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Diseases of the Skin
by Noel C. Santos, M.D.
Definition of Terms
      Macroscopic
         Macule: flat, circumscribed, discoloration
         Papule: elevated solid ...
Wheal: pruritic, erythematous elevated area resulting
  from dermal edema.
Scale: dry, plate-like excrescence resulting fr...
Microscopic
  Hyperkeratosis: stratum corneum hyperplasia, with
    aberrant keratinization.
  Parakeratosis: retention of...
Papillomatosis: elongation or widening of the dermal
  papillae.
Lentiginous: linear pattern of melanocyte proliferation
 ...
Erosion: focal, incomplete loss of epidermis.
Ulceration: focal complete loss of epidermis, may
  include dermis and subcu...
ACUTE INFLAMMATORY DERMATOSES
     short-lived, mononuclear cell infiltrates with
       edema, local tissue damage
     ...
URTICARIA (HIVES)
focal mast cell degranulation – histamine
  release: pruritus, edema & wheal
Angioedema: dermal & SC fat...
Hereditary Angioneurotic Edema
Recurrent attacks
With GIT and laryngeal involvement
Deficient C1 esterase inhibitor
Unregu...
ACUTE ECZEMATOUS DERMATITIS
       Pathogenetically different w/ same histologic features
       Cutaneous delayed-type HS...
5 Primary Types of Eczema
CONTACT DERMATITIS
ATOPIC DERMATITIS
DRUG-RELATED ECZEMATOUS DERMATITIS
PHOTO-ECZEMATOUS ERUPTIO...
Type                 Cause                  Histology                Clinical Features


Contact Dermatitis   Topically ap...
ERYTHEMA MULTIFORME
Uncommon, self-limited HS response
  (drugs, infections, systemic disorders)
Extensive epidermal degen...
ERYTHEMA MULTIFORME (Cont.)
Steven-Johnson syndrome: severe, febrile, erosions and
   hemorrhagic crusting
Toxic Epidermal...
ERYTHEMA NODOSUM/INDURATUM
Panniculitis or inflammation of SC fat
   Connective tissue septa – NODOSUM
   Fat lobules – IN...
Erythema Nodosum
Most common, acute onset
Idiopathic or Secondary
   (drugs, infections, sarcoidosis, IBD, visceral
   mal...
Erythema Induratum
Uncommon, unknown cause
Adolescent and menopausal women
Primary vasculitis of SC fat with subsequent
  ...
Weber-Christian disease (Relapsing
 Febrile Nodular Panniculitis)
  Rare form of panniculitis; crops of
   erythematous pl...
CHRONIC INFLAMMATORY DERMATOSES

Persistent inflammatory disorders
Scaling and shedding (desquamation)
PSORIASIS
LICHEN ...
PSORIASIS
Common, HLA types (genetic)
New lesions at sites of trauma (Koebner’s phenomenon) –
  exogenous stimuli
Damage t...
PSORIASIS (Cont.)
Gross: well-demarcated salmon pink plaques
  with silvery scaling;
  elbows, knees, scalp, lumbosacral
 ...
PSORIASIS (Cont.)
Micro: marked acanthosis with rete elongation, mitoses
  above the basal layer; thin or absent stratum
 ...
LICHEN PLANUS
Unknown cause, self-limited, after 1 to 2 yrs. Leaves
  postinflammatory hyperpigmentation
Oral may persist,...
LICHEN PLANUS (Cont.)
Micro: dense, bank-like dermoepidermal
  junction lymphocytic infiltrate with basal cell
  degenerat...
LUPUS ERYTHEMATOSUS
Discoid LE – localized cutaneous form w/o systemic
   manifestation
Immune complex-mediated and cell-m...
LUPUS ERYTHEMATOSUS (Cont.)
Micro: dermoepidermal junction perivascular &
  periappendiceal lymphocytic infiltrates
Prefer...
ACNE VULGARIS
Common, chronic, inflammatory dermatosis affecting hair
   follicles
Middle to late teens, males>females
Hor...
ACNE VULGARIS (Cont.)
Gross: Non-inflammatory – follicular papules with central
  black keratin plugs (open comedo); folli...
BLISTERING (BULLOUS) DERMATITIS
Primary conditions; level of blister
  involvement within the skin
   SUBCORNEAL: impetigo...
PEMPHIGUS
Rare, autoimmune, 4th to 6th decades
Circulating Ab’s to keratinocyte intercellular
  cement components that bin...
Pemphigus vulgaris
80%; oral mucosa, scalp, face, intertriginous
  zones, trunk, pressure points
Superficial and easily ru...
Pemphigus foliaceus
More benign, epidemic in S. America
Face, scalp and upper trunk
Extremely superficial bullae leaving o...
PEMPHIGUS (Cont.)
Micro: acantholysis leading to intercellular
   clefting and broad-based intraepidermal
   blisters
P. v...
BULLOUS PEMPHIGOID
Common, autoimmune, elderly
Circulating Ab’s, with complement activation and
   granulocyte recruitment...
DERMATITIS HERPETIFORMIS
Rare, 3rd to 4th decade, m>f
specific HLA types & celiac disease
Skin & GI lesions respond to glu...
DERMATITIS HERPETIFORMIS (Cont.)
Micro: neutrophils & fibrin accumulate in the
  tips of dermal papillae (microabscesses)
...
NONINFLAMMATORY BLISTERING DISEASES

Primary disorders with vesicles and bullae
  NOT mediated by inflammatory mechanisms...
PORPHYRIA
Inborn or acquired disturbances of porphyrin
  metabolism
Unknown pathogenesis
Urticaria and vesicles exacerbate...
