Dermatopathology (Part 2) Flashcards
Inflammatory blistering disorders
- Pemphigus
- Bullous Pemphigoid
- Dermatitis Herpetiformis
Noninflammatory blistering disorders
- Epidermolysis Bullosa
- Porphyria
Subcorneal blisters
- Stratum corneum forms the roof of the bulla (as in pemphigus foliaceus)
Suprabasilar blister
- Portion of the epidermis, including the stratum corneum, forms the roof (as in pemphigus vulgaris)
Subepidermal blister
- The entire epidermis separates from the dermis (as in bullous pemphigoid)
Pemphigus
- Etiological factor = autoantibodies
- Result in the dissolution of intercellular attachments (epidermis, mucosal epithelium)
Pemphigus in adults
- Fourth to 6th decades of life
- Men and women are affected equally
Multiple variants of pemphigus
- Pemphigus vulgaris
- Pemphigus vegetans
- Pemphigus foliaceus
- Pemphigus erythematosus
- Paraneoplastic pemphigus
- Disorders are benign
- Extreme cases can be fatal without treatment
Pemphigus vulgaris
- Most common type (80% of cases worldwide)
- Mucosa
- Skin
Pemphigus vulgaris affects the skin
- Scalp
- Face
- Axilla
- Groin
- Trunk
- Points of pressure
Pemphigus vulgaris as oral ulcers
- Persist for months before skin involvement appears
Pemphigus vulgaris primary lesions
- Superficial vesicles and bullae that rupture easily
- Shallow erosions covered with dried serum and crust
Pemphigus foliaceus
- Benign form (endemic in Brazil; fogo selvagem)
Pemphigus foliaceus sites of predilection
- Scalp
- Face
- Chest
- Back
- Mucous membranes (rarely affected)
Pemphigus folaceus bullae
- Blisters found in the superficial epidermis at the level of the stratum granulosum
- Present as areas of erythema and crusting
- Erosions of previous blister rupture
Common histologic feature of all forms of Pemphigus
- Acantholysis
Acantholysis in pemphigus
- Dissolution or lysis of the intercellular bridges
- Pemphigus vulgaris and Pemphigus vegetans
- Acantholysis selectively involves the cells immediately above the basal cell layer
- Suprabasal acantholytic blister
Pemphigus pathogenesis (autoimmune)
- IgG autoantibodies against desmogleins
- Disruption of intercellular adhesions
- Result – Blisters formation
- Direct immunofluorescence
Direct immunofluorescence in pemphigus
- Net-like pattern of intercellular IgG deposits
- Pemphigus vulgaris = IgG is usually seen at all levels of the epithelium in
- Pemphigus foliaceus = IgG distribution is superficial
Pemphigus vulgaris depositis
- Deposition of Ab along the plasma membranes of keratinocytes in a reticular pattern
- Accompanied by suprabasalar loss of cell-to-cell adhesion (acantholysis)
Pemphigus foliaceus deposits
- Ab deposits and acantholysis are more superficial
Bullous pemphigoid
- Affects the elderly
- Orla lesions
Bullous pemphigoid sites of involvement
- Inner aspects of the thighs
- Flexor surfaces of the forearms
- Axillae
- Groin
- Lower abdomen
Bullous pemphigoid oral lesions
- Present in 10% to 15% of affected individuals
- Appear after the cutaneous lesions
- Patients may present with urticarial plaques and severe pruritus
Bullous pemphigoid pathogenesis
- Autoantibodies binding to hemidesmosome proteins
- Linear deposition pattern at dermoepidermal junction
- Antibodies against BPAG2 cause blistering
- Autoantibodies activate complement
- Recruitment
Bullous pemphigoid antigens (BPAGs)
- Components of hemidesmosomes
Bullous pemphigoid recruits
- Neutrophils
- Eosinophils (inflammation and disruption of epidermal attachments)
Bullous pemphigoig morpology (1)
- Tense bullae filled with clear fluid
- Bullae are usually less than 2 cm in diameter (can reach 4 to 8 cm)
- Bullae do not rupture easily
- Heal without scarring
- Distinguishing Characteristic
- Subepidermal, nonacantholytic blisters
Bullous pemphigoig morphology (2)
- Deep perivascular infiltrate (lymphocytes, eosinophils, neutrophils)
- Superficial dermal edema
- Basal cell layer vacuolization
Dermatitis herpetiformis characteristics
- Rare
- Urticaria
- Vesicles (pruritic)
- Affects predominantly males
- Third and fourth decades of life
Dermatitis herpetiformis asociations
- Intestinal celiac disease
Dermatitis herpetiformis pathogenesis
- Genetic predisposition
- Individuals develop lgA Abs to dietary gluten
- Abs cross-react with reticulin
Abs cross-react with reticulin (dermatitis herpetiformis)
- Component of the anchoring fibrils
- Resultant subepidermal blister develops
