Benign and Premalignant Skin Lesions.31

7/28/2019 Benign and Premalignant Skin Lesions.31

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CME

Benign and Premalignant Skin LesionsErica H. Lee, M.D.

Kishwer S. Nehal, M.D.

Joseph J. Disa, M.D.New York, N.Y.

Learning Objectives: After reading this article, the participant should be able to:1. Clinically describe various cutaneous neoplasms. 2. Identify the corresponding

histopathologic findings. 3. Discuss the optimal treatment approach for each entity.Summary: Cutaneous neoplasms are broadly viewed as benign, premalignant, ormalignant. In dermatology, lesions are classified based on the primary cell of originor the component of the skin predominantly affected by the pathologic change(epidermis, dermis, or subcutaneous fat). The diagnosis and treatment of skinlesions rely on understanding the clinical presentation and corresponding histo-pathology. Surgical treatment is not always indicated and is dependent on multiple

variables. This review discusses several benign and premalignant neoplasms fre-quently encountered by the plastic surgeon. The emphasis is on clinical presen-tation, histopathologic correlation, and management approach. (Plast. Reconstr.Surg. 125: 188e, 2010.)

Benign and premalignant skin lesions are com-monly encountered by dermatologists andplastic surgeons for diagnosis and manage-

ment. Based on their origin in the skin, these lesionsare classified into categories such as epidermal,melanocytic, follicular, and dermal. Histologic eval-uation illustrates the predominant location of thelesion in the epidermis or dermis and provides in-sight into its evolution and natural progression. Thisclinical-pathologic correlation provides vital infor-mation and significantly influences management

and treatment.There are numerous cutaneous neoplasms;

however, some of the most common benign andpremalignant lesions are presented in this review.Classic clinical presentation, key histopathologiccomponents, and treatment options are discussed.The arsenal of treatment modalities is vast andranges from simple techniques to excisional andlaser surgery. A thorough understanding of the clin-ical and histologic presentation can guide the phy-sician in selecting the most appropriate treatmentapproach.

ACTINIC KERATOSESActinic keratoses, or solar keratoses, are epi-

dermal neoplasms that develop in response to pro-longed exposure to ultraviolet radiation. They typ-

ically present in older, fair-skinned individuals aserythematous scaly areas (Fig. 1). Other variantsinclude the thicker, hypertrophic actinic keratosesand pigmented actinic keratoses. These precan-cerous lesions may develop into squamous cellcarcinoma and are predictors of future squamousand basal cell carcinoma development.1

An actinic keratosis may regress spontaneously,persist, or transform into an invasive squamous cellcarcinoma. The progression to squamous cell car-cinoma is estimated at 10 percent.2 Due to the in-

ability to predict transformation, treatment is oftenadvocated. All modalities yield similar success ratesbut vary in terms of treatment duration and degreeof inflammation.

Cryotherapy is widely used and ideal for spottreatment in any location, without the need for an-esthesia or hemostasis (see Video 1, which demon-strates cryotherapy of actinic keratoses on the dorsalhand treated with liquid nitrogen dispensed from ahandheld apparatus, available in the Related Vid-eos section of the full-text article on www.PRSJour-nal.com). Liquidnitrogen (195.8C boilingpoint)

From the Dermatology Service and the Plastic and Recon-structive Surgery Service, Memorial Sloan-Kettering CancerCenter.Received for publication December 2, 2008; accepted April 1,2009.Copyright 2010 by the American Society of Plastic Surgeons

DOI: 10.1097/PRS.0b013e3181d6e89a

Disclosure: The authors have no financial interestto declare in relation to the content of this article.

Related Video content is available for this ar-ticle. The videos can be found under the Re-lated Videos section of the full-text article.

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is dispensed from a handheld apparatus with a spraytip. The duration and number of each freeze-thawcycle determine the level of destruction and subse-quent erythema and bulla formation.

