Dermatopathology (Part 1) Flashcards
Skin functions
- Protection
- Thermoregulation
- Vitamin D synthesis
- Excretion
- Monitor
- Immune function
Squamous epithelial cells (keratinocytes)
- Secrete soluble molecules influence cutaneous immune responses (cytokines, defensins)
- “Glued” tightly together by desmosomes
- Produce abundant amounts of keratin protein
- Keratin and desmosomes create a tough, durable physical barrier
Melanocytes
- Found within the epidermis
- Responsible for the production of melanin
Melanin
- Absorbs and protects against injurious ultraviolet (UV) radiation
Dendritic cells (Langerhans cells) functions
- First line of defense against microorganisms
- Process microbial cell antigens
- Augment innate immune responses
- Present antigens to T lymphocytes
- Stimulate the adaptive immune system
Afferent nerve fibers
- Responsible for physical sensations
- Pain
- Touch
- Vibration
- Itchiness
- Cold
- Heat
Receptive fields
- Meissner – pressure – fast adaptation
- Merkel – pressure – slow adaptation
- Pacinian – fast changing stimuli - respond to vibration
- Ruffini – slow adapting
Efferent nerve fibers
- Regulate adnexal components
- Sweat glands
- Erector pili muscles
- Influence immune response
- Merkel cell (basal location, neuroendocrine or mechanoreceptor function)
Adnexal components
- Sweat Glands = regulate body temperature
- Hair Follicles = harbor epithelial stem cells
- Sebaceous Glands = lubricate and waterproof the skin and hair
Skin histology
- Epidermis
- Dermis
- Subcutaneous tissue
Excoriation
- Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch)
- Often self-induced
Lichenification
- Thickened, rough skin (similar to a lichen on a rock); usually the result of repeated rubbing
Macule, patch
- Circumscribed, flat lesion distinguished from surrounding skin by color
- Macules are 5 mm in diameter or less, patches are greater than 5 mm
Onycholysis
- Separation of nail plate from nail bed
Papule, nodule
- Elevated dome-shaped or flat-topped lesion
- Papules are 5 mm or less across, while nodules are greater than 5 mm in size
Plaque
- Elevated flat-topped lesion, usually greater than 5 mm across (may be caused by coalescent papules)
Pustule
- Discrete, pus-filled, raised lesion
Scale
- Dry, horny, platelike excrescence
- Usually the result of imperfect cornification
Vesicle, bulla, blister
- Fluid-filled raised lesion 5 mm or less across (vesicle) or greater than 5 mm across (bulla)
- Blister is the common term for either
Wheal
- Itchy, transient, elevated lesion with variable blanching and erythema formed as the result of dermal edema
Hyperleratosis
- Thickening of the stratum corneum
- Often associated with a qualitative abnormality of the keratin
Letiginous
- A linear pattern of melanocyte proliferation within the epidermal basal cell layer
Papillomatosis
- Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae
Parakeratosis
- Keratinization with retained nuclei in the stratum corneum
- On mucous membranes, parakeratosis is normal
Spongiosis
- Intercellular edema of the epidermis
Ulceration
- Discontinuity of the skin showing complete loss of the epidermis revealing dermis or subcutis
Vacuolization
- Formation of vacuoles within or adjacent to cells
- Often refers to basal cell-basement membrane zone area
Acanthosis
- Diffuse epidermal hyperplasia
- Increased thickness of the Malpighian layer (stratum basale and stratum spinosum)
Dyskeratosis
- Abnormal, premature keratinization within cells below the stratum granulosum
Erosion
- Discontinuity of the skin showing incomplete loss of the epidermis
Exocytosis
- Infiltration of the epidermis by inflammatory cells
Hydropic swelling (ballooning)
- Intracellular edema of keratinocytes
- Often seen in viral infections
Hypergranulosis
- Hyperplasia of the stratum granulosum
- Often due to intense rubbing
Acantholysis
- Loss of intercellular cohesion between keratinocytes
Acute inflammatory dermatoses
- Urticaria
- Acute eczematous dermatitis
- Erythema multiforme
Acute lesions (acute dermatoses)
- Last from days to weeks
- Inflammatory Infiltrates
Inflammatory infiltrates in acute dermatoses
- Lymphocytes
- Macrophages
- Edema
- Variable degrees of epidermal, vascular, or subQ injury
Chronic lesions in actue dermatoses
- Persist for months to years
- Associated atrophy or hyperplasia or dermal fibrosis
Urticaria (hives) characteristics (1)
- Localized mast cell degranulation
- Dermal microvascular hyperpermeability
- Pruritic edematous plaques called wheals
Angioedema (related to urticaria)
- Edema of the deeper dermis and the subQ fat
Urticaria (hives) characteristics (2)
