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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.
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 disease, pemphigoid gestationis, pemphigus, 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
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
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)
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
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
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
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
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
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
Also called subcutis
Contains lobules of mature adipose tissue and thin connective tissue septa
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)
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
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
Virtual slides: abscess (furuncle)
“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
Bacterial images: bacteria; in cerebrospinal fluid (inhalation anthrax)
EM images: anthrax spores
References: slide show; Centers for Disease Control
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
Painful localized bacterial infection of skin and subcutis, usually with several openings through which pus is discharged
Virtual slides: carbuncle
Gross/clinical images: punched out ulcers in immunocompromised patient
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)
Streptococcal infection causing upper dermal edema and “orange peel” or peau d’orange appearance
Virtual slides: erysipelas
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
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-Candida
Micro images: Candida #1; #2; #3; culture
Fungi-Chromoblastomycosis
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
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
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
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
Spread of fungi to nails
Caused by Candida albicans, Scopulariopis brevicaulis, others; often multiple fungal species
Gross/clinical images: toenail infection
Fungi-Prototheca
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
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
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
Case reports: 22 year old man with ALL and post-chemotherapy disseminated fungal infection (Univ Pittsburgh)
References: more information and images
Fungi-Zygomycosis
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
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
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
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
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
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
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
Also called Hansen’s disease
Most US cases from immigrants
Diagnosis: PCR
Micro images: various images;
Lepromatous leprosy
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
Micro: bacilli are scanty; granulomas in and around cutaneous nerves or infiltrating and destroying arrectores pilorum muscle
Virtual slides: tuberculoid leprosy
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)
Rare; may occur in HIV+ patients
Micro: histiocytes have Michaelis-Gutmann bodies, rarely contain gram negative organisms
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
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)
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
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 images; immunostains 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
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
References: Archives 2004;128:1173, smallpox and mimics
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)
Cutaneous disease uncommon in US
Lupus vulgaris
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
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
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
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
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
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
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
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
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
On soles of feet; painful; covered by callus
Micro: invaginated with numerous coarse, basophilic, intracytoplasmic keratohyalin granules resembling molluscum bodies
Verruca vulgaris
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
Skin lesions due to direct irritant effects, immediate or delayed hypersensitivity or specific effects of venom
Bites: urticaria, inflammed papules or nodules, variable ulceration
Causes hyperpigmentation and scratch marks (excoriations)
Gross images: body louse #1; #2;
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
Bite causes extensive necrosis
Gross images: brown recluse spider and US quarter; brown recluse spider bite #1; #2
Mites are commonly present in inflamed follicles, but are usually nonpathogenic
Common in dogs
Causes pruritis, enlarged local lymph nodes
Eggs are attached to hair shaft (nits)
Gross images: various images; nit #1; #2; #3
References: more information
A sexually transmitted disease
Gross images: pubic louse
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
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
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)
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
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)
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
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
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
Micro: subcorneal vesicular lesion with erythrocytes trapped beneath thick stratum corneum of toes or fingers
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
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
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
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
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)
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
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
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
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
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
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
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
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 cells; low power #1; #2; #3; high power; C3; IgG; fishnet 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Permanent discoloration of skin due to overuse of medicinal silver preparations
Causes pigmentation of basement membranes of eccrine sweat glands
References: more information
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Pigmentation of basement membranes of eccrine sweat glands
References: more information #1, #2
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
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
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
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
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
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
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
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
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
No associated systemic symptoms
Micro: lipogranulomas of subcutis, but not in crops
DD: Weber-Christian disease (appears in crops; fever and malaise)
Chronic discoid lupus erythematosus
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)
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
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
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
Either urticaria pigmentosa, solitary mastocytoma, diffuse and erythrodermic cutaneous mastocytosis or telangiectasia macularis eruptiva perstans
Urticaria pigmentosa
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
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)
References: inborn errors of metabolism
Obstruction of sweat gland ducts during high heat and humidity
Gross images: miliaria profunda (most severe form)
References: more information #1; #2; #3
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
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
Usually on legs of diabetic patients
Gross: atrophic, yellow depressed plaques
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
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
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
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
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
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
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
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
Due to erythema nodosum or alpha-1-antitrypsin deficiency
Pityriasis lichenoides chronica
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
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)
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
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
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
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
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
Micro images: contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain - #1; #2; #3; #4
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)
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
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
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
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
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
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)
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