Precancers and Skin Cancers Adam O. Goldstein, MD, MPH Associate Professor Family Medicine University of North Carolina at Chapel Hill aog@med.unc.edu

Actinic Keratoses premalignant skin lesions = “keratinocytic intraepidermal neoplasia” chronic sun, radiation or polycyclic aromatic hydrocarbons Skin Type I-II organ transplant

Actinic Keratosis

Actinic Keratoses Distribution: Sunexposed, esp. dorsa hands/forearms Description: papules,plaques with scale and erythema, occasional crust or cutaneous horn Sandpapery feel

Actinic Keratoses epidermal atypia abnormal maturation

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

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

Differential Diagnosis squamous cell carcinoma: more indurated, thicker, recurrence of AK after treatment

Differential Diagnosis seborrheic keratosis: hyperpigmented,more stuck on appearing

Differential Diagnosis nummular eczema: coin-shaped scaling lesions; responds to emollients/topical corticosteroids

AK Treatment PREVENTION Screen for skin cancers Broad-brimmed hats sun protective clothing sunscreens avoidance of sunlight ed s/sx skin cancer avoidance of tobacco low fat diet?

AK Treatment 5-fluorouracil cream or solution Diclofenac Sodium-3% gel Cryosurgery(liquid nitrogen) 5-fluorouracil cream or solution Diclofenac Sodium-3% gel Imiquimod 2 x week/ 16 weeks

AK Treatment Excision Electrocautery Curettage Carbon dioxide laser

AK Treatment Photodynamic therapy Retinoids-topical/oral Chemical peels Photodynamic therapy Retinoids-topical/oral Investigational-dimericine

TREATMENT Liquid Nitrogen-Advantages cure rates of 98.8% common minimal patient ed multiple/thicker lesions quick recovery

TREATMENT Liquid Nitrogen-Disadvantages storage pain pigment alteration training

5-Fluorouracil Cure 50-80% Blocks methylation reaction of deoxyuridylic acid to thymidilic acid DNA (and RNA) synthesis

Diclonfenac Sodium 3% Topical Gel mechanism of action unknown NSAID inhibition of cyclo-oxygenase >>>PGE-2 90 days BID--overall 33-47% clearance vs 10-19% vehicle avoid ASA triad hypersensitivity

Photodynamic therapy (Pariser DM - J Am Acad Dermatol -2003)

Salasche SJ et al Am Acad Dermatol 2002;47:571-7. Cycle therapy of actinic keratoses of the face and scalp with 5% topical imiquimod cream: An open-label trial. Significant irritation Rest periods required Evolving protocols Expensive Effective Salasche SJ et al Am Acad Dermatol 2002;47:571-7.

Skin Cancer Statistics >1 million cases/yr >50% of all new cancers 1 in 5 Americans will develop skin cancer

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

BCC /SCC Most common skin cancers Most important risk factors sun exposure family history skin type Incidence of these cancers increase with age, probably related to cumulative sun exposure

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

Main Types Basal Cell Carcinomas Nodular BCCs - most common type Sclerosing BCCs (morpheaform) Superficial BCCs

Pattern of Nodular BCC raised pearly white, smooth translucent surface with telangiectasias

Pattern of Nodular BCCs may ulcerate leaving a small bloody crust may be pigmented

Pattern of Sclerosing BCCs ivory or colorless flat or atrophic indurated may resemble scars are easily overlooked

Pattern of Sclerosing BCCs ivory or colorless flat or atrophic indurated may resemble scars are easily overlooked

Pattern of Superficial BCCs and SCC in situ red or pink scaling plaques occasionally with shallow erosions or crusts differentiation between these two similar lesions usually requires a biopsy

Pigmented BCCs may look like melanoma increased brown or black pigment seen more commonly in dark-skinned individuals

Differential Diagnosis of Nodular BCC Intradermal nevus Sebaceous hyperplasia Fibrous papule of the face trichoepithelioma

Differentiating Intradermal Nevus from Nodular BCC Stable size Soft No crusting or ulceration May have telangiectasias

Differentiating Intradermal Nevus from Nodular BCC Stable size Soft No crusting or ulceration May have telangiectasias

Sebaceous Hyperplasia from Nodular BCC yellow coloration stable size umbilication without ulceration is hard to see after injecting anesthesia

Diagnosis of Basal Cell Carcinomas Shave biopsy nodular thick superficial types Punch biopsy morpheaform flat superficial types

Treatment options for Basal Cell Carcinomas C + D after a shave biopsy Cryotherapy with thermocouple if you have experience Excision with 3- 5 mm margins Superficial trunk/ext: imiquimod qd x 12 wks Mohs for recurrent BCC and areas of cosmetic importance

