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Skin-nontumor

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Revised: 2 November 2009

Last major update: November 2009

Copyright: (c) 2002-2009, PathologyOutlines.com, Inc.

 

Table of Contents-Skin

Primary references, skin-general, histology-epidermis, adnexae, dermis, subcutaneous, biopsies, grossing, common pathologic terms

 

Infectious disorders: abscess, anthrax, botryomycosis, carbuncle, CMV, Epstein-Barr virus, erysipelas, Erysipelothrix, folliculitis, fungi (various), hepatitis C, herpes simplex/zoster, hidradenitis suppurativa, HIV, impetigo Leishmaniasis, leprosy, Lyme disease, malakoplakia, molluscum contagiosum, mycobacteria-atypical, parvovirus, scrub typhus, smallpox vaccination, syphilis, tuberculosis, tularemia, virus associated trichodysplasia spinulosa, warts

 

Infestations: general, body louse, botfly, brown recluse spider, demodex, pediculosis (lice), pubic louse, scabies, Tunga penetrans

 

Granulomatous but noninfectious disorders: arthropod bites, foreign body reaction, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, sarcoidosis

 

Blistering disorders: general, blood blister, bullous impetigo, bullous pemphigoid, cicatricial pemphigoid, Darier’s disease, dermatitis herpetiformis, epidermolysis bullosa, epidermolytic hyperkeratosis, erythema multiforme, erythema toxicum neonatorum, Hailey-Hailey, impetigo contagiosa,  linear IgA diseasepemphigoid gestationispemphigus, porphyria, Stevens-Johnson syndrome, subcorneal pustular dermatosis,  transient acantholytic dermatosis

 

Other dermatoses: acanthosis nigricans, acne rosacea, acne vulgaris, acute eczematous dermatitis, allergic contact dermatitis, alopecia, alopecia mucinosa, alpha-1-antitrypsin deficiency panniculitis, amyloidosis, anetoderma, annular elastolytic giant cell granuloma, argyria, arsenic, Behcet’s disease, calciphylaxis, chondrodermatitis nodularis, chronic skin ulcer, Crohn’s, cytophagic histiocytic panniculitis, dermatomyositis, drug reaction, elastosis perforans, eosinophilic fasciitis, eosinophilic pustular folliculitis, erythema elevatum diutinum, erythema nodosum, exfoliative dermatitis/erythroderma, gangrene, graft versus host disease, granuloma annulare, granuloma faciale, gyrate erythema, hemochromatosis, ichthyosis, irritant contact dermatitis, lichen nitidus, lichen planus, lichen sclerosus et atrophicus, lichen simplex chronicus, lichen striatus, lichenoid dermatitis, lipogranulomatosis, lupus erythematosus, malignant atrophic papulosis, massive localized lymphedema, mastocytosis of skin, metabolic abnormalities, miliaria, mucinoses, myxedema, necrobiosis lipoidica, necrobiotic xanthogranuloma, ochronosis, pancreatic fat necrosis, panniculitis, pityriasis lichenoides chronica, pityriasis lichenoides et varioliformis acuta, pityriasis rosea, pityriasis rubra pilaris, poikiloderma atrophicans vasculare, polymorphous light eruption, porokeratosis, prurigoform acanthosis, pseudoxanthoma elasticum, psoriasis, pyoderma gangrenosum, radiation-associated, rheumatoid/rheumatic nodules, scleredema, scleroderma, seborrheic dermatitis, segmented hyalinizing vasculitis, skin graft rejection, spongiotic dermatitis, stasis dermatitis, subcutaneous fat necrosis of newborn, Sweet’s syndrome, synovial metaplasia, tattoo, urticaria, vasculitis, Weber-Christian disease

 

Go to Skin - Melanocytic tumors chapter

Go to Skin - Nonmelanocytic tumors chapter

 

Primary references

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American Journal of Surgical Pathology (AJSP), January 2000 to May 2005

Archives of Pathology and Laboratory Medicine (Archives), January 1999 to May 2005

Human Pathology (Hum Path), Jan 2000 to March 2005

Modern Pathology (Mod Path), Jan 2000 to April 2005

Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004

Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004

Journal search terms: skin, epidermis, dermis, cutaneous

 

Please refer to these primary references for more detailed discussions and photographs

 

Skin-general

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Also called integument

Protects deeper tissues from injury, drying and invasion by foreign organisms

Contains peripheral endings of sensory nerves

Has important role in thermoregulation, limited role in excretion and absorption

Has epidermis (cuticle) containing adnexae, underlying dermis and subcutis

Micro images: thickened skin; thick skin-various images; thin skin-various images; nailbed; nails-various images

Virtual slides: normal skin #1; #2 (pigmented), #3 (scalp), #4 (axilla)

 

Histology-Epidermis

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Epidermis is outer layer of skin; inner layers are dermis and subcutaneous tissue; superficial fascia marks deep boundary between skin and underlying soft tissue

Epidermis forms outer layer of keratin that is protective and waterproof

Thicker in palms and soles, which contain epidermal ridges that prevent slipping and comprise fingerprints and footprints

Stratified squamous epithelium composed of keratinocytes in 4 layers: inner basal, squamous, granular and outer cornified

Basal layer: mitotically active, produces other keratinocytes; contains low molecular weight keratin; separated from dermis by continuous basal membrane, keratinocytes are attached to this membrane by hemidesmosomes; also contains melanocytes

Squamous layer (stratum spinosum): also called prickle or malpighian layer; several layers of cells, larger than basal layer, become flat and eosinophilic as they approach the surface due to an increase in keratin component and reduction in ribosomes; may have clear vacuolated cytoplasm; cells are attached to each other by fine spiny bridges, with central dot-like desmosomes (Bizzozero’s nodule); loss of spiny bridges causes acantholysis

Granular layer (stratum  granulosum): 1-3 layers of flattened cells with intensely basophilic keratohyaline granules, which contain precursors of filaggrin protein, which causes aggregation of keratin filaments

Stratum lucidum: present only in soles and palms, between granular and cornified layer; homogenous eosinophilic zone

Cornified layer (stratum corneum): also called horny layer; basket weave pattern of multiple layers of polyhedral cells without nuclei (region is thicker and more compact in acral region [peripheral body-limbs, fingers, ears])

Rete ridges: undulating forms of epidermis and dermal papillae at dermoepidermal junction; flatten with aging

Keratinization: takes 30-45 days; alterations in pattern and speed cause dermatoses, hyperkeratosis or parakeratosis

Micro drawings: skin drawing; skin; epidermis (stratum mucosum is squamous layer); intraepithelial sweat gland

 

Cells present include melanocytes, keratinocytes, Langerhans’ cells, Merkel cells

Melanocytes

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Neural crest origin; in basal epidermis, hair follicles, most squamous mucous membranes, leptomeninges; produce melanin from tyrosine, transfer it (via cytocrinia) to adjacent epithelial cells, to protect against ultraviolet rays; have frequency of 10-25% of keratinocytes; racial skin color is due to amount of melanin in keratinocytes, not number of melanocytes; contain dendrites (delicate cytoplasmic processes that extend between keratinocytes); upwards or lateral migration within epidermis or into papillary dermis does not necessarily indicate malignancy; cytoplasm is clear due to retraction, nuclei typically smaller and slightly more hyperchromatic than nuclei of adjacent keratinocytes, have uniform chromatin, indented nuclear contour, no nucleoli

Positive stains: Fontana-Masson, tyrosinase, S100, NSE, MelanA/Mart1, microphthalmia transcription factor, vimentin, bcl2, HMB45 (activated melanocytes), variable keratin in activated melanocytes

Negative stains: GFAP, neurofilament, HMB45 and keratin (resting melanocytes)

EM: melanosomes (melanin-synthesizing organelle derived from Golgi)

DD: melanoblasts (immature counterpart), melanophages (macrophages with ingested melanin)

 

Langerhans’ cells

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Bone marrow derived dendritic cells that present antigens to T cells, are scattered in upper squamous layer but difficult to see on H&E; have characteristic Birbeck granules by EM (rod shaped structure with zipper-like striations, often with bulbous end), S100+, CD1a+, IgG Fc receptor+, C3+

 

Merkel cells

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Difficult to see with H&E or special stains; concentrated in skin of digits, lips, outer root sheath of hair follicles, tactile hair disks; EM shows dense core neurosecretory-type granules in cytoplasm beneath cell membrane or within unmyelinated neurites; anchored to adjacent keratinocytes by spinous processes; positive for NSE, neurofilament, keratin

 

Histology-adnexae

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Skin adnexa include hair follicles, sebaceous glands, eccrine sweat glands, apocrine glands

Pilar unit: functional complex of hair follicle, sebaceous gland, erector pili muscle and (depending on site) apocrine gland; often contains Demodex folliculorum mites, clumps of Staphylococcus epidermidis, Pityrosporum yeasts

Hair follicle: contains protected repositories of epithelial stem cells; forms hair via cyclic process of (a) anagen or growing phase, (b) catagen or involuting phase and (c) telogen or resting phase

Matrix (regenerative) cells line dermal papillae, are mitotically active, give rise to hair shaft and inner root sheath

Outer root sheath: layer of large cells that surround inner root sheath, undergo abrupt keratinization without a granular layer, at level of isthmus (mid hair follicle, extends to sebaceous duct), called trichilemmal keratinization

Usual type of keratinization occurs by cells of infundibulum (upper hair follicle)

Acrotrichium: intraepidermal portion of hair follicle

Sebaceous glands: lobulated structures, have outer germinative cells that differentiate, move inward and accumulate intracytoplasmic lipid droplets, causing multivacuolation and multiple indentations of nuclei; excretory duct of these glands empty into infundibulum of hair follicle

Sweat glands are either eccrine (regulate body temperature), apocrine or mixed

Eccrine sweat glands: tubular with secretory and excretory portions; secretory coil is in deep dermis or subcutis, has secretory and myoepithelial cells; excretory portion has dermal  (straight) and intraepidermal (spiral, also called acrosyringium) portions

Apocrine glands: concentrated in axilla, groin, perineum; also face and elsewhere; have secretory and excretory components; epithelial cells are larger than eccrine glands with larger ducts and decapitation secretion; secretory cells have abundant eosinophilic cytoplasm with lipid, iron or lipofuscin; positive for GCDFP-15

Positive stains: eccrine and apocrine glands - EMA, CEA, keratin, S100; myoepithelial cells - actin, calponin, caldesmon, S100

Micro images: hair follicle in skin #1; #2; #3; #4; #5; #6; #7; #8; #9; hair-various images; sweat gland drawing; sweat gland #1; #2; #3; sebaceous gland #1; #2

 

Histology - Dermis

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Contains collagen and elastic fibers in ground substance of mucopolysaccharides and mucoproteins

Also contains adnexa, nerves and blood vessels

Degenerates with age and sunlight and becomes basophilic

Divided into the superficial adventitial dermis and deeper reticular dermis

Adventitial dermis is divided into papillary dermis containing rete pegs and periadnexal dermis

Adventitial dermis has thin and delicate collagen fibers versus thicker fibers in reticular dermis

Dermis has varying thickness - thicker on back

Acral skin has Sucquet-Hoyel canals – specialized arteriovenous anastomoses, surrounded by glomus cells

Glomus cells are modified smooth muscle cells but round with clear cytoplasm and well defined cytoplasmic borders

Papillary dermis of palms and soles contains Wagner-Meissner corpuscles with a tactile function

Deep dermis and subcutis of weight bearing areas contain Pacinian corpuscles, sensitive to pressure

Normal dermis contains a few fibroblasts, mast cells, macrophages, lymphocytes and dermal dendrocytes (factor XIIIa+)

 

Histology - Subcutaneous tissue

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Also called subcutis

Contains lobules of mature adipose tissue and thin connective tissue septa

 

Biopsies

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For inflammatory lesions, should correlate with clinical differential diagnosis

Biopsy characteristic areas, not ruptured bullae, secondarily infected / scratched areas or involuting lesions

Punch biopsy of nearby normal skin may be helpful, particularly if changes in abnormal areas are quantitative (hyperkeratosis, acanthosis, etc.)

Must recognize that biopsy captures histopathology only at one point in time in evolution of a lesion

EM of axillary skin biopsy may be helpful to diagnose metabolic abnormalities, although results may be nonspecific (Hum Path 2001;32:649)

 

Grossing

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Breadloafing (serial section) of ellipses is often best – cut perpendicular to long axis at 3 mm intervals

Always ink margins

Bisect punch biopsies if 4 mm or larger

 

Common pathologic terms

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Acantholysis: loss of intercellular connections (desmosomes) between keratinocytes; occurs in pemphigus vulgaris and related disorders; causes change in cell shape from polygonal to round

Acanthosis: thickening of epidermis (squamous layer), rete ridges usually extend deeper into dermis

Atrophy: thinning of epidermis, associated with age or disease

Basophilic degeneration: age and sunlight related changes of collagen and elastic fibers

Blister: vesicle or bullae

Bullae: fluid filled area > 5 mm; intraepidermal or subepidermal; intraepidermal bullae are due to spongiosis or acantholysis; subepidermal bullae are due to extensive papillary dermal edema

Colloid bodies: also called Civatte bodies; apoptotic keratinocytes, oval/round, immediately above or below epidermal basement membrane

Dyskeratosis: abnormal, premature keratinization of keratinocytes below granular cell layer; often have brightly eosinophilic cytoplasm

Epidermolysis: alteration of granular layer with perinuclear clear spaces, swollen and irregular keratohyalin granules, increased thickness of granular layer; different from acantholysis

Epidermotropism: atypical lymphocytes present in epidermis (seen in cutaneous T cell lymphoma)

Erosion: discontinuity of skin causing partial loss of epidermis (compare to ulceration)

Excoriation: deep linear scratch, often self-induced

Exocytosis: nromal appearing lymphocytes in epidermis (spongiotic dematitis)

Hydropic (liquefactive) degeneration: basal cells become vacuolated, separated and disorganized

Hyperkeratosis: thickened cornified layer, often with prominent granular layer; keratin may be abnormal; orthokeratotic hyperkeratosis is exaggeration of normal pattern of keratinization (no nuclei in cornified layer); parakeratotic hyperkeratosis has retained nuclei in cornified layer

Lentiginous: linear pattern of melanocytic proliferation within epidermal basal cell layer

