Diseases of the Skin (Noel C. Santos, M.D.

) DEFINITION OF TERMS: Macroscopic y Macule: flat, circumscribed, discoloration y y y y y y y y y y y y Papule: elevated solid area e 5 mm. Nodule: elevated solid area > 5 mm. Plaque: elevated flat-topped > 5mm. Vesicle: elevated fluid-filled e 5 mm. Bulla: elevated fluid-filled > 5 mm. Blister: common term for vesicle or bulla Pustule: discrete, pus-filled raised area 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 due to repeated rubbing. Excoriation: linear, traumatic lesion resulting in epidermal breakage. Onycholysis: loss of nail substance.

y y y

Exocytosis: inflammatory cells infiltrating the epidermis. 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.

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 URTICARIA (HIVES) focal mast cell degranulation o histamine release:  pruritus  edema  wheal Angioedema: o dermal o 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

Microscopic y 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. 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.

y y

HEREDITARY ANGIONEUROTIC EDEMA Recurrent attacks With GIT and laryngeal involvement Deficient C1 esterase inhibitor Unregulated activation of the early complement components 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 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) 5 PRIMARY TYPES OF ECZEMA A. Contact Dermatitis B. Atopic Dermatitis C. Drug-Related Eczematous Dermatitis D. Photo-Eczematous Eruption E. Primary Irritant Dermatitis

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 ERYTHEMA NODOSUM/INDURATUM Panniculitis or inflammation of SC fat o Connective tissue septa NODOSUM o Fat lobules INDURATUM may be Acute or Chronic Early lesions: necrotizing vasculitis in deep dermis and subcutis Eventually develop granulomatous inflammation and necrosis Erythema Nodosum Most common, acute onset Idiopathic or Secondary o Drugs o Infections o Sarcoidosis o IBD o visceral malignancy Ill-defined, tender erythematous nodules with fever and malaise Old lesions flatten, ecchymotic without scarring while new lesions develop Bx: o early septal widening edema o fibrin deposition o neutrophil infiltration (giant cells & eosinophils) w/o vasculitis

ERYTHEMA MULTIFORME Uncommon, self-limited HS response o Drugs o Infections o systemic disorders Extensive epidermal degeneration and necrosis Due to cell-mediated immune injury (CD8+ cytotoxic T-cells) Gross :

multiform o Macules o Papules o Vesicles & o Bullae targets o red maculopapular with central vesicular or eroded pallor symmetric involvement of extremities

Steven-Johnson syndrome: severe, febrile, erosions and hemorrhagic crustingToxic Epidermal Necrolysis: diffuse mucocutaneous epithelial necrosis and sloughing; analogous to 3 burns

Psoriatic endothelium sensitive to cytokine-induced expression of adhesion molecules with subsequent enhanced neutrophil recruitment Associated with other disorders: o myopathies o enteropathies o AIDS o arthritis 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

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 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 CHRONIC INFLAMMATORY DERMATOSES  Persistent inflammatory disorders  Scaling and shedding (desquamation)  PSORIASIS  LICHEN PLANUSLUPUS  ERYTHEMATOSUS  ACNE VULGARIS 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

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

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

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)

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 : small keratotic plugs in hair follicles

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) 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 BLISTERING (BULLOUS) DERMATITIS  Primary conditions; level of blister involvement within the skin o SUBCORNEAL: impetigo, p. follaceus o SUPRABASAL: p. vulgaris o SUBEPIDERMAL: bullous pemphigoid, dermatitis herpetiformis  PEMPHIGUS  BULLOUS PEMPHIGOID  DERMATITIS HERPETIFORMIS 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: 1. P. vulgaris 2. P. vegetans 3. P. foliaceus 4. P. erythematosus

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)

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 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

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)

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

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)

