Disclosures I have no conflicts of interest to disclose Lindy P. Fox, MD Associate Professor Director, Hospital Consultation Service Department of Dermatology University of California, San Francisco 2 Applies to adults without history of malignancy or premalignant conditions Clinicians should remain alert for skin lesions with malignant features noted in the context of the physical exam performed for other purposes LOOK! for ABCDs, rapidly changing lesions, do a biopsy when indicated 1
Derm Speak Know who is at risk: Fair skin patients >65yrs Atypical nevi > 50 nevi Positive family history of skin cancer History of significant sun exposure and sunburns Pigmented Lesions: Moles, Seborrheic Keratoses, Melanoma Non-Pigmented Lesions: Actinic Keratoses, Basal Cell Carcinoma, Squamous Cell Carcinoma Nonmelanoma Skin Cancer (NMSC) Actinic Keratosis Basal Cell Carcinoma Squamous Cell Carcinoma Diagnosis of Skin Cancer Recognize the suspicious lesion BIOPSY TO CONFIRM YOUR DX Caused primarily by ultraviolet radiation SCC and Actinic Keratoses P53 tumor suppression gene mutated by UV BCC PTCH gene 2
Actinic Keratosis In-situ dysplasia from ultraviolet exposure. Sign of sufficient sun injury to develop NMSC. Precancerous (low rate <1%) Prevented by sun screen use, even in adults. Actinic Keratosis Diagnosis - Clinical inspection Red, scaly patch < 6mm. Tender to touch. Sandpaper consistency. Location - Scalp, face, dorsal hands, lower legs (women) When very thick, suspect hypertrophic AK or SCC Actinic Keratoses Actinic Keratoses- Treatment Liquid nitrogen (single freeze-thaw cycle) Topical treatment 5-fluorouracil (0.5-5%) 5% qd or BID for 2-4 weeks Imiquimod 5% cream (Aldara) TIW x 4 weeks, with repeated cycles PRN BIW or TIW x 16 weeks QW x 24 weeks Diclofenac Long term treatment (>120 days), moderately effective, side effects Photodynamic therapy 3
Actinic Keratoses- Treatment Always biopsy if an AK is not responding to appropriate therapy r/o SCC, superficial BCC Basal Cell Carcinoma Most common of all cancers > 1,000,000 diagnosed annually in USA Lifetime risk for Caucasians: up to 50% Intermittent intense sun exposure and overexposure (sunburns) Locally aggressive, very rarely metastasize Basal Cell Carcinoma- Clinical Subtypes Basal Cell Carcinoma- Nodular Nodular (classic) Superficial Pigmented Morpheaform (scar-like) Clinical subtypes have different biologic behavior Histologic subtypes also influence behavior 4
Basal Cell Carcinoma- Superficial Clinically pink, slightly scaly, slightly shiny patch Looks like an actinic keratosis May be treated with imiquimod, ED+C 5
Basal Cell Carcinoma- Pigmented May be entirely pigmented or there may be specks of pigment within what otherwise looks like a nodular or superficial BCC Melanoma is on the differential!! Basal Cell Carcinoma- Morpheaform Clinically scar-like Difficult to determine clinically where lesion begins and ends Treat with excision (have pathologist check margins) or Mohs micrographic surgery DO NOT ED+C 6
Basal Cell Carcinoma- Treatment Location, Size, and Subtype Guide Therapy Superficial Imiquimod Electrodesiccation and curettage (ED+C) Nodular or pigmented ED+C Excision (4mm margins) Mohs micrographic surgery Radiation- comorbidities, tumor size and location Morpheaform, infiltrative, micronodular Excision (4mm margins) Mohs micrographic surgery Topical Treatment of Skin Cancer Nonsurgical approaches for managing some skin cancers are available Patient selection is the key Topical treatments work for superficial cancers (not invasive ones) Superficial BCC, SCC in situ Long courses of treatment (months) may be required Biopsy to confirm diagnosis before treating Topical Treatment of Skin Cancer Imiquimod 5% cream can effectively treat superficial BCC s and SCC in situ Treatment regimen is 5X per week for 6-10 weeks depending on the host reaction Efficacy is relatively high (75%-85%) Scarring may be reduced compared to surgery Basal Cell Carcinoma- Treatment Mohs micrographic surgery Recurrent or incompletely excised tumors Aggressive histologic subtype (infiltrative, morpheaform, micronodular) Poorly defined clinical margins High risk location (face, ears, eyes) Large (>1.0 cm face, >2.0 cm trunk, extrem) Tissue sparing location (face, hands, genitalia) Immunosuppressed patients Tumors in previously irradiated skin or scar Tumors arising in setting of genetic diseases 7
