Post on 28-Dec-2015
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PATHOLOGY OF THE SKINPATHOLOGY OF THE SKIN
1. Inflammatory skin diseases and 1. Inflammatory skin diseases and bullous skin disordersbullous skin disorders
Máirín E. McMenamin MB MRCPI FRCPath Dip (Dermatopathol) RCPath
St. James’s Hospital and University of Dublin, Trinity College
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Skin is the largest organ in the body and acts as a cornified envelope
Skin has many properties:
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ECS
Glomus body: modified perivascular smooth muscle cells, involved in temperature regulation
Skin of forearm Skin of nose – numerous sebaceous glands
Regional variability in skin
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ECS
Langerhans’ cell in mid epidermis
Langerhans’ cells stain positively for S100 protein and CD1a
They are increased in number in contact allergic dermatitis
Electron microscopy:
Langerhan’s cells show intracytoplasmic rod and racket shaped cytoplasmic inclusions
OVERVIEW OF SKIN PATHOLOGYOVERVIEW OF SKIN PATHOLOGY• Congenital skin diseases• Papulosquamous diseases (scaly skin diseases)• Vesiculobullous diseases (blistering skin diseases)• Infections
– Bacteria (S.aureus, impetigo, staphylococcal scalded skin syndrome, Strep. cellulitis)
– Mycobacteria (e.g. T.B., leprosy) – Fungus (e.g. dermatophytosis and dermatomycosis)– Virus (e.g. Herpes simplex, molluscum contagiosum, orf)– Spirochaetes (e.g. syphilis, borrelia) – Protozoa (e.g. amoebiasis, leishmaniasis, toxoplasmosis)– Helminths (schistosomiasis, larva migrans)– Arthropod – induced diseases (demodex, scabies,
bedbugs, tick bites)Copyright M. McMenamin
• Skin diseases can be acute self limited (e.g. acute folliculitis), recurrent (herpes simplex infection), chronic (psoriasis)
• Some conditions can be life threatening
e.g. staphylococcal scalded skin syndrome, toxic epidermal necrolysis, severe pemphigus
SELECTED GENODERMATOSES• Urticaria pigmentosa (some cases have somatic mutations of ckit)
– Tan macules, accumulation of mast cells in dermis– Positive Darier sign (urtication (wheal) when skin is rubbed)– Rarely systemic involvement e.g. bone marrow
• Ichthyosis (disorder of keratinization) – Many variants of variable severity– Ichthyosis vulgaris due to mutations in filaggrin gene
• Acantholytic disorders (abnormal calcium channel proteins)– Usually autosomal dominant
• Hailey-Hailey disease (Greasy confluent papules in axillae)• Darier disease (Greasy confluent papules in seborrhoeic areas)
• Xeroderma pigmentosa (inability to repair UV- induced DNA breaks)– Autosomal recessive
• Severe actinic (sun-induced) damage• Squamous cell carcinomas at an early age
• Epidermolysis bullosa• Many variants of variable severity, autosomal dominant or recessive• Blistering, contractures, mitten deformities, squamous cell carcinomas
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Copyright M. McMenamin
Urticaria pigmentosa
Accumulation of mast cells in the dermis
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Dermatographism: urtication (wheals)
Positive Darier sign (urtication (wheal) when skin is rubbed
Ichthyosis (sex-linked variant)Disfiguring scaling of skin
Lamellar ichthyosis
Scaling and erythema
Ichthyosis vulgaris Lamellar ichthyosisIncrease in keratin in stratum corneum
Congenital ichthyosiform erythroderma
Intense erythema and fine scaling
Hyperkeratosis and vacuolation of epidermis
Congenital ichthyosiform erythroderma
Genetic bullous diseases
• Abnormalities in various proteins in basement membrane region– Dystrophic epidermolysis bullosa
• Mutations in collagen VII
– Junctional epidermolysis bullosa• Mutations in laminin 5
• Autoimmune bullous diseases can show antibodies to similar proteins e.g. bullous pemphigoid and bullous SLE
DERMATITISInflammation of the skin
Many aetiological factors:Many aetiological factors:
• Exogenous sensitizing agents – (contact allergic dermatitis and contact irritant dermatitis)
• Proteins (e.g. biological detergents)• Haptens (e.g. nickel)
• Endogenous agents• Drugs (e.g. trimethoprim)
• Atopic individuals (excess production of Ig E)• Atopic dermatitis (eczema)
– mutations in filaggrin gene
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DERMATITISDERMATITISCLINICAL FEATURESCLINICAL FEATURES
• Acute dermatitis– Sore, red, weeping skin +/- pruritic (itchy)
• Chronic dermatitis– Indurated lichenified skin (thickened skin)
Anatomic distribution of dermatitis can be helpful in elucidating cause
e.g. contact allergic dermatitis:
On exposed skin of arms (poison ivy) Under watch (nickel)
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Acute dermatitis
Spongiosis with epidermal vesicles
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With continuation of the dermatitis the skin shows features of subacute spongiotic dermatitis with elongated rete ridges and surface scale crust
DERMATOPATHIC LYMPHADENOPATHY
• Reactive enlargement of lymph nodes draining an area in which there is an inflammatory skin condition
• Histologically the node shows sinus histiocytosis with numerous Langerhans’ cells and phagocytosed melanin pigment and lipid
