Skin Pathology Flashcards
Epidermis Structure
Layers (5)
Cells with Function: Keratinocytes, Melanocytes, Dendritic, Merkel
Stratum Corneum Stratum Lucidum Stratum Granulosum Stratum Spinosum Stratum Basale
Keratinocytes: Connected by desmosomes to form physical barrier, stratified squamous epithelium
Melanocytes: Produce melanin for UV protection
Dendritic (Langerhans): migrate to lymph nodes to activate T cells
Merkel: afferent nerve fibers
Dermis Structure
Components (4) Adnexa Description and Components (4)
Connective tissue
Blood vessels
Nerves
Adnexa
Adnexa: adjacent structures derived from the skin
Includes hair follicles, sebaceous glands, sweat glands, nails
Freckle (Ephelis)
Description (4)
Most common pigmented lesion
Hyperpigmentation from increased melanin in basal keratinocytes
Normal melanocytes
Darken when exposed to light
Lentigo
Description (2) and Histology
Local hyperplasia of melanocytes
In cell layer immediately above basement membrane
Linear (non-nested) melanocytic hyperplasia
Melanocytic Nevi
Mutations (2) Progression (3) Distinguishing Features from Melanoma (2)
Activating mutations of:
NRAS
BRAF
Junctional Nevi
Compound Nevi
Intradermal Nevi
Loss of tyrosinase activity
Acquired cholinesterase activity
Dysplastic Nevi
Prognosis, Mutations (4) Morphology (3) Dermal Changes (3)
Possible progression to melanoma
Activation of : NRAS, BRAF
Loss of: CDKN2A
CDK4 mutations
> 5cm
Enlarged nevus cell nests that may coalesce
Cytologic Atypia
Lentiginous hyperplasia
Melanin incontinence
Linear Fibrosis
Melanoma
Most Common Form, Mutations (5)
Radial Growth Classes (3)
Vertical Growth Phase Characteristics (2)
Most deadly skin cancer
Sporadic: caused by UV radiation
CDKN2A: loss of p16INK4a RAS and PI3K/AKT pathway activation BRAF activation PTEN loss TERT: telomerase activation
Radial Growth Classes:
Lentigo maligna
Superficial spreading (most common)
Acral/Mucosal Lentiginous Melanoma
Vertical Growth Phase:
Appearance of a nodule
Metastatic potential
Melanoma Prognostic Factors (5) Clinical Features (5)
Tumor Depth (Breslow thickness) Number of mitoses Ulceration of skin Tumor infiltrating lymphocytes Sentinel node metastases
"ABCDEs" Asymmetry Borders - irregular Color - variable Diameter - increasing Evolution (change) over time
Seborrheic Keratoses
Pathogenesis (2) Morphology (4) Histology (4)
FGFR3 mutation
Paraneoplastic: Leser-Trelat sign
Superficial, round, flat, waxy plaques
Exophytic
Sharply demarcated
Invagination cysts
Horn cysts
Acanthosis Nigricans
Morphology (2) Disease Associations (3) Pathogenesis (4)
Thickened, hyperpigmented skin
Velvety texture to skin
Diabetes
Obesity
GI adenocarcinomas (paraneoplastic)
Increased growth factor signaling to skin
FGFR3 mutation
IGFR1 excess
TGF-alpha excess (increased EGFR)
Fibroepithelial Polyp (Acrochordon) Morphology, Histology (2) Associated Syndrome (2)
Soft, flesh colored bag like tumor with slender stalk
Fibrovascular core
Covered by squamous epithelium
Birt-Hogg-Dube Syndrome: skin tags with perifollicular mesenchymal tumors
Eccrine Poromas Locations (2)
Palms and Soles where sweat glands are numerous
Cylindromas
Locations (2) Mutation, Origin, Morphology, Associated syndromes (2)
Forehead and Scalp
CYLD inactivation
Ductal differentiation (eccrine/apocrine)
Islands of normal cells resembling normal appearing basaloid cells
Mutliple Familial Trichoepithelioma
Brooke-Spiegler syndrome
Syringomas
Morphology, Origin
Multiple small, tan papules near eyelid
Eccrine differentiation
Sebaceous Adenoma
Associated Syndrome, Mutations, Morphology
Muir-Torre syndrome (colorectal carcinoma)
Deficits in DNA mismatch repair proteins
Frothy or bubbly cytoplasm
Pilomatricomas
Mutation, Origin
Activation of CTNNB1
