEN, increased breast CA risk
cyclindroma: ductal differentiation, on forehead, can form turban
tumor, inactivated suppressor CYLD
syringomas: eccrine differentiation, tan papules in lower eyelids
sebaceous adenomas: internal malignancy related in Muir-Torre
syndrome like nonpolyposis colorectal carcinoma syndrome
pilomatricomas: follicular differentiation, activating mutations
CTNNB1 (B-catenin)
Premalignant & malignant epidermal tumors
actinic keratosis
precursor to carcinoma and showing worsening dysplastic
changes
usually sun damaged skin showing hyperkeratosis
may develop keratin “cutaneous horn”
<1cm
sandpaper consistency
squamous cell carcinoma
2nd MC tumor on sun exposed sites
damage from exposure to UV proportional to sun exposure time
P53 damage occurs early
immunosuppression by HPV 5 & 8
nodular, scaly, ulcerate
involve all levels of epidermis
keratoacanthoma = variant of well differentiated squamous cell
carcinoma
o
period of rapid growth  spontaneous regression
basal cell carcinoma
MC invasive CA in humans
common in sun exposed pale people
pearly papules, prominent, prominent telangiectasias (dilated
subepidermal BVs)
superficial variant = erythematous pigmented plaque; resembles
melanoma
nevoid basal cell carcinoma syndrome (NBVVS) or Gorlin
syndrome
o
AD multiple basal cell carcinomas before age 20
o
intracranial calcifications
o
cleft lip/palate
o
associated with PTCH gene (patched)
Tumors of the dermis
benign fibous histiocytoma (dermatofibroma)
firm, tan to brown papules
dimple inward on compression (melanomas protrude)
dermatofibrosarcoma protuberans
well differentiated primary fibrosarcoma of skin
rarely metastasize
solid nodules mostly on trunk
fibroblasts arranged in “storiform” pattern
overlying dermis is thinned
deep extension into fat = “honeycomb” pattern
translocation btwn COL1A1 and PDGFB where collagen promoter
causes overexpression of PDGF
Tumors of cellular migrants to skin
mycosis fungoides (cutaneous T cell lymphoma)
chronic proliferative process
may evolve into generalized lymphoma
red patches, scaling plaques, fungating nodules
development of large multiple red nodules correlates to systemic
spread
Sezary syndrome: seeding of blood by malignant T cells w/
erythemia & scaling of entire body (erythroderma)
Sezary-Lutzner cells = histologic hallmark of CTCL; T helper cells
CD4+ forming bandlike aggregates in superficial dermis
o
small clusters = Pautrier microabscesses
mastocytosis
mast cell degranulation  release histamine & heparin
urticarial pigmentosa
o
children, occurs for 50%
o
multiple round red nonscaling papules
Darier sign: localized dermal edema & erythemia when lesion
rubbed
Dermatographism: edema resembling hive in normal skin due to
stroking w/ pointed instrument
point mutation in c-KIT receptor tyrosine kinase
Disorders of epidermal maturation
icthyosis
green root “fishy”
excessive keratinization looks like scales
defective desquamation
buildup of compacted stratum corneum
X-linked = deficiency of steroid sulfatase
impaired epidermal maturation
Acute inflammatory dermatoses
urticaria (hives)
wheal and flare = pruritic edematous plaques
o
occur in areas exposed to pressure (trunk, extremities,
ears)
o
superficial dermal edema
IgE mediated type I hypersensitivity
o
dependent: antigens (pollen, food)
o
independent: degranulation of mast cells (opiates,
antibiotics, aspirin)
acute exzematous dermatitis (“to boil over”)
allergic contact dermatitis: poison ivy
o
Langerhans cells present to CD4+ and memory cells
recruit inflammatory cells on next exposure within 24
hrs

UV light injurious to Langerhans cells and
prevent sensitization
atopic dermatitis
drug-related eczematous dermatitis
photoeczematous dermatitis
primary irritant dermatitis
erythema multiforme
hypersensitivity rxn to infections, drugs, collagen vascular dz
o
macules, papules, vesicles, bullae
o
target lesions
Steven-Johnson syndrome = febrile, children, erosion of skin &
mucous membranes
toxic epidermal necrolysis = diffuse necrosis & sloughing of
cutaneous & mucosal epithelial surfaces (analogous to burns)
epithelial cells killed by skin homing (CLA+) CD8+ CTLs
Chronic inflammatory dermatoses
psoriasis
well-demarcated pink to salmon-colored plaques w/ silver-white
scale
arthritis, myopathy, enteropathy, spondylitic joint disease, AIDS
-
-
elbows, knees, scalp, lumbosacral areas, intergluteal cleft, glans
penis
nail changes: yellow-brown, pitting/dimpling/separation
pustular psoriasis = pustules form on plaques
o
can become generalized and life threatening w/ fever,
leukocytosis, arthralgia, electrolyte problems
stratum granulosum thinned or absent & extensive overlying
parakerototic scale seen
o
auspitz sign = minute bleeding points when scale
lifted from plaque
HLA-C & TNF major factors
Koebner phenomenon = psoriatic lesions induced by local trauma
where inflammatory response promotes lesions
seborrheic dermatitis