• May be misinterpreted as lymphoma
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NON-INFECTIOUS VESICULOBULLOUS SKIN DISEASE
• Pemphigus– P. vulgaris/ p. foliaceus/ paraneoplastic pemphigus
• Pemphigoid – Bullous pemphigoid– Herpes gestationis (bullous pemphigoid in pregnancy)– Mucous membrane pemphigoid (cicatricial pemphigoid) (scarring, can cause blindness)
• Dermatitis herpetiformis– association with coeliac disease
• Acquired epidermolyis bullosa (antibodies to collagen VII)
• Erythema multiforme– Frequently related to exposure to a drug or virus (herpes simplex)– Clinical spectrum with Stevens-Johnson syndrome and toxic epidermal necrolysis
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Basement membrane region of normal epidermis
Cartoon of basement membrane proteins
Anchoring fibrils
Hemidesmosome
Lamina lucida
Lamina densa
Electron microscopy
Anchoring fibrils: collagen VII
NON-INFECTIOUS VESICULOBULLOUS SKIN DISEASE
• For accurate diagnosis the clinical and histological features need to be correlated and frequently supportive immunological studies are needed for accurate diagnosis
• Histological study:– Performed on lesional skin (bulla)
• Immunological studies:– Direct immunofluorescence
• Performed on perilesional skin (skin adjacent to a bulla) – Indirect immunofluoescence: patient’s serum tested against a
substrate such as monkey oesophagus– Other serological tests such as ELISA used for quantitation of
autoantibodies in patient’s blood
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PEMPHIGUS VULGARISPEMPHIGUS VULGARIS• Uncommon blistering disease affecting scalp, face +/- mucous
membranes• M=F, 30-60 y• Acantholysis in apparently normal skin may be clinically
demonstrated by the Nikolsky sign: – Slippage of superficial layers of normal skin on application of a
shearing force• Generally chronic relapsing course• If extensive loss of fluid, protein, electrolytes +/- infection may
prove fatal • Histopathology: Separation (acantholysis) of epidermal cells leaves
basal cells attached to basement membrane by hemi-desmosomes– Characteristic “tombstone” appearance on biopsy
• Circulating autoantibodies to desmogleins (components of desmosomes)
• Direct immunofluorescence: intercellular deposition of IgG and C3• Paraneoplastic pemphigus can occur in malignancy e.g. lung cancer
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Pemphigus vulgaris: flaccid blisters and erosions
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Pemphigus vulgaris
Direct immunofluorescence:
Intercellular deposition of IgG and C3
BULLOUS PEMPHIGOIDBULLOUS PEMPHIGOID
• Large tense bullae on thighs, flexures and lower abdomen• Bullae do not rupture easily• M=F, elderly• Histology:
– Eosinophil infiltration in dermis– Subepidermal bulla (dissolution of lamina lucida of
basement membrane and separation of entire epidermis) • Direct immunofluorescence:
– Linear deposition of IgG and C3 along basement membrane• May have detectable levels of anti-basement membrane
antibodies:anti bullous pemphigoid antigens 1 and 2 (BPAG1 and BPAG2)
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Copyright M. McMenamin
Bullous pemphigoid: tense blisters on extremities
Basement membrane region of normal epidermis
Cartoon of basement membrane proteins
Anchoring fibrils
Hemidesmosome
Lamina lucida
Lamina densa
Electron microscopy
Anchoring fibrils: collagen VII
Lamina lucida
Lamina densa
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Bullous pemophigoid
Linear deposition of IgG and C3 along
dermo-epidermal junction
DERMATITIS HERPETIFORMIS
• Grouped intensely itchy vesicles over joints, upper back and buttocks
• M > F, 20-40y• Histology:
– Neutrophilic microabscesses in papillary dermis– Separation of epidermis at papillary tips in a festooned pattern,
coalescing to form bullae• Direct immunofluorescence:
– Granular deposits of IgA in dermal papillae (on anchoring filaments) • Strong association with coeliac disease (gluten sensitive
enteropathy)
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Copyright M. McMenamin
Dermatitis herpetiformis
Granular deposition of IgA along dermo-epidermal junction
ERYTHEMA MULTIFORME
• Cytotoxic skin reaction, commonly initiated by infections (e.g. herpes viral infection) or drugs (e.g. sulphonamides)
• M = F, any age• Typically gives rise to “targetoid lesions” but may appear as
macules, papules, vesicles or bullae• Extremities affected in most cases, but may be widespread,
(especially in children) with mucosal involvement (Stevens-Johnson syndrome)
• Histologic features:– Lymphocytes attack basal layer causing epidermal necrosis and
vesiculation
• Direct immunofluorescence: unhelpful
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Erythema multiforme: targetoid lesions on hands
PAPULOSQUAMOUS SKIN DISEASES
• Psoriasis• Cutaneous lupus erythematosus
– Discoid lupus, subacute lupus, bullous lupus erythematosus
• Lichen planus• Pityriasis rubra pilaris• Porokeratosis
• Graft-versus-host disease
– Seen especially after allogeneic transplantation (many organs can be affected and patients can present with rash / GI symptoms / elevated liver function tests)