Leukocytoclasis: karyorrhexis and destruction of neutrophils; occurs with neutrophilic vasculitis (also called leukocytoclastic vasculitis)

Lichenification: thick, rough skin with prominent skin markings usually due to repeated rubbing

Lichenoid interface change: destruction of basal keratinocytes, causing remodeling of basement membrane zone; also bandlike lymphocytic infiltrate

Macule: circumscribed flat colored area of any size

Nodule: deeply extending papule > 5 mm

Oncholysis: loss of integrity of nail substance

Papillomatosis: outward overgrowth of epidermis with elongation of dermal papillae

Papule: elevated and solid area, 5 mm or less

Parakeratosis: cells of cornified layer retain their nuclei, often less prominent or absent granular layer; normal for mucous membranes

Patch: large macule

Plaque: elevated flat topped area, usually > 5 mm

Pustule: intraepidermal or subepidermal vesicle or bullae filled with neutrophils

Scale: dry, horny, platelike excrescence usually due to imperfect cornification

Scale crust: parakeratotic debris, degenerating inflammatory cells and tissue exudate on surface of epidermis

Spongiosis: intraepidermal edema, causing splaying apart of keratinocytes in stratum spinosum (resembling a sponge), vesicles due to shearing of desmosomes

Ulceration: discontinuity of skin causing complete loss of epidermis and possible loss of dermis

Vesicle: fluid filed area, 5 mm or less

Wheal: itchy, transient, elevated area with variable blanching and erythema, due to dermal edema

 

 

Infectious disorders

Abscess

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Virtual slides: abscess (furuncle)

 

Anthrax

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 “Coal” in Greek; refers to black coloration of skin eschar

Due to endospores of Bacillus anthracis, a common soil organism

Causes cutaneous, pulmonary or gastrointestinal symptoms

Culture: nonhemolytic, nonmotile, ground-glass colonies that retain their shape when manipulated; grow readily on sheep red blood cell agar (no special conditions needed)

Gram stain: gram positive, spore-forming rods

Treatment: antibiotics, reduces mortality from 20% to less than 1%

Case reports: 51 year old woman with localized skin ulceration and prominent edema of forehead, culture negative for B. anthracis (Archives 2004;128:709)

Gross images: skin lesion #1; #2

Micro: eschar shows coagulative necrosis of superificial epidermis and dermis, with prominent edema of underlying viable dermis, frequent focal hemorrhages, intense, reactive-appearing mononuclear inflammatory infiltrates around small vessels and some adnexae; neutrophils only around necrotizing sebaceous glands; sharp demarcation between superficial necrotic and deeper edematous viable tissue (at periphery), occasional islands of regenerating epidermis under necrotic layer of eschar; vessels with degenerated endothelial cells and focal thrombi; no abscess; no granulation tissue

Micro images: figure 1: coagulative necrosis of superficial epidermis and dermis, edema of underlying viable dermis, frequent focal hemorrhage, intense mononuclear inflammation around small vessels and some adnexa; 2: sharp demarcation between superficial necrotic and deeper edematous viable tissue, with occasional islands of regenerating epidermis present under necrotic eschar; 3: mononuclear infiltrate

Bacterial images: bacteria; in cerebrospinal fluid (inhalation anthrax)

EM images: anthrax spores

References: slide show; Centers for Disease Control

 

Botryomycosis

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Definition: chronic pyogranulomatous lesion by sulfur granules resembling actinomycosis (Ann Trop Med Parasitol 2004;98:623), but actually due to Staphylococcus aureus and occasionally other organisms (Hum Pathol 2005;36:117, Clin Exp Dermatol 2008;33:266)

Often associated with depressed immune systems (Nephrol Dial Transplant 1998;13:3200)

Treatment: excision and antimicrobial therapy (J Rheumatol 2006;33:2545, J Eur Adac Dermatol Venereol 2003;17:87)

Micro images: contributed by Dr. Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain -  #1#2

 

Carbuncle

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Painful localized bacterial infection of skin and subcutis, usually with several openings through which pus is discharged

Virtual slides: carbuncle

 

CMV (cytomegalovirus)

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Gross/clinical images: punched out ulcers in immunocompromised patient

 

Epstein-Barr virus

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Ubiquitous virus in humans, usually infection by early adulthood

Primary EBV infections are asymptomatic or may cause infectious mononucleosis; Japanese or other Asians may develop chronic infections

Chronic active EBV infection: chronic recurrent infectious mononucleosis-like symptoms, has high mortality due to virus-associated hemophagocytic syndrome, NK/T cell lymphomas, EBV related cardiovascular disease and large vessel arteritis; also hypersensitivity to mosquito bytes in 1/3 (may be initial symptom), causing necrotic skin ulceration and scarring

Case reports: 11 year old Japanese-Filipino girl with chronic active EBV infection and mosquito byte hypersensitivity, leading to EBV+, NK/T cell lymphoma (Hum Path 2005;36:212)

 

Erysipelas

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Streptococcal infection causing upper dermal edema and “orange peel” or peau d’orange appearance

Virtual slides: erysipelas

 

Erysipelothrix

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Erysipelothrix rhusiopathiae is an animal bacteria that rarely causes cutaneous disease in humans that work with animals or fish

Causes cutaneous erysipeloid and rarely endocarditis of aortic and mitral valves

Insidious onset over months

May cause botryomycosis, a pseudomycosis due to nonfilamentous bacteria with characteristic hyaline granules

Case reports: 54 year old black man with fatal endocarditis, no skin lesions, no history of animal/fish exposure (Hum Path 2005;36:117)

Micro: slender or filamentous gram positive rod similar to actinomycetes

 

Folliculitis

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Inflammation around hair follicles, involving follicular opening or adjacent skin

Infectious cases are either superficial (fungi, bacteria, syphilis, viral) or deep (granulomatous, due to fungi or bacteria)

Fungal forms may be endothrix (spores within hair shaft) or ectothrix (spores on outer surface of hair shaft)

Noninfectious cases are superficial/suppurative (acne vulgaris, rosacea, follicular mucinosis, steroid-induced), deep/granulomatous (acne vulgaris-conglobate and keloidal forms or perforating) or spongiotic (Fox-Fordyce disease, atopic dermatitis, pruritic folliculitis of pregnancy)

Perifolliculitis forms are either primarily lymphocytic (lichen planopilaris, pityriasis rubra pilaris) or granulomatous (perioral dermatitis, rosacea)

Pseudolymphomatous folliculitis: facial lesion with dense, polymorphic, mixed lymphocytes around hair follicles and infiltrating follicular epithelium

Gross/clinical images: folliculitis

 

Fungi

 

Fungi-Candida

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Micro images: Candida #1; #2; #3; culture

 

Fungi-Chromoblastomycosis

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Clinically resembles carcinoma; color of lesion is due to brown spores

Indolent cutaneous disease due to Phialophora, Fonsecaea or Cladosporium fungi, that multiply by cross wall formation and splitting

Cultures (Phialophora): slow growing, dark gray-black and hairlike

Gross: verrucous or nodular, resembling carcinoma

Micro: marked pseudoepitheliomatous hyperplasia and mixed granulomatous-neutrophilic infiltrate; contains brown spores; fungi have cross walls but no budding

Gross/micro images: gross, micro and culture

DD: Blastomyces dermatitis (budding, double contoured)

References: more information and images

 

Fungi-Histoplasma capsulatum

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A dimorphic saprophytic fungus found in soil contaminated with bird or bat feces

Endemic to southeast US (80% of this population may have positive intradermal histoplasmin skin test), Mexico, Africa, Asia

Infection is via inhalation of spores, causing a primary pulmonary pneumonia

Pneumonia is self-limited in immunocompetent patients, but disseminates in immunocompromised (very young, very old, HIV+) to liver, spleen, bone marrow, nodes, lung, rarely to skin

Disseminated disease: strongly associated with AIDS; fever, weight loss, splenomegaly; variable cutaneous lesions

Culture: tan-white-brown wooly mold at 25-30C on Sabouraud dextrose agar; organisms have delicate, septate hyphae, 1-2 microns thick, with large rough-walled macroconidia 5-15 microns; revert to yeast at 37C on sheep blood agar; yeast is 2-4 microns, budding, single nuclei, round/oval with thin rigid walls

Treatment: antifungal drugs

Case reports: 27 year old woman with multiple cutaneous lesions (Archives 2004;128:e15), 33 year old HIV+ man with recurrent disseminated disease (Archives 2001;125:571); atypical variant causing disseminated cutaneous disease in healthy 5 year old (Rev Inst Med trop S Paulo;1999:41:195)

Gross: cutaneous lesions are nodules, papules, ulcers; less commonly macules, pustules or vesicles

Micro: isolated intracellular organisms, larger aggregates surrounded by chronic inflammatory cells and fibroblasts (but no neutrophils or eosinophils) or epithelioid granulomas with variable caseation; may be narrow based budding of spores

Micro images: (1) figure 1: multiple budding yeasts in deep dermis (arrow indicates yeast); 2: GMS stain; 3/4: lacto-phenol cotton blue stain of mold shows characteristic thick-walled tuberculate macroconidia and microconidia (arrow indicates macroconidia); (2) figure 1: 2-3 mm hyperpigmented papules; 2: dermal basophilic spherules 2-4 microns; (3) granulomatous infiltrate; (4) slide culture with small microconidia and tuberculate macroconidia; (5) within macrophages #1; (9) #2 in liver

Positive stains: PAS, GMS

References: more information #1; #2

 

Fungi-Maduramycosis

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Actinomadura is an aerobic actinomycetes, a filamentous bacterium found in soil

Initially believed (incorrectly) to be a fungi, so diagnostic procedures are often performed in mycology laboratories

Micro images: contributed by Professor Venna Maheshwar, Drs. Kiran Alam and Anshu Jain, J. N. Medical College, India - #1#2

 

Fungi-North American blastomycosis

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Skin lesions usually secondary to pulmonary blastomycosis; rarely occur at site of penetrating injuries

Due to Blastomyces dermatitidis, a spherical, double-contoured, 12 micron yeast that reproduces by budding

Endemic areas are Mississippi, Missouri and Ohio (USA) river valleys and southern Canada

May affect healthy patients via spore inhalation

Diagnosis: smears, cultures (Sabouraud dextrose agar at room temperature for 4 weeks generates a fluffy white colony), histology

Case reports: 53 year old African-American man with diabetes and knee mass (Archives 2005;129:e132)

Treatment: antifungal therapy

Gross: slowly enlarging verrucous plaques containing multiple small abscesses

Gross/clinical images: image #1; figure 1A: fungating and ulcerating lesion of knee

Micro: marked pseudoepitheliomatous hyperplasia of epidermis, granulomatous and neutrophilic infiltrate, fungi are within giant cells; Blastomyces dermatitidis is a 12 micron, spherical, double-countoured yeast with broad based buds

Micro images: budding yeast; various images; culture; figure 1A: gross; 1B: atypical squamous proliferation infiltrating into deep dermis; 1C: intraepithelial neutrophilic abscesses; giant cell with round, broad based budding yeast

DD: well differentiated squamous cell carcinoma

References: more information and images #1; #2

 

Fungi-Onchomycosis

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Spread of fungi to nails

Caused by Candida albicans, Scopulariopis brevicaulis, others; often multiple fungal species

Gross/clinical images: toenail infection

 

Fungi-Prototheca

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Not fungi but similar features

First recognized as human pathogen in 1964; two species associated with human disease - P. wickerhamii and P. zopfii

Aerobic, achlorophyllous, algae-like, unicellular organisms in water, sewage and soil

<100 cases of human infection reported, usually via trauma or contaminated water, involving face or exposed extremities

Primary cell or spherule is called the theca; species reproduce by internal septation, forming sporangia which contain up to 20 endospores

P. wickerhamii: cells are rounder than oval/cylindrical shapes of P. zopfii

Diagnosis: corn meal agar

Treatment: amphotericin B if disseminated, surgical excision if focal cutaneous or subcutaneous

Case reports: 34 year old woman with index finger pain and swelling and hobbies of scuba diving and maintaining an aquarium (Archives 2001;125:450)

Micro: necrotizing granulomas of subcutis containing spherical organisms with central basophilia, internal septation and double layer cell walls; also multiple endospores 2-4 microns

Micro images: A: necrotizing granulomas of subcutis containing organisms of varying size; B/D: GMS; C: mucicarmine - stains highlight internal septation and double layer cell wall; internal septation; culture

Positive stains: GMS, PAS, mucicarmine

 

Fungi-Superficial fungal infections

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Scalp and beard lesions may have superimposed bacterial folliculitis / perifolliculitis

May also be found on neoplastic skin lesions

Infections of stratum corneum are usually caused by dermatophytes

Spores, hyphae and neutrophils usually are present in stratum corneum or hair shafts

Associated with pseudoepitheliomatous hyperplasia

Kerion celsi: superimposed bacterial folliculitis on tinea of scalp

Majocchi’s granuloma: nodular granulomatous perifolliculitis; inflammation of dermis and subcutis by dermatophytes, usually Trichophyton rubrum

Sycosis barbae: tinera barbae with superimposed bacterial follicultis

Tinea barbae: infection of beard area of adult men

Tinea capitis: infection causing hairless patches of skin in scalp, usually in children

Tinea corporis: infection of trunk of children and adults, associated with excessive heat and humidity; scaly, red, annular plaques (“ringworm”)

Tinea cruris: "jock itch", infection of inguinal area of obese men during warm weather

Tinea pedis: "athletes foot", infection causing diffuse erythema and scaling, initially in web spaces, often with bacterial superinfection

Gross/clinical images: tinea barbae; tinea capitis; tinea pedis; Majocchi’s granuloma

Micro: cellulitis, abscesses, pseudoepitheliomatous hyperplasia, fungal spores and hyphae found in horny cell layer and near hair shafts; variable intercellular epidermal edema, dermal inflammation

Micro images: tinea pedis-epidermophyton

Positive stains: PAS, GMS

 

Fungi-Tinea versicolor

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Infection by Malassezia furfur of upper trunk

Micro: variably pigmented macules of all sizes, with orthokeratotic hyperkeratosis, yeast spores and pseudohyphae within stratum corneum; short hyphae and spores (“spaghetti and meatballs”) with GMS or PAS stains

