Disease Epidemiology Path diagnsosis Histo Gross Tx  
Vocabulary Hyperkeratosis (hyperplasia of stratum corneum) Parakeratosis (retention of nuclei in stratum corneum) Hypergranulosis (hyperplasia of stratum granulosum) Acanthosis (epidermal hyperplasia)[1] Papillomatosis (surface undulations due to hyperplasia of papillary dermis) Dyskeratosis (abnormal keratinization) Acantholysis (loss of intercellular connections)
Spongiosis (increased intercellular edema in epi) Exocytosis (Inflammatory cell epidermal infiltration) Erosion (incompete epidermal loss) ulceration (complete epidermal loss) Lentiginous (basal layer linear melanocyte proliferation) vacuolization (vacuoles b/w cells)
Melanocytic disease    
Melanocytes Originate in neural crest and migrate to basal layer of epidermis (8wk), hair matrix, inner ear, uveal tract, and leptomeninges Converts tyrosine to melanin and transfers to keratinocyte via dendritis process. Dendritic cells dispersed along basal layer (1 for ervery 10 keratinocyts)
Vitiligo 1) All ages and races, 2) 50% occur before 20yo, 3) Assd w/ autoimmune disorders (Addison, perncious anemia, autoimmune thyroiditis[2] 1) DEF: Partial or complete loss of melanocytes in epidermis., 2) MECH: Ab vs. melanocytes, 3) Repigmentation through melanocyte precursor in hair follicle ostia Flat, well-demarcated loss of melanocytes loss of pigment
Ephilis (freckle) 1) most common pigmented lesion of childhood 1) Appear in childhood after sun exposure, 2) fade and reappear with exposure increased melanin within basal keratinocytes (normal number of melanocytes) 1) 1-10mm diameter, 2) tan-red or light brown macule
Lentigo 1) All ages, 2) Kids = lentigo simplex; adults = solar lentigo (sun damage) Local hyperplasia of malanocytes  which do not darken when exposed to sun 1) increased melanocytes along the basal layer, 2) elongation and rete thinning
Junctional Nevus 1) Melanocytes that have lost their dendritic processes, 2) Mole junctional proliferation --> Proliferation of nevus cells are tips of rete ridges Macular, evenly diffiuse color
Compound Nevus junctional and dermal proliferation --> nevus cells invade dermis and raise skin Nodule (slightly elevated)
Intradermal Nevus Dermal proliferation --> Dermal nevus proliferation Nodule (elevated mole)
Spitz Nevus 1) Most common in children L) Junctional nests with dermal maturation, R) large spindle and epitheliod cells
Blue Nevus 1) maybe confused w/ melanoma 1) non-nested, dendritis, heavily pigmented black/blue nodule
Congenital Nevus 1) Present at birth, 2) large (giant) variant melanoma risk increase, 3) may have hair 1) look like conventional nevi w/ growth around adnexa and neovascular bundle
Halo Nevus Host immune response to nevus cells and adjacent melanocytes lymphocytic infiltrate halo around nevus
Dysplastic Nevus 1) dyplastic nevi + melanoma FH = 100% melanoma risk, 2) DN + (-)FH = sligh risk increase, 3) AD,  histo 1) sun and non-sun exposed areas, 2) large, variable pigmentation, irregular borders
Melanoma 1) 8th most common malignancy in US, 2) white, 3)RF: dyplastic & cong. Nevi, past history (900X), FH (8X), XP (1000X), brite/intense/intermitent UV, 4) 4mm = 10yr @ 0%, 5) Sites: skin, oral & anogenital mucosa, esophagus, meninges, eye 1) GENETICS: Sporadic (PTEN mutation), Familial (meth of CDKN2A; 50% of fam melanoma), 2) Radial (horizontal spread w/ no mets or angiogenesis) & Vertical (nodular lesion with downward growth and angiogenic metastatic potential related to depth) A (assymetry), B (border irregularity), C (color change), D (diameter >6mm), E (elevation) Melanoma in situ: Melanocytes have clearing around nucleus. Pagetoid is spread into epidermal layer. Dermal inflammation but no melanocytes pic Melanoma
Non-melanotic skin lesion      
