Skin

Jeffrey Sosnowski M.D., Ph.D.

Learning Objectives
Understanding of burn types
Knowledge of skin lesion terminology
Discuss lesions of epithelium, melanocyte
and dermis within context of lesion
terminology and pathology
Understanding of reactive and hypertrophic
skin lesions
Knowledge of blistering and infectious lesions

Skin Histology

Cutaneous Burns
1st - degree, congestion, pain, vasodilation,
edema but no necrosis
2nd - degree, necrosis of epidermis but spares
dermis
Blisters separating epidermis from dermis
Partial thickness burn

3rd - degree, carbonized epidermis and

dermis with lost of tissue structure
Full thickness burn

Healing of Cutaneous Burns

1st degree burns have little cellular damage and
requires basal cells to replace damages epithelial
cells, without scar formation
2nd degree burns also heal without a scar because
basal cells of the epidermis are spared and
regenerate the epidermis
3rd degree burns with spared skin appendages can
resurface the damaged skin. Dermal tissue replaces
damages skin with dense scar
Skin grafts can reduce the density of scar
Fluid loss and infection are major problmes

Lesion Terminology

Flat Lesions
Macule
Less than 5 mm,
different color than
surrounding skin

Patch
Greater than 5 mm

Raised Lesions
Papule
less than 5 mm,
discrete solid elevated
lesion

Plaque
Greater than 5mm

Fluid-Filled Lesions
Vesicle
Less than 5 mm, fluid
may be clear, serous,
hemorrhagic or
purulent

Bulla
Greater than 5 mm

Pustule
Usually less than 5
mm, filled with pus

Scale and Crust

Scale
Excess stratum corneum,
usually white or gray color

Crust
A hardened layer of
serum, blood or purulent
exudate on the surface of
skin

Eschar
Adherent thick, dry black
crust

Purpura
(skin hemorrhage)
Petechiae
1-2 mm, nonblanchable
macules resulting from
tiny hemorrhages

Ecchymosis
Collection of blood into
skin or mucous
membrane forming
macules and patches

Palpable purpura
Plaques of ecchymoses

Skin Loss
Ulcer
Loss of epidermis and
at least the upper
dermis

Erosion
Loss of epidermal or
mucosal epithelium

EPITHELIAL TUMORS OF
SKIN

Seborrheic Keratosis
Arise spontaneously in
adults
Round, flat, coin-like,
stuck on,
pigmented, velvety
papule
Exophytic proliferation of
basaloid cells above the
D/E junction
Hyperkeratosis,
acanthosis, horn cysts,
melanin pigmentation

Fibroepithelial Polyp
AKA skin tag, acrochordon,
squamous papilloma
Bag-like, flesh-colored protrusions
Fibrovascular core covered by
benign squamous epithelium
Axilla, neck, trunk, face,
intertriginous areas
A/W diabetes and intestinal
polyposis

Acanthosis Nigricans
Thickened hyperpigmented skin in flexural
areas
Acanthosis of epidermis, increased melanin pigment

Benign type 80%, develops gradually in

childhood or puberty
Associated with diabetes, obesity, endocrine
tumors, polycystic ovary syndromes

Malignant type adults, sudden onset,

associated with GI carcinoma

Acanthosis Nigricans

Actinic Keratosis
Dysplasia of the squamous epithelium
secondary to sun exposure
Ionizing radiation, hydrocarbons, arsenicals

Precursor of squamous cell carcinoma

Tan, red or skin colored; rough sandpaperlike consistency; cutaneous horn, < 1cm
Keratinocytic atypia, hyperkeratosis,
parakeratosis, and dermal elastosis

Actinic
Keratosis

Squamous Cell Carcinoma

Second most common tumor arising on
sun-exposed sites in older people
UV light, old scars, chronic ulcers, fair skin
Immunosuppression, xeroderma
pigmentosum

Males > females

Potential for metastases (<5%)

Squamous Cell
Carcinoma

Squamous Cell Carcinoma

invasive nests of cells showing keratinization glassy pink
cytoplasm (small arrow), squamous pearls of extracellular
keratin (large arrow)

Basal cell carcinoma

Most common invasive cancer,
>400,000 per year.