Note: presence of fungi does not rule out coexisting inflammatory and neoplastic disorders

Micro images: Malessezia furfur

 

Fungi-Trichosporon

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Case reports: 22 year old man with ALL and post-chemotherapy disseminated fungal infection (Univ Pittsburgh)

References: more information and images

 

Fungi-Zygomycosis

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Infections caused by fungi in class Zygomycetes, including Absidia, Mucor, Rhizomucor, Rhizopus, Apophysomyces elegans (rare human pathogen)

Most zygomycosis occur in immunocompromised patients (due to leukemia, lymphoma, diabetes, transplantation), with rhinocerebral or pulmonary infection, then dissemination

A. elegans causes progressive necrosis of wound in previously healthy patients after trauma or invasive procedures

Culture: A. elegans - rapidly growing mold with sporangiophores having dark brown, funnel shaped apophyses and pyriform sporangia

Micro: extensive coagulative necrosis due to fungi with broad, sparsely septate, thin-walled hyphae; angioinvasion with thrombosis

Micro images: figure 1: mycotic thrombus in kidney artery; 2: mat of Fusarium hyphae with macroconidia and microconidia at surface of wound; 3: hyphae of Apophysomyces in viable tissue below surface mat of Fusarium hyphae; PAS #1

References: Archives 1999;123:386, more information and images #1; #2

 

Hepatitis C

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Main cause of transfusion-associated hepatitis

Associated with IV drug abuse, organ transplant, hemodialysis and health care workers

Infection is associated with cutaneous eruptions, including dermatomyositis-like photodistributed eruptions, palpable purpura, folliculitis, violaceous acral lesions, ulcers, nodules, and urticaria

Dominant patterns are vasculopathies of neutrophilic, lymphocytic, and granulomatous vasculitis and pauci-inflammatory subtypes (most common); also sterile neutrophilic folliculitis, palisading granulomatous inflammation, neutrophilic dermatoses, pyoderma gangrenosum, interface dermatitis, lobular panniculitis; single cases of dermatitis herpetiformis, benign cutaneous polyarteritis nodosa, marginal zone lymphoma, clonal plasmacellular infiltrate

 

Herpes simplex or varicella zoster

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Painful diseases caused by herpes simplex virus or varicella zoster virus (also causes chickenpox)

After primary infection, viral particles reside in sensory ganglia and are dormant until they erupt as recurrent herpes simplex virus or shingles (zoster)

Associated with leukemia and lymphoma

Shingles has dermatomal distribution or severe involvement of trigeminal nerve-first division with corneal ulceration and herpetic keratitis

They two viruses are differentiated by culture (difficult to culture zoster) or immunologic methods

Case reports: 37 year old HIV+ man with nodules on leg

Gross: grouped vesicles on an erythematous base, later become pustules, then crusts

Gross/clinical images: dermatomal distribution of zoster

Micro: keratinocytes are multinucleated, acantholytic with distinct nuclear inclusions, found initially in follicular epithelium; late epidermal necrosis or full-thickness acantholysis; may have extensive dermal infiltrate, leukocytoclastic vasculitis

Micro images: Tzanck smear #1; #2

Virtual slides: herpes. varicella

 

Hidradenitis suppurativa

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Due to bacterial infection around apocrine glands of axilla, occasionally perineum or vulva

Usually due to anaerobes

May produce fistulas and scarring

Treatment: excision of involved skin if medical therapy fails

Gross: abscesses, sinuses, perianal fistulas with scarring

Micro: heavy neutrophilic or mixed inflammatory infiltrate around apocrine glands with dilated lumina

 

HIV associated

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Acute human immunodeficiency virus infection (HIV) is a transient illness, typically presents acute mononucleosis-like syndrome with mucocutaneous and constitutional symptoms, followed by detection of anti-HIV antibodies in peripheral blood

Associated with various conditions:

Dermatitis: interface dermatitis occurs early in HIV infection, with pronounced vacuolization of basal keratinocytes, inflammatory infiltrate is CD3+/CD8+ T cells expressing granzyme B7 and TIA1, and histiocytes; decreased Langerhans cells (Mod Path 2000;13:1232)

Drug reaction: see above

Folliculitis: infants and adults; perifollicular chronic inflammatory infiltrate, often with follicular rupture, often with marked eosinophils

Infections: scabies, fungi, mycobacteria, syphilis, bacterial angiomatosis

Maculopapular eruptions: in 25%, in trunk with possible extension to extremities; nonspecific perivascular lymphocytes and histiocytes in upper dermis, variable papulovesicular foci with necrotic keratinocytes

Papular neutrophilic xanthoma: foamy macrophages, extracellular nuclear dust, hyaline necrosis of collagen fibers

Papular pruritic eruptions: anywhere on body; may wax and wane; superficial and mid-dermal perivascular lymphocytes with eosinophils, acanthosis, parakeratosis

Psoriasis: see below

Seborrheic dermatitis: common, usually severe, involves trunk and extremities

Vasculitis: occasionally leukocytoclastic, may be due to HIV directly or CMV

Viruses: herpes simplex (20%; painful perianal or perioral ulcers with large intranuclear inclusions), severe varicella-zoster infection, CMV (ulcerative lesions at mucocutaneous junctions), molluscum contagiosum, hairy leukoplakia, anal warts, bowenoid papulosis

Gross images: A: widespread maculopapular rash; B: oral rash with ulceration

Micro images: A: interface dermatitis with necrotic keratinocytes and lymphocytic exocytosis; B: necrotic keratinocyte surrounded by lymphocytes (“satellite cell necrosis”); C: hair follicle infiltrated by lymphocytes, overlying epithelium has necrotic and vacuolated keratinocytes

 

Impetigo

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See also bullous impetigo

Usually affects hands and face of normal children or adults in poor health

Common, due to Staphylococcus or Streptococcus infection

Gross: erythematous macule

Micro: neutrophils beneath stratum corneum; may have subcorneal pustule

 

Leishmaniasis

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Protozoal disease in all continents except Australia and Antarctica

1-2 million new cases per year worldwide

Epidemics occur periodically in tropical regions of world; also infections in HIV+ patients

Produces crusted, indurated papule that slowly enlarges and is self limited, as well as fatal systemic illness

Disease either cutaneous, mucocutaneous or visceral

Cutaneous: usually restricted to face, scalp, arms or other exposed areas; localized, disseminated (if immune system doesn’t respond to invading parasites), recurrent (recidivans cutaneous) or post-kala azar (rare, years after visceral disease)

Mucocutaneous: usually New World disease of rural and jungle regions; occurs when primary infection with L. braziliensis becomes disseminated to upper respiratory tract, produces lesions of oral, pharyngeal or nasal mucosa with ulceration, mutilation or sometimes death

Visceral: also called kala azar; parasites throughout reticuloendothelial system, causing fever, malaise, hepatosplenomegaly, anorexia, pancytopenia, hypergammaglobulinemia; usually spares skin except for irregular areas of dark pigmentation (kala azar means “black sickness”); may cause death if untreated

Broadly divided into “old world” (tropical and subtropical Asia, India, Africa and Mediterranean) and “new world” (Americas)

Old world: usually Leishmania tropica complex

New world: L. braziliensis complex and L. mexicana complex

L. braziliensis may also produce espundia, a destructive mucocutaneous form

Human infection through bite of Phlebotomus sand fly (smaller than mosquitoes); rarely through blood contamination

Clinical presentation and prognosis vary based on species, duration of infection and immune status of patient

US infections primarily through travel and HIV infection

Diagnosis: intradermal delayed hypersensitivity test (Montenegro); culture on NNN agar; smears from ulcer; also ELISA, DNA probes, PCR

Treatment: drugs for cutaneous forms; mucocutaneous and diffuse cutaneous forms may be refractory to treatment

Micro: dermal granulomatous inflammation with prominent lymphocytes; histiocytes contain small oval organisms with bar shaped paranuclear kinetoplast

Micro images: figure 1: centrally ulcerated plaque on hand; 2: dermal granulomatous inflammation; 3: 2-4 micron organisms with bar shaped paranuclear kinetoplasts; various images of cutaneous disease #1; #2; #3; #4 (with case report)

contributed by Professor Venna Maheshwar, Drs. Kiran Alam and Anshu Jain, J. N. Medical College, India - #1#2

References: Archives 2002;126:471

 

Leprosy

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Also called Hansen’s disease

Most US cases from immigrants

Diagnosis: PCR

Micro images: various images;

 

Lepromatous leprosy

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Micro: numerous foamy macrophages (Virchow cells, lepra) stuffed with acid-fast bacilli; granulomas in and around cutaneous nerves or infiltrating and destroying arrectores pilorum muscle; may have subcutaneous nodules (erythema nodosum leprorum)

Micro images: acid-fast bacilli stain

Positive stains: acid-fast (Ziehl-Neelsen)

DD: fibrous histiocytoma

 

Tuberculoid leprosy

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Micro: bacilli are scanty; granulomas in and around cutaneous nerves or infiltrating and destroying arrectores pilorum muscle

Virtual slides: tuberculoid leprosy

 

Lyme disease

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Multisystem disorder caused by spirochete Borrelia burgdorferi

Usually transmitted by Ixodes dammini tick mite

Causes erythema chronicum migrans (red papule with central clearing that expands slowly), acrodermatitis chronica atrophicans (disease of extremities, usually women, with erythematous, edematous, pruritic phase, followed by sclerosis and atrophy), cutaneous lymphoid hyperplasia of skin

Also affects heart, joints, nervous system

Gross images: erythema chronicum migrans (and other images)

Micro: superficial and deep perivascular infiltrate of lymphocytes, plasma cells and eosinophils

Positive stains: Warthin-Starry (for spirochetes)

 

Malakoplakia

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Rare; may occur in HIV+ patients

Micro: histiocytes have Michaelis-Gutmann bodies, rarely contain gram negative organisms

 

Molluscum contagiosum

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Caused by human molluscum contagiosum poxvirus

Multiple nodules on skin, trunk, anogenital region, due to skin to skin contact; also sexually transmitted

Gross: multiple firm, pruritic, pink-tan nodules, up to 4 mm, with central cores containing white keratinous material

Gross images: raised, firm, flesh colored nodules

Micro: characteristic findings of sharply delimited dermal lesion containing proliferating epithelium; molluscum bodies present (large cells with cytoplasmic, faintly granular eosinophilic inclusions that displace nuclei; contain viral particles); may have intense dermal inflammatory infiltrate; rarely metaplastic ossification

Micro images: various images

contributed by Dr. Julia Braza, Beth Israel Deaconness Medical Center, Boston, Massachusetts - abdominal skin of 29 year old man - #1#2#3#4 

contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - #1#2;  #3;  #4

Virtual slides: molluscum contagiosum

DD: keratoacanthoma

 

Mycobacteria – atypical

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May cause ulcerations, abscesses, rheumatoid-like nodules, histiocytic reactions, panniculitis

Most commonly due to M. kansasii, M. marinum, M. ulcerans

Case reports:  52 year old woman with foot infection (Univ Pittsburgh)

 

Parvovirus B19

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Characteristic skin manifestations are petechial eruption in a glove and stocking distribution, reticular truncal erythema, and "slapped cheek" sign

Clinically manifests as Fifth’s disease; atypical presentations resemble asymptomatic papular eruption, Sweet’s syndrome, myopathic dermatomyosis, lupus, lower extremity palpable purpura

May be due to delayed type hypersensitivity, antibody dependent cellular immunity against microbial antigens in epidermis or endothelium, or circulating immune complexes

Gross images: “slapped cheek” appearance

Micro: interstitial histiocytic infiltrate with piecemeal fragmentation of collagen and mononuclear cell-predominant vascular injury pattern; also interface dermatitis, eczematous alterations, papillary dermal edema; occasionally mesenchymal mucinosis, leukocytoclastic vasculitis

References: Hum Path 2000;31:488

 

Scrub typhus

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Chigger-borne zoonosis of tropical Asia and western Pacific islands

Infected large number of soldiers in World War II

Today, a frequent cause of febrile illness leading to hospital admissions in indigenous populations

Caused by Orientia (formerly Rickettsia) tsutsugamushi, maintained in nature by trombiculid mites, transmitted to humans by larval mite (chigger) during feeding

Distinguished from Rickettsiaceae family by differences in cell wall

Gross images: chigger

Micro: detected in endothelial cells of skin biopsies, and other organs sampled

Micro images: various imagesimmunostains for O. tsutsugamushi in A: brain, B: lung, C: kidney, D: liver, E: cardiac muscle and endothelium, F: spleen

References: Mod Path 2001;14:752

 

Smallpox vaccination

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Diffuse, pruritic, erythematous macules and papules may occur 2 days to 7 weeks after routine smallpox vaccination (usually 7-11 days)

Serious but uncommon complications include eczema vaccinatum, vaccinia necrosum, generalized vaccinia

Less serious but more common include keloid, contact dermatitis, erythema multiforme, pityriasis rosea, granuloma annulare

Treatment: symptomatic

Gross images: vaccinia necrosum #1; #2

Micro images: figure 1: pink-red nonblanchable macules and papules; 2: patchy, mild epidermal spongiosis and associated superficial dermal perivascular chronic inflammatory infiltrate; 3: patchy epidermal spongiosis with intraepidermal lymphocytes and red blood cells, and superficial dermal chronic inflammatory infiltrate (pityriasis rosea-like pattern); 4: spongiotic dermatitis with scale crust laterally, associated with dense, superficial dermal perivascular and interstitial inflammation

References:  Archives 2004;128:1173, smallpox and mimics

 

Syphilis

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Secondary lesions are maculopapular, and resemble drug eruption, lichen planus, psoriasis

May present as moth-eaten alopecia on scalp, mucous patches on tongue

Occur on face and trunk

Diagnosis: serology

Gross: scaly, flesh-colored to erythematous papules or annular plaques; copper macules on palms and soles

Micro: dense perivascular or diffuse plasma cell infiltrate with marked endothelial swelling and proliferation in blood vessels is characteristic; may have noncaseating granulomas, vacuolar interface change, acanthosis, spongiosis, lymphocyte exocytosis

Micro images: primary syphilis; various images

Positive stains: Steiner stain (71% sensitive)

 

Tuberculosis

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Cutaneous disease uncommon in US

 