Seborheic keratosis 1) middle aged and elderly, 2) spontaneous 1) may become irritated, but benign and no Tx necessary, 2) Leser-Trelat (paraneoplastic syndrome with explosive onset due most commonly to TGF-a from gastric adenocarcinoma, lymphoma, brca, SCC of lung) 1) well demarcated w/ uniform benign basaloid proliferation, 2) hyperkeratosis, 3) epi horn cysts Round, flat velvety plaques appear "stuck on"
Keratoacanthoma 1) >50yo M, 2) sun exposed skin: ears, nose, cheek, and dorsum of hand 1) rapidly developing neoplasm which mimics SCC but may have spontaneous resolution w/o tx, 2) cytologic atypic and mitosis (controversial) Histo: Keratin filled crater. Well circumscribed cup shape w/ dark blue basal layer. Histo HP: Enlarged cells with a glassy eosinophilic cytoplasm and abrupt keratinization Well circumscribed ulcerated tumor with central keratinization
Actinic Keratosis 1) Pre-cancerous, 2) Sun-exposed Series of dysplastic changes related to cumulative sun exposure with elastic degeneration (solar elastosis) due to UV damage. Gross: plaques Gross: horns histo: parakeratosis, atrophy, basal atypica, solar elastosis
Squamous Cell Carcinoma 1) 2nd most common skin tumor, 2) RF (indust carcinogens, chronic ulcers, burn scars, arsenic, radiation, chewing tobacco, Betel nut) 1) UV (inhibits Langerhans cell presentation = defective immunosurveillance), 2) Immunosuppressed (chemo, transplant), 3) Xeroderma pigmentosa (DNA repair defect) SCC in situ: Atypical keratinocytes through entire epidermis[3] Invasive: Squamous eddies "pearls" and with nesting 1) In situ: sharply defined, red, scaling plaques, 2) Invasive: Lesion often nodular and ulcerated Excision (usually curative)
Basal Cell Carcinoma 1) Most common skin tumor, 2) slow growing w/ rare metastasis, 3) Sun exposed skin Cords and islands of "basophilic" cells 1) Pearly papule with telangectasia, 2) large tumors may ulcerate Excision curative
Dermatofibroma (benign fibrous histiocytoma) 1) Benign, 2) legs of young-middle aged women 3) antecedant trauma history Fibroblast infiltration into dermis w/ epidermal hyperplasia Firm tan to brown papule
Acute Inflammatory Dermatoses        
Mastocytosis 1) Typically adults, 2) Poor prognosis Systemic mastocytosis (increased mast cell in skin and organs) 1) Mast cell granule release (histamine & heparin)= Pruritis, flushing, GI and nasal bleed (rare), Bone pain, 2) Dariers sign - rubbing induced erythema and edema Variable histo from subtle dermal mast cell (spindle) increase to heavy round mast cell increase in upper dermis round to oval, red/brown, non-scaling papules and plaques
1) Most common type, 2) typically kids Uticaria pigmentosa (localized to skin)
1) Good prognosis Mastocytoma (solitary cutaneous lesion)
Urticaria 1) Typically 20-40yo (but all ages), 2) transient lesions resolve in 1-3 days, 3) Stimuli: pollens, food, drugs, ect. 1) MECH: IgE mediated mast cell degranulation (Type I hypersensitivity) results in microvascular permeability and intersitial edema, 2) Hereditary angioneurotic edema (face) - C1 esterase def = uncontrolled complement activation Normal looking biopsy w/ superficial dermal edema and dilated vessels erythematous, edematous, circular plaques w/ normal epithelial surface
Eczema 1) Types: Contact dermatitis (poison ivy), atopic dermatitis, drug-related eczematous, photoeczematous, primary irritant dermatitis MECH: Type IV hypersensitivity (Langerhans cells process antigen, present to naïve CD4 T-cells. Memory T cells release cytokines stimulating inflammatory response) Edematous epidermis with superficial dermal perivascular lymphocytic infiltrate Red, papulovesicular, oozing, crusted lesions atopic irritant
Erythema multiforme 1) Self limited, 2) Stevens-Johnsons and toxic epidermal necrolysis (same process) 1) MECH: Hypersensitivity to infection or drugs (CTL kill epidermal cells), 2) ASSN: Infections (HSV, mycoplasma), Drugs (sulfonamides, pen, barbs), Malignancy (carcinoma, lymphoma), Collagen vascular dx (SLE, dermatomyositis) Target lesions (central necrosis w/ rim of pervenular inflammation) symmetrically on extremities Lymphoyctes migrating from perivascular dermis to epidermis and killing keratinocytes Targetoid lesions (characteristic, but many presentations)