Dermatitis herpetiformis lesions
- Bilateral
- Symmetric
- Grouped
Dermatitis herpetiformis areas involved
- Extensor surfaces
- Elbows
- Knees
- Upper back
- Buttocks
Dermatitis herpetiformis morphology
- Fibrin and neutrophils accumulate at tips of dermal papillae
- Small microabscesses
- Direct Immunofluorescence (discontinuous, granular deposits of lgA at tips of dermal papillae)
Epidermolysis bullosa
- Inherited defects in structural proteins
- Formation of Blisters
- Sites of pressure
- Friction
- Trauma
Epidermolysis bullosa simplex type
- Autosomal dominant mode of inheritance
- Mutations in genes encoding keratin 14 or 5
- Pair with one another to make a functional keratin fiber
- Basal cell layer defect
Epidermolysis bullosa simplex
Weber-Cockayne subtype
- Mild bullous disease
- Characterized by localized blistering at sites of trauma such as the feet
Dermatitis herpetiformis
blisters are associated with
- Accumulation of neutrophils (microabscesses) at the tips of dermal papillae
Epidermolysis bullosa simplex
Koebner subtype
- Palmoplantar blistering and hyperkeratosis are noted
- Hyperkeratotic papules and plaques on the palm
Epidermolysis bullosa junctional type
- Blisters of normal skin at the lamina lucida
- Autosomal recessive defect
- Subunits of laminin
- Binds to hemidesmosomes and anchoring filaments
- Typical erosions in flexural creases
Junctional epidermolysis bullosa (Herlitz subtype)
- Severe disease characterized by generalized intralamina lucida blistering at birth
- Significant internal involvement
- Poor prognosis
Dystrophic Epidermolysis Bullosa
- Sublamina densa BMZ separation
Hemidesmosomal Epidermolysis Bullosa
New category
- Produces blistering at the hemidesmosomal level
Dominantly inherited dystrophic epidermolysis bullosa
- Blistering often is localized and is characterized by scarring and milia in healed blister sites
Dominantly inherited dystrophic epidermolysis bullosa can result in
- Nail dystrophy and loss
oral cavity blistering and scarring
Epidermolysis bullosa types
- Epidermolysis bullosa simplex (intraepidermal skin separation)
- Junctional epidermolysis bullosa (skin separation in lamina lucida or central BMZ)
- Dystrophic epidermolysis bullosa (sublamina densa BMZ separation)
Junctional Epidermolysis Bullosa histology
- Subepidermal blister at the level of the lamina lucida
- No associated inflammation
Acne vulgaris
- Teenagers
- Affects both males and females
- Males tend to have more severe disease
- Induced or exacerbated by drugs
- Noninflammatory/inflammatory
Drugs that exacerbate or induce acne
- Corticosteroids
- Adrenocorticotropic hormone
- Testosterone
- Gonadotropins
- Contraceptives
- Trimethadione
- Iodides
- Bromides
Acne vulgaris occupational exposures/conditions favoring sebaceous gland occlusion
- Heavy clothing
- Cosmetics
- Tropical climates
- Familial
Acne vulgaris open comedones
- Small follicular papules
- Contain a central black keratin plug
- Color is the result of melanin pigment oxidation
Acne vulgaris closed comedones
- Follicular papules without a visible central plug
- Keratin plug trapped beneath the epidermal surface
- Potential sources of follicular rupture and inflammation
Acne vulgaris grade I
- Multiple open comedones
Acne vulgaris grade II
- Closed comedones
Acne vulgaris pathogenesis (incompletely understood/multifactorial) contributing factors
- Development of a keratin plug that blocks outflow of sebum
- Hypertrophy of sebaceous glands during puberty
- Lipids converted to proinflammatory fatty acids (probionibacterium acnes)
Inflammatory acne vulgaris
- Erythematous papules, nodules, and pustules
- Severe Variants
- Acne conglobata
- Result in sinus tract formation and dermal scarring
- Deep inflammatory nodules may develop
Inflammatory acne characteristics
- Open Comedones (large, patulous orifices)
- Closed comedones (microscopic identification only)
- Variable infiltrates of lymphocytes and macrophages around affected follicles
- Extensive acute inflammation (occurs with follicular rupture)
- Dermal abscesses may form in association with rupture
Acne vulgaris grade III
- Papulopustules
Acne vulgaris grade IV
- Multiple open comedones, closed comedones, and papulopustules
- Plus cysts
Rosacea
- Common disease of middle age and beyond
- Affects up to 3% of the US population
- Predilection for females
Rosacea four stages
- Flushing episodes (pre-rosacea)
- Persistent erythema and telangiectasia