Topical treatment with 5-fluorouracil (Carac orEfudex) specifically targets actinic damage while

sparing normal skin, causing erythema and erosionslasting 3 to 6 weeks. Imiquimod (Aldara), a newerFood and Drug Administrationapproved topicalagent, induces the skins immune system and mayresult in less inflammation. Both are good alterna-tives to cryotherapy when diffuse actinic damage ispresent.3 Diclofenac sodium 3% gel (Solaraze) is atopical nonsteroidal anti-inflammatory agent withantineoplastic effects that is used for mild actinicdamage.4 Superficialglycolicpeels andmedium-depthpeels, such as trichloroacetic acid and Jessners solu-tion, are useful for diffuse actinic damage5,6 and offer

the additional advantage of treating related signs ofphotodamage, such as lentigines and fine rhytids.

Photodynamic therapy is a newer treatment op-tion for diffuse actinic keratoses with the advantageof minimal recovery time. 5-Aminolevulinic acid , atopical photosensitizer, is applied as a 20% solution(Levulan Kerastick) after the area is cleansed anddegreased with acetone. Incubation for 1 to 3 hoursis followed by exposure to theblue light, long-pulsedpulsed dye laser or intense-pulse light for severalminutes (see Video 2, which demonstrates photo-dynamic therapy, available in the Related Videos

section of the full-text article on www.PRSJournal.com; the treatment area is prepared with acetonefollowed by application of the 5-aminolevulinic acid;

Fig.1. Actinickeratosesclassicallypresentaspinkscalymacules

(above). On histopathologic analysis (below), there are atypical,

pleomorphickeratinocytesinthebasalcelllayeroftheepidermis

(arrows) with overlying hyperkeratosis (*). Underlying inflamma-

tion may be present in the dermis. Hematoxylin and eosin stain;

original magnification, 20.

Video 1. Video demonstrates cryotherapy of actinic keratoses

on the dorsal hand treated with liquid nitrogen dispensed from

ahandheldapparatus,availableintheRelatedVideossectionof

the full-text article on www.PRSJournal.com.

Video 2. Video demonstrates photodynamic therapy of the

face. The treatment area is prepared with acetone followed by

applicationof the 5-aminolevulinicacid. Afterthe incubationpe-

riod, the treatment area is exposed to blue light for approxi-

mately16 minutes. This video is availablein theRelatedVideos

section of the full-text article on www.PRSJournal.com.

Volume 125, Number 5 Benign and Premalignant Skin Lesions

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after the incubation period, the treatment area isexposed to blue light for approximately 16minutes).7,8 Mild erythema and edema similar to asunburn can last a few days. Ablative lasers, such asthe carbon dioxide and erbium:yttrium-aluminum-garnet, are good options for actinic keratoses of the

mucosal lip (actinic cheilitis).

DERMATOFIBROMADermatofibroma is a benign fibrohistiocytic tu-

mor of the skin with a predilection for the lowerextremities of women. It typically presents as aslightly raised to dome-shaped papule ranging incolor from pink to light brown to dark brown (Fig.2). If the lesion is pinched, puckering of the over-lying skin,or the dimplesign, occurs. Inthesolitarypresentation, minor trauma is implicated, whereasthe eruptive form is associated with immunosuppres-sion, autoimmune diseases, and atopic dermatitis.9

Dermatofibromas are largely asymptomatic andwith time may undergo partial regression. If there isno clinical suspicion to prompt removal, it is best toavoid treatment. If necessary, surgical excision withnarrow margins is preferred. Cryotherapy is an op-tion, but results vary and multiple treatments may berequired. Successful treatment with the 600-nmpulsed dye laser has been reported. A recent reportshows that three treatmentsimprove color andsymp-toms and, in 75 percent, led to complete resolutionof the lesion.10

DYSPLASTIC/ATYPICAL NEVUSDysplastic melanocytic nevi present as clinical

variants of melanocytic nevi with irregular appear-ance in terms of border, symmetry, color, and size(Fig. 3). They occur sporadically or in the setting ofa personal or family history of melanoma or atypicalmoles termed familial atypical multiple mole mela-noma syndrome (FAMMM). Dysplastic melanocyticnevi are considered an important risk factor for mel-anoma; however, the majority are stable with lowtransformation rates to melanoma.11,12