Basaloid cells showing hairlike differentiation
Actinic Keratosis
Triggers (3) Mutation, Progression, Morphology (3)
Ionizing radiation
Industrial hydrocarbons
Arsenicals
TP53 mutations
May progress to cutaneous squamous cell carcinoma
Actinic cheilitis (if lip involved)
Elastosis of superficial dermis
Parakeratosis of stratum corneum
Squamous Cell Carcinoma
Pathogenesis (4) Associated Conditions with Mutations (2) Morphology (4)
Correlated with lifetime sun exposure
Progression from actinic keratosis
Chronic immunosuppression: increased HPV 5/8 infections
Ataxia-Telangiectasia: ATM defect
Xeroderma Pigmentosum: XPA defect
Red scaling plaques
Variable keratin production
Ulceration
Variable differentiation
Basal Cell Carcinoma
Associated Condition with Mutation, Pathogenesis (3) Growth Patterns (2) Morphology (3)
*Most common malignancy worldwide but rearely mestastasizes
Nevoid Basal Cell Carcinoma Syndrome: PTCH defect
Increased SHH signaling:
PTCH defect causes
Constitutive activation of SMO/GL1 (tumor growth)
Multifocal growth: outward
Nodular Lesions: downward
Pearly papules with telangiectasias
Ulceration (on sinuses causes Rodent Ulcer)
Peripheral palisading
Benign Fibrous Histiocytoma (Dermatofibroma)
Histology (3)
Benign spindle shaped cells
Nonencapsulated mass in mid-dermis
Pseudoepitheliomatous hyperplasia: downward elongation of rete ridges
Dermatofibrosarcoma Protuberans
Mutation, Morphology (3)
COL1A1-PDGFB translocation
Storiform closely packed fibroblasts
Honeycomb pattern of extension into subcutaneous fat
Protuberant firm nodule
Mycosis Fungoides (Cutaneous T cell Lymphoma) Lesion Progressions (3) Prognostic Factors (2) Histology (3) Cell Type Involved, Severe Complication
Scaly, red-brown patches
Raised, scaling plaques
Fungating nodules
% of body covered
Progression through to nodules
Bandlike aggregates of Sezary-Lutzner cells
Infolded nuclear membranes
Pautrier microabscesses in epidermis
CD4+ Th cells
Sezary Syndrome: erythroderma (whole body covered in scaling lesions)
Mastocytosis
Pathogenesis (2) Cutaneous Form, Clinical Signs with Descriptions (2)
KIT mutations
Increased mast cells in skin
Urticaria Pigmentosa
Darier sign: edema and erythema when lesion rubbed
Dermatographism: hives from rubbing normal skin
Ichthyosis
Pathogenesis (2) Morphology
Defective desquamation
Hyperkeratosis causes fishlike scaly skin
Buildup of compacted stratum corneum
Urticaria (Hives)
Pathogenesis, Types (3) Morphology (2)
Microvacular hyperpermeability
Types:
IgE mediated mast cell degranulation
Mast cell degranulation via direct substance stimulation
Direct Vasodilation: Aspirin induced, Hereditary Angioneurotic edema (C1 inh defect)
Pruritic edematous plaques
Contained to dermis
Eczematous Dermatitis
Pathogenesis (4) Morphology (6) Histology
T cell mediated Type IV hypersensitivity reactions:
Reactive chemicals are haptens
Haptens taken up by Langerhans cells
Presented to Th cells, memory cells cause strong second reaction
Red, Papulovesicular, Oozing, Crusted Lesions
Can develop reactive acanthosis and hyperkeratosis
Spongiotic Dermatitis: Edema in epidermis and dermis
Erythema Multiforme
Pathogenesis, Morphology (5) Complications (2)
CD8+ CTL-mediated damage to Keratinocytes
Targetoid lesions**
Perivascular lymphocytic infiltrate
Interface dermatitis: dermoepidermal junction
Stevens Johnson Syndrome: fever and mucosal lesions
Toxic Epidermal Necrolysis: epidermal sloughing
Psoriasis
Associated HLA, Pathogenesis (3) Presentation (2) Morphology (3)
HLA-Cw*0602 association
CD8+ CTL’s, Th1 and Th17 cell mediated inflammation
TNF highly involved
Can be trauma induced: Koebner phenomenon
Pink-salmon colored plaques covered by white scale