PORPHYRIA Inborn or acquired disturbances of porphyrin metabolismUnknown pathogenesis Urticaria and vesicles exacerbated by sun exposure; heals w/o scarring Subepidermal vesicles with marked superficial dermal vascular thickening EPIDERMOLYSIS BULLOSA Blistering at pressure sites and trauma TYPES: o JUNCTIONAL:  blistering at the lamina lucida o DYSTROPHIC:  scarring, blistering beneath the lamina lucida due to defective anchoring fibrils o SIMPLEX:  epidermal basal cell degeneration INFECTION and INFESTATION  VERRUCAE (WARTS)  MOLLUSCUM CONTAGIOSUM  IMPETIGO  LEPROSY  SUPERFICIAL FUNGAL INFECTIONS  ARTHROPOD-ASSOCIATED LESIONS VERRUCAE (WARTS) Common, HPV, direct contact V. Vulgaris: o most common, dorsum of hand o gray-white to tan o flat to convex o up to 1 cm. papules with rough pebbly surface V. plana (flat wart): o face or dorsum of hand o flat, smooth, small, tan papules V. plantaris or palmaris: o rough, scaly, up to 2 cm o may coalesce - confused with callous Condyloma acuminatum (Anogenital and Venereal Warts): o soft, tan, cauliflower-like Micro : undulant (verrucous) epidermal hyperplasia and koilocytosis

Micro : neutrophils & fibrin accumulate in the tips of dermal papillae (microabscesses) with overlying basal vacuolization; : microscopic blisters coalescing to large subepidermal blisters

NONINFLAMMATORY BLISTERING DISEASES  Primary disorders with vesicles and bullae NOT mediated by inflammatory mechanisms  PORPHYRIAE  PIDERMOLYSIS BULLOSA

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)

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

MOLLUSCUM CONTAGIOSUM Common, poxvirus, direct contact Gross : : : :

firm, pruritic pink to skin-colored umbilicated papules, up to 2 cm trunk & anogenital regions

Pustule rupture releases serum and necrotic debris to form the crust

LEPROSY slowly progressive, unsightly & disabling deformities, peripheral neural sensory deficits Aerosol transmission, bipolar disease o TUBERCULOID  Granulomas  (+) 48-hr lepromin test o LEPROMATOUS  anergic to lepromin  nodular lesions with macrophages stuffed with bacilli  may coalesce leonine facie

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 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

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 cellmediated HS Rxn Specific effects of venom Associated with secondary invaders

SCABIES Pruritic caused by mite Sarcoptes scabiei Female burrows beneath the stratum corneum linear, poorly defined furrows: o interdigital skin o palms o wrists o periareolar area o scrotal folds 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 DISORDERS OF PIGMENTATION AND MELANOCYTES  VITILIGO  FRECKLE (EPHELIS)  MELASMA  LENTIGO  NEVOCELLULAR NEVUS (PIGMENTED NEVUS, MOLE)  DYSPLASTIC NEVI  MELANOMA 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

FRECKLE (EPHELIS) Pigmented lesions: o tan-red to brown macules occurring after sun exposure o fading and recurring with subsequent cycles of winter and summer Micro : normal melanocyte number : ?slight hypertrophy : increased melanin within basal keratinocytes 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) 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 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) 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

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 : melanoma cells larger than nevus cells, irregular nuclei, prominent eosinophilic nucleoli; : grow as loose nests lacking melanocyte maturation

Micro : : : : :

cytologic and architectural atypia; enlarged & fused epidermal nevus cell nests, lentiginous hyperplasia, linear dermo- epidermal junction fibrosis, pigment incontinence

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 Clinical behavior & probability of metastasis: : characteristics and depth of invasion of the vertical growth; mitotic rates and degree of lymphocytic infiltrates

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 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 : : : :

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 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

Uniform tan-brown velvety/granular, round plaques keratin-filled plugs

Micro : exophytic, hyperplasia of basaloid cells : hyperkeratosis : keratin-filled horn cysts

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 o normal epidermis : Pilar (Trichilemmal) Cyst o follicular epithelium w/o granular cell layer : Dermoid Cyst o epidermis w/ multiple skin appendages, hair follicles : Steatocystoma multiplex o sebaceous gland ductal epithelium w/ numerous compressed sebaceous lobules

