epidermal nevi, neoplasms and cysts – part 1 epidermal nevi, neoplasms and cysts – part 1
TRANSCRIPT
Epidermal Nevi, Neoplasms and Cysts – Part 1
JoAnne M. LaRow, D.O.
March 23, 2004
Keratinizing Epidermal Nevi
• Aka hard nevus of Unna
• Soft epidermal nevus
• Nevus verrucosus (verrucous nevus)
• Nevus unius lateris
• Linear epidermal nevus
• Systematized nevi
• Ichthyosis hystrix
Keratinizing Epidermal Nevi
• Hyperkeratosis without cellular atypia characteristic of all
• Nevus cells do not occur
Linear Verrucous Epidermal Nevus
• Not pruritic, onset birth or before age 10.• Verrucous papules, pink, gray or brown.• Horny excrescences, comedos may be interspersed.• Bilateral = Icthyosis hystrix• Extensive = “systematized”(linear hyperkeratotic
papules & plaques-often showing a parallel arrangement);unilateral or bilateral (often symmetrical)
• Extensive + CNS abnormalities = Syndrome
Linear Verrucous Epidermal Nevus
• Histology: hyperkeratosis, acanthosis, & papillomatosis (60% of the time)
• 16% show epidermolytic hyperkeratosis
• Rare malignancies have been reported:trichoepithelioma, keratoacanthoma, & verruciform xanthoma
Linear Verrucous Epidermal Nevus
• Note shedding of scale within several lesions
Linear Verrucous Epidermal Nevus
• 62% variable hyperkeratosis, acanthosis and papillomatosis
• Rarely trichoepithelioma, KA, verruciform xanthoma
• Etiology possibly chromosomal mosaicism
• Tx: Phenol, 5-FU, Tretinoin, Shave excision, Cryotherapy, CO2 laser.
• Linear erythematous scaly plaque with a psoriasform appearance on leg
• Acanthotic epidermis with zones of parakeratosis devoid of a granular layer alternating with zones of orthohyperkeratosis
ILVEN
• Inflammatory Linear Verrucous Epidermal Nevus.
• Pruritic, usually on female extremity.• Onset usually childhood, can be 40’s, 50’s• Chronic, resistant to topical or IL treatments• Psoriasiform histo – linear psoriasis?• Tx: Deep shave excision, dermabrasion,
Protopic?
ILVEN
• Believed to be a type of epidermal nevus• Familial patterns reported & sporadic mosaic
forms exist• May be associated with CHILD syndrome
(congential hemidysplasia with ichthyosiform erythroderma & limb defects)
• Differs from LEN by presence of erythema & pruritus clinically & histologically by inflammation & parakeratosis
LVEN
Blaschko’s lines
• Albert Blaschko
• 1901
• Do not follow nerves, lymphatics or vessels.
• Proposed embryologic origin
LVEN following Blaschko’s lines
ILVEN
Epidermal Nevus Syndrome
ENS – 5 Syndrome types
• Schimmelpenning – sebaceous nevus, cerebral anomalies, coloboma, lipdermoid conjunctiva
• Nevus Comedonicus - cataracts• Pigmented hairy EN – Becker nevus, ipsilateral
breast hypoplasia, scoliosis• Proteus –Hyperplasia of hands and feet,
hemangiomas, lipomas, macrocephaly, hyperostosis, hypertrophy of long bones
• CHILD – Congenital Hemidysplasia, Icthyosiform erythroderma, Limb Defects
Nevoid Hyperkeratosis of the Nipple
Nevoid Hyperkeratosis of the Nipple
• Extremely rare, usu. females, any race• Isolated finding, unassociated with other conditions• Unilateral NHN Should be distinguished from breast
carcinoma via biopsy, in addition, mammography may be warranted.
• Bx results identical to seb. K.• Course varies, unpredictable.• Tx: Keratolytics such as Lactic Acid 12%, Salicylic
acid Gel 6%, topical corticosteroids; oral retinoids are ineffective
Nevus Comedonicus
• Closely arranged slightly elevated papules, with keratin plugs resembling comedos.
