Precancers and Skin CancersPrecancers and Skin CancersAdam O. Goldstein, MD, MPHAdam O. Goldstein, MD, MPH

Associate ProfessorAssociate ProfessorFamily MedicineFamily Medicine

University of North Carolina at Chapel HillUniversity of North Carolina at Chapel Hillaog@med.unc.eduaog@med.unc.edu

Actinic KeratosesActinic Keratoses

premalignant skin lesions = premalignant skin lesions = “keratinocytic “keratinocytic intraepidermal neoplasia”intraepidermal neoplasia”

chronic sun, radiation or chronic sun, radiation or polycyclic aromatic polycyclic aromatic hydrocarbonshydrocarbons

Skin Type I-II Skin Type I-II organ transplantorgan transplant

Actinic KeratosisActinic Keratosis

Actinic KeratosesActinic Keratoses Distribution: Sunexposed, esp. dorsa Distribution: Sunexposed, esp. dorsa

hands/forearmshands/forearms Description: papules,plaques with scale and Description: papules,plaques with scale and

erythema, occasional crust or cutaneous hornerythema, occasional crust or cutaneous horn Sandpapery feelSandpapery feel

Actinic KeratosesActinic Keratoses epidermal atypiaepidermal atypia abnormal maturationabnormal maturation

Actinic KeratosesActinic Keratoses 60% predisposed >40 have at least 1 AK60% predisposed >40 have at least 1 AK 6-10% lifetime >> invasive SCC6-10% lifetime >> invasive SCC >10 AK - 14% an SCC w/n 5 yrs>10 AK - 14% an SCC w/n 5 yrs 60-97% of SCC from AK60-97% of SCC from AK ~ 40% of met SCC>> AK~ 40% of met SCC>> AK ^ aggressive immsupp^ aggressive immsupp

Actinic KeratosesActinic Keratoses lip lesions: actinic cheilitis/leukoplakialip lesions: actinic cheilitis/leukoplakia white plaques-mucosa white plaques-mucosa persistent scaling lesions on the lippersistent scaling lesions on the lip ^ aggressive behavior^ aggressive behavior tobacco/suntobacco/sun

Differential DiagnosisDifferential Diagnosis squamous cell carcinoma: more indurated, squamous cell carcinoma: more indurated,

thicker, recurrence of AK after treatmentthicker, recurrence of AK after treatment

Differential Diagnosis Differential Diagnosis seborrheic keratosis: hyperpigmented,more seborrheic keratosis: hyperpigmented,more

stuck on appearingstuck on appearing

Differential DiagnosisDifferential Diagnosis nummular eczema: coin-shaped scaling lesions; nummular eczema: coin-shaped scaling lesions;

responds to emollients/topical corticosteroidsresponds to emollients/topical corticosteroids

AK TreatmentAK Treatment PREVENTIONPREVENTION

Screen for skin cancersScreen for skin cancers Broad-brimmed hatsBroad-brimmed hats sun protective clothingsun protective clothing sunscreenssunscreens avoidance of sunlightavoidance of sunlight ed s/sx skin cancered s/sx skin cancer avoidance of tobaccoavoidance of tobacco low fat diet?low fat diet?

AK TreatmentAK Treatment

CCryosurgery(liquid nitrogen)ryosurgery(liquid nitrogen) 5-fluorouracil cream or solution5-fluorouracil cream or solution Diclofenac Sodium-3% gelDiclofenac Sodium-3% gel Imiquimod 2 x week/ 16 weeksImiquimod 2 x week/ 16 weeks

AK TreatmentAK Treatment Excision Excision ElectrocauteryElectrocautery CurettageCurettage Carbon dioxide laserCarbon dioxide laser

AK TreatmentAK Treatment Chemical peelsChemical peels Photodynamic therapy Photodynamic therapy Retinoids-topical/oralRetinoids-topical/oral Investigational-dimericineInvestigational-dimericine

TREATMENTTREATMENT Liquid Nitrogen-AdvantagesLiquid Nitrogen-Advantages

cure rates of 98.8% cure rates of 98.8% commoncommon minimal patient edminimal patient ed multiple/thicker lesionsmultiple/thicker lesions quick recoveryquick recovery