Lupus vulgaris

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Reactivation form of tuberculosis

Chronic cases are associated with squamous cell carcinoma

Diagnosis: culture or PCR

Gross: facial lesions with small, firm nodules in underlying, irregular red patch with elevated borders; nodules become pale and tan when pressed with a glass slide; variable ulceration

Micro: sarcoid-like or necrotic granulomas in dermis; rare acid-fast bacilli

Micro images: various images

contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - #1#2#3#4

 

Papulonecrotic tuberculid

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Associated with tuberculosis, but usually no organisms present

Gross images: various images (also other forms of cutaneous tuberculosis)

Micro: dermal necrosis, poorly formed granulomas, vasculitis, edema

 

Erythema induratum of Bazin

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Also called nodular vasculitis if no coexisting tuberculosis

Rare, more common in past

Presents as recurrent tender subcutaneous nodules on calves of women with tuberculin hypersensitivity

Gross images: adult woman with erythrocyanotic circulation and ulcerated lesions

Micro: granulomatous vasculitis affecting subcutaneous large vessels (may need multiple serial sections to identify); also granulomatous inflammation of lobules of subcutis; lesions may contain acid-fast bacilli by PCR

 

Tularemia

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Caused by bacterium Francisella tularensis found in animals (especially rodents, rabbits, and hares), transmitted by ticks, deer flies

Symptoms: sudden fever, chills, headaches, diarrhea, muscle aches, joint pain, dry cough, progressive weakness

Also pneumonia, skin/mouth ulcers, lymphadenopathy, eye involvement

Gross/clinical images: thumb erosion; girl with ulcerating lymphadenitis in Kosovo; deer fly

Micro images: various images

References: outbreak in Kosovo

 

Virus associated trichodysplasia spinulosa

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Very rare; <10 cases reported

Cutaneous eruption of spiny papules due to polyoma virus infection

Usually affects face and ear, less often trunk and extremities, may cause alopecia

Associated with kidney transplant, acute lymphocytic leukemia

Similar to cyclosporine-induced follicular dystrophy and pilomatrix dysplasia

Micro: abnormally maturing anagen hair follicles (no papillae, ectatic infundibula) with excessive inner root sheath differentiation, and hyperkeratotic infundibula

EM: intranuclear polyoma-type virus particles

DD: keratosis pilaris (usually arms and legs, small ecstatic infundibula with keratin plugs), lichen spinulosis (children and adolescents, extensor arms, lateral thighs, neck and buttock, minute filiform horny spines grossly due to follicular infundibular hyperkeratosis), drug induced folliculitis

References: AJSP 2005;29:241

 

Warts

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Also called verrucae

Cutaneous and mucosal lesions caused by various types of human papillomaviruses (HPV), a type of papova virus

Usually resolve in 6-24 months

Micro: focal epidermal hyperplasia with hyperkeratosis and parakeratosis, papillomatosis (not verruca plana), may have trichilemmal keratinization; koilocytes (keratinocytes in upper squamous layer with vacuoles, large cytoplasmic eosinophilic aggregates, pyknotic nuclei); tangential sections may show squamous cells surrounded by inflamed stroma; older lesions may lack cytoplasmic changes; viral nuclear inclusions are basophilic

Micro images: Viral warts #1#2#3

Positive stains: HPV by in situ hybridization

EM: eosinophilic aggregates are tonofilaments

DD: squamous cell carcinoma (may resemble tangential cuts of condyloma accuminatum)

 

Condyloma accuminatum

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Also called venereal wart

Usually due to HPV6

Perianal, vulva, glans penis, mucosal membranes of oral cavity

Gross: soft, tan, cauliflower-like masses

Gross images: oral lesions in HIV+ patients;

See also Vulva, Penis, Cervix, Anus chapters

 

Epidermodysplasia verruciformis

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Autosomal recessive disorder of multiple flat warts on face or distal extremities, often disseminated throughout the body

Usually HPV 5 or 8, less commonly 3, 4, 51

Rarely X linked recessive or autosomal dominant transmission

Often appear before age 10 years or after renal transplantation

30-50% progress to invasive squamous cell carcinoma, mean age 31 years

Equivocal cases are best distinguished by histology and viral testing, in context of clinical setting

Treatment: excision or locally destructive methods

Gross: flat, skin-colored, red or hyperpigmented papules resembling flat warts or scaly brown pityriasis versicolor-like macules and patches; also seborrheic keratosis-like

Micro: classic features are mild to moderate acanthosis and hyperkeratosis; large cells with blue-gray cytoplasm, perinuclear halos, often dysplastic changes; more commonly has irregular granular layer with rare perinuclear halos

Micro images: various images; arm

Positive stains: HPV

References: AJSP 2000;24:1400

 

Verruca plana

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Usually due to HPV10

Flat, occurs in crops/clusters on face and hands

Micro: involuting lesions may have chronic inflammatory infiltrates in dermis and epidermis with degenerative epithelial changes

Micro images: various images

 

Verruca plantaris

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On soles of feet; painful; covered by callus

Micro: invaginated with numerous coarse, basophilic, intracytoplasmic keratohyalin granules resembling molluscum bodies

 

Verruca vulgaris

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Usually due to HPV2

Occur on hands as elevated, hard, rough, flesh-colored lesion

If surface is peeled, undersurface is pink and granular

Gross: exophytic papules, either single lesions or linear; appear serrated

Gross images: verruca vulgaris on palm

Micro: striking papillomatosis (upward displacement of dermal papillae), stratum corneum exhibits parakeratosis with pointed mounds resembling church spires, extravasated erythrocytes or hemosiderin; granular layer is thickened with prominent keratohyalin granules and keratinocytes displaying perinuclear clearing (koilocytosis, lost in older lesions); lymphocytic infiltrate in upper dermis

Micro images: verruca vulgaris #1; #2; #3

Virtual slides: verruca vulgaris

 

 

Infestations

Infestations-general

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Skin lesions due to direct irritant effects, immediate or delayed hypersensitivity or specific effects of venom

Bites: urticaria, inflammed papules or nodules, variable ulceration

 

Body louse

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Causes hyperpigmentation and scratch marks (excoriations)

Gross images: body louse #1; #2;

 

Botfly

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Dermatobia hominis flies are acquired during travel to endemic area

Female botfly attaches eggs to abdomen of biting arthropod, eggs hatch, and first stage larvae burrow into skin through insect bite, hair follicle or other wound; larvae spend 4-14 weeks in skin developing into third stage larva or “instar”, up to 2 cm; larvae then emerge

Treatment: petroleum jelly over skin opening to cause larvae to migrate to surface

Case reports: 61 year old woman who traveled to Belize for jungle hiking and ocean snorkeling with pruritic lesions on back, thigh and supraclavicular area (Archives 2001;125:453)

Gross: resemble insect bites, allergic reactions, herpes virus, molluscum contagiosum, bites of mite Sarcoptes scabiei; enlarging lesions may resemble cellulite, pyogenic furuncle or infected sebaceous cyst

Micro images: figure 1: larvae with anterior end is wider than posterior end; 2: larvae has 2 curved oral hooks on anterior end (for grasping and tearing tissue for feeding); 3: parallel concentric rows of posterior pointing spines on body

 

Brown recluse spider

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Bite causes extensive necrosis

Gross images: brown recluse spider and US quarter; brown recluse spider bite #1; #2

 

Demodex

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Mites are commonly present in inflamed follicles, but are usually nonpathogenic

Common in dogs

 

Pediculosis (lice)

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Causes pruritis, enlarged local lymph nodes

Eggs are attached to hair shaft (nits)

Gross images: various images; nit #1; #2; #3

References: more information

 

Pubic louse (crabs)

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A sexually transmitted disease

Gross images: pubic louse

 

Scabies (mite)

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Produces burrows and extremely pruritic erythematous papules on interdigital skin, palms, wrists

Micro: burrow appears as cleft in upper epidermis containing mite body parts; epidermis exhibitis acanthosis, parakeratosis, spongiosis, with dense eosinophilic dermal infiltrate

Micro images: various images

 

Tunga penetrans

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Sand flea that burrows into human skin and skin of mammals, causing the disease tungiasis

Parasite common in tropical locations (South America, Caribbean, Africa, Pakistan, west coast of India)

Single flea causes local discomfort; multiple bites cause debilitation and secondary infections (tetanus, gas gangrene)

Gross: nodular lesion

Gross images: infected sores

Micro: skin biopsies have exoskeleton, hypodermal layer, trachea, digestive tract and developing eggs; striated muscle in 47%, posterior end in 43%; head usually absent

Micro images: single flea; figure 1: varied arthropod body parts; 2: trachea (open arrows), striated muscle (solid arrow); 3: eggs (solid arrows), hypodermal layer (open arrow); 4: posterior end (solid arrow); 5: tick (for comparison, no developing eggs); various images

References: Archives 2002;126:714

 

 

Granulomatous but non-infectious disorders

Arthropod bites

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Small clusters of erythematous papules or large, deep, indurated, violaceous nodules resembling lymphoma

Micro: inflammatory and granulomatous reactions with dense superficial and deep lymphocytes, eosinophils and plasma cells; variable parakeratosis, spongiosis, acanthosis, epidermal erosion; may have lymphoid germinal centers resembling lymphoma, with destruction of adnexae and atypia

Positive stains: CD30 (focal, may involve atypical cells, AJSP 2003;27:912)

 

Foreign body reaction

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Due to talc, silicon, lipid, zirconium, beryllium, prior surgery or arthropod bites, tattoos, keratin or urates; all may cause granulomatous reactions

Micro: polarizing microscope demonstrates talc, silica, lipids; beryllium is associated with necrotizing and granulomatous reaction

Micro images: post-surgical with suture material

 

Interstitial granulomatous dermatitis with arthritis

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Uncommon; first described in 1993

Linear inflammatory indurations on lateral aspects of trunk (“rope sign”), also plaques or papules, associated with systemic connective tissue disease; usually in women

Arthritis is usually symmetric, and involves fingers, wrists, elbows and shoulders; associated with positive rheumatoid factor, autoantibodies and elevated erythrocyte sedimentation rate

Case report: disease without rope sign (Hum Path 2004;35:892)

Micro: diffuse dense inflammatory infiltrate of histiocytes within reticular dermis, focal degenerated collagen and elastic fibers, palisading histiocytes; variable neutrophils, eosinophils, lymphocytes, mucin and vasculitis

DD: granulomatous drug reactions (vacuolar interface changes and often epidermotrophism of lymphocytes, resolve with discontinuance of drug), rheumatoid dermatosis, interstitial granuloma annulare, necrotizing granuloma

References: Hum Path 2004;35:779 (editorial)

 

Interstitial granulomatous drug reaction (dermatitis)

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Due to beta blockers, calcium channel blockers, lipid lowering agents, ACE inhibitors, diuretics, NSAIDs, antihistamines, antidepressants, oral hypoglycemic agents; often more than one of above

Mean duration of 5 years before onset of eruptions; resolve an average 8 weeks (range 1-40) after drug is stopped

May be due to exaggerated immune response to drugs

Case report: 74 year old woman with violaceous/erythematous nonpruritic plaques for 18 months (Archives 2004;128:e129), delayed cutaneous hypersensitivity reaction to hirudin (Archives 2001;125:1585)

Gross: violaceous to erythematous, nonpruritic plaques with bizarre shapes or annular morphology on skin folds (axilla, inner arms, groin, medial thighs, popliteal fossa)

Micro: diffuse granulomatous dermatitis with interstitial histiocytes and giant cells near collagen and elastic fibers, often with piecemeal fragmentation of collagen, giant cell engulfment of elastic fibers and variable interstitial mucin; rare collagen necrobiosis; usually interface dermatitis with basilar vacuolopathy, focal dyskeratosis with lymphocytes at dermoepidermal junction; usually tissue eosinophilia, lymphoid atypia with hyperchromatic nuclei, convoluted nuclear contours (including a few cerebriform nuclei in dermis), variable involvement of hair follicles and acrosyringia; usually no fibrin deposition within vessels or vasculitis

Gross/micro images: (1) figure 1: ankle plaques; 2-4: diffuse interstitial and perivascular histiocytic infiltrate in dermis and subcutis, with occasional lymphocytes and eosinophils; epidermis has basilar vacuolopathy and dermoepidermal lymphocytes; (2) figure 1: granulomatous inflammatory infiltrate in response to extravasated hirudin, with lymphocytes, epithelioid histiocytes, occasional Langerhans giant cells and variable calcification of collagen; 2: von Kossa stain for calcium shows staining along collagen bundles

DD (clinical): cutaneous T cell lymphoma (cerebriform nuclei in epidermis), erythema annulare centrifugum, granuloma annulare (vasculitis or vasculopathy present), subacute cutaneous SLE

 

Sarcoidosis

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Affects skin, lymph nodes, organs

Diagnosis of exclusion

Patients often have anergy to delayed hypersensitivity tests

Gross: variable cutaneous features – single/multiple, macules to large plaques or nodules; may have central clearing

Micro: dermal nests and clusters of noncaseating epithelioid granulomas with minimal inflammatory cells and variable giant cells

Gross images: lesion on face

Micro images: granulomas #1; #2; #3

DD: tuberculosis, atypical mycobacteria, syphilis, fungi, reaction to metals (zirconium, beryllium) or lymphoma, foreign body reaction

 

 

Blistering disorders

Blistering disorders-general

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Key features are level of plane of separation, presence or absence of acantholysis and immunofluorescent pattern

Large intraepidermal bullae without acantholysis may represent healed subepidermal bullae

Blisters can also be secondary to herpes infection, spongiotic dermatitis, burns, lupus erythematosus, lichen planus, scleroderma

Diagnosis requires clinical information, often immunofluorescence

Intraepidermal bullae:

Suprabasal: pemphigus vulgaris and variants, paraneoplastic pemphigus, Darier’s diasease

Spinous: spongiotic dermatitis, friction blister, miliara rubra, incontinentia pigmenti, IgA pemphigus, epidermolytic hyperkeratosis, Hailey-Hailey disease

Subcorneal: Staphylococcal scalded skin syndrome, pemphigus foliaceus and variants, bullous impetigo, IgA pemphigus, subcorneal pustular dermatosis, erythema toxicum neonatorum, transient neonatal pustular melanosis, acropustulosis of infancy, miliaria crystallina