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 KERATOACANTHOMA Spontaneously heal, rapidly growing, sun-exposed Gross : flesh-colored, superficial : with central keratin-filled craters : face/hands Ex:      Cylindromas Syringomas Trichoepitheliomas Trichilemmomas Sebaceous Gland Adenoma/Adenocarcinoma

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 PREMALIGNANT AND MALIGNANT EPIDERMATUMORS  ACTINIC KERATOSIS  BOWEN S/BOWENOID LESIONS and ERYTHROPLASIA OF QUEYRAT  SQUAMOUS CELL CARCINOMA  BASAL CELL CARCINOMA  MERKEL CELL CARCINOMA 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 : entire thickness of epidermis exhibits cytologic nuclear atypia

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 cytologic atypia in the lower epidermis, parabasal cell hyperplasia, dyskeratosis hyperkeratosis, parakeratosis; epidermal atrophy; dermis is thick with blue-gray elastic fibers (elastosis) Gross : : nodular, variably hyperkeratotic, ulcerates; leukoplakia (mucosal surface)

Micro : : : :

May metastasize to regional LN Micro : from well differentiated to highly anaplastic with necrosis & abortion keratinization

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

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

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 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 aberrant healing Gross : : Micro : Micro DERMATOFIBROSARCOMA PROTUBERANS : basal cell proliferation extending deeply into the dermis; superficial or nodular Gross : firm solid nodules arising as protuberant, ulcerated aggregates within an indurated plaque Well-differentiated, slow-growing fibrosarcoma; locally aggressive but rarely metastasize dermatofibroma spindle shaped fibroblasts, unencapsulated in the mid-dermis extending to SC fat tan-brown, firm papules, may be tender; lateral compression exert dimpling

: Micro : : : radially oriented (storiform) fibroblasts; scanty mitosis; thin overlying epidermis with extension into SC fat

Micro : dermal aggregates of macrophages with vacuolated cytoplasm containing cholesterol, phospholipids, and triglycerides

XANTHOMAS Not true neoplasm, focal accumulation of foamy histiocytes Idiopathic or Secondary (familial or acquired hyperlipidemias, lymphoproliferative disorders) Types (gross & hyperlipidemia):  Eruptive Xanthoma o sudden showers of yellow papules that wax & wane w/ plasma triglycerides & lipid levels Tuberous Xanthoma o yellow, flat-to-round nodules over the joints Tendinous Xanthoma o yellow nodules over the Achilles tendon and finger extensor tendons Plane Xanthoma o linear yellow lesions in skin folds (palmar creases); 1O biliary cirrhosis Xanthelasma o soft yellow plaques on the eyelids

DERMAL VASCULAR TUMORS Hemangiomas vascular malignant tumors Kaposi s sarcoma and angiomatosis

TUMORS OF CELLULAR IMMIGRANTS TO THESKIN  Proliferative disorders of cells arising elsewhere but which homed to the skin  HISTIOCYTOSIS X  MYCOSIS FUNGOIDES (CUTANEOUS T-CELL LYMPHOMA)  MASTOCYTOSIS HISTIOCYTOSIS X Cutaneous form solitary or multiple papules or nodules; scaling erythematous plaques resembling seborrheic dermatitis Histo : variable numbers of eosinophils and different patterns: o Diffuse dermal infiltrates of mononuclear cells with bland, indented nuclei o Similar cells clustered to resemble granulomas o Dermal infiltrates composed of mononuclear cells with foamy cytoplasm

Micro : Sezary-Lutzner cell malignant CD4-positive (Thelper) cell with hyperconvoluted or cerebriform nucleus; band-like dermal infiltrates with invasion of single cells or small clusters into the epidermis (Pautrier s microabscess)

Birbeck granules, CD1 Ag s Langerhans cell derivation MYCOSIS FUNGOIDES Cutaneous T-cell Lymphoma, 3 patterns o Mycosis Fungoides (MF) o MF d emblee: nodular eruptive variant o 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 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)

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

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