Most common tumor on sun-exposed skin

UV light, fair skin, immunosuppression, XP

Pearly papules, pigmentation, ulceration

Locally invasive rodent ulcer
May invade bone, other deep tissues

Rarely metastasize

Basal Cell
Carcinoma

Basal cell carcinoma

Cells resemble normal basal epithelial cells

Nodules, islands or cords extend downward from
epidermis or outward from follicular epithelium
Peripheral palisading, clefts, mucinous or fibrous
matrix

Skin Carcinoma Pathogenesis

Enivironmental carcinogens UV light
DNA damage (PTCH, p53)
direct immunosuppressive effects (Langerhans cells)

Viral transformation
HPV sequences detected in precursors

Chemical Mutagens

Adnexal Tumors

Adnexal Tumors
Tumors arising from skin appendages

Hair follicle origin trichoepithelioma, trichilemmoma,

trichofolliculoma
Eccrine gland origin eccrine poroma, chondroid
syringoma
Apocrine gland origin - cylindroma
Sebaceous gland origin sebaceous adenoma,
carcinoma

Usually benign, but malignant forms exist

Clinically may be confused with basal cell
carcinoma
Flesh colored papule or nodule

Cylindroma
Common on forehead
and scalp
Often multiple
Islands of basaloid
cells (puzzle pieces)
Fibrous matrix

Melanocyte Lesions

DISORDERS OF PIGMENTATION
Vitiligo: melanocyte loss
Albinism: tyrosinase enzyme defect
Freckle (ephelis): increased melanin
production
Melasma: increased melanin
Epidermal type
Dermal type

VITILIGO

Loss of melanocytes within

epidermis, resulting in areas
of hypopigmentation
All ages and races
Asymptomatic, flat
May occur at sites of
repeated trauma
?Autoimmune mechanism
NOT albinism (tyrosinase
deficiency)

LENTIGO
Oval tan brown
macules, that do not
darken when exposed
to sun (ddx freckle)
<10mm
Involve mucous
membranes and skin
Linear melanocytic
hyperplasia,
non-nested, basal,
(lentiginous)

Nevi

Junctional Nevi
nests of melanocytes at DE jct

Benign Nevi
Junctional, compound,
dermal

MALIGNANT MELANOMA
Neoplasm derived from melanocytes (or
possibly from nevus cells)
Most rapidly increasing cancer
Incidence has doubled over last 30 years
6th most common cancer (1st in young
females)

Melanoma Risk Factors

Fair skin
Multiple benign nevi (>50)
Dysplastic nevi
Personal or family history of melanoma
UV radiation, severe blistering sunburns
and chronic tanning
Immunodeficiency

Risk factors for Melanoma

Fair skin, multiple nevi, severe
sunburns

MELANOMA Clinical Features

Usually arise in skin, but not exclusively (oral,
anogenital, meninges, eye)
Sun exposed skin

Usually asymptomatic, some itching

Large, usually >10mm
Dark and variably pigmented
Irregularly shaped
New or changing lesion, especially in
adulthood

Malignant Melanoma
Irregular shape and color,
large, intensely black, nodular
and flat

Melanoma
unusual sites

Warning signs of melanoma

Asymmetry
Border irregularity
Color variation
Diameter >10 mm
Elevation or formation of a
nodule
Any change in a nevus

Growth patterns of melanoma

Radial growth phase (non-tumorigenic)
Horizontal growth within epidermis and
superficial dermis: no capacity to metastasize
Lentigo maligna melanoma sun damaged facial
skin
Superficial spreading melanoma
Acral lentiginous melanoma

Vertical growth phase (tumorigenic):

Growth into deeper dermis: capacity to
metastasize
Nodule formation, expansile mass

Diagram of tumor progression in

melanoma

Better Prognosis in Melanoma if

Depth < 1.7 mm

Low mitotic/proliferative rate
Lack of ulceration
Brisk lymphocytic inflammation
Absence of regression
Female gender
Location on extremity
Lack of metastasis

Molecular Genetics of Skin Carcinoma

(Gorlin Syndrome)
Nevoid basal cell carcinoma
syndrome
Multiple BCC at young age +
numerous systemic
abnormalities
Autosomal dominant, ch9q22
Defect of PTCH gene with
mutations characteristic for
UV damage
Similar PTCH gene mutations
in sporadic BCC