Mohs micrographic surgery removal of tumor by scalpel in sequential horizontal layers. each tissue sample is frozen, stained, and microscopically examined repeated until all the margins are clear treatment of choice for BCCs with poorly defined margins especially those on the nose or eyelids

Recurrence rates after Tx of BCCs C + D 10% Cryotherapy 10% Excision 2 - 5% Imiquimod ??? Mohs <1%

Factors that increase recurrence rates sclerosing vs others larger size of BCC margins experience of the surgeon

Sclerosing BCC is most dangerous tend to be deeply invasive often not diagnosed until they have caused extensive damage invade muscle, nerve, and bone nodular BCC can also invade deeply

Bowen’s disease - features SCC in situ Mainly sun exposed areas Slightly elevated red scaly plaque with well-demarcated borders

Bowen’s disease - features May resemble psoriasis, superficial BCC, chronic eczema, SK Curable using C & D, cryo, 5-FU, imiquimod, excision

Keratoacanthoma Appear suddenly, grow rapidly Central crater with keratin plug May grow to 2cm in size May resolve spontaneously May look like SCC

Keratoacanthoma C and D elliptical excision 5-FU topically tid 5-FU intralesional injection

Location of SCCs Same distribution as bccs. Especially on the lips, ears, and scalp Initially grow by direct extension Metastasize to local lymph nodes and then to distant sites

SCCs with an increased risk of metastasis larger, advanced lesions SCC on mucous membranes (in the oral cavity, on the lips) BCCs rarely metastasize

SCC more aggressive (local & mets) Size >2 cm SCC in a scar Patient is immunosuppressed Poorly differentiated There is perineural invasion

Importance of early diagnosis of BCC and SCC especially in facial cancers the nose is the single most frequent site of BCC reconstruction is difficult extension into underlying bone and cartilage may occur

The differential diagnosis of superficial BCC and SCC in situ Actinic keratosis, nummular eczema Nummular eczema can usually be distinguished by its coin-like shape, transient nature, and itchiness Biopsy any thickened and crusting actinic keratosis to rule out BCC or SCC

Treatment options for SCC C + D after a shave biopsy cryotherapy with thermocouple if you have experience excision with 5 mm margin Mohs for recurrent SCC and areas of cosmetic importance

Erythroplasia of Queyrat SCC in situ on the penis Usually under the foreskin of the uncircumcised penis May occur on the vulva 5-FU, imiquimod or mohs

Indications for Referral for Mohs Surgery

Indications for Referral for Mohs Surgery Recurrent tumors, sclerosing BCC Primary tumors in locations with high tumor-recurrence rates Nasolabial fold,temple, periauricular area, periocular area, scalp, nasal alae, center face Preservation of normal tissue is vital (for cosmetic and functional reasons) Nose, eyelids, lips, fingers, ears, penis

When to consider referral Aggressive and recurrent skin cancers A large skin cancer lesion A lesion located in a sensitive area (cosmetic or functional) When treatment or diagnosis of the lesion is beyond the scope of one’s skills If mohs surgery is the treatment of choice

Melanoma Risk Factors Family history Personal history Atypical Nevi Blistering Sunburns Type 1 skin

History of a changing lesion

Melanoma Statistics Fastest rising incidence rates Most common cancer in 25-9 y/o 2nd only to breast CA in 30-4 y/o women

Melanoma Facts 87,900 new cancers 7400 deaths in 2003 due to melanoma 34,300 in situ 53,600 invasive 4% increase from 2001 7400 deaths in 2003 due to melanoma

Melanoma

Melanoma-Early detection Total treatment costs by stage Stage I 5.5% Stage II 5.5% Stage III 34% Stage IV 55%

MNEMONIC FOR MALIGNANT MELANOMA RECOGNITION A- ASYMMETRY B- BORDER IRREGULARITY C- VARIATION IN COLOR D- DIAMETER> .6CM E- ELEVATION ABOVE SKIN SURFACE

Melanoma with regression

Melanoma

Acral lentiginous Melanoma

Lentigo Maligna Melanoma

Venous Lake

Blue Nevus

Seborrheic Keratosis

Pyogenic Granuloma

Look everywhere

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

Breslow’s Measurement Depth of granular cell layer to deepest malignant cell Strongest correlation with prognosis

Melanoma Managment Sentinel lymph node biopsy 1mm or greater depth, regression, >Level III or IV Interferon Vaccine clinical trials

Melanoma Management Full skin exam Family screening Follow up Education

Take home points Prevent skin cancers by risk factor reduction Early detection of pre-cancers and skin cancers can prevent morbidity and mortality Use the appropriate biopsy technique for diagnosing skin cancers Treat or refer based on your skills

Online References Derm Online Atlas is at www.dermis.net/bilddb/index_e.htm Derm Image Bank is at medstat.med.utah.edu/kw/derm/ Basal Cell Carcinoma is at emedicine.com/derm/topic47.htm