EPIDERMOLYSIS BULLOSA
Blistering at pressure sites and trauma
TYPES:
   JUNCTIONAL: blistering at the lamina lucida
   DYS...
INFECTION and INFESTATION
VERRUCAE (WARTS)
MOLLUSCUM CONTAGIOSUM
IMPETIGO
LEPROSY
SUPERFICIAL FUNGAL INFECTIONS
ARTHROPOD-...
VERRUCAE (WARTS)
Common, HPV, direct contact
V. Vulgaris: most common, dorsum of hand; gray-white to
   tan, flat to conve...
MOLLUSCUM CONTAGIOSUM
   Common, poxvirus, direct contact
   Gross: firm, pruritic, pink to skin-colored,
     umbilicated...
IMPETIGO
Streptococcal & Staphylococcal infection
erythematous macule progressing to small
  papules and eventually shallo...
LEPROSY
Slowly progressive, unsightly & disabling
  deformities, peripheral neural sensory deficits
Aerosol transmission, ...
SUPERFICIAL FUNGAL INFECTIONS
Dermatophytes; confined to nonviable stratum corneum;
  by location
Reactive epidermal chang...
FUNGAL INFECTIONS (Cont.)
Tinea cruris: inguinal areas among obese, warm
  weather; moist patches with raised scaling bord...
ARTHROPOD-ASSOCIATED LESIONS
Bites, stings, infestations
Reactions: trivial to fatal
Gross: urticarial, inflamed papules o...
SCABIES
Pruritic caused by mite Sarcoptes scabiei
Female burrows beneath the stratum corneum –
  linear, poorly defined fu...
PEDICULOSIS
Pruritic, caused by louse: insect or eggs attach to hair
  shafts
May be complicated by impetigo with lymphade...
DISORDERS OF PIGMENTATION AND
MELANOCYTES
VITILIGO
FRECKLE (EPHELIS)
MELASMA
LENTIGO
NEVOCELLULAR NEVUS (PIGMENTED
  NEVUS...
VITILIGO
Irregular, well-demarcated macules devoid of
  pigmentation
Autoimmunity (melanocyte autoAb’s, T-cell
  abnormali...
FRECKLE (EPHELIS)
Pigmented lesions: tan-red to brown macules
  occurring after sun exposure, fading and
  recurring with ...
MELASMA
Masklike facial hyperpigmentation
Hyperestrogenic states, fades postpartum
Gross: blotchy, irregular, ill-defined ...
LENTIGO
Benign, hyperpigmented macules, do not
  darken with sun exposure
Unknown etiology and pathogenesis
Micro: linear ...
NEVOCELLULAR NEVUS
Group of congenital or acquired melanocyte neoplasm
Well-demarcated, tan-brown papules
Melanocytes deri...
NEVOCELLULAR NEVUS (Cont.)
  Lost epidermal component resulting in
    dermal nevi
  Progressive dermal downgrowth, nevus ...
Nevus Variant      Diagnostic Architectural Features   Diagnostic Cytologic        Clinical Significance
                 ...
DYSPLASTIC NEVUS
Autosomal dominant or sporadic
Larger than acquired nevi; as hundreds of
  irregular macules/plaques with...
MELANOMA
Sun exposure, lightly pigmented individuals, hereditary
   component
Pruritic, variegated, irregular maculopapula...
MELANOMA (Cont.)
Clinical behavior & probability of metastasis –
   characteristics and depth of invasion of the
   vertic...
BENIGN EPITHELIAL TUMORS
biologically inconsequential lesions derived
  from keratinocytes or skin appendages
SEBORRHEIC ...
SEBORRHEIC KERATOSIS
Spontaneous lesions; trunk, smaller facial lesions
  (dermatosis papulosa nigra)
Large number as part...
ACANTHOSIS NIGRICANS
Thick hyperpigmented zones in flexural areas
Associated with benign or malignant conditions
  elsewhe...
FIRBOEPITHELIAL POLYP
Acrochordon, squamous papilloma, skin tag
Soft, flesh-colored attached by slender stalk
  with fibro...
EPITHELIAL CYSTS
Well-circumscribed, firm, SC nodules
Downgrowth and cystic expansion of the epidermal and
  follicular ep...
KERATOACANTHOMA
Spontaneously heal, rapidly growing, sun-exposed
Gross: flesh-colored, superficial, with central keratin-f...
ADNEXAL (APPENDAGE) TUMORS
Benign neoplasms, few malignant variants;
  Mendelian pattern; indicate visceral
  malignancy (...
PREMALIGNANT AND MALIGNANT EPIDERMA
TUMORS
ACTINIC KERATOSIS
BOWEN’S/BOWENOID LESIONS and
  ERYTHROPLASIA OF QUEYRAT
SQUAM...
ACTINIC KERATOSIS
Premalignant dysplastic lesion, chronic sun exposure;
  ionizing radiation, hydrocarbons, and arsenicals...
CARCINOMA IN-SITU
Full thickness epidermal cytologic atypia
  (Bowen’s disease; Bowenoid papulosis;
  Erythroplasia of Que...
SQUAMOUS CELL CARCINOMA
Most common; sunlight/UV light directly
  damages DNA & exerts immuno-suppressive
  effect to Lang...
SQUAMOUS CELL CARCINOMA (Cont.)
Gross: nodular, variably
  hyperkeratotic, ulcerates; leukoplakia
  (mucosal surface)
May ...
BASAL CELL CARCINOMA
Common, slow-growing, sun-exposed and rarely
  metastasize
Immunosuppression & xeroderma pigmentosum
...
MERKEL CELL CARCINOMA
Rare, neural crest derived Merkel cells (tactile
  sensation)
Potentially lethal; small, round malig...