TREATMENTTREATMENT Liquid Nitrogen-DisadvantagesLiquid Nitrogen-Disadvantages

storagestorage painpain pigment alterationpigment alteration trainingtraining

5-Fluorouracil5-Fluorouracil

Cure 50-80%Cure 50-80% Blocks methylation Blocks methylation

reaction of reaction of deoxyuridylic acid to deoxyuridylic acid to thymidilic acidthymidilic acid

DNA (and RNA) DNA (and RNA) synthesissynthesis

Diclonfenac Sodium 3% Topical GelDiclonfenac Sodium 3% Topical Gel mechanism of action mechanism of action

unknownunknown NSAIDNSAID inhibition of cyclo-inhibition of cyclo-

oxygenase >>>PGE-oxygenase >>>PGE-22 90 days BID--overall 90 days BID--overall

33-47% clearance vs 33-47% clearance vs 10-19% vehicle10-19% vehicle

avoid ASA triadavoid ASA triad hypersensitivityhypersensitivity

Photodynamic therapyPhotodynamic therapy

(Pariser DM - J Am Acad Dermatol -2003)

Cycle therapy of actinic keratoses of the face and scalp Cycle therapy of actinic keratoses of the face and scalp with 5% topical imiquimod cream: An open-label trial.with 5% topical imiquimod cream: An open-label trial.

Salasche SJ et al Am Acad Dermatol 2002;47:571-7.

Significant irritation

Rest periods required

Evolving protocols

Expensive

Effective

Skin Cancer StatisticsSkin Cancer Statistics >1 million cases/yr>1 million cases/yr

>50% of all new cancers >50% of all new cancers

1 in 5 Americans will develop skin cancer1 in 5 Americans will develop skin cancer

Types of Skin CancersTypes of Skin Cancers Basal Cell Carcinoma - 80%Basal Cell Carcinoma - 80% Squamous Cell Carcinoma - 16%Squamous Cell Carcinoma - 16% Melanoma - 4%Melanoma - 4%

BCC /SCCBCC /SCC Most common skin cancers Most common skin cancers Most important risk factors Most important risk factors

sun exposure sun exposure family history family history skin typeskin type

Incidence of these cancers increase with Incidence of these cancers increase with age, probably related to cumulative sun age, probably related to cumulative sun exposure exposure

Basal Cell CarcinomaBasal Cell Carcinoma the most common skin cancer the most common skin cancer 90% appear on face, ears, head90% appear on face, ears, head

Main Types Basal Cell Main Types Basal Cell Carcinomas Carcinomas

Nodular BCCs - most common typeNodular BCCs - most common type Sclerosing BCCs (morpheaform)Sclerosing BCCs (morpheaform) Superficial BCCsSuperficial BCCs

Pattern of Nodular BCC Pattern of Nodular BCC raised pearly white, raised pearly white,

smooth translucent smooth translucent surface with surface with telangiectasias telangiectasias

Pattern of Nodular BCCs Pattern of Nodular BCCs may ulcerate leaving may ulcerate leaving

a small bloody crusta small bloody crust may be pigmentedmay be pigmented

Pattern of Sclerosing BCCs Pattern of Sclerosing BCCs ivory or colorlessivory or colorless flat or atrophicflat or atrophic induratedindurated may resemble scarsmay resemble scars are easily overlookedare easily overlooked

Pattern of Sclerosing BCCs Pattern of Sclerosing BCCs ivory or colorlessivory or colorless flat or atrophicflat or atrophic induratedindurated may resemble may resemble

scarsscars are easily are easily

overlookedoverlooked

Pattern of Superficial BCCs and SCC in Pattern of Superficial BCCs and SCC in situsitu

red or pink scaling red or pink scaling plaquesplaques

occasionally with occasionally with shallow erosions or shallow erosions or crustscrusts

differentiation differentiation between these two between these two similar lesions usually similar lesions usually requires a biopsyrequires a biopsy