Management of dysplastic melanocytic nevi isinfluenced by the number and character of back-ground lesions, personal and family history of mel-anoma, and history of new or changing lesions.In patients with multiple dysplastic melanocyticnevi, skin self-examinations, interval completeskin examinations with a dermatologist, totalbody photography, and dermoscopy can aid insurveillance and early detection of changing le-sions (see Video 3, which demonstrates total bodyphotography, available in the Related Videos sec-tion of the full-text article on www.PRSJournal.com;total body photography and dermoscopy are usefultools to follow and detect changing nevi; saucerizedexcision of a pigmented lesion is performed follow-ing administration of local anesthesia).13 Change inpigmented lesions is a significant feature in earlyevolving melanomas and is a key component of theABCDE acronym for melanoma screening.14,15

Fig. 2. A dermatofibroma on the lower extremity (left) is histologically characterized by a hyperplastic

epidermis(*) overlyinga dermal proliferation of spindled-shaped fibroblasts(right; inset). Hematoxylinand

eosin stain; original magnification, 2; inset, 10.

Plastic and Reconstructive Surgery May 2010

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For clinically suspicious lesions, removal with a2-mm margin is recommended. A full-thickness ex-cision, saucerized removal, or punch biopsy is fa-

vored over a partial biopsy to minimize sampling

error. After infiltration of local anesthesia, a no. 15blade at an angle almost parallel to the skin surfacecan beusedto shave or saucerize thelesion andleavea shallow defect. Subtle angulation of the bladechanges the depth, affecting whether the upper pap-illary or the deeper reticular dermis is removed. Ina punch biopsy, the diameter of the metal barrel ofthe punch instrument (ranging from 2 to 6 mm) ischosen to encompass a narrow margin around thelesion, and the defect is typically sutured to reap-proximate the defect. If on histologic evaluationthere is severe melanocytic atypia, recommendedmargins for reexcision vary from 2 to 5 mm.16

HALO NEVUSA halo nevus is a pigmented melanocytic nevus

surrounded by a ring of hypopigmentation or de-pigmentation (Fig. 4). One or multiple lesions canbe present, and the torso is a common location.The pathogenesis is unclear; however, a cell-mediated

immune response is suspected to be involved in thenevus destruction.17 The natural progression is vari-able, with the central nevus persisting indefinitely orinvoluting over time. Because the majority of lesionsoccur before age 20, the onset of multiple lesions inadults older than 40 may signal an occult or remotemelanoma, and a comprehensive skin and ocular ex-amination is warranted. A halo phenomenonmayalsooccur around congenital melanocytic neviandregress-ing melanoma.

Removal or observation of a halo nevus dependson the clinical setting. Atypical features of the central

nevus, an asymmetric halo, presence of severalatypical

Fig. 3. Multipledysplastic nevi(above) are characterized by asym-

metry, borderirregularity,andcolorvariegation(center).TheABCDE

acronymalsoincludes diametergreaterthan6mmand evolutionor

change. Histopathologic analysis (below) shows elongated rete

ridges(arrows)andincreasedmelanocytesinaconfluentmannerat

thebasal layer of the epidermis (*). Cytologicatypia of themelano-

cytes is typically present and is designated as mild, moderate, or

severe. Hematoxylin and eosin stain; original magnification, 20.

Video 3. Video demonstrates total body photography. Total

body photography and dermoscopy are useful tools to follow

and detect changing nevi. Saucerized excision of a pigmented

lesionis performed following administration of local anesthesia.

Physician in video, Dr. Ashfaq Marghoob, Memorial Sloan-Ket-

tering Cancer Center. This video is available in the Related Vid-eos section of the full-text article on www.PRSJournal.com.


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nevi,or a history of melanoma raises suspicion,andthelesion should be excised for histologic examination.Nevi that appear benign do not require removal.

KERATOACANTHOMAKeratoacanthoma is an epithelial neoplasm of

sun-exposed skin. Classically, a solitary papule rap-idly increases in size to become a crater-like nod-ule with a central keratotic core (Fig. 5). The lesionmay spontaneously involute over months. Keratoac-anthoma is considered by many to be a variant of

squamous cell carcinoma.18 Chronic ultraviolet ra-diation, chemical carcinogens, trauma, human pap-illomavirus, and genetic factors are implicated in itspathogenesis.19 The giant keratoacanthoma anderuptive types have also been described.