- Condition usually resolves in less than 24 hours
- Episodes may last for days or persist for months
- Sites of predilection –> areas exposed to pressure
- Persistent episodes (underlying disease, underlying cause not identified)
Urticaria pathogenesis
- Antigen-induced release of vasoactive mediators from mast cells
- Mast cell-dependent, IgE-dependent (exposure to pollens, foods, drugs, insect venom)
- Localized immediate hypersensitivity (type I) reaction
Urticaria morphology
- Small pruritic papules –> large edematous plaques
- Individual lesions may coalesce
- Sparse superficial peri-venular infiltrate (Mononuclear)
- Dilated Superficial lymphatic channels
- Epidermis (No change)
Urticaria clinical presentation
- Isolated event without systemic reaction
- Prelude to an anaphylactic reaction
- Features of Anaphylaxis
Features of anapylaxis
- Hypotension
- Respiratory distress
- Stridor
- Gastrointestinal distress
- Swallowing problems
- Joint swelling, joint pain (immediate medical intervention necessary)
Acute eczematous dermatitis categories
- Allergic contact dermatitis
- Atopic dermatitis
- Drug-related eczematous dermatitis
- Photoeczematous dermatitis
- Primary irritant dermatitis
Acute eczematous dermatitis causes
- Reaction from external application of an antigen (e.g., poison ivy)
- Reaction to an internal circulating antigen (derived from ingested food or drug)
Acute eczematous dermatitis
pathogenesis
- T cell-mediated inflammatory reaction (Type IV hypersensitivity)
- Reactive chemical induction of neo-antigens
- Neoantigens are processed in lymph nodes
Acute eczematous dermatitis morphology (1)
- Red, papulovesicular, oozing, crusted lesions
- Small and large blisters (vesicles and bullae)
- Spongiosis
- Raised scaling plaques (produced by reactive acanthosis and hyperkeratosis)
Stages of eczema development
A) Initial dermal edema and perivascular infiltration by inflammatory cells
B) Epidermal spongiosis and microvesicle formation
C) Abnormal scale, including parakeratosis, along with progressive acanthosis
D ,E) Progressive acanthosis and hyperkeratosis as lesion becomes chronic
Acute eczematous dermatitis morphology (2)
- Edema seeps to level of the stratum spinosum (result in the formation of intraepidermal vesicles)
- Lesion are pruritic
Erythema multiforme
- Hypersensitivity reaction to infections and drugs
Erythema multiforme associations
- Infections
- Exposure to certain drugs
- Cancer
- Collagen vascular disease
Infections associated with erythema multiforme
- Herpes simplex
- Mycoplasma
- Histoplasmosis
- Coccidioidomycosis
Drugs associated with erythema multiforme
- Sulfonamides
- Penicillin
- Barbiturates
- Salicylates
- Hydantoins
- Antimalarials
Cancers associated with erythema multiforme
- Carcinomas
- Lymphomas
Collagen vascular disease associated with erythema multiforme
- Lupus erythematosus
- Dermatomyositis
- Polyarteritis nodosa
Erythema multiforme pathogenesis
- Keratinocyte injury mediated by CD8+ T cells
- Lesions (CD8+ T cells in the central portion, CD4+ helper T cell and Langerhans cells in the peripheral portions)
- Epidermal antigens recognized by the infiltrating T cells remain unknown
Erythema multiforme morphology/presentation
- Macules
- Papules
- Vesicles
- Bullae
- Targetoid (target-like) lesions
- The lesions may occur in a variety of distributions
- Limited cases show symmetry
- Often involve the extremities
Stevens-Johnson Syndrome (SJS) consensus definiton (variant of erythema multiforme)
- SJS separated from EM spectrum and added to toxic epidermal necrolysis
- SJS and toxic epidermal necrolysis (TEN) are considered severity variants of a single entity
- A febrile form of EM with extensive involvement of the skin (also considered a minor form of toxic epidermal necrolysis)
Steven-Johnson Syndrome lesions (seen most often in children)
- Skin
- Lips
- Oral mucosa
- Conjunctiva
- Urethra
- Genital and perianal areas
- Secondary Infection: life-threatening sepsis
Toxic Epidermal Necrolysis (TEN)
- Potentially life-threatening dermatologic disorder
- Widespread erythema
- Necrosis
- Bullous detachment of epidermis and mucous membranes
- Exfoliation (secondary to bullous detachment)
- Sepsis and/or death
- Mucous membrane involvement
Mucous membrane involvement in TEN
- GI hemorrhage
- Respiratory failure
- Ocular abnormalities
- Genitourinary complications
Immunopathologic pathways leading to keratinocyte apoptosis
- Fas ligand activation on keratinocytes leading to apoptosis
- Release of destructive proteins (perforin and granzyme B) from cytotoxic T cells
- Cytokine overproduction