• Hamartomas of pilosebaceous unit-resulting in dilated, keratin-filled pores
• Rarely pruritic; usually asymptomatic • Onset usually before age 10, but variable• Most common site is face, then trunk• Tx: difficult;localized lesions:excise; manual extraction,
dermabrasion, keratolytics(helpful); ammonium lactate applied every 2 weeks has been helpful to remove keratin plugs
Nevus Comedonicus
Nevus Comedonicus
Clear Cell Acanthoma
• AKA Degos Acanthoma or Acanthome cellules claires of Degos and Civatte
• Usually solitary lesion on leg• Blanchable, erythematous, discrete papule or
plaque; may have attached ‘wafer-like’ scale at periphery
• 1-2 cm, shin, calf, thigh, asymptomatic, slow growing
• SCC has been reported• Tx: EDC, Shave biopsy, Excision, Cryo
Clear Cell Acanthoma
• A: erythematous papule on lower extremity;note peripheral scale & erosion in superior portion
• B:psoriasiform epidermis contains large pale keratinocytes
Seborrheic Keratosis• Onset 4th-5th decade• Chest and back most common• Only on hair-bearing areas• Etiology: Local arrest of maturation of keratinocytes.• At least 6 different types of histologic types:
acanthotic, hyperkeratotic, reticulated, clonal, irritated, & melanoacanthoma
• Borst Jadhasson phenomenon may occur, this is normal.
• Sign of Leser Trelat
Seborrheic Keratosis
Sign of Leser Trelat
• Sudden appearance of numerous itchy SK’s
• Pathogenesis? Neoplasm may secrete growth factor leading to epithelial hyperplasia
• Validity controversial
• 60% Adenocarcinoma of Stomach
• Lymphoma, Breast CA, Lung SCC.
• For sign to be valid SK’s must parallel the course of the cancer, ie, resolve with removal of cancer.
Borst-Jadhasson Phenomenon
• Descrete groups or ‘clones’ of basaloid, squamatized, or pale keratinocytes in epidermis appear different than their neighbors
• This can be benign or malignant
• Mainly seen with irritated seborrheic keratosis, Bowen’s dx, & rarely with hidroacanthoma simplex ( a form of eccrine poroma limited to epidermis)
Borst-Jadhasson Phenomenon
• Clonal variant
• “Nested”
• Diagnosis is still SK
• R/O porocarcinoma via neg. CEA stain.
• R/O Bowen’s via lack of atypical cells
Inverted Follicular Keratosis
Inverted Follicular Keratosis
• Bengin lesion of middle-aged & older adults
• Typically solitary; most commonly on face & neck
• Asymptomatic, firm, white-tan to pink papule
• Histologically, endophytic growth pattern with squamous eddies & inflammation
Inverted Follicular Keratosis
• Irritated SK?
• 2-10mm papules
• Flesh colored
• Firm w/ central scaling
• Sharply marginated
• Squamous Eddies
• Tx: shave
• An endophytic proliferation of keratinocytes with prominent squamous eddies
Dermatosis Papulosa Nigra
• Multiple hyperpigmented sessile to filiform papules
• Most common in individuals of African descent with darkly pigmented skin
• Found almost exclusively on face ( malar & forehead areas)
• Histologic features similar to acanthotic SKs
Dermatosis Papulosa Nigra
• Familial predisposition• Variant of SK? Delayed presentation of nevoid
condition like patterned lentiginoses? Variant of acrochordon?
• Irregular Acanthosis and heavy deposits of pigment at the basal layer.
• Tx: Light electrodessication with curettage, cryo( may produce hypopigmentation), snip excision or curettage without electrodesiccation
Dermatosis Papulosa Nigra
Stucco Keratosis
• AKA Keratoelastoidosis verrucosa or keratosis alba
• Males >40 years old.• “Stuck on” appearance• Lower legs near Achilles tendon• Easily scratched off• Histo: Hyperkeratotic SK• Tx: Lac Hydrin 12%, Emollients or topical
retinoids
Stucco Keratosis
Multiple Minute Digitate Hyperkeratosis
• AKA Spiny keratoderma• 3 types-AD, sporadic type, and postinflammtory• All characterized by multiple minute keratotic
papules unassociated with follicular orifices• A spiked projection occurs at top of papule• No associated abnormalities• 6 families described• Post-inflammatory variant usually result of
irradiation therapy.