Stevens-Johnson Syndrome Erosion and crusting of mucosal surfaces casued by sulfonamide antibiotics major = mucous membranes; minor = other EM major
Toxic epidermal necrolysis Diffuse necrosis and sloughing of cutaneous and mucosal surfacs Sloughing of entire epidermis
Chronic Inflammatory Dermatoses      
Psoriasis 1) common on elbows, knee, scalp, lumbsacral, glans, interglueal cleft 1) MECH: Sensitized T cells secrete cytokine (IL-10, TNF-a, IL-8) and growth factors resulting in increased cell turnover, vascular proliferation, and inflammation., 2) ASSN: Arthritis, myopathy, enteropathy, spondylitic heart disease, & AIDS Epidermal hyperplasia, parakeratotic scales, and minute microabscesses of PMN within superficial epidermis 1) well-demarcated, pink plaque with loose silver scales, 2) Oil-slick nail discoloration, 3) nail pitting
Lichen planus 1) Self limited (1-2yr) 1) MECH: Unknown, theory = antigen stimulated cell-mediated cytoxic rxn at basal level Bandlike infiltrate of lymphocytes at dermal-epidermal jnct with pointed rete ridges 1) Pruritic, purple, polygonal papules which may coalesce to form plaques, 2) symmetric
Discoid Lupus Erythematosus 1) Localized cutaneous form of lupus (>33% SLE px develop DLE), 2) worse in sun-exposed skin Perivascular lymphocytic infiltrate Atrophic epidermis 1) Malar erythema (systemic), 2) plaques with hypopigmented center and hyperpigmented periphery
Blistering Dermatoses      
Pemphigus vulgaris 1) uncommon, 2) M=F, 3) middle aged to elderly, 4) Location: scalp, face, axilla, groin, trunk 1) MECH: Type II Hypersensitivity w/ anti-desmoglein IgG (intercellular desmosomal attachment loss), 2) Mixed inflammation IF: "fish net" Suprabasal acantholysis Flaccid vessicles which rupture resulting in shallow erosions w/ crust
Bullous Pemphigoid 1) Elderly, 2) Location: thighs, forearm flexor surf, axilla, groin, lower ab, and oral (30%) 1) MECH: Type II hypersensitivity anti-pemphigoid antigen IgG (lamina lucida, bm zone, and hemidesmosome protein), 2) Eosinophils IF: bm deposition Subepidermal nonacantholytic blister Tense bullae filled w/ clear fluid
Dermatitis Herpetiformis 1) 30-40yo, 2) M>F, 3) Location: extensor, elbows, knees, upper back, buttock, 4) ASSN: celiac disease 1) MECH: anti-gluten IgA (Gut B cell Ab cross reacts with transglutaminase a component of anchoring fibrils), 2) PMN inflammation IF: IgA deposits at dermal papillae tips PMN microabscesses in dermal papilale Pruritic grouped vesicles
Epidermolysis bullosa aquisita 1) Usually adults (any age), 2) Location: trauma-prone surfaces w/ variable mucous membrane involvement 1) MECH: anti-collagen VII Ab (anchoring fibrils), 2) No inflammation IF: Linear BM Non inflammatory subepidermal blister Flexural crease bullae
Inflammatory Dermatoses: Viral      
Verrucae vulgaris 1) Most common, 2) Location: Hands 1) Anogenital warts (HPV 6 & 11), 2) Dysplasia (HPV 16), 3) Bowenoid papulosis (HPV 16; genital lesions appear as SCCIS but spontaneously regress), 4) Epidermodysplasia verruciformis (HPV 5 & 8: muliple flat warts which may evolve to SCC) Large papillomatous projections. Hyperkeratosis w/ parakeratosis. Capillary loops in each projection. Epidermal hyperplasia with atypia and keratohyaline granules Grey papule with rough surface
Verruca Plana 1) Location: face and hands Tan slightly elevated smooth papules The virus is in the epidermis around the warts (so must freeze a border)
Verruca plantaris 1) Location: palm and soles Rough scaly lesions
Condyloma accuminatum 1) Location: genital and perianular warts Cauliflower masses
Molluscum contagiosum 1) children and young adults, 2) self-lmited 1) MECH: Pox virus spread through autoinnoculation Endophytic epidermal prolif w/ large eosinophilic inclusions (virion) protruding out of invagination umbilicated papules (central depression)