- Drug-induced secretion of granulysin from CTLs natural killer cells, and natural killer T cells
- How inciting agent trigger pathways is unclear
Chronic inflammatory dematoses
- Psoriasis
- Seborrheic Dermatitis
- Lichen Planus
- Inflammatory skin disorders persist for many months to years
Psoriasis
- Chronic inflammatory dermatosis
- Autoimmune basis
- Affects 1% to 2% of people in US
- All ages may develop the disease
- Approximately 15% of the patients have arthritis
Psoriasis associations
- Myopathy
- Enteropathy
- AIDS
Psoriasis pathogenesis
- Association with HLA-C
- Culprit antigens remain elusive
- Sensitization of CD4+ TH1 and TH17 cells
- Activated CD8+ accumulate in the epidermis
- Stimulate secretion of cytokines and growth factors
- Induction of keratinocyte proliferation
- Lymphocytes also produce growth factors
- Epidermal thickening
Psoriasis areas frequently affected (morphology)
- Elbows
- Knees
- Scalp
- Lumbosacral areas
- Intergluteal cleft
- Glans penis
Psoriasis lesions
- Well-demarcated
- Pink to salmon-colored plaque
- Covered by loosely adherent silver-white scale
Koebner phenomenon (psoriasis)
- Formation of psoriatic lesions in uninvolved skin of psoriatic patients after cutaneous trauma
Psoriasis morpholoy variations/configurations
- Annular, linear, gyrate, or serpiginous configurations
Changes seen in psoriasis
- Cause of total body erythema and scaling (erythroderma)
- Nail changes
Nail changes seen in psoriasis
- Yellow-brown discoloration
- Pitting, dimpling
- Onycholysis
- Thickening
- Crumbling
Auspitz sign (psoriasis histology)
- Abnormal proximity of vessels in dermal papillae overlying parakeratotic scale
- Bleeding points occur when scale is lifted from the plaque
- Spongiform pustules
- Munro microabscesses
Psoriatic arthritis
- Seronegative oligoarthritis
- Found in patients with psoriasis
- 1/5 patients with psoriasis has psoriatic arthritis
Psoriatic arthritis differentiating features
- Distal joint involvement
- Arthritis mutilans
Psoriatic arthritis classifications
- Mild
- Severe (deformities resembling RA)
- Any joint affected
- Symmetrical or asymmetrical
Seborrheic dermatitis
- More common than psoriasis
- Affecting up to 5 % of the general population
- Classically involves regions with a high density of sebaceous glands
Seborrheic dermatitis typical locations
- Scalp
- Head
- External auditory canal
- Retroauricular area
- Nasolabial folds
- Presternal area
Seborrheic dermatitis pathogenesis
- Etiology unknown
- Related with increased sebum production (androgenic response)
- Parkinson Disease
Parkinson disease in seborrheic dermatitis
- Increased sebum production
secondary to dopamine deficiency - Increased incidence of seborrheic dermatitis
Seborrheic dermatitis in parkinsons Tx
- Levodopa treatment
- Oiliness of the skin decreases
- Seborrheic dermatitis improves
Seborrheic dermatitis morphology
- Lesions are macules and papules
- Erythematous-yellow, greasy base
- Extensive scaling and crusting
- Fissures
- Dandruff (scalp involvement)
Seborrheic dermatitis histology
- Early lesions are spongiotic
- Later lesions acanthotic (follicular lipping)
- Mounds of Parakeratosis
- Superficial perivascular inflammatory infiltrate
Follicular lipping (seborrheic dermatitis histology)
- Neutrophils and serum present at the ostia of hair follicles
Lichen planus
- Disorder of skin and mucosa
- Self-limited (resolves spontaneously 1 to 2 yrs after onset)
- Post-inflammatory hyperpigmentation (Residual)
- Oral lesions can persist for years
- Squamous cell carcinoma can occur in chronic mucosal and paramucosal
- Koebner phenomenon seen
Lichen planus pathogenesis
- Unknown
- Altered antigen expression
- Basal epidermal cells
- Dermoepidermal junction
- Elicit CD8+ T cell responses
- T-lymphocyte infiltrates
- Hyperplasia of Langerhans cells
6 P’s of lichen planus (morphology)
- Pruritic
- Purple
- Polygonal
- Planar
- Papules
- Plaques
Lichen planus cutaneous lesions (morphology)
- Violaceous
- Flat-topped papules
- Coalesce to form plaques
- Wickham striae
- Areas of hypergranulosis
Lichen planus histology
- Dense dermoepidermal continuous infiltrate of lymphocytes
- Basal keratinocytes destruction
- Dermoepidermal interface (angulated / zigzag contour (sawtoothing))
- Civatte bodies
- Chronic
Lichen planus civatte bodies (histology)
- Anucleate, necrotic basal cells may become incorporated into inflamed papillary dermis
Chronic Lichen planus (histology)
- Epidermal hyperplasia
- Thickening of the granular cell layer and stratum corneum (hypergranulosis and hyperkeratosis, respectively)