The treatment modality selection depends onthe lesion size, location, and patient comorbidi-

ties. Standard excision with a narrow margin al-lows for histologic evaluation; however, recurrencesat the scar margin can occur. Mohs micrographicsurgery is preferred for recurrences or areas withlimited tissue laxity.20,21

Fig. 4. A classic halo nevus (left) with a dense infiltrate of lymphocytes and histiocytes (*) obscuring nests of

nevus cells in the dermis (right). Hematoxylin and eosin stain; original magnification, 10.

Fig. 5. A classic clinical presentation of a keratoacanthoma (left). On histopathologic analysis, a cup-shaped lesion (solid line) with

well-differentiated, glassy-appearing keratinocytes surrounds a large keratin-filled core (right). There is minimal cytologic atypia.

Hematoxylin and eosin stain; original magnification, 2.


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Oral retinoids may be considered for eruptiveor multiple keratoacanthoma.22 Radiotherapy isalso an option but risks poor wound healing ifencountered on the lower extremity. Intralesionaltreatment with 5-fluorouracil and methotrexate isa tissue-conserving, inexpensive, and noninvasive

procedure. Approximately one to four injectionsspaced at an average of 18 days apart can lead tocomplete resolution. The literature does not sup-port significant adverse effects.23

NEVUS SEBACEUSNevus sebaceus is a congenitalepidermalhamar-

toma of sebaceous glands that typically presents as alinear yellowish plaque on the scalp or face (Fig. 6).At birth the lesion is flat, but becomes raised andverrucous during puberty. The development of sec-

ondary adnexal neoplasms, most commonly benignbut also malignant, is well established.24 The risk ofa basal cell carcinoma was initially believed to behigh; however, the evidence nowshows an incidenceof less than 1 percent.25,26

Historically, prophylacticexcision was advocatedto prevent the development of basal cell carcinoma.Excision is now recommended when secondary neo-plasms are present or for cosmetic removal. A con-servative excision with 2- to 3-mm margins to theadipose or galea is usually adequate. On the scalp,

the lack of tissue laxity is a challenge, and in largelesions, sequential excisions may be performed.Avoiding absorbable sutures around hair folliclesand limiting them to the galea may prevent inflam-mation and subsequent alopecia.27 Shave excisionand ablation with the carbon dioxide laser28 are

other options but are not very successful.

PILAR CYSTPilar or trichilemmal cyst is a common scalp

lesion originating from the outer root sheath of thehair shaft. Clinically difficult to distinguish from anepidermoid cyst, it presents as one or multiple le-sions (Fig. 7). A proliferating pilar cyst or tumorpresents as a slow-growing scalp nodule varying froma few millimeters to over 20 cm in size. Malignantchanges, aggressive local growth, and nodal metas-

tasis have been reported in proliferatingpilar cysts ortumors.

In a noninflamed pilar cyst, a small incision fol-lowed by tissue dissection, rather than an ellipticalexcision, successfully removes the cyst without rup-ture. For a benign proliferating pilar cyst or tumor,a simple excision can be performed; however, localrecurrence is common. If the lesion has features ofmalignant transformation, a wide local excision,nodal evaluation, and other workup may be neces-sary on a case-by-case basis.29

Fig.6. Nevussebaceusonthescalp(left)withepidermalhyperplasiaandpapillomatosis(arrows) on

histopathologicanalysis(right).Inthedermis,thereareenlargedsebaceous(**)andapocrineglands

(*). Hematoxylin and eosin stain; original magnification, 4.


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SEBORRHEIC KERATOSES

Seborrheic keratoses are common lesions ofthe epidermis presenting as well-demarcated pap-ules or plaques (Fig. 8, above). Seborrheic kerato-ses vary from a light brown to waxy brown-black,develop a verrucous surface with follicular prom-inence, and appear stuck on. A familial predis-position and sunlight are suggested risk factors.

Requests for removal are often for cosmeticreasons or due to irritation. Curettage is mostfrequently used (Fig. 8, below).A3-to6-mmcuretteis chosen based on the lesion size (see Video 4,which demonstrates curettage, available in the

Related Videos section of the full-text article onwww.PRSJournal.com; a seborrheic keratosis isanesthetized with local anesthesia and removed bycurettage). An advantage of this technique is min-imal scarring. A disadvantage is that the removedlesion is fragmented and may not be optimal ifhistopathologic evaluation is required.