Multiple Minute Digitate Hyperkeratosis
Hyperkeratosis Lenticularis Perstans (Flegel’s Disease)
• Very rare, possibly AD disorder• Multiple keratotic papules with disc-like appearance is
symmetric distribution• Usually expressed mid-to-late adulthood-cases as young
as 13 yrs reported• Individual papules are small-1-5mm; larger
lesions>5mm often have collarette of scale& bleed when scale removed
• Most common on dorsum of feet, legs, palms & soles too• Flegel’s dx has been associated with endocrine disorders
(DM & hyperthyroidism)
Flegel’s Disease
• Etiology unknown• Absent or altered keratinocyte membrane-
coating granules (Odland bodies) on microscopic exam
• Lipid-by-products within Odland bodies felt to influence stratum corneum desquamation, & if absnt or abnormal hyperkeratosis may occur
Hyperkeratosis Lenticularis Perstans (Flegel’s Disease)
Hyperkeratosis Lenticularis Perstans (Flegel’s Disease)
Flegel’s Disease
• Pathology: discrete compact hyperkeratotic mound, contrasting with normal basket-weave cornified layer of normal epidermis
• Focal parakeratosis & hypogranulosis
• Thin atropic stratum spinosum often sharply indented or depressed at lateral margin
• Band-like infiltrate or lymphocytes present in papillary dermis along with dilated blood vessels
• A.multiple symmetric keratotic papules on shins
• B. spinous layer is maredly thinned, & there is a lichenoid infiltrate & obvious hyperkeratosis
HK & PK overlying a thinned epidermis, irreg. acanthosis at
periphery, band-like infilt.
Warty Dyskeratoma
• Solitary skin-colored to red-brown papule or nodule with a central pore containing a keratotic plug
• Usually located on head: face, neck, scalp.
• Relatively uncommon, without a genetic predisposition
• No malignant degeneration has been reported
• Histology is characteristic…
Keratotic Plug, Cup-like Invagination
• A portion of cup-shaped lesion is seen. The central keratotic plug is seen on left.
• Lower portion of cup is occupied by numerous villi with acantholytic epithelium
Corps ronds and grains
Benign Lichenoid Keratosis
• Solitary papules
• Dusky red/violaceous
• Women, photodist.
• Forearms, hands, chest
• Tx: LN
Lichenoid Keratosis• Aka: lichen planus-like-keratosis, solitary lichen
planus, solitary lichenoid keratosis
• Solitary, usually asymptomatic, lesion
• Most commonly on upper chest or forearms
• Represents an inflammatory stage of solar lentigo, actinic keratosis, or seborrheic keratosis
• Histologically, appears almost identical to lichen planus
Colloid or Civatte bodies in BLK
• LP-like
• Parakeratosis
• Lichenoid Infiltrate
• DIF + IgM @ DEJ
• Plasmas, Eos, Lymphs
• Histo mimics MF, LP
Arsenical Keratoses• Precancerous papules seen most often on palms & soles• Present as symmetric, punctate, yellow, corn-like
papules 2-10 mm • Common areas are thenar & hypothenar eminences,
distal plams, lateral fingers & dorsal interphalangeal joints
• Weight-bearing plantar surfaces on feet• Persistent lesions may coalesce into kertotic plaques• SCC may arise, often producing pain, bleeding,
fissuring, or ulceration
Arsenical Keratosis
• Arsenic is ubiquitous elemental metal• Exists in nature as metalloids, alloys, and chemical
compounds• Deposited into water, soil, & vegetation• Pesticides, rodentcides, herbicides• Dessicants, feed additives• Pressure treated lumber – shipbuilders, carpenters• American cigarette tobacco in 1960’s(mostly from use
of arsenic-containing insecticides)• Chinese proprietary medicines
• A. guttate hypopigmentation superimposed on hyperpigmentaion resembles ‘raindrops on a dusty road’
• B. arsenical keratoses on plantar surface
Actinic Keratosis
• Multiple, discreet, flat or elevated, verrucous or keratotic, red, pigmented or skin colored usually with adherent scale but sometimes smooth
• Photodistributed, 3-10mm
• Hypertrophic AK may become cutaneous horn, and SCC may be present at the base.
Actinic Keratosis
• 0.25% to 20% risk of nonmelanoma CA
• P53 mutation present in SCC and AK usu.