TUMORS OF THE DERMIS
BENIGN FIBROUS HISTIOCYTOMA
DERMATOFIBROSARCOMA PROTUBERANS
XANTHOMAS
DERMAL VASCULAR TUMORS
BENIGN FIBROUS HISTIOCYTOMA
Indolent neoplasms of dermal fibroblasts &
  histiocytes
Unknown cause, antecedent trauma and
...
DERMATOFIBROSARCOMA PROTUBERANS
Well-differentiated, slow-growing fibrosarcoma;
  locally aggressive but rarely metastasiz...
XANTHOMAS
Not true neoplasm, focal accumulation of foamy
  histiocytes
Idiopathic or Secondary (familial or acquired
  hyp...
XANTHOMAS (Cont.)
   Tendinous Xanthoma: yellow nodules over
     the Achilles tendon and finger extensor
     tendons
   ...
DERMAL VASCULAR TUMORS
Hemangiomas, vascular malignant
  tumors, Kaposi’s sarcoma and angiomatosis
TUMORS OF CELLULAR IMMIGRANTS TO THE
SKIN
 Proliferative disorders of cells arising
   elsewhere but which homed to the s...
HISTIOCYTOSIS X
Cutaneous form – solitary or multiple papules or nodules;
   scaling erythematous plaques resembling sebor...
MYCOSIS FUNGOIDES
Cutaneous T-cell Lymphoma, 3 patterns
  Mycosis Fungoides (MF)
  MF d’emblee: nodular eruptive variant
 ...
MYCOSIS FUNGOIDES
Gross: eczema-like lesions evolving into scaly, red-
  brown patches or plaques; to nodules (nodular
  c...
MASTOCYTOSIS
Rare, cutaneous (visceral) mast cell
  proliferation; degranulation (histamine and
  heparin)
Pruritus & flus...
MASTOCYTOSIS (Cont.)
Urticaria pigmentosa (50%) exclusively
  cutaneous, favorable prognosis, children;
  10% adults, syst...
That’s all folks!!!
  Thank you very much!!!
    Good morning!!!
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Diseases of Skin

  1. 1. Diseases of the Skin by Noel C. Santos, M.D.
  2. 2. Definition of Terms Macroscopic Macule: flat, circumscribed, discoloration Papule: elevated solid area  5 mm. Nodule: elevated solid area > 5 mm. Plaque: elevated flat-topped > 5mm. Vesicle: elevated fluid-filled  5 mm. Bulla: elevated fluid-filled > 5 mm. Blister: common term for vesicle or bulla Pustule: discrete, pus-filled raised area
  3. 3. Wheal: pruritic, erythematous elevated area resulting from dermal edema. Scale: dry, plate-like excrescence resulting from aberrant cornification. Lichenification: thick, rough skin with prominent skin markings, usually 2o repeated rubbing. Excoriation: linear, traumatic lesion resulting in epidermal breakage. Onycholysis: loss of nail substance.
  4. 4. Microscopic Hyperkeratosis: stratum corneum hyperplasia, with aberrant keratinization. Parakeratosis: retention of nuclei in stratum corneum, normal in mucous membranes. Acanthosis: epidermal hyperplasia Dyskeratosis: abnormal keratinization below the stratum granulosum.
  5. 5. Papillomatosis: elongation or widening of the dermal papillae. Lentiginous: linear pattern of melanocyte proliferation within the epidermal basal cell layer, reactive or neoplastic. Spongiosis: epidermal intercellular edema. Exocytosis: inflammatory cells infiltrating the epidermis.
  6. 6. Erosion: focal, incomplete loss of epidermis. Ulceration: focal complete loss of epidermis, may include dermis and subcutaneous fat. Vacuolization: vacuoles within or adjacent to cells.
  7. 7. ACUTE INFLAMMATORY DERMATOSES short-lived, mononuclear cell infiltrates with edema, local tissue damage URTICARIA (HIVES) ACUTE ECZEMATOUS DERMATITIS ERYTHEMA MULTIFORME ERYTHEMA NODOSUM and ERYTHEMA INDURATUM
  8. 8. URTICARIA (HIVES) focal mast cell degranulation – histamine release: pruritus, edema & wheal Angioedema: dermal & SC fat edema Perivascular mononuclear infiltrates and edema Mediated by Ag-specific IgE or IgE-independent (chemical-induced, PG’s suppression) Persistent – inability to clear the inciting Ag, cryptic collagen-vascular disorders, Hodgkin/s disease
  9. 9. Hereditary Angioneurotic Edema Recurrent attacks With GIT and laryngeal involvement Deficient C1 esterase inhibitor Unregulated activation of the early complement components
  10. 10. ACUTE ECZEMATOUS DERMATITIS Pathogenetically different w/ same histologic features Cutaneous delayed-type HS response Cytokine release and nonspecific recruitment of inflammatory cells Gross: pruritic, red, papulovesicular to blistered, oozing and subsequently crusted, and may evolve into psoriasis-like scaling plaques Micro: spongiosis, progressive fluid accumulation, intraepidermal vesicles; dermal perivascular lymphocytic infiltrate, mast cell degranulation, papillary dermal edema; eosinophils (drug); progressive acanthosis & hyperkeratosis (chronic)
  11. 11. 5 Primary Types of Eczema CONTACT DERMATITIS ATOPIC DERMATITIS DRUG-RELATED ECZEMATOUS DERMATITIS PHOTO-ECZEMATOUS ERUPTION PRIMARY IRRITANT DERMATITIS
  12. 12. Type Cause Histology Clinical Features Contact Dermatitis Topically applied Spongiotic dermatitis Itchy or burning; chemicals; delayed antecedent exposure HS Atopic Dermatitis Unknown; heritable ? Spongiotic dermatitis Erythematous plaques (flexors); + family Hx Drug-related Systemically Spongiotic dermatitis; Eruption after exposure & administered eosinophils remits when discontinued Photo-eruption UV light Spongiotic dermatitis Sun-exposed skin; phototesting help in diagnosis Primary irritant Repeated trauma Spongiotic dermatitis Localized to site of trauma (rubbing) (early stage)