Smaller lesions may be treated with light elec-trodessication using a monoterminal apparatus orcryotherapy with liquid nitrogen in a single freeze-thaw cycle. Melanocytes are easily destroyed at tem-peratures of4 to7C30; therefore, in darkly pig-

mentedindividualspermanent hypopigmentation iscommon and should be avoided. A superficial shaveremoval may be indicated for larger lesions.

SOLAR LENTIGOA solar lentigo is an oval or irregularly shaped

brown macule on sun-exposed skin (Fig. 9). Solarlentigines are regarded as the first signs of pho-toaging, affecting more than 90 percent of Cau-casians 50 years of age and older.31 These can bedifficult to distinguish clinically from other pig-

mented lesions, including lentigo maligna and ac-

tinic keratoses; however, histopathology and stainssuch as Melan-A aid in their differentiation.32

Treatment is divided intodestructive andtopical

therapy. A single freeze-thaw cycle with cryotherapy

Fig. 7. A pilar cyst on the vertex of the scalp.

Fig. 8. A seborrheic keratosis along the jawline (above). Histo-

logic analysis showed epidermal acanthosis (arrow) and hyper-

keratosis (*) (center). Invaginations of the epidermis createhorned pseudocysts (**), a characteristic feature of this lesion.

Curettage is an effective treatment modality to remove sebor-

rheic keratoses. Thecuretteis placedat thebaseand thelesion is

removedinasmooth,firmmotion(right).Ifremnantsremain,the

process is repeated. Hematoxylin and eosin stain; original mag-

nification, 10.


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is simple; however, central hypopigmentation withperipheral hyperpigmentation may occur in darkerskin types. Lasers selectively target and destroy mel-anin due to its broad absorption spectrum (351 to1064 nm) and are a preferred method of treatmentin lighter skin types (see Video 5, which demon-strateslaser treatment of solar lentigines, available intheRelated Videos sectionof thefull-text articleonwww.PRSJournal.com; the 595-nm pulsed dye laserwithout cryogen spray cooling and the compressionmethod are utilized to treat solar lentigines). TheQ-switched ruby (694 nm) laser delivers excellentresults with no scarring or recurrence after 6 to 8weeks in a single treatment.33 There is mild post-

treatment hypopigmentation with the alexandritelaser (755 nm), and transient pigmentary and tex-tural changes with the frequency-doubled neodymi-um:yttrium-aluminum-garnet laser (532 nm).34 Theintense pulsed light, a broadband visible light, resultsin no hyperpigmentation or scarring in Asians.35

Hydroquinoneandtretinoin arethe most widelyused topical therapies. Other agents used as mono-therapy or in combination are mequinol (4-hydroxy-anisole) and azelaic acid.34 Double-blind random-ized controlled trials show the combination of 2%mequinol and 0.01% tretinoin is superior when

Fig. 9. Multiple solar lentigines on the forehead (left). There is increased basal layer pigmentation, rete

ridge elongation (arrows), and variable melanocytic proliferation (right). Solar elastosis is present in the

dermis (*). Hematoxylin and eosin stain; original magnification, 20.

Video4. Videodemonstratingcurettage.Aseborrheickeratosis

is anesthetized with local anesthesia and removed by curettage.

This video is available in the Related Videos section of the full-

text article on www.PRSJournal.com.

Video 5. Video demonstrating laser treatment of solar lentigi-

nes. The595-nm pulsed dyelaserwithoutcryogen spray cooling

andthecompressionmethodareutilizedtotreatsolarlentigines.

This video is available in the Related Videos section of the full-

text article on www.PRSJournal.com.


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compared with its active components separately orthe vehicle. Common side effects are erythema andburning.36 Topical therapy is not ideal for multiplelesions, as compliance with daily application is difficultand several weeks are required for clinical results.