• Be most suspicious of AK’s on lip, temple and hand as higher risk metastasis if SCC.
• Risk of SCC metastasis is related to thickness, so palpate “AK’s” before deciding whether to destroy vs biopsy.
Actinic Keratosis
• Risk factors other than UV:
• Tanning beds
• X-rays
• Polycyclic aromatic hydrocarbons
• Arsenic exposure
• Thermal injuries, Scars, HPV
• Organ transplants, BCC/SCC ratio flips
Actinic Keratoses
• Tx: varied• Cryo with liquid nitrogen most effective & practical with
limited number of sites• Repetitive superficial freezes (3 cycles) very effective &
minimizes scarring• Healing usually occurs within 1 week on face & up to 4
weeks on arms & legs• 5-fluorouracil topically for extensive, broad or numerous
lesions• Fluoroplex crm or solution, 1%, or Efudex, 2% recommended
for face; 5% Efudex crm for trunk, scalp, hands, arms, neck
Actinic Keratosis
• Rub 5-FU gently BID for 3-4 weeks on head & neck, 4-6 weeks for other areas, or until there is a severe inflammatory rxn
• 1% solution is effective on lips• Use extreme care around eyes & mouth• Individual sensitivity differs:burning rxn will
occur within several days• Stop tx when peak response occurs-characterized
by color change from bright to dusky red, by re-epithelialization, & crust formation
Actinic Keratosis
• Another tx cycle for –FU is 4 times daily for 7-21 days
• Shorter cycle may result in better compliance?• Topical application of a 20% solution of
aminolevulinic acid to lesions followed by exposure to a red light source (580-740 nm) (photodyna,ic therapy)
• Dermabrasion for severe ak’s useful on hairless scalp
• Chemical peels, CO2 laser
Cutaneous Horn
• Face, scalp, hands, penis, eyelid
• Horny excresences, skin colored
• Diagnosis at the base varies, often benign
• 55% SK, VV, Angioma, Tricholemmoma
• 25% AK
• 20% SCC or BCC
• More malignancy in elderly, fair skin
Cutaneous Horn
Leukoplakia
• Whitish thickening of mucosal epithelium• Glistening, opalescent, may be reticulated or
pigmented• Attempts to remove it cause bleeding• Common sites: floor of mouth, lateral & ventral
surfaces of tongue, soft palate• May arise on genitalia, anus• Seen mainly in males over age of 40• Non-homogeneous lesions & those of tongue & floor
of mouth have higher rate of malignant transformation
• Sharply demarcated, white plaque involving ventral surface of tongue & floor of mouth
Leukoplakia• Bx reveals orthokeratosis or parakeratosis with
minimal inflammation or varying degrees of dysplasia • Benign form usually occurs from chronic irritation;
very little chance of conversion to dysplasia• Premalignant features seen in only 10-20%• Dysplasia is clinically impossible to predict• Changes may be more or less hyperemia &
tenderness-with bleeding tendency• Most commonly has a chronic course in which
malignant transformation follows 1-20 year lag time.
Leukoplakia
• Vulvar often mistaken for LS&A; mainly in obese women after menopause
• Penile more often Erythroplasia of Queyrat• Risks: UV, Biter, Smoker, esp. pipe• Oral Hairy Leukoplakia (white, corrugated
plaques occurring primarily on sides of tongue)in pt with AIDS - virally induced lesion
Leukoplakia Treatments
• If dysplastic complete removal is the goal.• Cryo, CO2 Laser, surgical excision.• In actinic cheilitis + leukoplakia of tongue
exposed surface of lip may be removed & replaced by sliding forward mocosa from inner aspect of lip
• Cryotherapy is effective or Isotretinoin 1 to 2mg/kg/day for 3 months or 5-FU
Leukoplakia with Tylosis and Esophageal Carcinoma
• Extremely rare, AD• PPK age 5-15• Howell-Evans Synd.• 38x risk esoph ca• TOC gene 17q25• H-E Synd 17q23• Variable oral
leukokeratosis and follicular keratosis
White Sponge Nevus
• Spongy overgrowth of mucosa• Most common on buccal, but can be vaginal or rectal• No extramucosal lesions; no tx• Progression stops at puberty-usually• AD mut of K4, K13• Tetracycline is helpful• EM show aggregated tonofilaments.• Histo: Acanthosis, vacuolated prickle cells and
acidophilic condensations in cytoplasm.