Subepidermal bullae:

Damage to basal keratinocytes: epidermolysis bullosa simplex, thermal injury, erythema multiforme, herpes gestationis

Destruction or damage to epidermal basement membrane:

Lamina lucida layer

Bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, linear IgA dermatosis, porphyria cutanea tarda, epidermolysis bullosa acquisita, epidermolysis bullosa letalis (junctional), herpes gestationis, suction blister, thermal injury

Sublamina densa layer

Cicatricial pemphigoid, linear IgA dermatosis, epidermolysis bullosa dystrophica, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus

Derma layer

Penicillamine-induced blisters

 

Blood blister

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Micro: subcorneal vesicular lesion with erythrocytes trapped beneath thick stratum corneum of toes or fingers

 

Bullous impetigo

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See also impetigo

Due to impetigo (Staphylococcus aurueus infection) and its exfoliative toxins A and B, which target desmoglein 1, a desmosomal adhesion molecule in upper epidermis

Usually indicates penicillin resistance

Gross: confluent pustules with honey-colored crusts

Gross/clinical images: image

Micro: cleavage plane is subcorneal or upper granular layer; roof of pusture is parakeratotic stratum corneum, floor is keratinocytes; variable acantholysis; pustule is filled with neutrophils and bacterial clusters are evident with Gram stain

 

Bullous pemphigoid

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Common subepidermal autoimmune disease affecting elderly

Immunoglobulin to bullous pemphigoid antigens 1 and 2 and C3; 25% have other antibodies

Gross: large tense blisters on flexor surfaces, trunk, intertriginous regions and mucosa; bullae don't rupture easily, and heal without scarring

Gross images: subepidermal nonacantholytic blister

Micro: subepidermal nonacantholytic unilocular blisters with festooning (“suspended in a loop between two points”) of dermal papillae, mild dermal infiltrate including eosinophils, no microabscesses

Micro images: #1#2#3

Positive stains: linear IgG and C3 antibodies to hemidesmosomes at lamina lucida of basement membrane (versus granular pattern for discoid lupus), occasional IgA and IgM; 70% have circulating antibodies that bind to basement membrane of normal skin or mucous membranes

DD: dermatitis herpetiformis

References: more information

 

Cicatricial pemphigoid

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Also called benign mucous membrane pemphigoid

Affects mucosa of mouth and eyes; lesions heal with scarring; may cause blindness

Due to circulating autoantibodies against basement membrane proteins

Gross images: erosions on oral mucosa of palate

Micro: similar to bullous pemphigoid

Positive stains: linear IgG and C3 antibodies to basement membrane

References: more information

 

Darier’s disease

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Also called keratosis follicularis

Uncommon

Usually back, also chest, axillae and neck; may involve hairless skin and oral mucosa

Gross: symmetrical distribution of red-brown keratotic papules; may be unilateral or localized; may be verrucoid if lesions are close together

Micro: suprabasal clefts contain dyskeratotic, basophilic cells with large nuclei and a paranuclear halo; called grains if present in stratum corneum and corps ronds if present in granular layer; also prominent irregular acanthosis and papillomatosis; may have prominent upper dermis infiltrates of lymphocytes

Micro images: grains, corps ronds; various images

DD: warty dyskeratoma (isolated follicular lesion)

 

Dermatitis herpetiformis

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Rare, bilateral and symmetric, small, intensely pruritic papules and vesicles on elbows, knees, buttocks, posterial nuchal area

Ages 20-39 years; more common in males

Associated with celiac disease because of antibodies to gliadin, a gluten protein

Associated with HLA B8 and DR3; have anti-endomysium antibodies

May be due to IgA antibodies to gliadin in gut which cross-react with or are deposited in dermal papillae of skin

Treatment: gluten free diet, sulfapyridine

Gross: “herpetiform” because vesicles are small (pinhead sized) and grouped symmetrically, as with herpes; may appear as erosions due to intense scratching

Gross images: lesions on knee

Micro: subepidermal multilocular blister with papillary neutrophilic microabscesses that may contain eosinophils, basal cell vacuolization; reticular dermis has sparse neutrophilic infiltrate

Micro images: subepidermal blister with microabscess #1; #2; IgA granular basement membrane staining with stippling in dermal papillae

Virtual slides: dermatitis herpetiformis

Positive stains: granular IgA pattern in dermal papillae by direct immunofluorescence; no circulating antibodies

DD: bullous pemphigoid

References: more information

 

Epidermolysis bullosa

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At least 12 genetic disorders with site of cleavage in dermis, lower epidermis or at dermoepidermal junction

Blisters form shortly after birth due to pressure, rubbing or trauma

Cause scarring or milia on dorsum of hands, elbows and knees and oromucosal lesions

Dystrophic types: blisters beneath lamina densa (associated with anchoring fibrils), cause scarring

Hallopeau-Siemens recessive dystrophic form associated with aggressive squamous cell carcinoma

Junctional: blisters at lamina lucida, skin appears normal

Simplex: degeneration of basal cell layer causes clinical bullae

Epidermolysis bullosa acquisita: rare autoimmune disorder of antibodies to hemi-desmosomes; rarely occurs following drug therapy, usually unkown cause

Gross images: junctional epidermolysis bullosa

Micro: subepidermal blister with variable inflammation; superficial dermis is fibrotic

Micro images; epidermolysis bullosa acquisita #1; #2; various images

Virtual slides: epidermolysis bullosa

Positive stains: linear C3 and IgG deposits along epidermal basement membrane

EM: may be necessary for classification

EM images: epidermolysis bullosa acquisita

References: more information

 

Epidermolytic hyperkeratosis

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Also called bullous congenital ichthyosiform erythroderma

Autosomal dominant disorder with ichthyosis, rows of confluent, verrucous and scaly papules in flexural areas arising shortly after birth and persisting

Micro: thickened granular layer with bizarre, distorted, basophilic keratohyaline granules (epidermolysis) and perinuclear clear spaces; stratum corneum is hyperkeratotic; also superficial lymphocytic infiltrate

Micro images: image #1

References: more information

 

Erythema multiforme

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Acute, self limited, hypersensitivity reaction to infections (herpes simplex, mycoplasma, histoplasmosis, coccidioidomycosis, typhoid, leprosy), drugs (penicillin, sulfa, salicylates, phenytoin, phenylbutazone), carcinoma / lymphoma, or collagen vascular disorders

Affects skin (distal extremities, palms, soles) and mucous membranes with target lesions; also sore throat and malaise

Any age

Gross: variable (multiform) lesions – papules, macules, vesicles, bullae, target lesions; commonly in mucous membranes

Gross images: target lesions #1; #2; #3

Micro: subepidermal bullae with basement membrane in bullae roof due to dermal edema; severe dermal inflammatory infiltrate (includes cytotoxic T cells) with nuclear dust; overlying epidermis often demonstrates liquefactive necrosis and degeneration, dyskeratotic keratinocytes; variable epidermal spongiosis and eosinophils

No microabscesses, no festooning of dermal papillae

Note: erythema multiforme may have variable histologic changes from toxic epidermal necrolysis to dermal disturbances; may also have dermoepidermal bullae with basal lamina at floor of bullae

Virtual slides: erythema multiforme

Positive stains: granular C3 and IgM at basement membrane and in vessels

References: more information

 

Erythema toxicum neonatorum

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Common, asymptomatic, transient, limited to neonates

Gross: erythematous pustular eruption

Gross images: red patches with raised clear central bumps

Micro: intraepidermal pustule filled with eosinophils, adjacent epidermis is spongiotic

 

Hailey-Hailey disease

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Also called benign familial pemphigus

Autosomal dominant

Crusts, vesicles and erosions in intertriginous regions

Micro: prominent suprabasal acantholysis, also acantholysis at all levels of epidermis, with upper keratinocytes held only loosely together; no/rare dysplastic keratoinocytes, no/rare inflammation

Micro images: suprabasal acantholysis

 

Impetigo contagiosa

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Also called bullous impetigo

Affects face, trunk and extremities of infants and children

Contagious superficial infection of skin, associated with staphylococci

Gross: small vesicles or pustules that rupture easily; may be covered by yellow crust

Micro: vesicles just below keratin layer

 

Pemphigus

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Rare, nonhereditary, chronic, autoimmune disease wtih flaccid blisters and denuded skin

Ages 30-59; no gender preference

Associated with internal malignancies, including thymoma

Variants: Vulgaris, Vegetans, Foliaceus, Erythematosus, Paraneoplastic

 

Vulgaris: 80% of all pemphigus; oral mucosa; also scalp, face, axilla, groin, trunk; numerous small, flaccid, suprabasilar bullae with single row of keratinocytes attached to basement membrane; prominent extension of acantholysis into follicular infundibula; ruptured bullae cause skin erosions; minimal dermal infiltrate; fatal if untreated because oral erosions impair swallowing

 

Vegetans: rare, verrucous plaques studded with pustules on groin, axilla and flexural surfaces; markedly acanthotic epidermis, resembling verruca; large intraepidermal microabscesses filled with eosinophils and occasional acantholytic keratinocytes

 

Foliaceus: endemic in Brazil (called fogo selvagem or “wild fire” in Portugese, Br J Dermatol 2006;155:446, Int J Dermatol 2005;44:293); crusts and shallow erosions on healthy appearing skin (often trunk) with blisters that form after rubbing (Nikolsky’s sign); typically spares mucous membranes; lesions may not appear bullous because crusts and erosions replace the bullae; mild clinically because only the granular cell layer is affected with a discrete acantholytic bullae containing rounded, acantholytic keratinocytes and few inflammatory cells; stratum corneum may be denuded; often eosinophilic spongiosis

 

Erythematosus: involves a localized area, like lupus malar rash on face; otherwise identical to pemphigus foliaceus

 

Paraneoplastic: associated with lymphoma, thymoma, squamous cell carcinoma; oral and cutaneous erosions and bullae; treat by treating the tumor

 

Serum antibodies react to epithelium in most cases

Case reports: 85 year old Mexican woman with plaques on trunk (Pathology Case of the Week #56, Dermatology Case of Month #3)

Treatment: corticosteroids or immunosuppressive agents

Gross/clinical images: crusted lesion of pemphigus vulgaris; pemphigus erythematosus

Micro: intraepidermal blister is just above basal layer and due to acantholysis from IgG against desmosomes and production of plasminogen activator; epithelial cells are rounded due to loss of desmosomes; often eosinophilic spongiosis

Micro images:

vulgaris - various images with antidesmoglein antibody

foliaceus - acantholytic granular cellslow power #1#2#3high powerC3;  IgGfishnet staining (antibody not designated)

Positive stains: necessary to confirm diagnosis - IgG against desmoglein 1 (usually) or 3 (desmosome components) or C3 are present in a fishnet-like pattern in intercellular squamous region; against IgA in IgA pemphigus

In paraneoplastic pemphigus, granular deposits of C3 are also present at basement membrane

DD of acantholysis: Darier's disease, familial benign pemphigus, Hailey-Hailey disease, viral vesicles, D-penicillamine related pemphigus like lesions, actinic keratosis and associated squamous cell carcinoma, warty dyskeratoma, transient acantholytic dermatosis; focal changes also associated with other tumors

 

Porphyria

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Noninflammatory blistering disorder

Disturbance of porphyrin metabolism (porphyrins are present in hemoglobin, myoglobin, cytochromes)

Urticaria and vesicles heal with scarring; exacerbated by sunlight

Types: congenital erythropoietic, acute intermittent, porphyria cutanea tarda, erythrohepatic protoporphyria, mixed

Porphyria cutanea tarda: dermal papillae protrude into bulla with festooned pattern; roof of blister has eosinophilic, PAS+, diastase resistant linear globules

Gross images: porphyria cutanea tarda #1; #2

Micro: subepidermal vesicle, marked thickening of superficial dermal vessels (may appear rigid), no/minimal inflammation

Micro images: intense IgG staining on dermal size of basement membrane and around dermal blood vessels

References: more information #1; #2; #3

 

Stevens-Johnson syndrome

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Systemic form of erythema multiforme with fever

Common in children, often involving lips, oral mucosa or other mucosa with erosions and hemorrhagic crusts

Infection of affected areas may cause life threatening sepsis

Toxic epidermal necrolysis: variant with full thickness epidermal necrosis but intact cornified layer, subepidermal bullae and sloughing of skin/mucosal epithelium; analogous to severe burn

Micro: full thickness epidermal necrosis with separation of epidermis from dermis; necrotic keratinocytes at edge of bullae

DD: staphylococcal scalded skin syndrome (similar clinically, but plane of cleavage is in granular layer), necrolytic migratory erythema (glucagonoma syndrome – has superficial epidermal necrosis)

References: more information #1; #2

 

Subcorneal pustular dermatosis

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Also called Sneddon-Wilkinson disease

Gross: large pustules on trunk and body folds

Micro: large unilocular subcorneal pustule containing neutrophils; may be psoriasiform; superficial dermis has neutrophils and lymphocytes

References: more information

 

 

Other dermatoses

Acanthosis nigricans

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80% are benign type, either autosomal dominant or associated with tissue resistance to insulin, including diabetes, obesity, Cushing’s disease

20% are associated with GI or other internal malignancies; usually age 40+ years

Gross: brown, velvety, verrucous plaques in axillae, back of neck and other skin folds

Gross images: axillary hyperpigmentation

Micro: orthokeratotic hyperkeratosis (not actually acanthosis) and papillomatosis of stratum spinosum; hyperpigmentation of basal cell layer, but no melanocytic hyperplasia

References: more information #1; #2

 

Acne rosacea

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Also called rhinophyma

Erythema of central face, with acneiform pustules and papules, telangiectasia, blepharitis

Micro: perinfundibular lymphocytic or granulomatous inflammation

Virtual slides: rhinophyma

References: more information #1; #2

 

Acne vulgaris

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Usually teenagers, either gender, although often more severe in males

Due to hormonal variations and alterations in hair follicle maturation

Worsens with drugs (steroids, testosterone, contraceptives), oils/tars, heavy clothing, tropical climates

Noninflammatory acne is due to open and closed comedones

Open comedones: small follicular papules with central black keratin plug (due to oxidation of melanin)