- Pustules and papules
- Rhinophyma
Rhinophyma
- Permanent thickening of the nasal skin
- Confluent erythematous papules
- Prominent follicles
Rosacea pathogenesis
- High cutaneous levels of cathelicidin (AMP)
- Cathelicidin peptides distinct from individuals without rosace
Cathelicidin peptides in rosacea
- Expressed by PMNs and lymphocytes
- Stimulates angiogenesis
- Induces inflammation
- Telangiectasia formation
Rosacea morphology
- Nonspecific perifollicular lymphocytic infiltrate
- Lymphocytes surrounded by dermal edema and telangiectasia
- Pustular Phase
Pustular phase of rosacea morphology
- Neutrophils may colonize the follicles
- Follicular rupture may cause a granulomatous dermal response
- Development of Rhinophyma
Rhinophyma (rosacea pustular phase)
- Hypertrophy of sebaceous glands
- Follicular plugging by keratotic debris
Panniculitis
- Inflammatory reaction in the subcutaneous adipose tissue
- Preferentially affect
- Lobules of fat
- Connective tissue that separates fat into lobules
- Involves the lower legs
Panniculitis forms
- Erythema nodosum (most common)
- Erythema induratum (uncommon)
Erythema induratum (uncommon)
- Affects adolescents and menopausal women
- Cause is not known
- Vasculitis of deep vessels supplying the fat lobules of the subQ
- Vascular compromise leads to fat necrosis and inflammation
- Presents as an erythematous, slightly tender nodule that usually ulcerates
Erythema nodosum
- Poorly defined, tender, erythematous plaques and nodules
- Associated Infections
Associated infections with erythema nodosum
- β-hemolytic streptococcal infection
- Tuberculosis
Erythema nodosum (panniculitis) drug administration
- Sulfonamides
- Oral contraceptives
Erythema nodosum (panniculitis) conditions
- Sarcoidosis
- Inflammatory bowel disease
- Malignant neoplasms
Erythema nodosum pathogenesis
- Remains mysterious
- DTH reaction to microbial or drug related antigens
Immune complexes have been implicated
Erythema nodosum clinical presentation
- Fever and malaise may accompany the cutaneous signs
Panniculitis early lesions morphology
- Connective tissue septae are widened by edema, fibrin exudation, and neutrophilic infiltration
Panniculitis later lesions morphology
- Septal fibrosis
- Infiltration (lymphocytes, histiocytes, multinucleated giant cells, eosinophils)
Classic presentation of erythema nodosum
- Nodular red swellings over the shins
Erythema induratum
- Tender, erythematous nodules confined to the lower third of the legs
- Panniculitis exhibiting lobular, granulomatous, and lymphohistiocytic inflammation
Positive Mantoux test
- Reaction in a patient with erythema induratum
Verrucae (warts)
- Squamoproliferative disorders caused by HPV
- Common lesions of children and adolescents
Verrucae (warts) transmission
- Direct contact between individuals or autoinoculation
- Self-limited
- Regress spontaneously / 6 months to 2 years
Verrucae (warts) clinical variants (associated with distinct HPV subtypes)
- HPV types 1-4
- HPV types 6 and 11
- HPV type 16
Verrucae associated with HPV types 1 – 4
- Common warts on hands and feet
Verrucae associated with HPV types 6 and 11
- Anogenital warts (Condyloma accuminatum)
Verrucae associated with HPV type 16
- In situ squamous cell carcinoma of the genitalia
- Bowenoid papulosis
Verruca vulgaris
- Most common
- Occur frequently on hands (dorsal surfaces, periungual areas)
- Appear as gray-white to tan
Flat to convex (0.1- to 1-cm papules with a rough, pebble-like surface)
Verruca plana
- Flat wart
- Common on face
- Dorsal surfaces of the hands
- Slightly elevated
- Flat, smooth, tan papules
- Smaller than verruca vulgaris
Verruca Plantaris and Verruca Palmaris
- Occur on the soles and palms
- Rough, scaly lesions
- 1 to 2 cm
- Coalesce
- Confused with calluses
Condyloma Acuminatum (Venereal wart)
- Penis
- Female genitalia
- Urethra
- Perianal areas
- Rectum
- Soft, tan, cauliflower-like masses
- Can reach many centimeters in diameter
Common histological features of verrucae
- Epidermal hyperplasia
- Undulant in character, termed verrucous or papillomatous epidermal hyperplasia
- Cytoplasmic vacuolization (Koilocytosis)
Cytoplasmic vacuolization (Koilocytosis)
- Involving the more superficial epidermal layers
- Haloes of pallor surrounding infected nuclei
Molluscum contagiosum
- Common
- Self-limited viral disease
- Cause / poxvirus
- Infection is usually spread by direct contact
