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Epidermal Nevi, Neoplasms and Cysts – Part 1 Epidermal Nevi, Neoplasms and Cysts – Part 1

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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)…
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  1. Epidermal Nevi, Neoplasms and Cysts – Part 1 JoAnne M. LaRow, D.O. March 23, 2004
  2. 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
  3. Keratinizing Epidermal Nevi
    • Hyperkeratosis without cellular atypia characteristic of all
    • Nevus cells do not occur
  4. 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
  5. 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
  6. Linear Verrucous Epidermal Nevus
    • Note shedding of scale within several lesions
  7. 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
  8. 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?
  9. 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
  10. LVEN
  11. Blaschko’s lines
    • Albert Blaschko
    • 1901
    • Do not follow nerves, lymphatics or vessels.
    • Proposed embryologic origin
  12. LVEN following Blaschko’s lines
  13. ILVEN
  14. Epidermal Nevus Syndrome
  15. 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 – C ongenital H emidysplasia, I cthyosiform erythroderma, L imb D efects
  16. Nevoid Hyperkeratosis of the Nipple
  17. 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
  18. 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
  19. Nevus Comedonicus
  20. Nevus Comedonicus
  21. 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
  22. Clear Cell Acanthoma
    • A: erythematous papule on lower extremity;note peripheral scale & erosion in superior portion
    • B:psoriasiform epidermis contains large pale keratinocytes
  23. Seborrheic Keratosis
    • Onset 4 th -5 th 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
  24. Seborrheic Keratosis
  25. 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.
  26. 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)
  27. 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
  28. Inverted Follicular Keratosis
  29. 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
  30. 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
  31. 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
  32. 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
  33. Dermatosis Papulosa Nigra
  34. 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
  35. Stucco Keratosis
  36. 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.
  37. Multiple Minute Digitate Hyperkeratosis
  38.  
  39.  
  40.  
  41. 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)
  42. 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
  43. Hyperkeratosis Lenticularis Perstans (Flegel’s Disease)
  44. Hyperkeratosis Lenticularis Perstans (Flegel’s Disease)
  45. 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
  46. HK & PK overlying a thinned epidermis, irreg. acanthosis at periphery, band-like infilt.
  47. 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…
  48. 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
  49. Corps ronds and grains
  50. Benign Lichenoid Keratosis
    • Solitary papules
    • Dusky red/violaceous
    • Women, photodist.
    • Forearms, hands, chest
    • Tx: LN
  51. 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
  52. Colloid or Civatte bodies in BLK
    • LP-like
    • Parakeratosis
    • Lichenoid Infiltrate
    • DIF + IgM @ DEJ
    • Plasmas, Eos, Lymphs
    • Histo mimics MF, LP
  53. 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
  54. 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
  55.  
    • A. guttate hypopigmentation superimposed on hyperpigmentaion resembles ‘raindrops on a dusty road’
    • B. arsenical keratoses on plantar surface
  56.  
  57. 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.
  58. 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.
  59. 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
  60. 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
  61. 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
  62. 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
  63. 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
  64. Cutaneous Horn
  65. 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
  66. 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.
  67. 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
  68. 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
  69.  
  70. 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
  71. 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.
  72. White Sponge Nevus
  73. 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
  74. Oral Florid Papillomatosis
  75. 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
  76. Elastotic Nodules of Antihelix
  77. Keratoacanthoma
    • 4 types
    • Solitary
    • Multiple
    • Eruptive
    • KA Centrifugum Marginatum
  78. 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
  79. Solitary KA
  80. 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
  81. Multiple KA
  82. 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
  83. Eruptive KA – Generalized, esp. shoulders and arms, but palms and soles are spared
  84. Eruptive KA – oral lesions, bilateral ectropion and narrowing of oral aperture
  85. 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)
  86. KA Centrifugum Marginatum
  87. KA Centrifugum Marginatum
  88. 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
  89. 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
  90. 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)

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