Chemical peels improve irregular pigmentation

and also treat solar lentigines. Superficial peels, suchas glycolic acid, an alpha hydroxyl acid, penetrateinto the epidermis and have minimal downtime butrequire repeated treatments at regular intervals. Me-dium-depth and deep peels, such as trichloroaceticacid and phenol, penetrate and produce necrosis atthe level of the papillary or reticular dermis. Theserequire a minimum of 1 to 2 weeks for healing andcarry a higher risk of scarring, infection, and postin-flammatory hyperpigmentation. Forty percent tri-chloroacetic acid with 70% glycolic acid or 30% tri-chloroacetic acid alone improves the appearance of

lentigines with a low risk profile of pigmentary andtextural changes in skin types I to III.37 A more in-depth review is highly recommended before its ini-tial use.

SPITZ NEVUSSpitz nevus commonly presents as a homoge-

nous, dome-shaped reddish or dark brown papule(Fig. 10). Spitz nevus is common in children andrare in older adults. The majority occur on thehead and neck, but in patients younger than age40, the thigh is a common location.38 They may

occur in an agminated or disseminated pattern orbe associated with atypical clinical and histologicfeatures. In melanocytic tumors with spitzoid fea-tures, termed atypical spitzoid tumors, a sentinellymph node biopsy may be performed to determinemalignant potential.39

Management of a histologically confirmed Spitznevus requires observation or reexcision. A classicSpitz nevus does not require further surgery. If re-excision is indicated for residual lesions, there isinsufficient evidence and a lack of consensus onoptimal margins.40 An algorithm stratifying the le-

sion into low, moderate, and high risk may helpguide therapeutic management.41 Margins approach-ing or equal to those recommended for melanoma insitu (5 mm) are favored for atypical lesions. Sentinellymph biopsy may be consideredfor markedly atypicallesions with a Breslow thicknesses of 1 mm or greater.

SYRINGOMASyringoma is a benign neoplasm that most com-

monly presents as firm, skin-colored to slightly yellow-ish papules in the lower eyelidareaofwomen (Fig. 11).Lesions may also develop on the upper trunk,

genital skin, scalp, palms, and soles. On histo-

pathology, well-circumscribed small ducts witheccrine differentiation that resemble tadpole-

like structures are confined to the upper dermis.

Fig. 10. A classic Spitz nevus(above)presentswith(below) large

nests of epithelioid or spindle cells (*) surrounded by clefts ( ar-rows). Occasional mitotic figures, atypia, and eosinophilic glob-

ules, or Kamino bodies can be present. Hematoxylin and eosin

stain; original magnification, 4.

Fig. 11. Multiple syringomas along the eyelid.


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13. Banky JP, Kelly JW, English DR, Yeatman JM, Dowling JP.Incidence of newand changednevi and melanomas detectedusing baseline images and dermoscopy in patients at highrisk for melanoma. Arch Dermatol. 2005;141:998.

14. Abbasi NR, Shaw HM, Rigel DS, et al. Early diagnosis ofcutaneous melanoma: Revisiting the ABCD criteria. JAMA.2004;292:2771.

15. Rigel DS, Friedman RJ, Kopf AW, et al. ABCDE: An evolvingconcept in the early detection of melanoma. Arch Dermatol.2005;141:1032.

16. Tripp JM, Kopf AW, Marghoob AA, Bart RS. Management ofdysplastic nevi: A survey of fellows of the American Academyof Dermatology. J Am Acad Dermatol. 2002;46:674.

17. Mollet I, Ongenae K, Naeyaert JM. Origin, clinical presen-tation and diagnosis of hypomelanotic skin disorders. Der-matol Clin. 2007;25:363.

18. Beham A, Regauer S, Soyer HP, Beham-Schmid C. Kerato-acanthoma: A clinically distinct variant of well differentiatedsquamous cell carcinoma. Adv Anat Pathol. 1988;5:269.

19. Pattee SF, Silvis NG. Keratoacanthoma developing in sites ofprevious trauma: A report of two cases and review of theliterature. J Am Acad Dermatol. 2003;48:S35.

20. Shriner DL, McCoy DK, Goldberg DJ, Wagner RF. Mohsmicrographic surgery. J Am Acad Dermatol. 1998;39:79.

21. Kleinerman R, Greenspan A, Hale EK. Mohs micrographicsurgery for an unusual case of keratoacanthoma arising froma longstanding tattoo. J Drugs Dermatol. 2007;6:931.