Pigmented BCCsPigmented BCCs may look like may look like

melanomamelanoma increased brown or increased brown or

black pigmentblack pigment seen more commonly seen more commonly

in dark-skinned in dark-skinned individualsindividuals

Differential Diagnosis of Nodular BCCDifferential Diagnosis of Nodular BCC

Intradermal nevusIntradermal nevus Sebaceous hyperplasiaSebaceous hyperplasia Fibrous papule of the faceFibrous papule of the face trichoepitheliomatrichoepithelioma

Differentiating Intradermal Nevus from Differentiating Intradermal Nevus from Nodular BCCNodular BCC Intradermal nevusIntradermal nevus

Stable sizeStable size SoftSoft No crusting or No crusting or

ulcerationulceration May have May have

telangiectasiastelangiectasias

Differentiating Intradermal Nevus from Nodular Differentiating Intradermal Nevus from Nodular BCCBCC

Intradermal nevusIntradermal nevus Stable sizeStable size SoftSoft No crusting or No crusting or

ulcerationulceration May have May have

telangiectasiastelangiectasias

Sebaceous Hyperplasia from Nodular Sebaceous Hyperplasia from Nodular BCCBCC Sebaceous Sebaceous

hyperplasiahyperplasia yellow colorationyellow coloration stable sizestable size umbilication without umbilication without

ulcerationulceration is hard to see after is hard to see after

injecting anesthesiainjecting anesthesia

Diagnosis of Basal Cell Diagnosis of Basal Cell CarcinomasCarcinomas

Shave biopsyShave biopsy nodularnodular thick superficial typesthick superficial types

Punch biopsyPunch biopsy morpheaformmorpheaform flat superficial typesflat superficial types

Treatment options for Basal Cell Treatment options for Basal Cell CarcinomasCarcinomas C + D after a shave biopsyC + D after a shave biopsy Cryotherapy with thermocouple if you have Cryotherapy with thermocouple if you have

experienceexperience Excision with 3- 5 mm marginsExcision with 3- 5 mm margins Superficial trunk/ext: imiquimod qd x 12 wksSuperficial trunk/ext: imiquimod qd x 12 wks Mohs for recurrent BCC and areas of Mohs for recurrent BCC and areas of

cosmetic importancecosmetic importance

Mohs micrographic surgeryMohs micrographic surgery removal of tumor by scalpel in sequential removal of tumor by scalpel in sequential

horizontal layers. horizontal layers. each tissue sample is frozen, stained, and each tissue sample is frozen, stained, and

microscopically examinedmicroscopically examined repeated until all the margins are clearrepeated until all the margins are clear treatment of choice for BCCs with poorly treatment of choice for BCCs with poorly

defined marginsdefined margins especially those on the nose or eyelidsespecially those on the nose or eyelids

Recurrence rates after Tx of Recurrence rates after Tx of BCCsBCCs

C + D 10%C + D 10% Cryotherapy 10%Cryotherapy 10% Excision 2 - 5%Excision 2 - 5% Imiquimod ???Imiquimod ??? Mohs <1%Mohs <1%

Factors that increase Factors that increase recurrence ratesrecurrence rates

sclerosing vs otherssclerosing vs others larger size of BCClarger size of BCC marginsmargins experience of the surgeonexperience of the surgeon

Sclerosing BCC is most Sclerosing BCC is most dangerousdangerous

tend to be deeply invasivetend to be deeply invasive often not diagnosed until they have often not diagnosed until they have

caused extensive damagecaused extensive damage invade muscle, nerve, and boneinvade muscle, nerve, and bone nodular BCC can also invade deeply nodular BCC can also invade deeply

Bowen’s disease - featuresBowen’s disease - features SCC in situSCC in situ Mainly sun exposed Mainly sun exposed

areasareas Slightly elevated Slightly elevated

red scaly plaque red scaly plaque with well-with well-demarcated bordersdemarcated borders