Molluscum contagiosum multiple lesions
- Skin and mucous membranes
- Predilection for the trunk and anogenital areas
Molluscum contagiosum lesion characteristics
- Firm, pruritic
- Pink to skin-colored
- Umbilicated papules
- Range from 0.2 cm to 0.4 cm
- Curd-like material expressed from central umbilication
- Material contains diagnostic molluscum bodies
Molluscum contagiosum microscopic examination
- Cuplike verrucous epidermal hyperplasia
- Diagnostic structure is the molluscum body
- H&E Stains
Diagnostic structure is the molluscum body
- Large (up to 35 µm), ellipsoid, homogeneous, cytoplasmic inclusion
- Cells of the stratum granulosum and the stratum corneum
H&E stains
- Eosinophilic in the blue-purple stratum granulosum
- Acquire a pale blue hue in the red stratum corneum
- Numerous virions are present within molluscum bodies
Impetigo
- Superficial bacterial infection of skin
- Highly contagious
- Causative agent – S. aureus
Impetigo two forms
- Impetigo contagiosa
- Impetigo bullosa
- Differ by the size of the pustules
Impetigo pathogenesis
- Innate immune response
- Responsible for epidermal injury
- Serous exudate and formation of a scale crust (scab)
- Bacterial toxin that cleaves desmoglein 1
Impetigo presentation
- Erythematous macule
- Multiple small pustules
- Shallow erosions
- Covered with dry serum
Impetigo characteristic appearance
- Honey-colored crust
- Bullous forms occur in children
Impetigo microscopic featur
- Accumulation of neutrophils beneath the stratum corneum
- Often producing a subcorneal pustule (containing serum protein, inflammatory cells)
- Special stains reveal the presence of bacteria in these foci
Superficial fungal infections basic characteristics
- Confined to the stratum corneum
- Caused by dermatophytes
Tinea capitis (superficial fungal infection)
- Commonly seen in children
- Rarely in infants and adults
- Dermatophytosis of the scalp
- Asymptomatic
- Presents as hairless patches of skin
Tinea capitis associated with
- Mild erythema
- Crust formation
- Scaling
Tinea barbae
- Dermatophyte infection of the beard area
- Affects adult men
- Uncommon disorder
Tinea corporis
- Superficial fungal infection of the body surface
- Affects persons of all ages
- Particularly children
Tinea corporis predisposing factors
- Excessive heat
- High humidity
- Exposure to infected animals
- Chronic dermatophytosis of the feet or nails
Tinea corporis (Ringworm)
- Expanding, round, slightly erythematous plaque
- Elevated scaling border
Tinea cruris (Jock Itch)
- Inguinal areas
- Obese men
- Athletes
Tinea cruris (jock itch) predisposing factors
- Heat
- Friction
- Maceration
Tinea cruris (jock itch) appearance
- Appears on the upper inner thighs
- Moist, red patches with raised scaly borders
Tinea pedis (Athlete’s foot)
- Affects 30% to 40% of the population
- Diffuse erythema and scaling
- Initially localized to the web spaces
- Inflammatory reaction (result of bacterial superinfection)
Tinea pedis (Athlete’s foot) may involve finger and toenails
- Onchomycosis
- Discoloration
- Thickening
- Deformed nail plate
Tinea pedis (athlete’s foot) appearance
- Diffuse erythema and scaling
- Initially localized to the web spaces
- Inflammatory reaction
Tinea versicolor
- Occurs on the upper trunk
- Causative agent = Malassezia furfur (a yeast, not a dermatophyte)
- Lesions = groups of macules of varied size and color
- Fine peripheral scaling
Tinea versicolor morpholoy
- Mild eczematous dermatitis
Intraepidermal neutrophils - Periodic acid–Schiff stain (bright pink to red)
- Found in the anucleate cornified layer
- Scrapes use to identify offending species
Lichen planus cutaneous lesions morphology
- Darkly pigmented individuals (melanin release into the dermis, basal cell layer destruction)
- Lesions / multiple and symmetrically distributed
- Extremities, wrists, elbows
- Oral lesions (white, reticulated, or netlike)
Porphyria
- Disturbances of porphyrin metabolism
- Porphyrins (Pigments): hemoglobin, myoglobin, cytochromes
Classification of porphyrias (based on both clinical and biochemical features)
- Congenital erythropoietic porphyria
- Erythrohepatic protoporphyria
- Acute intermittent porphyria
- Porphyria cutanea tarda
- Mixed porphyria
Cutaneous manifestations of porphyria
- Urticaria and vesicles
- Associated scarring
- Condition exacerbated by sunlight exposure
- Vesicles have subepidermal location
- Pathogenesis not understood