Dermal lesions

Tumors of Dermis
Xanthomas
collections of foamy histiocytes within
dermis
appear as yellow streaks or nodules

eruptive xanthomas
tuberous/tendinous xanthomas
plane xanthomas
xanthelasma

Lipoma

Skin leiomyoma

Keloid

Skin Vascular Lesions

Hemangiomas
Benign, more common in females (5:1)
Appear at birth and usually involute by
fibrosis with time (90% of cases by 9 yrs of
age)

Salmon Patches (Stork Bite)

Flat vascular malformations commonly
found on the head and neck, most fade
within the first year of life

Port Wine Stains

Flat often large hemangiomas, present at
birth and grow in size as the child grows.
Common on the face

Sturge-Weber Syndrome
5% of patients with PWS that involve the
upper eyelid or forehead
PWS with distribution of the trigeminal
nerve and includes vascular malformation
in the CNS

Kaposi Sarcoma
Neoplastic cells that line lymph or blood vessels
Lesions are purple, red to brown, violaceous
plaques
Most commonly found on legs and face but could
also be mucosal
Types

AIDS-related
Classic (Mediterranean)
Endemic (African)
Transplant-related

Caused by Kaposis sarcoma-associated

herpesvirus or HHV-8

Skin 2

Jeffrey Sosnowski M.D., Ph.D.

Neurofibromatosis I
Neurofibromas are the
most common tumors
Usually develop
around puberty
6 or more caf-au-lait
spots, pigmented
macules
Lisch nodules on the
iris

Infections

Shingles (Herpes Zoster)

Caused by the
varicella zoster virus,
the same virus that
causes chickenpox
The virus remains in
the dorsal root
ganglia and becomes
reactivated

Herpes Simplex Virus I and II

I, oral herpes
II genital herpes
Spread through
kissing, sharing
toothbrushes, eating
utensils and sexual
contact

Infection/Infestation
Molluscum contagiosum
poxvirus
contagious, but self-limited
spread by direct contact
umbilicated papules seen especially on
trunk and anogenital region
molluscum bodies seen microscopcally

Fungal Tinea
Group of fungal
infection that include
ringworm, athletes
foot and jock itch

Trichotillomania
A disorder that
involves recurrent
urges to pull out hair
from your scalp

Bed Bugs (Mites)

Parasitic insects that
feed on blood

Disorders of Epidermal
Maturation

Ichthyosis
fishy
Genetically inherited
disorders
Hyperkeratosis resulting
in fish-like scales
Some acquired variants
exista/w lymphoid and
visceral malignancies

Acute Inflammatory
Dermatoses

Urticaria
Also known as hives
Common; localized mast cell
degranulation with resultant dermal
microvascular hyperpermeability
Results in pruritic edematous plaques
called wheals
Angioedema is similar but with deeper
edema of dermis and subcutaneous fat

Urticaria, pathogenesis
Antigen-induced release of vasoactive mediators
from mast cell granules through sensitization
from specific IgE antibodies
Follows exposure to antigens such as: pollens,
foods, insects, drugs
Can also be IgE-independent as in reactions to
opiates, curare, radiographic contrast media,
and antibiotics
These substances directly cause mast cell
degranulation

Figure 25-22 Urticaria. Clinically, there are erythematous, edematous, often circular plaques covered by a normal epidermal surface.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 5 December 2007 09:06 PM)
2007 Elsevier

Acute Eczematous Dermatitis

Eczema is a clinical term describing red,
papulovesicular, oozing, and crusted lesions that
develop into raised scaling plaques
Eczema categories:

allergic contact dermatitis

Atopic dermatitis
Drug-related eczematous dermatitis
Photoeczematous dermatitis
Primary irritant dermatitis

Acute Eczematous Dermatitis

Eczema means to boil over
Seen best with acute contact reaction to
topical antigens such as poison ivy

Lesions prone to bacterial superinfection

Persistent lesions become less wet with
time and become scaly (hyperkeratotic) as
the epidermis thickens (acanthosis)

Acute Eczematous Dermatitis

Histology:
Characterized by spongiosis (synonym is
spongiotic dermatitis)
Causes intercellular bridges to appear
prominent
May result in shearing of intercellular
attachment sites and the formation of
intraepidermal vesicles