Bowen’s disease - featuresBowen’s disease - features May resemble psoriasis, superficial BCC, May resemble psoriasis, superficial BCC,

chronic eczema, SKchronic eczema, SK Curable using C & D, cryo, 5-FU, Curable using C & D, cryo, 5-FU,

imiquimod, excisionimiquimod, excision

KeratoacanthomaKeratoacanthoma Appear suddenly, grow rapidlyAppear suddenly, grow rapidly Central crater with keratin plugCentral crater with keratin plug May grow to 2cm in sizeMay grow to 2cm in size May resolve spontaneouslyMay resolve spontaneously May look like SCCMay look like SCC

KeratoacanthomaKeratoacanthoma C and DC and D elliptical excisionelliptical excision 5-FU topically tid5-FU topically tid 5-FU intralesional injection5-FU intralesional injection

Location of SCCs Location of SCCs Same distribution as Same distribution as

bccs. bccs. Especially on the lips, Especially on the lips,

ears, and scalp ears, and scalp Initially grow by direct Initially grow by direct

extension extension Metastasize to local Metastasize to local

lymph nodes and then to lymph nodes and then to distant sitesdistant sites

SCCs with an increased risk of SCCs with an increased risk of metastasis metastasis

larger, advanced lesionslarger, advanced lesions SCC on mucous membranes (in the oral SCC on mucous membranes (in the oral

cavity, on the lips) cavity, on the lips) BCCs rarely metastasizeBCCs rarely metastasize

SCC more aggressive (local & SCC more aggressive (local & mets)mets)

Size >2 cmSize >2 cm SCC in a scarSCC in a scar Patient is immunosuppressedPatient is immunosuppressed Poorly differentiated Poorly differentiated There is perineural invasionThere is perineural invasion

Importance of early diagnosis of Importance of early diagnosis of BCC and SCCBCC and SCC

especially in facial cancers especially in facial cancers the nose is the single most frequent site the nose is the single most frequent site

of BCCof BCC reconstruction is difficultreconstruction is difficult extension into underlying bone and cartilage extension into underlying bone and cartilage

may occurmay occur

The differential diagnosis of superficial BCC The differential diagnosis of superficial BCC and SCC in situand SCC in situ

Actinic keratosis, nummular Actinic keratosis, nummular eczemaeczema

Nummular eczema can usually Nummular eczema can usually be distinguished by its coin-like be distinguished by its coin-like shape, transient nature, and shape, transient nature, and itchinessitchiness

Biopsy any thickened and Biopsy any thickened and crusting actinic keratosis to rule crusting actinic keratosis to rule out BCC or SCCout BCC or SCC

Treatment options for SCCTreatment options for SCC C + D after a shave biopsyC + D after a shave biopsy cryotherapy with thermocouple if you cryotherapy with thermocouple if you

have experiencehave experience excision with 5 mm marginexcision with 5 mm margin Mohs for recurrent SCC and areas of Mohs for recurrent SCC and areas of

cosmetic importancecosmetic importance

Erythroplasia of QueyratErythroplasia of Queyrat SCC in situ on the SCC in situ on the

penispenis Usually under the Usually under the

foreskin of the foreskin of the uncircumcised penisuncircumcised penis

May occur on the May occur on the vulvavulva

5-FU, imiquimod or 5-FU, imiquimod or mohsmohs

Indications for Referral for Mohs SurgeryIndications for Referral for Mohs Surgery

Indications for Referral for Mohs Indications for Referral for Mohs SurgerySurgery

Recurrent tumors, sclerosing BCCRecurrent tumors, sclerosing BCC Primary tumors in locations with high Primary tumors in locations with high

tumor-recurrence ratestumor-recurrence rates Nasolabial fold,temple, periauricular area, Nasolabial fold,temple, periauricular area,

periocular area, scalp, nasal alae, center faceperiocular area, scalp, nasal alae, center face Preservation of normal tissue is vital (for Preservation of normal tissue is vital (for

cosmetic and functional reasons)cosmetic and functional reasons) Nose, eyelids, lips, fingers, ears, penisNose, eyelids, lips, fingers, ears, penis

When to consider referralWhen to consider referral Aggressive and recurrent skin cancersAggressive and recurrent skin cancers A large skin cancer lesionA large skin cancer lesion A lesion located in a sensitive area A lesion located in a sensitive area