Closed comedones: follicular papules with a deeper plug below the surface

Follicles may rupture and become inflammed

Treatment: antibiotics, isotretinoin

Gross images: severe lesions

Micro: lipid (sebum) and keratin within hair follicle; variable lymphocytes and histiocytes

Virtual slides: acne

References: more information #1; #2; #3

 

Acute eczematous dermatitis

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Allergic contact dermatitis: see below

Atopic dermatitis: unknown cause (not allergic); may be familial (hay fever, asthma, eczema); occurs on flexural surfaces

Drug-related: usually systemic (penicillin), eosinophils present in deep dermis

Eczema: red, papulovesicular, oozing, crusted lesions (spongiotic dermatitis) which evolves to raised, scaling plaques (epidermal hyperplasia and excessive scale)

Irritant contact dermatitis: see below

Photo-dermatitis: due to UV light exposure

Primary irritant dermatitis: due to repeated rubbing

Gross images: atopic dermatitis #1; #2; #3

Micro: spongiosis, perivascular lymphocytic infiltrate

DD: drug reaction (prominent eosinophilic infiltrate)

References: more information on atopic dermatitis

 

Allergic contact dermatitis

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Due to topically applied antigens, such as poison ivy or nickel, which cause delayed hypersensitivity reaction with itching or burning

Dermatitis occurs at site of contact

Antigens initially taken up by Langerhans cells and carried to lymph nodes; upon reexposure, have cytokine release, causing endothelial activation and adherence of memory T cells, which release lymphokines, causing spongiotic dermatitis

May get bacterial superinfection (impetiginization)

Case reports: textile dyes

Gross/clinical images: hair dye

Micro: extensive spongiosis, initially acute spongiotic dermatitis, evolving into subacute or chronic spongiotic dermatitis, then resolves; may have intraepidermal vesicles, exocytosis, papillary dermal edema, perivascular lymphocytic infiltrates in upper dermis, numerous eosinophils

Micro images: with intraepidermal vesicle #1; #2; spongiosis

 

Alopecia

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Hair loss from head or body

Micro images: contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - folliculitis decalvans #1#2#3#4

 

Alopecia mucinosa

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Also called follicular mucinosis

Edematous and erythematous plaques of alopecia on head and neck

Children: benign, self-limited

Adults: associated with cutaneous T cell lymphoma; nodular or plaquelike lesion

Micro: follicular infundibulum keratinocytes and outer root sheath are separated by pools of mucin; variable lymphocytes within hair follicles and adjacent dermis, causing near complete loss of hair shaft, variable eosinophils

Micro images: mucin between follicular keratinocytes

Positive stains: mucin

References: more information

 

Alpha-1-antitrypsin deficiency panniculitis

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Associated with trauma

Extensor surfaces of arms, legs, thighs

Low serum alpha-1-antitrypsin, may have emphysema and cirrhosis

Gross: diffuse indurated erythematous plaques that drain serosangineous fluid

Micro: early-diffuse neutrophilic infiltrate through dermis into subcutaneous septa; next-destruction of collagen, reduction of inflammatory cells, lobules of fat are detached from fibrous septa floating in neutrophils; draining lesions have channels lined by squamous epithelium; late-extensive scarring of dermis and subcutis

DD: bacterial cellulitis

 

Amyloidosis

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In primary localized cutaneous amyloidosis, by definition, there is no systemic or other dermatologic disorder

May be due to rubbing, scratching, scrubbing during bathing, which may displace discharged remnants of degenerated epidermal cells into the dermis

Either macular (Central/South America, India, Middle East), lichenoid (China), biphasic or nodular

Macular: moderately pruritic dark brown papules in reticulated or rippled pattern, symmetric over upper back and arms

Lichenoid: intensely pruritic, discrete, firm, hyperkeratotic plaques and papules of anterior shins and extensor forearms, with amyloid deposits in papillary dermis accompanied by hyperkeratosis, papillomatosis and epidermal hyperplasia

Biphasic: lichenoid and macular

Case reports: 27 year old man with hyperpigmented black patches on upper back and limbs (Archives 2005;129:697), 72 year old woman with 20 year history of easy eyelid bruising

Gross/micro images: figure 1: flat, dusky brown patch of upper back; 2: Sirius red+ amorphous material; 3: cytoplasm is MNB+

References: more information

 

Anetoderma

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Benign; focal loss of dermal elastic tissue, causing focal flaccid or saclike skin

Either idiopathic or secondary to various skin conditions, penicillamine, neonatal prematurity

Case reports: 14 year old boy (with micro images)

Gross: erythematous macules and urticarial plaques, progressing to flaccid, easily reduced papules; also fine, diffuse wrinkling

Gross images: back and flank

Micro: no abnormality on H&E; elastic stains show no/marked reduction in elastic fibers of reticular dermis; variable perivascular mixed inflammatory infiltrate

 

Annular elastolytic giant cell granuloma

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Also called O’Brien’s actinic granuloma or Miescher’s granuloma

May be a variant of granuloma annulare

Neck or dorsa of hands of heavily sun-exposed individuals

Gross: erythematous or brown annular infiltrate in face of elderly

Gross images: raised forehead lesion

Micro: giant cells with elastic fibers

 

Argyria

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Permanent discoloration of skin due to overuse of medicinal silver preparations

Causes pigmentation of basement membranes of eccrine sweat glands

References: more information

 

Arsenic

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Skin related problems are rare in US

Arsenic is well water contaminant, used in industrial, agricultural and medicinal substances

Risk factor for Bowen’s disease, squamous cell carcinoma, basal cell carcinoma and visceral tumors

Often causes hyperkeratotic lesions of skin called arsenical keratoses

Gross images: arsenic related skin lesions

Virtual slides: arsenical keratosis

References: more information

 

Behcet’s disease

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Aphthous ulcers of oral cavity and genitalia; pustular vasculitis

Micro: leukocytoclastic vasculitis and panniculitis; also superficial and deep perivascular infiltrates of lymphocytes and neutrophils; some vessels contain thrombi; also suppurative folliculitis, intraepidermal or subepidermal vesicles

References: more information #1; #2

 

Calciphylaxis

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Also called calcifying panniculitis or vascular calcification-cutaneous necrosis syndrome

Rare, life-threatening condition of progressive cutaneous necrosis due to small and medium sized vessel calcification; lesions are bilateral and symmetric, often lower extremity, with preservation of pulses

Due to primary, secondary or tertiary hyperparathyroidism and associated elevated calcium and phosphate levels, which exceed their solubility and deposit in vessels, causing progressive vascular compromise in skin and subcutaneous fat, and less often muscle

Mortality rate of up to 60%

Case reports: 69 year old woman with primary hyperparathyroidism due to parathyroid adenoma (Archives 2001;125:1351), 70 year old woman with end stage renal disease

Treatment: surgical removal of autonomous parathyroid gland (if due to primary hyperparathyroidism); also hyperbaric oxygen, antihistamines, corticosteroids

Gross images: necrosis resembling a burn injury #1; #2

Micro: involves intima and media of large and small blood vessels; deposits associated with thrombi

Micro images: A: marked calcification of small and intermediate sized arteries in subcutis; B: fibrous septal calcification in subcutis; fsee also above case report of 70 year old woman

DD: metastatic calcification (hyperparathyroidism or chronic renal failure), dystrophic calcinosis cutis (deposits in areas of previously abnormal skin), tumoral calcinosis (no known cause), idiopathic calcinosis of scrotum, subepidermal calcified nodule (childhood papule, small, fleshy, firm, on face)

References: more information

 

Chondrodermatitis nodularis chronica helicis

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Also called Winkler disease

Idiopathic, nonneoplastic ulcerative lesion of auricle

Usually men ages 40+; uncommon in women

Symptoms: appears spontaneously; unilateral, painful nodule

Treatment: wedge or cartilage excision; glucocorticoid injection

Gross: dome shaped nodule, 0.3 to 1.8 cm, with crusty scale covering central area of ulceration

Micro: central ulceration of epidermis with adjacent acanthosis, hyperkeratosis, parakeratosis and pseudoepitheliomatous hyperplasia; base of ulcer has granulation tissue that usually involves perichondrium and cartilage; no dermal adnexa at site of lesion; may have foci of fibrinoid necrosis; vascular proliferation may resemble a glomus tumor

DD: clinically resembles carcinoma

 

Chronic skin ulcer

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In ulcers that don’t heal, keratinocytes from margins fail to move over the wound bed, although they do proliferate normally

Gross/clinical images: chronic skin ulcer

Virtual slides: ulcer on amputation stump

 

Crohn’s disease – cutaneous manifestations

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Occur in 14-44% of patients with Crohn’s disease; includes pyoderma gangrenosum, erythema nodosum and so-called metastatic Crohn’s disease (non-necrotizing sarcoid-like granulomatous dermatitis)

Above are all associated with vascular injury, typically with prominent extravascular neutrophilic or histiocytic dermal infiltrate

No identifiable microbes in skin lesions

References: Hum Path 2003;34:1185

 

Cytophagic histiocytic panniculitis

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Spiking fever, erythematous subcutaneous skin nodules, anemia, leukopenia

A form of cutaneous T cell lymphoma

Micro: florid lobular panniculitis with large histiocytes containing fragmented white blood cells

 

Dermatomyositis

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Autoimmune inflammatory disease of skeletal muscle and skin

Usually women

Symmetric proximal muscle weakness and skin lesions

Affects face, dorsal hands and feet, particularly knuckles

15% have adenocarcinoma of stomach, breast, ovary, lung and colon, with remission of dermatomyositis following tumor resection

Polymyositis: similar muscle changes without skin changes

Treatment: steroids, tumor resection (if present)

Gross: poorly demarcated, scaly, erythematous patches; also heliotrope erythema of upper eyelids and extensor joint surfaces

Gross images: purple plaques on knees; scaly plaque on back

Micro: chronic nonspecific dermatitis or resembling systemic lupus erythematosus; often atrophic epidermis with prominent vacuolar interface change; sparse perivascular lymphocytic infiltrate with markedly increased dermal mucin; muscles show myositis with myofiber necrosis, fragmentation and phagocytosis; late myofiber atrophy, fibrosis and fatty change

Positive stains: C5-9 (by immunofluorescence)

Negative stains: IgG and IgM by immunofluorescence

References: more information #1; #2

 

Drug reaction

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May cause urticaria, erythema multiforme, erythema nodosum, folliculitis, pustules, purpura, hyperpigmentation, vasculitis

Procainamide may induce SLE-like disease

Anti-cancer drugs may cause acute necrotizing changes in sweat glands (neutrophilic eccrine hidradenitis or syringosquamous metaplasia)

Drug induced coma may cause necrosis of eccrine sweat coils and other adnexae, also epidermis

Other drugs include gold salts, thiazides, antimalarial drugs, color film developers, tetracycline, barbiturates, phenolphthalein

Sites: genitalia and face

Fixed drug reaction: repeated administration causes recurrence of red-brown patch in same location, variable bullae

Treatment: discontinue drug

Micro: eosinophils and marked vascular wall thickening; may cause granulomatous infiltrate; also vacuolar interface changes and often epidermotrophism of lymphocytes (exocytosis), dyskeratotic keratinocytes, parakeratosis with eosinophils and plasma cells in dermis

DD: lichen planus

 

Elastosis perforans

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Back of neck in teenage boys

Gross images: back of shoulder

Micro: clumps of coarse elastic fibers penetrate epidermis and cause focal epidermal hyperplasia

Positive stains: elastic stains (highlights elastic fibers)

DD: reactive perforating collagenosis, perforating folliculitis, Kyrle’s disease

References: more information #1; #2

 

Eosinophilic fasciitis

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Swelling, tenderness and stiffness of an extremity, often lower forearm

May be associated with carpal tunnel syndrome

Case reports: 76 year old woman

Micro: marked inflammation and thickening of deep fascia with variable eosinophils

Micro images: lymphoplasmacytic infiltrate of fascia and skeletal muscle

DD: scleroderma (no fascial involvement)

References: more information

 

Eosinophilic pustular folliculitis

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Also called Ofuji disease

Associated with HIV in US

Sudden onset of disseminated pustules on trunk

Micro: eosinophilic infiltration of hair follicle; follicular epithelium is spongiotic, adjacent dermis has lymphocytic and eosinophilic infiltrate

References: more information

 

Erythema elevatum diutinum

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May be related to granuloma faciale

Systemically ill patients or associated with HIV

Bilaterally symmetric erythematous or violaceous plaques or nodules, often over outer surface of joints

Case reports: 53 year old HIV+ man with 2 year history of nodules on extensor surfaces of extremities

Micro: leukocytoclastic vasculitis, progressing to fibrosis and onion skinning around vessels; extracellular lipid deposits may be present in late lesions; no/rare eosinophils

Micro images: small vessel vasculitis

DD: localized chronic fibrosing vasculitis (different clinical findings)

References: more information

 

Erythema nodosum

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Red, painful, subcutaneous lesions on anterior surface of legs that usually involute in days/weeks, leaving depressed pigmented lesions

No ulceration

Immune mediated, but precise mechanism is unknown

May be associated with streptococcus infection, tuberculosis, sarcoidosis, coccidioidomycosis, ulcerative colitis, Behcet’s disease, drug reactions or idiopathic

Micro: inflammatory infiltrate at junction of dermis and subcutis, extending along fibrous septa separating fat lobules and in dermal vessels; may be neutrophilic, lymphocytic, histiocytic or granulomatous (noncaseating or with occasional giant cells); variable vasculitis

Miescher’s radial granuloma: cluster of small histiocytes arranged around a central cleft

Micro images: perivascular infiltrate; inflammatory infiltrate extending along fibrous septa of adipose tissue

DD: nodular vasculitis or subacute nodular migratory panniculitis (usually septal), Weber-Christian disease associated panniculitis (usually lobular inflammation)

References: more information

 

Exfoliative dermatitis and erythroderma

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Total body erythema and scaling

Due to drug reaction, allergic contact dermatitis, psoriasis, pityriasis rubra pilaris, malignancy

Associated with dermatopathic lymphadenitis

Micro: nonspecific changes; may have lichenoid dermatitis

DD: Sezary’s syndrome / mycosis fungoides

References: more information #1; #2

 

Gangrene

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Dry gangrene: coagulation necrosis of extremity due to slowly developing vascular occlusion

Wet gangrene: infection and liquefaction of “dry gangrenous” tissue by saprophytic bacteria