Nail discoloration and pitting
Auspitz Sign: multiple small bleeds in plaque
Thin/Absent Stratum Granulosum
Spongiform Pustules in superficial epidermis
Munro microabscesses in corneum
Seborrheic Dermatitis
Pathogenesis (2) Correlations (2) Presentation (2) Morphology (4)
Increased sebum from androgen exposure
Fungal colonization
HIV
Parkinsons
Fissures behind ears
Dandruff
Follicular lipping: Mounds of parakeratosis at ostia of hair follicle
Lymphocyte and Neutrophil mediated perivascular inflammation
Lichen Planus
Presentation (6) Morphology (3)
Pruritic Purple Polygonal Planar Papules and Plaques
Wickham striae (white dots along plaques)
Interface dermatitis
Civatte bodies: necrotic basal cells in dermis
Pemphigus
Variants (5) Pathogenesis, Histology, Presentation
Vulgaris (most common) Vegetans Foliaceus Erythematosus Paraneoplastic
IgG auto-Abs against desmogleins
Acantholysis: loss of squamous intercellular bridges
Suprabasal acantholytic blister
Bullous Pemphigoid
Pathogenesis and Presentation (2)
Autoantibodies to basal keratinocyte hemidesmosomes
Cutaneous and oral subepidermal, nonacantholytic blisters
Dermatitis Herpetiformis
Pathogenesis, Disease Association, Morphology (3)
IgA antibodies to gluten cross react with reticulin
Celiac’s Disease
Pruritic subepidermal blisters
Fibrin and neutrophil at tips of dermal papillae
Granular IgA deposits
Epidermolysis Bullosa
Pathogenesis, Presentation (2)
Types with Descriptions
Simplex (3) Junctional (2) Dystrophic (2)
Defect in skin structural proteins
Blisters at sites of pressure/rubbing/trauma
Show up at birth
Simplex: most common
Keratins 14 and 5 affected
Basal cell layer blisters
Junctional:
Laminin defects (AR)
Blisters at lamina lucida
Dystrophic:
COL7A1 defects
Blisters beneath lamina densa
Porphyria
Pathogenesis, Presentation (3) Types (5)
Porphyrin defects
Urticaria and subepidermal vesicles exacerbated by sunlight
Causes scarring
Congenital erythropoietic Erythrohepatic protoporphyria Acute intermittent porphyria Porphyria cutanea tarda Mixed
Acne Vulgaris
Pathogenesis (4) Morphology (2) Severe Variant
Keratin plug formation
Sebaceous gland hypertrophy
Lipase synthesizing bacteria (Propionbacterium acnes)
Secondary inflammation of follicle
Open comedones
Closed comedones
Acne conglobata
Rosacea
Pathogenesis (3) Morphology, Stages (4)
Elevated kallikrein 5 (stimulated by TLR2)
Causes increased antimicrobial cathelicidin
Perifollicular infiltrate
Flushing episodes (pre-rosacea)
Persistent erythema and telangiectasia
Pustules and papules
Rhinopyma
Erythema Nodosum
Classification, Pathogenesis, Histology (2) Presentation (3)
Panniculitis
Delayed hypersensitivity to drug/microbial antigens
Early lesions: widened septae in connective tissue
Late Lesions: Septal Fibrosis
Poorly defined, tender, erythematous plaques
Fever
Malaise
Erythema Induratum
Classification, Pathogenesis (2) Histology (3) Presentation (2)
Panniculitis
Primary vasculitis of vessels supplying fat lobules
Fat necrosis
Granulomatous inflammation
Caseous necrosis
Necrotizing vasculitis
Erythematous, slightly tender nodule
Ulceration of nodule
Verrucae
Etiologies (2) Types (4) Common Histology
HPV 6 and 11
Verruca vulgaris (most common) Verruca Plana (flat wart) Verrucae Plantaris/Palmaris Condyloma accuminatum (genital)
Verrucous epidermal hyperplasia
Impetigo
Pathogenesis (3) Morphology and Histology
Bacterial infection causes epidermal damage
Scale crust (scab) forms
Blister caused by desmoglein 1 cleavage by toxin
Honey-colored crust to blisters
Accumulation of neutrophils under stratum corneum
Pneumonic for Painful Skin Lesions (6)
“GLENDAB”
Glomus Tumor Leimyoma Eccrine Spiradenoma Neurofibroma Dermatofibroma Angiolipoma Blue Rubber Bleb Nevus