  13. 13. ERYTHEMA MULTIFORME Uncommon, self-limited HS response (drugs, infections, systemic disorders) Extensive epidermal degeneration and necrosis Due to cell-mediated immune injury (CD8+ cytotoxic T-cells) Gross: “multiform” – macules, papules, vesicles, and bullae; “targets” – red maculopapular with central vesicular or eroded pallor; symmetric involvement of extremities
  14. 14. ERYTHEMA MULTIFORME (Cont.) Steven-Johnson syndrome: severe, febrile, erosions and hemorrhagic crusting Toxic Epidermal Necrolysis: diffuse mucocutaneous epithelial necrosis and sloughing; analogous to 30 burns Micro: dermoepidermal junction & superficial perivascular lymphocytic infiltrates; dermal edema, focal basal keratinocyte degeneration and necrosis; Exocytosis with epidermal necrosis, blistering and shallow erosions; Target lesions – central epidermal necrosis w/ perivenular inflammation
  15. 15. ERYTHEMA NODOSUM/INDURATUM Panniculitis or inflammation of SC fat Connective tissue septa – NODOSUM Fat lobules – INDURATUM may be Acute or Chronic Early lesions: necrotizing vasculitis in deep dermis and subcutis Eventually develop granulomatous inflammation and necrosis
  16. 16. Erythema Nodosum Most common, acute onset Idiopathic or Secondary (drugs, infections, sarcoidosis, IBD, visceral malignancy) Ill-defined, tender erythematous nodules with fever and malaise Old lesions flatten, ecchymotic without scarring while new lesions develop Bx: early septal widening - edema, fibrin deposition, neutrophil infiltration (giant cells & eosinophils) w/o vasculitis
  17. 17. Erythema Induratum Uncommon, unknown cause Adolescent and menopausal women Primary vasculitis of SC fat with subsequent inflammation and necrosis of adipose tissue Erythematous, slightly tender nodule that ulcerates and scars Early: necrotizing vasculitis in deep dermis and subcutis Late: fat lobules develop granulomatous inflammation and necrosis
  18. 18. Weber-Christian disease (Relapsing Febrile Nodular Panniculitis) Rare form of panniculitis; crops of erythematous plaques or nodules, mainly on the legs Deep lymphohistiocytic infiltrates and giant cells Factitial Panniculitis Self-administered foreign substances Deep mycotic infections in immunocompromised Others: SLE
  19. 19. CHRONIC INFLAMMATORY DERMATOSES Persistent inflammatory disorders Scaling and shedding (desquamation) PSORIASIS LICHEN PLANUS LUPUS ERYTHEMATOSUS ACNE VULGARIS
  20. 20. PSORIASIS Common, HLA types (genetic) New lesions at sites of trauma (Koebner’s phenomenon) – exogenous stimuli Damage to stratum corneum – deposition of complement- fixing Ab’s with 20 complement-mediated injury Psoriatic endothelium – sensitive to cytokine-induced expression of adhesion molecules with subsequent enhanced neutrophil recruitment Associated with other disorders: myopathies, enteropathies, AIDS, arthritis
  21. 21. PSORIASIS (Cont.) Gross: well-demarcated salmon pink plaques with silvery scaling; elbows, knees, scalp, lumbosacral area, intergluteal cleft, glans penis Annular, linear, gyrate or serpiginous ERYTHRODERMA - total body scaling and erythema Nail changes: discoloration, pitting, onycholysis Pustular psoriasis: rare, life-threatening
  22. 22. PSORIASIS (Cont.) Micro: marked acanthosis with rete elongation, mitoses above the basal layer; thin or absent stratum granulosum; extensive overlying parakeratosis Thin epidermis overlying dermal papillae with dilated vessels – pinpoint bleeds when overlying scale is removed (Auspitz sign) Aggregates of neutrophils in epidermis within small spongiotic foci in the stratum spinosum (spongiform pustules) or within the parakeratotic stratum corneum (Munro’s microabscesses); large, abscess-like
  23. 23. LICHEN PLANUS Unknown cause, self-limited, after 1 to 2 yrs. Leaves postinflammatory hyperpigmentation Oral may persist, may become malignant Cell-mediated immune injury to basal cells With Koebner’s phenomenon Gross: pruritic, purple, polygonal papules that may coalesce into plaques; highlighted by white dots or lines (Wickham’s striae) Multiple, symmetrically distributed; hair follicle epithelium (lichen planopilaris)
  24. 24. LICHEN PLANUS (Cont.) Micro: dense, bank-like dermoepidermal junction lymphocytic infiltrate with basal cell degeneration and necrosis; jagged rete “saw- toothing” Necrotic basal cells may be sloughed into inflamed papillary dermis forming colloid or Civatte bodies With chronic changes: acanthosis, hyperkeratosis, thick granular cell layer
  25. 25. LUPUS ERYTHEMATOSUS Discoid LE – localized cutaneous form w/o systemic manifestation Immune complex-mediated and cell-mediated injury to pigment-containing basal cells Sun exposure exacerbates the lesion Gross: ill-defined malar erythema; sharply demarcated “discoid” erythematous scaling plaques with zones of irregular pigmentation and small keratotic plugs in hair follicles