Figure 25-25 Eczematous dermatitis. A, In an acute allergic contact dermatitis, numerous vesicles appear at the site of antigen exposure (in this case, laundry detergent
that persisted in clothing). B, Histologically, intercellular edema produces widened intercellular spaces within the epidermis, eventually resulting in small, fluid-filled
intraepidermal vesicles.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 5 December 2007 09:06 PM)
2007 Elsevier

Chronic Inflammatory
Dermatoses

Introduction

Persistent
Roughened skin surface
Four conditions:
Psoriasis
Seborrheic dermatitis
Lichen planus
Lupus erythematosis

Psoriasis

Common
All ages
Arthritis, myopathy, enteropathy,
spondylitic joint disease, or AIDS
Skin of extensor surfaces, scalp,
intergluteal cleft, and glans penis

Psoriasis, gross
Well-demarcated, salmon-colored plaque
covered by loosely adherent silver-white
scale

Psoriasis, histology
Acanthosis
Regular downward elongation of rete
ridges
Mitotic figures above basal layer
Parakeratosis

Psoriasis, histology
Auspitz sign Thinned suprapapillary
plates overlying dilated vessels within the
dermal papillae
spongiform pustules and Munro
microabscesses

Lupus erythematosus

Acute, subacute, and chronic

Acute: malar erythema; 99% will have SLE
Subacute: small, generalized,
erythematous, sometimes scaly lesions;
50% will have SLE
Chronic: Localized cutaneous form with no
associated systemic manifestations,
discoid lupus erythematosus (DLE)

Blistering (Bullous) Diseases

Blistering (Bullous) Diseases

Inflammatory and non-inflammatory
Inflammatory:
Pemphigus
Bullous pemphigoid
Dermatitis herpetiformis

Non-inflammatory:
Porphyria
Epidermolysis bullosa

Level of the blister essential for diagnosis

Pemphigus
Rare, autoimmune disease, M=F, age 3050
Loss of integrity of the normal intercellular
attachments within the epidermis and
mucosal epithelium
Four variants:
Pemphigus vulgaris
Pemphigus vegetans
Pemphigus foliaceus
Pemphigus erythematosus

Pemphigus vulgaris
80% of pemphigus cases worldwide
Mucosa and skin; often presents with ulcers in
the mouth
Superficial vesicles and bullae that rupture
easily; can involve the whole body
Acantholysis selectively involves the layer of
cells above the basal cell layer (suprabasal
acantholytic blister)
Uniformly fatal if untreated

Pemphigus, morphology
All forms exhibit acantholysis
Epithelial cells lose attachments and
become rounded
The single layer of basal cells at the blister
base resembles a row of tombstones
In all forms, there is a superficial dermal
infiltrate of lymphocytes, histiocytes, and
eosinophils

Pemphigus vulgaris

Pemphigus, pathogenesis
Sera contain IgG to intercellular cement
substance of skin and mucous
membranes
DIF: net-like pattern of intercellular IgG
deposits to sites of acantholysis
Vulgaris: antibody to desmoglein 3

Bullous pemphigoid

Distinct from pemphigus

Common, autoimmune
Generally affects elderly
Many clinical presentations
Less common mucosal involvement than
pemphigus (10-15%)

Bullous pemphigoid
Tense bullae with clear fluid on normal or
erythematous skin
Do not rupture as easily as the blisters in
pemphigus
Heal without scarring, unless infected
Inner thigh, flexor surfaces of forearms,
axilla, groin, and lower abdomen

Bullous pemphigoid, pathogenesis

Antibodies directed to proteins at the
dermo-epidermal junction
(hemidesmosome)
Linear zone deposition of Ig and
complement (Lupus=granular)
Blister develops within the lamina lucida

Dermatitis herpetiformis
Rare; M > F; age 20-30
Papules, vesicles, and occasional bullae
on an erythematous, urticarial base
Major association with celiac disease
Responds to gluten free diet

Extremely pruritic
Bilateral and symmetrical; extensor
surfaces, upper back, and buttocks

Dermatitis herpetiformis, histo

Microabscesses at the tips of dermal
papillae
Microscopic blister formation beneath the
basal cells overlying these
microabscesses (subepidermal blisters)
Eosinophils causes confusion with bullous
pemphigoid (look at blister edge)

Dermatitis herpetiformis
DIF: granular deposits of IgA at the tips of
the dermal papillae
Pathogenesis: antibodies against gliadin
HLA-B8 and HLA-DRw3