L-3 Integ Pathology of Skin

• Pathology of Disease of Skin Lecture 3 covers skin lesions of the epidermis and dermis.
• The lecture objectives are to identify gross and microscopic features of diseases of the epidermis and dermis, recognize pathological features of bullous diseases of the skin, and recognize the pathology and findings of inflammatory diseases of the vascular bed and describe the main bullous disease of the epidermis.

Classification (Morphologic)

• Acute inflammatory dermatoses include urticaria and acute eczematous dermatitis.
• Chronic inflammatory dermatoses include psoriasis, lichen planus, and lichen simplex chronicus.
• Infectious dermatoses include bacterial infections, fungal infections, and verrucae (warts).
• Blistering or bullous disorders are pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, and dermatitis herpetiformis.
• Tumors of the skin include benign epithelial lesions, premalignant epithelial lesions, malignant epidermal tumors, and melanocytic proliferations.
• Skin disorders can affect the epidermis, the deeper dermal tissue, or both.
• Disorders can be pigmented, hyper-pigmented, or hypo-pigmented.
• Disorders can arise from the blood vessels of the dermis, the connective tissue, or fat (panniculitis).
• Urticaria can present with wheels/hives; contact dermatitis from allergy can retain the shape of the object touched.
• Sclerotic disorders such as systemic sclerosis can affect the skin.
• Neoplasms can arise from a variety of tissue types, including fibroma, lipoma, and sarcoma.

Primary Lesions

• Macule: Flat, less than 5mm, examples include tinea.
• Patch: Flat, greater than 5mm, examples include vitiligo.
• Plaque: Elevated, domed or flat topped, less than 5mm, examples include psoriasis.
• Nodule: Elevated, domed or flat topped, less than 5mm, examples include cysts, warts, and lipomas.
• Tumor: Skin cancers.
• Bullae: Greater than 0.5cm, fluid-filled, raised, examples include pemphigus.
• Pustule: Pus filled, examples include impetigo.
• Cyst: Epidermal inclusion cyst.

Secondary Lesions

• Scales: Heaped-up horny epithelium, examples include crust, psoriasis, and contact dermatitis.
• Crust: Dried secretions over the skin, such as a scab.
• Excoriations: Traumatic lesion breaking the epidermis and causing a raw linear area, often self-inflicted, deep scratch.
• Lichenification: Thick, hyperpigmented skin, from constant rubbing.
• Maceration: Increased moisture, for example, exposure, bed sores, venous ulcers, diabetic ulcers, burns.
• Fissure: Cracked, dry skin, for example, psoriasis.
• Erosions: Superficial, spares BM (basement membrane), for example, pemphigus.
• Ulcers: Deep wounds, poor circulation, for example, with diabetes mellitus.

Distinct Lesions

• Wheal/Hive: Migratory, elevated, purple reddish plaques, examples include urticaria and allergens.
• Comedone: Skin bumps from clogged pores.
• Keloid: Firm, rubbery, fibrous, can be pink, red, itchy, exuberant scar tissue.
• Telangiectasia: Small blood vessel dilatation.
• Fibrosis: Connective tissue replaces normal epithelium.
• Milium: Clog of eccrine sweat gland, keratin-filled cyst, on baby's face.
• Atrophy: Wasting away of tissue due to aging, blood supply, poor nourishment.
• Burrow: Slightly elevated, grayish, tortuous line, skin tracts due to scabies mite.

Macule and Patch

• Macule: flat, discolored lesions less than 1 cm in size.
• Patch: flat, discolored lesion greater than 1 cm in size.
• Examples of Macules and Patches include vitiligo, tinea, moles, freckles, sunspots, and lentigenes.

Pustules

• Pustules are small patches of bulging skin filled with pus.
• Examples include acne, boils, candida, chickenpox, and impetigo.

Verruca Vulgaris (Warts)

• Characterized by inward bending of rete ridges.

Epidermal Inclusion Cysts

• These show up as a nodule with a central punctum.
• They contain cheesy, yellow, keratin material.
• The cyst lining has flat epidermal cells and a granular layer surrounding the keratin.

Plaque-Skin Diseases

• Psoriasis exhibits a rapid buildup of epidermal cells.
• Typically found on elbows, scalp, and knees.
• Associated with diabetes, heart disease, and depression.
• Histopathology shows Parakeratosis, where cell nuclei are present within the stratum corneum.
• Characterized by a lack of a granular layer and a thickened prickle cell layer.
• The condition involves the infiltration of polymorphonuclear leukocytes and lymphocytes into the dermis, with CD8+ in the dermis and CD4+ in the epidermis, causing Munro's abscesses (stratum corneum) and Kogoj micropustules in the epidermis.