  26. 26. LUPUS ERYTHEMATOSUS (Cont.) Micro: dermoepidermal junction perivascular & periappendiceal lymphocytic infiltrates Preferential involvement of SC fat – lupus profundus Basal cell vacuolization, epidermal atrophy, variable hyperkeratosis Immunofluorescence: granular band along the dermoepidermal and dermal-follicular junctions (lupus band test)
  27. 27. ACNE VULGARIS Common, chronic, inflammatory dermatosis affecting hair follicles Middle to late teens, males>females Hormonal changes, alteration in hair follicle maturations, infection (P. acnes) Sex hormones, corticosteroid, occupational exposure, occlusive conditions, heritable component Lipase degradation of sebaceous oils to highly irritating fatty acids Antibiotics and vit. A (retinoic acid)
  28. 28. ACNE VULGARIS (Cont.) Gross: Non-inflammatory – follicular papules with central black keratin plugs (open comedo); follicular papules w/ central plugs trapped beneath the epidermis (closed comedo) Rupture – Inflammatory: erythematous papules, nodules, pustules Micro: lipid & keratin at the midportion of hair follicles, follicular dilatation; epithelial and sebaceous gland atrophy Lymphohistiocytic infiltrates; acute & chronic inflammation with scar formation
  29. 29. BLISTERING (BULLOUS) DERMATITIS Primary conditions; level of blister involvement within the skin SUBCORNEAL: impetigo, p. follaceus SUPRABASAL: p. vulgaris SUBEPIDERMAL: bullous pemphigoid, dermatitis herpetiformis PEMPHIGUS BULLOUS PEMPHIGOID DERMATITIS HERPETIFORMIS
  30. 30. PEMPHIGUS Rare, autoimmune, 4th to 6th decades Circulating Ab’s to keratinocyte intercellular cement components that bind and trigger release of plasminogen activator by keratinocytes FOUR variants: P. vulgaris P. vegetans P. foliaceus P. erythematosus
  31. 31. Pemphigus vulgaris 80%; oral mucosa, scalp, face, intertriginous zones, trunk, pressure points Superficial and easily ruptures that leave shallow & crusted erosions Untreated – uniformly fatal Pemphigus vegetans Rare; large, moist verrucous plaques studded with pustules Flexural and intertriginous zones
  32. 32. Pemphigus foliaceus More benign, epidemic in S. America Face, scalp and upper trunk Extremely superficial bullae leaving only slight erythema and crusting after rupture Pemphigus erythematosus Localized, milder variant of P. foliaceus Malar zone on the face
  33. 33. PEMPHIGUS (Cont.) Micro: acantholysis leading to intercellular clefting and broad-based intraepidermal blisters P. vulgaris & vegetans: immediately above the basal layer (suprabasal blisters) P. foliaceus: stratum granulosum Immunofluorescence staining around each keratinocyte (anti-Ig and anti-complement)
  34. 34. BULLOUS PEMPHIGOID Common, autoimmune, elderly Circulating Ab’s, with complement activation and granulocyte recruitment, against Ag’s of the lamina lucida in the epidermal BM underlying lymphoreticular neoplasm Gross: tense bullae (up to 8 cm) w/ clear fluid, do not rupture easily and heal w/o scarring Micro: subepidermal nonacantholytic blister; linear dermoepidermal junction fluorescence; superficial perivascular infiltrates
  35. 35. DERMATITIS HERPETIFORMIS Rare, 3rd to 4th decade, m>f specific HLA types & celiac disease Skin & GI lesions respond to gluten-free diet Immune complex deposition in the skin Anti-gliadin Ab’s cross reacting with junction anchoring components (reticulin) Granular IgA deposits dermal papillae tips Gross: pruritic, urticarial plaques & vesicles, symmetric (extensors, upper back & buttock)
  36. 36. DERMATITIS HERPETIFORMIS (Cont.) Micro: neutrophils & fibrin accumulate in the tips of dermal papillae (microabscesses) with overlying basal vacuolization; microscopic blisters coalescing to large subepidermal blisters
  37. 37. NONINFLAMMATORY BLISTERING DISEASES Primary disorders with vesicles and bullae NOT mediated by inflammatory mechanisms PORPHYRIA EPIDERMOLYSIS BULLOSA
  38. 38. PORPHYRIA Inborn or acquired disturbances of porphyrin metabolism Unknown pathogenesis Urticaria and vesicles exacerbated by sun exposure; heals w/o scarring Subepidermal vesicles with marked superficial dermal vascular thickening
  39. 39. EPIDERMOLYSIS BULLOSA Blistering at pressure sites and trauma TYPES: JUNCTIONAL: blistering at the lamina lucida DYSTROPHIC: scarring, blistering beneath the lamina lucida due to defective anchoring fibrils SIMPLEX: epidermal basal cell degeneration
  40. 40. INFECTION and INFESTATION VERRUCAE (WARTS) MOLLUSCUM CONTAGIOSUM IMPETIGO LEPROSY SUPERFICIAL FUNGAL INFECTIONS ARTHROPOD-ASSOCIATED LESIONS
  41. 41. VERRUCAE (WARTS) Common, HPV, direct contact V. Vulgaris: most common, dorsum of hand; gray-white to tan, flat to convex, up to 1 cm. papules with rough pebbly surface V. plana (flat wart): face or dorsum of hand; flat, smooth, small, tan papules V. plantaris or palmaris: rough, scaly, up to 2 cm; may coalesce, confused with callous Condyloma acuminatum (Anogenital and Venereal Warts): soft, tan, cauliflower-like Micro: undulant (verrucous) epidermal hyperplasia and koilocytosis