22. Street ML, White JW Jr, Gibson LE. Multiple keratoacan-thomas treated with oral retinoids. J Am Acad Dermatol.1990;23:862.

23. Annest NM, VanBeek MJ, Arpey CJ, Whitaker DC. Intrale-sional methotrexate treatment for keratoacanthoma tumors:A retrospective study and review of the literature. J Am AcadDermatol. 2007;56:989.

24. Bolognia JL, Jorizzo JL, Rapini RP. Adnexal neoplasms. In:Dermatology. Elsevier, Inc. 2008.

25. Cribier B, Scrivener Y, Grosshans E. Tumors arising innevus sebaceus: A study of 596 cases. J Am Acad Dermatol.2000;42:263.

26. Santibanex-GalleraniA, MarshallD, DuarteAM, et al. Shouldnevus sebaceous of Jadasssohn in children be excised? Astudy of 757 cases and literature review. J Craniofac Surg.2003;14:658.

27. Davison SP, Khachemoune Am Yu D, Kauffman LC. Nevussebaceus of Jadassohn revisted with reconstruction options.Int J Dermatol. 2005;44:145.

28. Ashinoff R. Linear nevus sebaceus of Jadassohn treated withthe carbon dioxide laser. Pediatr Dermatol. 1993;10:189.

29. Satyaprakash AK, Sheehan DJ, Sangueza OP. Proliferatingtrichilemmal tumors: A reviewof the literature.Dermatol Surg.2007;9:1102.

30. Gage AA, Meenaghan MA, Natiella JR, Green GW Jr. Sen-sitivity of pigmented mucosa and skin to freezing injury.Cryobiology1979;16:348.

31. Castanet J, Ortonne JP. Pigmentary changes in aged and

photoaged skin. Arch Dermatol. 1997;133:1296.32. Helm K, Findeis-Hosey J. Immunohistochemistry of pig-

mented actinic keratoses, actinic keratoses, melanomas insitu and solar lentigines with Melan-A. J Cutan Pathol. 2008;35:931.

33. Kopera D, Hohenleutner U, Landthaler M. Quality-switchedruby laser treatment of solar lentigines and Beckers nevus:A histopathological and immunohistochemical study. Der-matology 1997;194:338.

34. Ortonne JP,Pandya AG, Lui H, Hexsel D. Treatment of solarlentigines. J Am Acad Dermatol. 2006;54:S262.

35. Kawada A, Shiraishi H, Asai M, et al. Clinical improvementof solar lentigines and ephelides with an intense pulsed lightsource. Dermatol Surg. 2002;28:504.

36. Fleischer AB Jr, Schwartzel EH, Colby SI, Alrtman DJ, theDepigmenting Solution Study Group. The combination of2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is ef-fective in improving the appearance of solar lentigines andrelated hyperpigmented lesions in two double-blind multi-center clinical studies. J Am Acad Dermatol. 2000;42:459.

37. Clark E, Scerri L. Superficial and medium-depth chemicalpeels. Clin Dermatol. 2008;26:209.

38. Schmoeckel C, Wildi G, Schafer T. Spitz nevus versus ma-lignant melanoma: Spitz nevi predominate on the thighs inpatients younger than 40 years of age, melanomas on thetrunk in patients 40 years of age or older. J Am Acad Dermatol.56:753, 2007.

39. Murali R, Sharma RN, Thompson JF, et al. Sentinel lymphnode biopsy in histoloigcally ambiguous melanocytic tumorswith spitzoid features (so-called atypical spitzoid tumors).Ann Surg Oncol. 2008;15:302.

40. Gelbard SN, Tripp JM, Marghoob AA, et al. Management ofSpitz nevi: A survey of dermatologists in the United States.

J Am Acad Dermatol. 2002;47:224.41. Murphy ME, Boyer JD, Stashower ME, Zitelli JA.The surgical

management of Spitz nevi. Dermatol Surg. 2002;28:1065.42. Thomas L, Chamchikh N, Audefray D, Moulin G. Syringoma

and trisomy 21. Ann Dermatol Venereol. 1993;120:689.43. Rallan D, Harland CC. Brooke-Spiegler syndrome: Treat-

ment with laser ablation. Clin Exp Dermatol. 2005;30:355.


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Benign and Premalignant Skin Lesions.31