PSORIASIS
• Disorder of epidermal proliferation, affecting 2% of population• M = F, mean age of onset 25-30 y• Typically affects elbows, knees, scalp, natal cleft chronically but can be acute and
generalized (erythroderma) and can be pustular• Mucous membranes rarely affected e.g. tongue• Guttate variant typically affects children, commonly after streptococcal infection (small
drop-sized plaques)• Clinical features:
– Silvery scaly lesions on an erythematous background with pinpoint bleeding when scraped or scale is removed (Auspitz sign)
• Histological features: – Elongated rete ridges, club-shaped papillae, suprapapillary thinning, loss of granular cell layer
and neutrophils in epidermis and stratum corneum (spongiform pustules of Kojog and Munro microabscesses)
• Turnover of epidermis is increased – (4 days from basal cell layer to shedding, normally takes several weeks)
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Chronic plaque psoriasis affecting arm and trunk
Pustular psoriasis: sterile pustules on an erythematous base
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Psoriasis showing elongated rete ridges
Neutrophils in epidermis (spongiform pustule)
PSORIASIS• Aetiology unknown
– Probably related to damage to the stratum corneum in certain HLA types, unmasking antigens against which antibodies form
– Complement activation attracts neutrophils which unmask further antigens– Epidermal growth factor (EGF) released by damaged keratinocytes causes
persistent proliferation
• Other important points about psoriasis– Pustular variant involves palms and soles– Nail changes common - nail pitting in 30%, onycholysis– Associated with arthritis - several forms
• (asymmetrical arthritis hands and feet, symmetrical seronegative [rheumatoid arthritis-like], arthritis mutilans, ankylosing spondylitis)
– Exacerbated by certain drugs (e.g. lithium, beta blockers)– HIV seroconversion can be accompanied by acute psoriasis
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Copyright M. McMenamin
Nail pitting in psoriasis
PorokeratosisSeveral clinical variants all characterised by
cornoid lamella (tier of parakeratosis)
LUPUS ERYTHEMATOSUS
• Chronic discoid lupus erythematosus (DLE) is characterized by scaling rash affecting central face (cheeks, nose) can have butterfly distribution
• DLE can cause scarring alopecia• Frequently exacerbated by ultraviolet light• DLE rarely progresses to systemic lupus
erythematosus (SLE)• Histology:
– Autoimmune destruction of basal cell layer – Vacuolar interface damage of basal keratinocytes
• Direct immunofluorescence: – Granular deposition of IgG and C3 along basement
membrane (“lupus band”)• Variable detection of anti-nuclear antibodies (ANA)
in serum in DLE, high titre suggests SLECopyright M. McMenamin
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Discoid lupus erythematosus
vacuolar interface damage to basal cell layer
Apoptotic keratinocytes
LICHEN PLANUSLICHEN PLANUS
• Pruritic polygonal purple papules on wrists, ankles and elbows, papules can coalesce to form plaques
• Often involves mucous membranes with a white reticulate (net-like) pattern
• Self-limited condition
• Aetiology unknown (probably autoimmune)
– Sometimes associated with drugs (e.g naproxen)
• Histologic features:
– Characterized by band-like T cell infiltrate at the dermo-epidermoid junction (lichenoid reaction) with damage (wipe-out) of basal cells
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LICHEN PLANUS
Skin infections
• Bacterial: (especially Staph aureus, Streptococcal species) cellulitis, folliculitis, abscesses, impetigo, Staphylococcal scalded skin syndrome: superficial exfoliation due to toxin
• Fungal: ringworm (dermatophytosis), deep fungal infections (dermatomycoses) especially in immunosuppression
• Mycobacterial: mycobacterium tuberculosis, ermycobacterium marinum (fish-tank granuloma) mycobacterium leprae (leprosy)– Granulomatous inflammation, mycobacteria can be seen on Ziehl
Neelson or modified Ziehl Neelson stains• Viruses e.g. verrucae (HPV), herpes simplex, varicella
zoster, molluscum contagiosum (pox virus)
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Herpes viral infection
Bulla with multinucleate epidermal cells showing herpetic nuclear inclusions
(herpes simplex, varicella zoster)
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Molluscum contagiosum (Pox virus)
Viral inclusions
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Verruca vulgaris (wart) HPV viral infection
Dermatopathology – some important facts for the clinician
• Histological features are not always specific• Careful correlation is needed with clinical features and
other studies, where appropriate (special histological stains, immunology, microbiology, genetics)
• Appropriate clinical information on request forms and timely delivery to lab where appropriate, direct communication with pathologist / dermatologist can help prior to biopsy
• Responsibility in choice of site of biopsy can be very important and is informed by potential diagnosis (e.g. edge of intact bulla not ulcerated bulla, get cornoid lamella in porokeratosis)