Erosion and Ulcers of the Skin

• Erosions are superficial, wearing away the epidermis and causing a shallow depression, they do not extend into the dermis and heal by regeneration.
• Ulcers are a defect of the skin with complete loss of epidermis, dermis and subcutaneous tissue and heal by scarring.

Hyperkeratosis

• Defined as thick skin due to an increased keratin (stratum corneum) layer.
• Often occur on the plantar surface (soles of feet).
• Vitamin deficiencies (Vitamins E, A, and D) are implicated in causing hyperkeratosis.

Nevi

• Nevi are benign neoplasms of melanocytes.
• Congenital nevi are present at birth.
• Acquired nevi appear later in life.
• They grow as nests of melanocytes at the dermal-epidermal junction and can extend into the dermis (compound).
• Their morphology is a flat macule or raised papule with sharp boarders and even color, usually smaller than 6mm.
• Dysplastic nevus are a precursor to melanoma.

Melanoma

• Characterized by S100 immunostaining.

Bullous Diseases of the Skin:

Pemphigus Vulgaris

• Affects older patients and has common mucosal involvement (oral lesions).
• Antibodies target desmoglein3 (desmosomes).
• Blisters are intraepidermal (superficial) and rupture easily.
• Nikolsky's sign is positive with Acantholysis on Tzanck smear.
• Immunofluorescence shows a net-like IgG pattern.
• Untreated it is often fatal, with cells showing a Tombstone appearance of basal layer.

Bullous Pemphigoid

• Affects the elderly, mucosal lesions are rare.
• Antibodies are against hemidesmosomes.
• Blisters are subepidermal (deep), tense, and firm.
• Nikolsky's sign is negative with no acantholysis on Tzanck smear.
• Immunofluorescence shows linear IgG.
• Patients have a good prognosis.
• Eosinophilic infiltration is seen on histopathology.

Pemphigus Vulgaris

• Autoimmune destruction of desmosomes between keratinocytes.
• Caused by antibodies against desmoglein 3, classified as a type 2 hypersensitivity reaction.
• Features skin and oral mucosa bullae.
• Acantholysis: Separation of the stratum spinosum keratinocytes, results in suprabasal blisters.
• The basal layer remains attached to the basement membrane.
• Has thin-walled blisters that easily rupture; positive Nikolsky sign.
• Shows Immunofluorescence, IgG around individual keratinocytes, presenting a "fish net" pattern.

Bullous Pemphigoid

• An autoimmune bullous skin disorder affecting older people (over 60). It is milder than pemphigus vulgaris, and oral mucosa is spared.
• Blisters or bullae form between the epidermis and dermis but do not rupture easily.
• Type 2 hypersensitivity reaction with the formation of anti-hemidesmosomes antibodies.
• Immunofluorescence highlights IgG along the basement membrane in a linear pattern.

Dermatitis Herpetiformis

• An autoimmune bullous disease of IgA at the tips of dermal papillae.
• The condition presents with pruritic vesicles and bullae (filled with watery fluid, PMN's, and eosinophils) group together.
• It is not related to the herpes virus.
• The disease is associated with celiac disease and resolves with a gluten-free diet.
• Immunofluorescence shows granular deposits within the dermal papillae.

Inflammatory Skin Diseases of the Vascular Bed:

Polyarteritis Nodosa (Systemic Necrotizing Vasculitis)

• Multisystem blood vessel disease occurring mainly in the 4th and 5th decade.
• Characterized by inflammation of small and medium-sized arteries.
• More common in men than women.
• Symptoms include fever, night sweats, and weight loss.
• May be associated with hepatitis B in some patients.
• Can cause Neuropathy, and CNS disturbances.
• Skin may show gangrene, nodules, and purpura, often on the legs.
• It will present with skin rashes, ulcers, and subcutaneous nodules and livido reticularis

Erythema Multiforme

• Hypersensitivity reaction affecting dermal blood vessels.
• The reaction of dermal blood vessels is characterized by targeted rashes and bullae of skin and mucous membranes.
• Targeting is due to central epidermal necrosis surrounded by erythema.
• Commonly associated with herpes simplex infection, drugs (penicillin), systemic lupus erythematosus (SLE), and malignancy
• In Steven-Johnson syndrome there is mucosal involvement, EM and fever.
• Vacuolar interface dermatitis with lymphocytes along the dermo-epidermal junction, hydropic changes, and dyskeratosis of basal keratinocytes.
• Immunofluorescence is non-specific.