White Sponge Nevus
Oral Florid Papillomatosis
• Distinctive “Cauliflower” white mass• Covering tongue & adjacent mucosa• Slow growing, fungating, no lymphadenop.• Expect eventual epidermoid carcinoma in most pts• Well differentiated SCC- mets rare, late• Progressive, may become SCC• AKA Verrucous Carcinoma• TX: Surgical Excision; however often recurs &
spreads; recombinant-alpha 2a interferon + CO2 laser has been used
Oral Florid Papillomatosis
Elastotic Nodules of Antihelix
• Bilateral semi-translucent nodules • Exclusively upper antihelix location• “Orange peel” surface appearance• Histo: HK, basal cell proliferation, collagen
replaced by amorphous elastotic material.• Frequently mistaken for BCC.• Sun damage suspected as etiology.• Tx: removal via shave excision & fulguration of
base
Elastotic Nodules of Antihelix
Keratoacanthoma
• 4 types
• Solitary
• Multiple
• Eruptive
• KA Centrifugum Marginatum
Solitary KA
• Type of KA rapidly growing papule enlarging from 1mm to as large as 25 mm in 3-8 weeks
• Fully developed is dome-shaped, skin-colored nodule with a smooth crater filled with central keratin plug
• Smooth shiny lesion is sharply demarcated from its surroundings
• Telangiectases may run through it
Solitary KA
Multiple KA
• Ferguson-Smith type of multiple self-healing keratoacanthomas
• Histologically & clinically identical to solitary type • Most common on face, 3-10 lesions localized to 1 site
usu. young men• Familial type-Ferguson-Smith type of self-healing
squamous epithelioma • Key is pruritis leading to erroneous dx of pruritus
nodularis
Multiple KA
Eruptive KA• Eruption of dome-shaped, skin-colored papules from 2-7
mm in diameter• Eruption is generalized but spares palms & soles• Oral mucous membranes can be involved • Immunosuppression is key• SLE, Leukemia, Leprosy, Kidney transplant,
photochemotherapy, thermal burn, radiation therapy have all been associated.
• Lesions may be in linear array• Pruritis sometimes associated, plus bilateral ectropin &
narrowing of oral aperture
Eruptive KA – Generalized, esp. shoulders and arms, but palms and soles are spared
Eruptive KA – oral lesions, bilateral ectropion and narrowing of oral aperture
KA Centrifugum Marginatum
• 16 cases (uncommon variant)
• Peripheral expansion with central healing leaving atrophy
• Dorsum hands, pre-tibial
• No tendency for spontaneous resolution (unlike giant solitary KA’s no tendency for spontaneous involution)
KA Centrifugum Marginatum
KA Centrifugum Marginatum
KA-Etiology
• ? Variant of regressing SCC
• Conditions known to promote progression of AK’s & malignant degeneration of premalignant lesions also promote expression & development of KA’s (sun exposure, tar therapy, & immunosuppressed states)
• Inflammatory cells in KA’s mostly are CD4+ T lymphoctes activated by interleukin 2 adhesion molecules-like inflammatory cells in SCC’s
• KA-note keratin-filled crater
KA- Treatment• Can spontaneously involute, but impossible to tell how long it will
take.• Grade I SCC cannot be excluded even with a bx-biopsy excision or
ED&C of an ordinary lesion < 2cm can & should be done –safest course
• 5-FU solution straight from ampule & intralesional (0.5- 1 ml of 25 mg/ml methotrexate)
• IM methotrexate (25 mg/week)• IL Bleomycin (1mg/mL, dil. w/ Xylocaine)-clearing occurred
within 20 days of tx• Recommend excision if involution is not complete after 3 weeks of
topical tx• Mohs’ sx for facial lesions
KA-tx
• Podophyllum in compound tincture of benzoin useful in giant keratoacanthomas
• Oral retinoids are therapeutic & helpful in large or recalcitrant lesions
• Eruptive forms tend to be very resistant to tx-good results achieved with oral & topical retinoids & cyclophosphamide
• Radiation tx on giant KA’s• Intralesional IFN-alpha-1 report of regression of 5
of 6 large (>2cm) KA’s (Grob et al)