  42. 42. MOLLUSCUM CONTAGIOSUM Common, poxvirus, direct contact Gross: firm, pruritic, pink to skin-colored, umbilicated papules, up to 2 cm, trunk & anogenital regions Cheezy material with molluscum bodies expressed from central umbilication Micro: cuplike verrucous epidermal hyperplasia with molluscum bodies (large eosinophilic cytoplasmic inclusions in the stratum granulosum or corneum)
  43. 43. IMPETIGO Streptococcal & Staphylococcal infection erythematous macule progressing to small papules and eventually shallow erosion with honey-colored crust Micro: subcorneal pustules filled with neutrophils and Gm+ cocci; dermal inflammation Pustule rupture releases serum and necrotic debris to form the crust
  44. 44. LEPROSY Slowly progressive, unsightly & disabling deformities, peripheral neural sensory deficits Aerosol transmission, bipolar disease TUBERCULOID: granulomas, (+) 48-hr lepromin test LEPROMATOUS: anergic to lepromin, nodular lesions with macrophages stuffed with bacilli, may coalesce – leonine facie
  45. 45. SUPERFICIAL FUNGAL INFECTIONS Dermatophytes; confined to nonviable stratum corneum; by location Reactive epidermal changes similar to mild eczematous dermatitis Tinea capitis: asymptomatic hairless patches, mild erythema, crusting and scales Tinea barbae: beard area among adult men Tinea corporis: excessive heat & humidity, infected animals, chronic infection of the feet/nails; expanding erythematous plaque with elevated scaling border – “ringworm”
  46. 46. FUNGAL INFECTIONS (Cont.) Tinea cruris: inguinal areas among obese, warm weather; moist patches with raised scaling borders Tinea pedis (Athlete’s foot): erythema & scaling in the webbed spaces, 2O bacterial infections Onychomycosis: discoloration, thickening and deformity of the nail plate Tinea versicolor: Malassezia furfur, upper trunk, vari- sized hyper- or hypopigmented macules with peripheral scale
  47. 47. ARTHROPOD-ASSOCIATED LESIONS Bites, stings, infestations Reactions: trivial to fatal Gross: urticarial, inflamed papules or nodules, expanding erythematous plaques (erythema migrans) Direct irritant effect Immediate IgE-mediated or delayed cell- mediated HS Rxn Specific effects of venom Associated with secondary invaders
  48. 48. SCABIES Pruritic caused by mite Sarcoptes scabiei Female burrows beneath the stratum corneum – linear, poorly defined furrows: interdigital skin, palms, wrists, periareolar area, scrotal folds
  49. 49. PEDICULOSIS Pruritic, caused by louse: insect or eggs attach to hair shafts May be complicated by impetigo with lymphadenopathy; urticaria-like Excoriations and hyperpigmentation Micro: wedge-shaped dermal perivascular lymphohistiocytic and eosinophilic infiltrates; central zone of epidermal necrosis w/ birefringent insect mouth parts; florid inflammatory infiltrates or spongiosis – intraepidermal blisters
  50. 50. DISORDERS OF PIGMENTATION AND MELANOCYTES VITILIGO FRECKLE (EPHELIS) MELASMA LENTIGO NEVOCELLULAR NEVUS (PIGMENTED NEVUS, MOLE) DYSPLASTIC NEVI MELANOMA
  51. 51. VITILIGO Irregular, well-demarcated macules devoid of pigmentation Autoimmunity (melanocyte autoAb’s, T-cell abnormalities); neurohormonal factors; toxic intermediates in melanin synthesis Micro: loss of melanocytes
  52. 52. FRECKLE (EPHELIS) Pigmented lesions: tan-red to brown macules occurring after sun exposure, fading and recurring with subsequent cycles of winter and summer Micro: normal melanocyte number, ?slight hypertrophy; increased melanin within basal keratinocytes
  53. 53. MELASMA Masklike facial hyperpigmentation Hyperestrogenic states, fades postpartum Gross: blotchy, irregular, ill-defined macules; accentuated by sunlight Enhanced melanin transfer from melanocytes to other cell types w/ subsequent accumulation Micro: increased melanin deposition in basal layers (epidermal type); papillary dermal macrophage phagocytosis of melanin released from the epidermis – pigment incontinence (dermal type)
  54. 54. LENTIGO Benign, hyperpigmented macules, do not darken with sun exposure Unknown etiology and pathogenesis Micro: linear basal hyperpigmentation due to melanocyte hyperplasia; with elongation and thinning of rete ridges
  55. 55. NEVOCELLULAR NEVUS Group of congenital or acquired melanocyte neoplasm Well-demarcated, tan-brown papules Melanocytes derive from basal dendritic cells that differentiate into round-to-oval cells with uniform nuclei and prominent nucleoli Natural History: Begin as well-defined nests along the dermoepidermal junction (junctional nevi); lentigo-like (lentiginous) melanocyte proliferation Extension of melanocytes forms nests within both dermis and epidermis (compound nevi)
  56. 56. NEVOCELLULAR NEVUS (Cont.) Lost epidermal component resulting in dermal nevi Progressive dermal downgrowth, nevus cells undergo maturation to resemble neural tissue Variants: Congenital nevus Blue nevus Spindle & Epithelioid cell (Spitz) nevus Halo nevus Dysplastic nevus