Virtual slides: dry gangrene

 

Graft versus host disease

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Important cause of post-bone marrow transplant morbidity, usually 10-30 days after allogeneic bone marrow transplant

Due to immunocompetent donor lymphocytes reacting against recipient tissues, causing cutaneous and intestinal lesions

Prognosis is associated with amount of inflammation

Initially is pruritic, maculopapular skin rash, often on acral surfaces and pinnae

May progress to diffuse eruption on trunk and extremities with oral mucosal stomatitis and ulceration

Chronic GVHD: develops 100 days after transplant

Micro: early - basal layer vacuolization and necrosis, spongiosis, apoptosis, acantholysis, chronic inflammation of upper dermis with perivascular lymphocytic infiltrate and intraepidermal lymphocytes; late - diffuse fibrosis of dermis; resembles scleroderma or lichen planus; also IgM deposition at basement membrane

Micro images: contributed by Dr. Amy Lynn, Toledo, Ohio - image

Positive stains: IgM deposition (granular or linear) in basement membrane zone

References: more information

 

Granuloma annulare

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Usually dorsum of hands and legs, occasionally generalized

Self-limited, asymptomatic

Rarely associated with diabetes and disseminated

Pseudorheumatoid nodules: also called giant granuloma annulare; large, isolated, deep necrobiotic collagen granulomas in extremities or occupit of children, may be limited to penis; not associated with rheumatoid or rheumatic disease; may affect siblings

Gross: circinate or grouped clusters of pink nodules with slight central depressions

Gross images: granuloma annulare of leg; knee; various images

Micro: mid dermal necrobiotic collagen center surrounded by palisading histiocytes, as well as fibroblasts and lymphocytes; occasional foreign body giant cells, vasculitis, mucin; may need multiple sections to find necrobiotic collagen

Positives stains (histiocytes): vimentin, lysozyme

Negative stains (histiocytes): CD68, Ham56

EM: degenerated elastic fibers

DD: rheumatoid arthritis and rheumatic fever nodules (different clinical presentation), annular elastolytic giant cell granuloma

References: more information #1; #2; #3

 

Granuloma faciale

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Adults

Facial lesions resemble infected nevus, sarcoidosis, tumor; also on trunk

Case reports: 59 year old man, successfully treated with tacrolimus; 52 year old man with classic features

Gross: thickened purple patches, plaques or nodules

Micro: normal epidermis, dermal chronic inflammatory infiltrate below band of normal dermis; often mild to moderate eosinophilic vasculitis; diffuse dermal infiltrate of neutrophils; no atypia, no granulomas

Micro images: dermal chronic inflammatory infiltrate below band of normal dermis

DD: mycosis fungoides (has Pautrier microabscesses and atypical cells), arthropod bites (rare on face), localized chronic fibrosing vasculitis (similar but not classic microscopic findings), erythema elevatum diutinum

References: more information

 

Gyrate erythema

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Also called figurate erythema

Various eruptions including erythema annulare centrifugum, erythema gyratum repens, erythema chronicum migrans

Erythema annulare centrifugum: due to various infections

Erythema gyratum repens: associated with internal malignancy (PathologyOutlines Case of Week #71, Dermatology Case of Month #4)

Erythema chronicum migrans: occurs after a tick bite, may be associated with Lyme disease (see above)

Gross: multiple waves of curvilinear erythema

Micro: dense perivascular lymphocytic infiltrate of superficial dermis and possibly deep reticular dermis; lymphocytes are well demarcated and adjacent to vessels; variable epidermal spongiosis

References: eMedicine

 

Hemochromatosis

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Pigmentation of basement membranes of eccrine sweat glands

References: more information #1, #2

 

Ichthyosis

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Disorder of epidermal maturation; skin resembles fish scales

Associated with excessive keratin buildup due to desquamation defect, leading to retention of abnormally formed scale

Usually apparent at birth; in adults, is associated with malignancies

Ichthyosis vulgaris: common type

Lamellar ichthyosis: rare, inherited skin condition of newborn with shedding of plate-like layers of skin

X linked variant: deficiency in steroid sulfatase, which removes proadhesive cholesterol sulfate from intracellular spaces

Gross: skin resembles fish scales; rough scaly patches and plaques

Gross images: lamellar ichthyosis

Micro: increased stratum corneum with loss of normal basket weave pattern, little inflammation; loss of granular layer in ichthyosis vulgaris

Virtual slides: lamellar ichthyosis

References: X linked variant; lamellar ichthyosis; ichthyosis vulgaris; ichthyosis

 

Irritant contact dermatitis

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Due to contact with an irritant (soaps and detergents)

Unlike allergic contact dermatitis, prior sensitization is not required

Gross images: due to unknown irritant; due to garlic; due to toxic plants

Micro: similar to allergic contact dermatitis but no/rare eosinophils; may have superficial epidermal necrosis associated with intraepithelial neutrophils and scale crust

References: more information

 

Lichen nitidus

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Children with pinpoint, round, flesh-colored papules on trunk, genitalia, abdomen and forearms

Asymptomatic

Gross images: tiny papules #1; #2

Micro: epidermis with clawlike pattern of curvilinear fingerlike extensions and surrounding papillary dermal lymphocytic and histiocytic infiltrate; parakeratosis, variable dyskeratotic keratinocytes at dermoepidermal junction; minimal lichenoid change

Micro images: lichen nitidus

References: more information

 

Lichen planus

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Purple, pruritic, polygonal papules of unknown origin

Usually flexor arms and legs, glans penis and mucous membranes; may be confined to oral mucosa

Self limiting lasting 1-2 years, although longer for oral lesions; may have zone of hyperpigmentation after resolution

Wickham straie: white dots or lines within papules

Koebner phenomenon: new lesions at sites of trauma

Lichen planopilaris: primary site of involvement is epithelium of hair follicles, causing alopecia

Gross/clinical images: flexor upper extremity #1; #2

Micro: classic example of a lichenoid dermatitis; hyperkeratosis and acanthosis; prominent granular cell layer, sawtoothing of rete pegs, band like chronic inflammatory infiltrate (T cells and macrophages) that destroys the dermoepidermal junction; Civatte bodies (apoptotic basal cells, PAS+); artifactual cleft formation between epidermis and papillary dermis; occasional subepidermal bullae; no atypia

Micro images: various images

Micro images: contributed by Dr. Amy Lynn, Toledo, Ohio - image#1#2

Variants: bullous, pemphigoid, hypertrophic, atrophic, follicular

Virtual slides: lichen planus

Positive stains: immunoglobulins along dermoepidermal junction

DD: lichenoid dysplasia (atypia present), lichenoid dermatitis

 

Lichen sclerosus et atrophicus

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Usually upper trunk, neck, flexor wrist, anogenital region; often women near menopause

Associated with HLA DQ7 and autoimmune disorders, but cause unknown

Kraurosis: vulvar involvement

Balanitis xerotica obliterans: involvement of glans penis

Gross: atrophic, hypopigmented patches or plaques

Micro: orthokeratotic hyperkeratosis, epidermal atrophy, hydropic degeneration of basal layer, replacement of papillary dermis by edematous, hypocellular, faintly staining band with chronic inflammatory infiltrate; early lesions may have inflammation but no band; late lesions may have hyalinization

Micro images: lichen sclerosus et atrophicus

DD: localized scleroderma (morphea), keratoses

 

Lichen simplex chronicus

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Also called neurodermatitis

Due to chronic rubbing and scratching

Gross: thick, scaly plaques with erythema, well demarcated from surrounding skin; associated with excoriation, lichenification, crusting; raised nodules are called prurigo nodularis

Gross images: #1; #2; #3

Micro: irregular acanthosis, orthokeratosis and parakeratosis; dermal fibrosis, hyperplasia of small dermal nerve trunks within dermal scars; no/minimal spongiosis

Micro images: lichen simplex chronicus

References: more information

 

Lichen striatus

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Extremities of children

Small papules that expand over time to form bands or streaks, then disappear

Gross: linear, small, fleshy papules

Gross images: lichen striatus

Micro: spongiosis and vacuolar interface change; also acanthosis and parakeratosis; dermal lymphocytic infiltrate around superficial vessels and at dermoepidermal junction

Micro images: various images

 

Lichenoid dermatitis

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A histological pattern, not a distinct clinical entity

May present as a neoplasm

Due to drug eruption, actinic keratosis, lupus erythematosus, acute graft versus host disease, regressing melanoma, dermatofibroma

May be a delayed hypersensitivity reaction

Micro: dense, bandlike lymphocytic infiltrate in dermis that obscures dermoepidermal junction; cytoplasmic vacuolization of basal keratinocytes with brightly eosinophilic cytoplasm, nucleus becomes extruded to become round/oval eosinophilic bodies (colloid bodies); regenerated epithelium has disorderly basement membrane; may have large cell acanthoma or solar lentigo within the lesion

 

Lipogranulomatosis subcutanea of Rothmann and Makai

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No associated systemic symptoms

Micro: lipogranulomas of subcutis, but not in crops

DD: Weber-Christian disease (appears in crops; fever and malaise)

 

Lupus erythematosus

Chronic discoid lupus erythematosus

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Distinct entity from systemic lupus erythematosus (SLE), despite similar names

No systemic manifestations, although 1/3 with SLE have discoid type lesions

Common, usually women; may be exacerbated by sunlight

Lupus profundus: preferential lymphocytic infiltration of subcutaneous fat

Gross: sharply circumscribed erythematous, atrophic or hyperkeratotic, shiny and scaling plaques on face, neck, scalp, arms or trunk; plaques may have follicular keratotic plugs

Micro: follicular hyperkeratosis, epidermal atrophy and acanthosis with degeneration of basal layer, periadnexal lymphocytic infiltrate; may have flask-shaped plugs of stratum corneum filling follicular orifices; older lesions have thick and irregular basement membranes; usually reticular dermal mucin; rare plasma cells

Micro images: C3 granular staining

Positive stains: lupus band test - IgG, IgM, C5b-C9 (by direct immunofluorescence) in clinically involved skin as irregular band at dermoepidermal junction; IgG and IgM only in 50% in normal skin; also mucin stains (Alcian blue, colloidal iron)

DD: verrucous and hyperkeratotic chronic discoid lupus lesions on upper extremities resemble hypertrophic lichen planus or keratoacanthoma; polymorphous light eruption, chronic dermatitis, Jessner’s lymphocytic infiltrate of skin

 

Systemic lupus erythematosus (SLE)

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Due to anti-DNA antibodies

Usually women

Fatigue, fever, arthritis, erythematous bilateral butterfly (malar) rash of face, renal disease, lymphadenopathy, serositis

Exacerbated by sunlight

Discoid lupus-type lesions in 1/3

Gross images: malar rash of face

Micro: fibrinoid necrosis at dermoepidermal junction with liquefactive degeneration and atrophy of epidermis; more mucin deposition in reticular dermis than discoid lupus

Micro images: lupus erythematosus #1; #2 (bullous)

Positive stains: IgG, IgM, C5b-C9 (by direct immunofluorescence) in clinically involved skin as irregular band at dermoepidermal junction; IgG and IgM only in 50% in normal skin

DD: polymorphous light eruption, Jessner’s lymphocytic infiltration of skin

 

Malignant atrophic papulosis

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Also called Degos’ disease

Intimal proliferation of deep-seated arteriole causes infarct

Often only involves the skin

Gross images: malignant atrophic papulosis; various images

References: more information

 

Massive localized lymphedema in morbidly obese patients

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Huge masses affecting thigh, popliteal fossa, scrotum, suprapubic region, inguinal region and abdomen of morbidly obese patients

Duration 9 months to 8 years

Clinically resembles lipoma or recurrent cellulitis, but also suspicious for malignancy

May be due to obstruction of efferent lymphatics by prior surgery, massive abdominal pannus or hypothyroidism

Gross: nonencapsulated, poorly defined, mean 51 cm (range 38-75 cm), mean weight 6.8 kg (range 2-12 kg); overlying skin has marbled appearance resembling chronic lymphedema with induration and peau d’orange

Micro: fibrous bands intersect lobules of adipose tissue; lymphatic vascular ectasia, chronic inflammatory infiltrate, edema between collagen fibers, infarction and fat necrosis; no atypia

DD: sclerosing well differentiated liposarcoma (lipoblasts, atypical stromal cells, atypical adipocytes)

References: Hum Path 2000;31:1162, AJSP 1998;22:1277

 

Mastocytosis of skin

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Either urticaria pigmentosa, solitary mastocytoma, diffuse and erythrodermic cutaneous mastocytosis or telangiectasia macularis eruptiva perstans

 

Urticaria pigmentosa

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Most common form of mastocytosis of skin

Usually childhood onset of multiple brown macules

Darier’s sign: stroking skin releases histamine, causing hives

Dermatographism: dermal edema resembling hives due to stroking with pointed instrument

Systemic variant is malignant and involves liver, spleen, bone marrow, lymph nodes and occasionally peripheral blood (mast cell leukemia)

Gross images: urticaria pigmentosa; various images; dermatographism #1; #2

Micro: mast cells have distinct cytoplasmic boundaries, faintly granular cytoplasm, large pale nuclei; some cells are elongated and resemble fibroblasts, accumulate around dermal vessels; also dermal eosinophils

Positive stains: toluidine blue highlights metachromatic granules; chloroacetate esterase (Leder stain), tryptase, CD117, calretinin

Molecular: CD117 mutations in patients with mastocytosis

 

Metabolic abnormalities

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EM of axillary skin biopsy may be helpful to diagnose metabolic abnormalities, although results may be nonspecific (Hum Path 2001;32:649)

Case reports: skin biopsy to diagnosis adult polyglucosan body disease (Archives 2001;125:519)

Micro images: skin biopsy of adult polyglucosan body disease shows A: inclusions at periphery of apocrine gland, one that indents the nucleus; B: apocrine coil cross section has inclusion on each side of nucleus forming a bow tie; C: apocrine coil cross section with 3 inclusions in 1 cell, which resembles a myoepithelial cell

References: inborn errors of metabolism

 

Miliaria

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Obstruction of sweat gland ducts during high heat and humidity

Gross images: miliaria profunda (most severe form)

References: more information #1; #2; #3

 