(cosmetic or functional)(cosmetic or functional) When treatment or diagnosis of the lesion When treatment or diagnosis of the lesion

is beyond the scope of one’s skillsis beyond the scope of one’s skills If mohs surgery is the treatment of choiceIf mohs surgery is the treatment of choice

Melanoma Risk FactorsMelanoma Risk Factors Family historyFamily history Personal historyPersonal history Atypical NeviAtypical Nevi Blistering SunburnsBlistering Sunburns Type 1 skinType 1 skin

History of a changing lesionHistory of a changing lesion

Melanoma StatisticsMelanoma Statistics Fastest rising incidence ratesFastest rising incidence rates

Most common cancer in 25-9 y/oMost common cancer in 25-9 y/o

2nd only to breast CA in 30-4 y/o women2nd only to breast CA in 30-4 y/o women

Melanoma FactsMelanoma Facts 87,900 new cancers87,900 new cancers

34,300 in situ34,300 in situ 53,600 invasive53,600 invasive 4% increase from 20014% increase from 2001

7400 deaths in 2003 due to melanoma7400 deaths in 2003 due to melanoma

MelanomaMelanoma

Melanoma-Early detectionMelanoma-Early detection Total treatment costs by stageTotal treatment costs by stage

Stage I 5.5%Stage I 5.5% Stage II 5.5%Stage II 5.5% Stage III 34%Stage III 34% Stage IV 55%Stage IV 55%

MNEMONIC FOR MALIGNANT MNEMONIC FOR MALIGNANT MELANOMA RECOGNITIONMELANOMA RECOGNITION

A- ASYMMETRY A- ASYMMETRY B- BORDER IRREGULARITYB- BORDER IRREGULARITY C- VARIATION IN COLORC- VARIATION IN COLOR D- DIAMETER> .6CMD- DIAMETER> .6CM E- ELEVATION ABOVE SKIN SURFACEE- ELEVATION ABOVE SKIN SURFACE

Melanoma with regressionMelanoma with regression

MelanomaMelanoma

Acral lentiginous MelanomaAcral lentiginous Melanoma

Lentigo Maligna MelanomaLentigo Maligna Melanoma

Venous LakeVenous Lake

Blue NevusBlue Nevus

Seborrheic KeratosisSeborrheic Keratosis

Pyogenic GranulomaPyogenic Granuloma

Look everywhereLook everywhere

Melanoma ManagementMelanoma Management Excisional “biopsy”Excisional “biopsy” 1-2 mm margins1-2 mm margins Dermatopathologist consultationDermatopathologist consultation

Breslow’s MeasurementBreslow’s Measurement Depth of granular cell layer to deepest Depth of granular cell layer to deepest

malignant cellmalignant cell Strongest correlation with prognosisStrongest correlation with prognosis

Melanoma ManagmentMelanoma Managment Sentinel lymph node biopsySentinel lymph node biopsy

1mm or greater depth, regression, 1mm or greater depth, regression, >Level III or IV>Level III or IV

InterferonInterferon Vaccine clinical trialsVaccine clinical trials

Melanoma ManagementMelanoma Management Full skin examFull skin exam Family screeningFamily screening Follow upFollow up EducationEducation

Take home pointsTake home points Prevent skin cancers by risk factor reductionPrevent skin cancers by risk factor reduction Early detection of pre-cancers and skin Early detection of pre-cancers and skin

cancers can prevent morbidity and mortalitycancers can prevent morbidity and mortality Use the appropriate biopsy technique for Use the appropriate biopsy technique for

diagnosing skin cancersdiagnosing skin cancers Treat or refer based on your skills Treat or refer based on your skills

Online ReferencesOnline References Derm Online Atlas is at Derm Online Atlas is at www.dermis.net/www.dermis.net/

bilddbbilddb/index_e./index_e.htmhtm Derm Image Bank is at Derm Image Bank is at

medstat.med.utah.edu/kw/derm/medstat.med.utah.edu/kw/derm/ Basal Cell Carcinoma is at Basal Cell Carcinoma is at

emedicine.com/derm/topic47.htmemedicine.com/derm/topic47.htm