  57. 57. Nevus Variant Diagnostic Architectural Features Diagnostic Cytologic Clinical Significance Features Congenital nevus Deep dermal, SC growth around Same as ordinary acquired At birth; large variants adnexae, neuro-vascular bundles nevi have increased melanoma & blood vessel walls risk Blue nevus Non-nested dermal infiltration, Highly dendritic, heavily Black-blue nodule; often with fibrosis pigmented nevus cells confused with melanoma Spitz’s nevus Fascicular growth Large, plump cells with Children; red-pink nodule; pink-blue cytoplasm; confused with fusiform hemangioma Halo nevus Lymphocytic infiltration Identical to ordinary Immune response vs surrounding nevus cells acquired nevus nevus cells & surrounding normal melanocyte Dysplastic nevus Large, coalescent intraepidermal Cytologic atypia Potential precursor of nests malignant melanoma
  58. 58. DYSPLASTIC NEVUS Autosomal dominant or sporadic Larger than acquired nevi; as hundreds of irregular macules/plaques with pigment variegation in both sun-exposed and nonexposed skin Micro: cytologic and architectural atypia; enlarged & fused epidermal nevus cell nests, lentiginous hyperplasia, linear dermo- epidermal junction fibrosis, pigment incontinence
  59. 59. MELANOMA Sun exposure, lightly pigmented individuals, hereditary component Pruritic, variegated, irregular maculopapular lesions; CHANGE IN COLORATION Initially extends horizontally within the epidermis and superficial dermis (RADIAL GROWTH PHASE); don’t metastasize – LENTIGO MALIGNA and SUPERFICIAL SPREADING VERTICAL GROWTH PHASE – extension into the deep dermis, loss of cellular maturation, dev’t of the capacity to metastasize
  60. 60. MELANOMA (Cont.) Clinical behavior & probability of metastasis – characteristics and depth of invasion of the vertical growth; mitotic rates and degree of lymphocytic infiltrates Micro: melanoma cells – larger than nevus cells, irregular nuclei, prominent eosinophilic nucleoli; grow as loose nests lacking melanocyte maturation
  61. 61. BENIGN EPITHELIAL TUMORS biologically inconsequential lesions derived from keratinocytes or skin appendages SEBORRHEIC KERATOSIS ACANTHOSIS NIGRICANS FIBROEPITHELIAL POLYP EPITHELIAL CYST (WEN) KERATOACANTHOMA ADNEXAL (APPENDAGE) TUMORS
  62. 62. SEBORRHEIC KERATOSIS Spontaneous lesions; trunk, smaller facial lesions (dermatosis papulosa nigra) Large number as part of paraneoplastic syndrome (sign of Leser-Trelat) due to tumor elaboration of growth factors] Gross: uniform, tan-brown, velvety/granular, round plaques, keratin-filled plugs Micro: exophytic, hyperplasia of basaloid cells, hyperkeratosis, keratin-filled “horn cysts”
  63. 63. ACANTHOSIS NIGRICANS Thick hyperpigmented zones in flexural areas Associated with benign or malignant conditions elsewhere in the body BENIGN: 80%, childhood through puberty, autosomal dominant, obesity or endocrine disorders, part of rare congenital disorders MALIGNANT: middle-aged & older, occult adenocarcinoma Micro: hyperkeratosis, prominent rete ridges, basal hyperpigmentation w/o melanocyte hyperplasia
  64. 64. FIRBOEPITHELIAL POLYP Acrochordon, squamous papilloma, skin tag Soft, flesh-colored attached by slender stalk with fibrovascular core covered by benign epidermis Associated with pregnancy, diabetes or intestinal polyposis
  65. 65. EPITHELIAL CYSTS Well-circumscribed, firm, SC nodules Downgrowth and cystic expansion of the epidermal and follicular epithelium Micro: based on cyst wall characteristic Epidermal Inclusion Cyst: normal epidermis Pilar (Trichilemmal) Cyst: follicular epithelium w/o granular cell layer Dermoid Cyst: epidermis w/ multiple skin appendages, hair follicles Steatocystoma multiplex: sebaceous gland ductal epithelium w/ numerous compressed sebaceous lobules
  66. 66. KERATOACANTHOMA Spontaneously heal, rapidly growing, sun-exposed Gross: flesh-colored, superficial, with central keratin-filled craters, face/hands Micro: cup-shaped epithelial proliferations w/ atypical cells, enclose central keratin-filled plug. Pattern of keratinization recapitulates hair follicle (no granular cell layer) Minimal inflammation during rapid proliferative phase; evolves – dermal inflammation and fibrosis; eventually regress & disappear
  67. 67. ADNEXAL (APPENDAGE) TUMORS Benign neoplasms, few malignant variants; Mendelian pattern; indicate visceral malignancy (Cowden’s syndrome – multiple trichilemmomas with breast Ca) Single or multiple, nondescript papules and nodules, site predilection Ex: Cylindromas, Syringomas, Trichoepitheliomas, Trichilemmomas, Sebaceous Gland Adenoma/Adenocarcinoma
  68. 68. PREMALIGNANT AND MALIGNANT EPIDERMA TUMORS ACTINIC KERATOSIS BOWEN’S/BOWENOID LESIONS and ERYTHROPLASIA OF QUEYRAT SQUAMOUS CELL CARCINOMA BASAL CELL CARCINOMA MERKEL CELL CARCINOMA
  69. 69. ACTINIC KERATOSIS Premalignant dysplastic lesion, chronic sun exposure; ionizing radiation, hydrocarbons, and arsenicals Gross: tan-brown, red or flesh-colored, rough consistency, cutaneous horns Micro: cytologic atypia in the lower epidermis, parabasal cell hyperplasia, dyskeratosis; hyperkeratosis, parakeratosis; epidermal atrophy; dermis is thick with blue-gray elastic fibers (elastosis)
  70. 70. CARCINOMA IN-SITU Full thickness epidermal cytologic atypia (Bowen’s disease; Bowenoid papulosis; Erythroplasia of Queyrat) Perineal/groin area with erythematous patches; leukoplakia; well-demarcated, red, scaling plaques Micro: entire thickness of epidermis exhibits cytologic nuclear atypia