areas w/ sebaceous glands (scalp, forehead, face, presternal area)
o
not a disease of these glands though

often presents as dandruff

Leiner disease: generalized and associated w/ diarrhea and FTT

Cradle cap: infants

HIV: worse prognosis

worse in Parkinson disease ( sebum as result of  dopamine)

Yeast Malassezia furfur may cause
lichen planus

6 P’s: pruritic, purple, polygonal, planar papules, plaques

Resolves in 1-2 years

Wickham striae: papules w/ white dots/lines by areas of
hypergranulosis

Civatte bodies (colloid): anucleate necrotic basal cells

Lichen planopilaris: lichen planus affecting epithelium of hair
follicles
Blistering (bullous) diseases
inflammatory

Pemphigus
o
IgG Autoantibodies that result in dissolution of
intracellular attachments within the epidermis and
mucosal epithelium
o
Can be life threatening
o
Pemphigus vulgaris: most common type, effects
mucosa and skin

May present as oral ulcers months before
on skin

Suprabasal acantholytic blister
o
Acantholysis: lysis of intercellular adhesions that
connect squamous epithelial cells, cause cells to
become rounded

Bullous pemphigoid
o
Subepidermal, nonacantholytic blisters difficult to
rupture
o
Linear deposition of Ig & complement in the BM zone
o
BPAG1 and BPAG2 that are constituents of
hemidesmosomes in which antibodies attack

Dermatitis herpetiformis
o
Urticaria and grouped vesicles,
o
Celiac disease association: IgA antibodies to gliaden
cross react with reticulin

Discontinuos granular deposits of IgA on
tips of dermal papillae

Involve symmetric extensor surfaces
noninflammatory

Epidermolysis Bullosa: inherited defects in structural proteins

Porphyria: inborn errors in porphyrin metabolism, pigments in
hemoglobin
o
Subepidermal vesicle w/ associated marked
thickening of walls of superficial dermal vessels
Disorders of epidermal appendages
acne vulgaris

Noninflammatory
o
open comedones: small follicular papules central
black keratin plug (oxidation of melanin)
o
closed comedones: follicular papules w/o central plug,
only seen microscopically

Inflammatory: erythematous papules, nodules, pustules

Propionibacterium acnes: lipase synthesizing bacteria in upper
portion hair follicle
o
Convert lipids in sebum to proinflammatory fatty
acids

Androgens may cause

Treated with antibiotics and synthetic vitamin A (anti-sebaceous
action)
rosacea

Inappropriate activation of the innate immune system
o
High levels of antimicrobial peptide cathelicidin
(mediator of innate)

4 stages
o
Flushing (pre-rosacea)
o
Persistent erythema and telangiectasia
o
Pustules/papules
o
rhinophyma
Panniculitis

Inflammatory rxn in subQ adipose tissue preferentially affecting
CT separating lobules of fat or lobules themselves usually in lower
legs
Erythema nodusum

Acute presentation associated with infection by B-hemolytic strep

Tender erythematous plaques readily palpated rather than seen

Over weeks become flattened and bruise-like

Widening of connective tissue septa due to edema, fibrin
exudation, neutrophilic infiltration w/o vasculitis
Erythema induratum (uncommon)

Primary vasculitis deep vessels supplying lobules

subsequent necrosis and inflammation of fat

Erythematous tender nodule goes on to ulcerate

Without underlying cause

Shows caseous necrosis of fat lobule & granulomatous
inflammation
Infection
Verrucae (warts): HPV

Based on appearance and location

Verruca vulgaris: most common type
o
Frequently on dorsum of hand
Molluscum contagiosum: pox virus, self limited umbilicated lesions

Spread by direct contact

Predilectation for trunk

Staining with giemsa reagent shows diagnostic molluscum bodies
Impetigo: superficial bacterial infection of skin

Contagiosa: group A B-hemolytic strep

Bullosa: s. aureus

Face and hands

honey-colored crust

Accumulation of neutrophils beneath stratum corneum
o
Subcorneal pustule

Blister formation: toxin that cleaves desmoglein 1

No dermis involvement: so no scarring
Superficial fungal infections:

tinea capitis (scalp), barbae (beard), corporis (body surface),
cruris (inguinal obese), pedis (athletes foot), onychomycosis
(nails), dermatophytes

Versicolor: yeast malassezia furfur