Mucinoses of skin

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Includes pretibial myxema of hyperthyroidism, generalized myxedema of hypothyroidism, papillary mucinosis (lichen myxedematosus), myxoid cyst, cutaneous focal mucinosis, follicular mucinosis, Carney’s syndrome related myxoid nodules

Micro images: contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - #1#2#3

 

Myxedema

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Often in pretibial skin

Due to accumulation of mucopolysaccharides in dermis, similar to that in orbital tissues, caused by excess TSH secretion or hypothyroidism

Skin is thick, dry, waxy

Elephantiasis: extreme disease

Case reports: 75 year old woman with Grave’s disease

Gross: large nodular lesion in patients with thyrotoxicity or euthyroid

Micro: eccrine sweat glands contain aggregates of mucoprotein that separates collagen strands

Positive stains: mucicarmine, Hale’s colloidal iron, PAS+ diastase resistant

References: more information

 

Necrobiosis lipoidica

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Usually on legs of diabetic patients

Gross: atrophic, yellow depressed plaques

Gross images: #1; #2; #3

Micro: ill defined areas of disintegrating dermal collagen, surrounded by palisading lymphocytes and histiocytes, with thick walled vessels, usually in reticular dermis

Micro images: necrobiosis lipoidica #1; #2

Negative stains: lysozyme, mucin

DD: granuloma annulare (mucin+, lysozyme+, no association with diabetes), necrobiotic xanthogranuloma (head and neck of patients with paraproteinemia, not associated with diabetes)

References: more information

 

Necrobiotic xanthogranuloma

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Head, neck and trunk lesions similar to necrobiosis lipoidica, but associated with IgG paraproteinemia and not diabetes

Micro: associated with extracellular deposits of lipid, cholesterol clefts and foam cells, multinucleated histiocytes including Touton giant cells; often extends into subcutis

Micro images: necrobiotic xanthogranuloma #1; #2; various images

References: more information

 

Ochronosis

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Autosomal recessive disorder of increased urinary excretion of homogentisic acid (alkaptonuria), with deposition of “ochre-colored” pigment in collagen-rich regions (ochre: moderate orange-yellow)

Occurs in 50% with alkaptonuria

Due to disorder of homogentisic acid oxidase gene on #3q, intermediate component in metabolism of tyrosine and phenylalanine, causing accumulation of benzoquinone acetic acid, which binds to collagen irreversibly

Clinically black pigmentation of joints (arthritis with pigment deposition in cartilage and intervertebral disks), cardiovascular system (valvular calcifications and stenosis), kidney (black urine, pigmented stones) and skin (cutaneous pigmentation); also involvement of sclera of eye

Case reports: pigment in dura matter of brain (Archives 2001;125:961), ochronotic arthropathy

Gross images: blue-black skin and 2 case reports

References: more information

 

Pancreatic fat necrosis

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Associated with elevated serum amylase and lipase

Due to acute pancreatitis or pancreatic carcinoma

Lesions may be widespread, may drain chalky material

Micro: deeply basophilic lipocytes containing calcium salts, basophilic rings due to loss of nuclei, extracellular calcium deposits within fat lobules; variable granulomatous reaction at periphery

Micro images: contributed by Dr. Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - fat necrosis #1#2#3

 

Panniculitis

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Inflammation of subcutaneous fat affecting connective tissue septa separating lobules, usually in lower legs

Poorly defined, tender, erythematous nodules

Variable fever, malaise

Lesions are transient

Either septal (involve fibrous septa) or lobular (involving lipocyte lobules)

References: more information

 

Lobular panniculitis

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Due to nodular vasculitis (erythema induratum), subcutaneous fat necrosis of newborn (see below), pancreatic fat necrosis, lupus panniculitis, physicial and factitial panniculitis, other

 

Lupus panniculitis

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Also called lupus profundus

May develop in normal skin or preexisting skin lesion of patient with systemic or discoid lupus erythematosus

Case reports: 45 year old woman with plaques and nodules on lower extremities

Micro: in lupus-related skin lesions, see vacuolar interface change and lymphoid infiltrates in dermis; if no lupus-related skin lesions, see ghost cells due to loss of nuclei and basophilic material replacing cell membranes, causing basophilic sclerosis of lobules; dense lymphoplasmacytic infiltrates present in lobules and septa; variable dermal and septal mucin; becomes fibrotic with time

 

Physical and factitial panniculitis

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Due to blunt force, pinching, cold or injection of foreign substances for secondary gain

Diagnosis of exclusion

Micro: lobular neutrophils, variable focal fat necrosis; refractile material may be present if substances were injected

 

Septal panniculitis

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Due to erythema nodosum or alpha-1-antitrypsin deficiency

 

Pityriasis lichenoides chronica

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Presents with red-brown papules with wafer-like scale

Overlaps with pityriasis lichenoides et varioliformis acuta (below)

Case reports: 19 year old woman with 5 year history of guttate macules and yellow-pink papules on trunk and extremities

Gross images: pityriasis lichenoides chronica

Micro: similar to PLEVA (below), but less destructive; parakeratosis present in well-demarcated zones; vacuolar interface change and lymphocyte exocytosis less than PLEVA; similar wedge shaped pattern of dermal lymphocytic infiltrate

References: more information

 

Pityriasis lichenoides et Varioliformis Acuta

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Also called PLEVA, Mucha-Habermann disease

Overlaps with pityriasis lichenoides chronica

Sudden onset of crops of small, ulcerated papules on trunk

May heal with superficial scarring resembling variola (smallpox)

Gross images: PLEVA #1; #2

Micro: broad zone of full thickness epidermal necrosis with overlying parakeratosis and variable neutrophils; frequent marked lymphocytic exocytosis, spongiosis and red blood cell extravasation into epidermis; wedge shaped lymphocytic infiltrate with base along epidermis and point in reticular dermis; contains transformed lymphocytes

References: more information

 

Pityriasis rosea

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Initially a single large “herald” patch, then a generalized rash 1-2 weeks later, lasting 2-6 weeks

Self-limited, benign

Children, young adults

Gross images: lesions on chest; abdominal rash; herald patch #1; #2

Micro: subacute spongiotic dermatitis with papillary dermal microhemorrhage and discrete mounts of parakeratosis

DD: secondary syphilis (usually plasma cells in dermis)

References: more information #1; #2

 

Pityriasis rubra pilaris

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Rare

Elbows/knees or entire body

Usually adults > age 40 years

Treatment: Accutane

Case reports: 61 year old man

Gross: salmon-colored scaly patches surrounding normal skin

Gross images: red scaly patches of chest; entire body affected except trunk; left axilla; various images #1; #2

Micro: horizontal and vertical tiers of orthokeratosis and parakeratosis in stratum corneum; few dermal inflammatory cells

DD: psoriasis

References: more information #1; #2

 

Poikiloderma atrophicans vasculare

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Also called poikilodermatomyositis

Circumscribed violaceous erythema with associated telangiectasia, hypopigmentation and superficial atrophy

Sites: posterior shoulders, back, buttocks, V shaped area of the anterior neck and chest

Often a late finding in dermatomyositis

Also an unusual variant of myocosis fungoides (cutaneous T cell lymphoma)

Micro images: contributed by Dr. Asmaa Gaber Abdou, Menofiya University, Egypt - 30 year old woman with erythematous patches mainly on the trunk and limbs - #1#2#3#4

 

Polymorphous light eruption

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Erythematous papules and vesicles on face and other sun-exposed skin

Large plaques or diffuse erythema

Gross images: polymorphic light eruption on arm

Micro: superficial and deep perivascular lymphocytic infiltrate; may have vesicles with papillary dermal edema or spongiosis; no/minimal vacuolar interface change; no perifollicular inflammation

Micro images: polymorphous light eruption

DD: systemic lupus erythematosus

References: more information

 

Porokeratosis - skin nontumor chapter

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Micro images: contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - #1#2#3#4 

 

Prurigoform acanthosis

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A type of chronic spongiotic dermatitis

Due to sustained skin irritation, often from rubbing or scratching

Micro: marked epidermal hyperplasia, spongiosis may not be prominent

DD: cutaneous T cell lymphoma, hypertrophic actinic keratosis (atypia), early keratoacanthoma (atypia)

 

Pseudoxanthoma elasticum

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Genetic disorder with ocular, vascular and skin lesions due to mutations of ABCC/MRP6 gene at 16p13.1, coding for ATP-binding protein, causing degeneration of elastic fibers

Variable penetrance even within the same family

Autosomal dominant or recessive, usually women

Vessels: degenerative changes in arteries causing mineralization, occlusion or rupture

Eyes: angioid streaks in retina causing hemorrhage and visual loss

Skin: yellow streaks and plaques, particular in creases of axillae, groin, neck; appear before puberty

Case reports: 26 year old with sudden death while dancing due to intramyocardial arteriolar involvement (Hum Path 2000;31:1002), 51 year old man with plaques on arm

Micro: clumps of altered, basophilic elastic material with dystrophic calcification in mid/lower dermis

Micro images: various images

EM: fragmented and polymorphic elastic fibers in reticular dermis; fibers may contain finely disbursed mineral crystals; similar changes in carriers

References: more information #1; #2

 

Psoriasis

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Also called psoriasis vulgaris

Common, affects 1% of population, all ages

Chronic, bilaterally symmetric, nonpruritic lesion of elbows, knees, umbilicus, lower back, scalp, glans penis; may be generalized

Associated with arthritis, myopathy, enteropathy, spondylitic heart disease, AIDS

30% have nail discoloration and onycholysis

Cause unknown

Usually not biopsied unless atypical

Pustular psoriasis: rare; prominent small pustules in plaque; either localized (hands/feet) or generalized and life threatening with fever, leukocytosis, diffuse infections, secondary infections and electrolyte disturbances

Auspitz sign: bleeding when scale is lifted from the plaque

Koebner phenomenon: new lesions form at site of trauma

Parapsoriasis: similar morphologically but no pain or itching; small plaque variants are considered benign; large plaque variants and parapsoriasis variegata are consistered early stages of cutaneous T cell lymphoma

Treatment: photochemotherapy (psoralen) and ultraviolet A light (PUVA) – associated with increased risk of melanoma and squamous cell carcinoma

Gross: well demarcated erythematous plaques covered by fine, loosely adherent, silvery-white scales

Gross/clinical images: guttate psoriasis

Micro: parakeratosis but usually no hyperkeratosis, acanthosis with downward elongation of rete ridges (resembles a comb), thin/no granular cell layer, suprapapillary thinning (attenuated layer of epidermal cells above tips of dermal papillae), Munro microabscesses (neutrophils in parakeratotic scale); increased mitotic figures above basal layer; prominent dermal capillaries, mixed dermal infiltrate of lymphocytes, macrophages and neutrophils

Micro images: contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - #1#2#3#4 

DD: psoriasiform lesions - lichen simplex chronicus, florid seborrheic dermatitis, pityriasis rubra pilaris, mycosis fungoides, Reiter’s syndrome

References: pustular psoriasis

 

Pyoderma gangrenosum

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50% of cases are associated with inflammatory bowel disease, myeloma, leukemia, hepatitis

Usually extremities

Probably immune mediated

Also new ulcers in areas of trauma (pathergy)

Gross: usually deep seated lesions; early-necrotic pustule or furuncle, evolving to large necrotic ulcer with violaceous border and surrounding erythema

Gross images: ankle; lower leg; various images #1; #2; #3

Micro: hemorrhagic necrosis with abscess formation, evolving to marked lymphoplasmacytic infiltrate with marked epidermal hyperplasia at the edges

References: more information #1; #2; #3

 

Radiation associated

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May cause various benign vascular proliferations including benign lymphangiomatous papules (the lymphatic counterpart of telangiectases due to destruction/obstruction of lymphatic drainage), atypical vascular lesions mimicking benign lymphangioendothelioma, patch stage Kaposi’s sarcoma or well differentiated angiosarcoma (involves subcutaneous tissue, marked cytologic atypia, piling up of endothelial cells, Ki-67+)

Often women treated for breast cancer

Occurs 3-20 years after radiation

Case reports: 49 year old woman with external radiotherapy on chest wall for breast carcinoma and subsequent benign lymphangiomatous papules, angiomas and atypical vascular proliferation mimicking patch stage Kaposi’s sarcoma (AJSP 2002;26:1372)

Gross: papules, small vesicles or erythematous plaques on irradiated field

Micro: benign lymphangiomatous papules/plaques - superficial dermal involvement by irregularly dilated vascular spaces in branching and anastomosing pattern; vessels have thin walls and lymphatic appearance, with single layer of  discontinuous flattened endothelial cells; also numerous small stromal papillary formations lined by endothelial cells that project into lumina

atypical vascular proliferations mimicking benign lymphangioma or patch stage Kaposi’s sarcoma - poorly circumscribed and focally infiltrating, irregular jagged vascular spaces involving entire dermis; lined by inconspicuous endothelial cells; variable dissection of dermal collagen bundles

Positive stains: CD31

Negative stains: CD34, smooth muscle actin

References: AJSP 2002;26:328

 

Rheumatoid / rheumatic nodules

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Associated with adult and juvenile rheumatoid arthritis and rheumatic fever

Usually subcutis, but also skin of extensor aspects of elbow and other joints

Large, may be painful

Gross images: rheumatoid nodules of fingers

Micro: extensive homogeneous necrobiosis with numerous giant cells and stromal fibrosis

Micro images: rheumatoid nodule-subcutis #1; #2

Virtual slides: rheumatoid nodule

 

Scleredema of Buschke

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Nonpitting, woody induration of upper back skin

Associated with diabetes

Case reports: 72 year old man with diabetes associated disease

Micro: normal collagen but prominent clear spaces in reticular dermis due to mucin; minimal inflammation

Micro images: left-H&E; right-colloidal iron

References: more information #1; #2; persistent scleredema of obesity (49 cases)

 

Scleroderma

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Either localized (morphea) or systemic (involving skin of face, upper trunk, hands and arms, esophagus, heart and lungs)

Usually adults, cause unknown

May have visceral disease without skin disease

May be associated with Raynaud’s phenomenon, Borrelia burgdorferi infection

Micro: increase in normal appearing collagen; often in papillary dermis, extends to eccrine sweat glands; epidermis is often atrophic; mild dermal perivascular and periadnexal inflammatory infiltrate, particularly