  71. 71. SQUAMOUS CELL CARCINOMA Most common; sunlight/UV light directly damages DNA & exerts immuno-suppressive effect to Langerhans’ cells; industrial carcinogens, chronic skin ulcers, old burn scars, draining osteomyelitis, ionizing radiation, tobacco or betel nut chewing Immunosuppression; xeroderma pigmentosum; HPV infection
  72. 72. SQUAMOUS CELL CARCINOMA (Cont.) Gross: nodular, variably hyperkeratotic, ulcerates; leukoplakia (mucosal surface) May metastasize to regional LN Micro: from well differentiated to highly anaplastic with necrosis & abortion keratinization
  73. 73. BASAL CELL CARCINOMA Common, slow-growing, sun-exposed and rarely metastasize Immunosuppression & xeroderma pigmentosum Gross: pearly papules or expanding plaques; may be pigmented; ulcerate with extensive local invasion “rodent ulcer” Micro: basal cell proliferation extending deeply into the dermis; superficial or nodular
  74. 74. MERKEL CELL CARCINOMA Rare, neural crest derived Merkel cells (tactile sensation) Potentially lethal; small, round malignant cells containing neurosecretory type cytoplasmic granules Resemble small cell Ca of the lung
  75. 75. TUMORS OF THE DERMIS BENIGN FIBROUS HISTIOCYTOMA DERMATOFIBROSARCOMA PROTUBERANS XANTHOMAS DERMAL VASCULAR TUMORS
  76. 76. BENIGN FIBROUS HISTIOCYTOMA Indolent neoplasms of dermal fibroblasts & histiocytes Unknown cause, antecedent trauma and aberrant healing Gross: tan-brown, firm papules, may be tender; lateral compression exert dimpling Micro: dermatofibroma – spindle shaped fibroblasts, unencapsulated in the mid-dermis extending to SC fat
  77. 77. DERMATOFIBROSARCOMA PROTUBERANS Well-differentiated, slow-growing fibrosarcoma; locally aggressive but rarely metastasize Gross: firm solid nodules arising as protuberant, ulcerated aggregates within an indurated plaque Micro: radially oriented (storiform) fibroblasts; scanty mitosis; thin overlying epidermis with extension into SC fat
  78. 78. XANTHOMAS Not true neoplasm, focal accumulation of foamy histiocytes Idiopathic or Secondary (familial or acquired hyperlipidemias, lymphoproliferative disorders) Types (gross & hyperlipidemia): Eruptive Xanthoma: sudden showers of yellow papules that wax & wane w/ plasma triglycerides & lipid levels Tuberous Xanthoma: yellow, flat-to-round nodules over the joints
  79. 79. XANTHOMAS (Cont.) Tendinous Xanthoma: yellow nodules over the Achilles tendon and finger extensor tendons Plane Xanthoma: linear yellow lesions in skin folds (palmar creases); 1O biliary cirrhosis Xanthelasma: soft yellow plaques on the eyelids Micro: dermal aggregates of macrophages with vacuolated cytoplasm containing cholesterol, phospholipids, and triglycerides
  80. 80. DERMAL VASCULAR TUMORS Hemangiomas, vascular malignant tumors, Kaposi’s sarcoma and angiomatosis
  81. 81. TUMORS OF CELLULAR IMMIGRANTS TO THE SKIN Proliferative disorders of cells arising elsewhere but which homed to the skin HISTIOCYTOSIS X MYCOSIS FUNGOIDES (CUTANEOUS T-CELL LYMPHOMA) MASTOCYTOSIS
  82. 82. HISTIOCYTOSIS X Cutaneous form – solitary or multiple papules or nodules; scaling erythematous plaques resembling seborrheic dermatitis Histo: variable numbers of eosinophils and different patterns: Diffuse dermal infiltrates of mononuclear cells with bland, indented nuclei Similar cells clustered to resemble granulomas Dermal infiltrates composed of mononuclear cells with foamy cytoplasm Birbeck granules, CD1 Ag’s – Langerhans’ cell derivation
  83. 83. MYCOSIS FUNGOIDES Cutaneous T-cell Lymphoma, 3 patterns Mycosis Fungoides (MF) MF d’emblee: nodular eruptive variant Adult T-cell leukemia or lymphoma: aggressive course, HTLV-1 Lymphoproliferative disorder arising from the skin & eventually seed the blood (Sezary’s syndrome) and evolve into more generalized T- cell leukemia or lymphoma
  84. 84. MYCOSIS FUNGOIDES Gross: eczema-like lesions evolving into scaly, red- brown patches or plaques; to nodules (nodular cutaneous growth – deep dermal invasion; onset of LN & visceral involvement) Micro: Sezary-Lutzner cell – malignant CD4-positive (T-helper) cell with hyperconvoluted or “cerebriform” nucleus; band-like dermal infiltrates with invasion of single cells or small clusters into the epidermis (Pautrier’s microabscess)
  85. 85. MASTOCYTOSIS Rare, cutaneous (visceral) mast cell proliferation; degranulation (histamine and heparin) Pruritus & flushing – specific foods, temperature, alcohol, certain drugs Dermal edema & erythema (wheal) when skin (Darier’s sign) or normal skin (dermatographism) is rubbed Epistaxis or GI bleeding
  86. 86. MASTOCYTOSIS (Cont.) Urticaria pigmentosa (50%) exclusively cutaneous, favorable prognosis, children; 10% adults, systemic, poorer prognosis Gross: multiple, round-to-oval, nonscaling, red- brown papules & plaques Micro: dermal fibrosis, edema, eosinophils and mast cells
  87. 87. That’s all folks!!! Thank you very much!!! Good morning!!!
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