Herpes Simplex Virus 1) HSV 1 & 2 Intraepidermal ballooning Cowdery A bodies
Inflammatory Dermatoses: Bacterial      
Staphlococcal scalded skin syndrome 1) pre-existing infection focal cutaneous, 2) conjucntivits prior to rash, 3) most common in chldren (adults w/ immuno/renal compromise), 4) post-nasopharynx/skin staph infection 1) MECH: Staph A exfoliative toxin (serine protease cleaves desmoglein 1 in desmosome) Nikolsky's sign (push on skin gets extension of blister) 1) intraepidermal vesicle in granular layer, 2) IF neg Sunburn-like rash not involving mucuos membrane (SJ diff) w/ bullae and large desquamation 1) antibiotics, 2) heals 1-2wk w/o scarring
Impetigo (pyoderma) 1) children, 2) highly contagious superficial skin infection 1) MECH: Focal SSSS, 2) Staph aureus and streptococcus disease causing superficial skin infection Focal bullae
Ecthyma Presentations: 1) lower extremeties of children, 2) neglected elderly, 3) lymphedema of limbs, 4)  Immunocompromised 1) MECH: SSSS extending into dermis (ulcer) Ulcerated round lesion with peripheraly erythema
Erysipelas 1) ASSN: abrupt fever, chills, malaise, nausea onset 1) MECH: Dermis infection w/ significant lymphatic involvemnet by Streptococcus pyogenes 1) Spongiotic epidermis, 2) Edematous dermis, 3) PMN infiltrate, 4) dlated lymphatics Well demarcated erythemaous and indurated lesion
Cellulitis 1) Following skin abrasion 1) MECH: Deep dermis and subcutaneous tissue infection, 2) S. pyogenes or S. aureus fever, chills, malaise, warm, tender, erythematous lesion which is indefined with non-palpable borders 1) Dermal infiltrate of PMN and lymphocytes, 2) edema & lymphatic dilation, 3) Gram stain positive erythematous ildefined lesion w/ non-palpable borders
Leprosy 1) Incubation months to years (5yr ave.), 2) Viable 7 days in dried secretions (viable), 3) Armadillos 1) Mycobacterium leprae w/ 3 forms: Indeterminate, tuberculoid,  lepromatous, 2) MECH: CMI determines disease form (intact = tuberculoid, depressed = lepromatous) Tuberculoid gross: Patches w/ erythematous periphery and bland center  Tuberculoid: 1) Non-caseating granulomas w/ multinucleation, 2) lymphocytic infiltrate, 3) NO organisms Lepromatous gross:  Lepromatous histo: 1) dense mac infiltrate, 2) Neurovascular bundle involvement, 3) Fite stain shows organisms
Dermatophyte  
Dermatophyte Location based name: 1) Tinea versicolor (hypopigmented macules on trunk; Malassezia furfur - yeast), 2) Tinea capitis (head), 3) Tinea barbae (beard), 4) Tinea corporis (body), 5) Tinea pedis (feet), 6) Onychomycosis (nail) 1) Stratum corneum fungal infection, 2) GROSS: Diffuse erythema,, scaling, circinate w/ an expanding border, 3) HISTO: slight to moderate dermis inflammation (PMN) + spongy epi + hyperkeratosis + PAS Tinea corporis (pustule due to PMN migration) Tinea capitis (follicle w/ hairshaft filled w/ fungus)
Inflammatory Dermatoses: Parasitic  
Scabies 1) Presentation: Papulovesicular (most common), Nodules, Crusted (immunosuppressed), 2) Location: interdigital folds, palms, fingers, wrists Biopsy of immunosuppressed with scabies Crust
Nevoid basal cell carcinoma syndrome 1) AD, 2) PTCH,  1) PTCH gene product couples w/ smoothened. In absence of SHH the PTCH stays coupled and smoothened in inactive. SSH released smoothen resulting in gene expression w/ unregulated cell division , 2) two-hit hypothesis
Neurofibromatosis I
Neurofibromatosis II
Mueir-Torre 1) AD, 2) mismatch repair defect

[1]
Acantho -
"Thorny, horn-like"

[2]
Addison's is an autoimmunc disease which destoyrs adrenals resulting in high ACTH (pigmentation via MSH fragment), and low cortisol (hypoglycemia, hypotension via alpha 2 sensitivity), low aldosterone (hypotension), and low DHEA.
[3]
distinguish from actinic keratosis b/c atypica only in basal layer