Squamous Cell Carcinoma Presents as red plaque, ulceration, or wart like lesion Risk factors: Fair skin Inability to tan Chronic sun exposure Special situations: Organ transplant recipients Keratoacanthoma Squamous Cell Carcinoma Treatment SCC in situ 5FU, imiquimod, liquid nitrogen, electrodesiccation and curettage Invasive SCC Excision with 4 mm margins Mohs micrographic surgery Rapidly growing (1month) Dome-shaped nodule with central core of keratin May spontaneously regress, but treat as an SCC 8
Squamous Cell Carcinoma- Treatment Mohs micrographic surgery Recurrent or incompletely excised tumors Aggressive histologic subtype (perivascular, perineural) Poorly defined clinical margins High risk location (face, ears, eyes) Large (>1.0 cm face, >2.0 cm trunk, extrem) Tissue sparing location (face, hands, genitalia) Immunosuppressed patients Tumors in previously irradiated skin or scar Tumors arising in setting of genetic diseases Skin Cancers on the Lower Legs BCC and SCC in situ is common on the lower legs, especially in women They presents as a fixed, red, scaly patch(es) It looks very much like a spot of eczema Think of skin cancer when red patches on the lower legs don t clear with moisturizing. Question: Which of the following is FALSE about skin cancer in organ transplant recipients 1. Basal cell cancers are more common than squamous cell cancers 2. Voriconazole use is associated with skin cancer in transplant patients 3. The skin cancers are more aggressive 4. The skin cancers are potentially fatal 5. Skin cancers are the most common type of malignancy in this group 9
Skin Cancer in Organ Transplant Recipients Skin cancer is the most common malignancy in sold organ transplant patients Incidence increases with survival time post transplant Ongoing debate as to whether one or another immunosuppressive is more associated with skin cancer risk 90% are nonmelanoma skin cancer Squamous cell carcinoma (SCC) 65X the incidence in the general population Basal cell carcinoma (BCC) 65X the incidence in the general population Skin Cancer in Organ Transplant Recipients Biologic behavior much more aggressive than in the general population SCC Presents at a younger age Presents 3-5 years after transplantation High frequency of local recurrence in first 6 mo after excision (13.4%) 7% LN metastasis during second year after excision Grow rapidly Aggressive histologic growth pattern Derm Surg 2004. 30: 642-50 Skin Cancer in Organ Transplant Recipients Risk Factors Increased age Increased exposure to UV radiation Increased amount of immunosuppression (SCC) Fair skin (Fitzpatrick skin types I, II, III) Personal history of AK, NMSC, melanoma Heart > kidney > liver transplants HPV infection Skin Cancer in Organ Transplant Recipients To reduce skin cancer risk in transplants: Reduce total immunosuppressive dose to minimum required Absolute sun protection Oral acitretin (25 mg daily) may reduce rate of SCC development Please refer your organ transplant patients to a dermatologist for regular skin checks Traywick and O Rielly. Derm Therapy. 2005; 18: 12-18 10
Seborrheic Keratoses BENIGN Appear beginning at age 40, earlier in sunny regions Stuck-on morphology (above the skin) Greasy/waxy/warty texture, horn cysts Face, under breasts, trunk 0.1 to 2.0 cm in diameter Treatment: Reassure, cryotherapy 11
Acquired Nevi (Moles) Almost universal In areas of sun exposure Change throughout life, appearing at preschool age, growing during young adulthood, and involuting in old age 5mm in diameter or less (size of pencil eraser) Size (>6mm), number (more than 50) and pattern (not in sun exposed sites) predicts melanoma Atypical Moles Not in sun exposed sites Larger than 6 mm in diameter Greater than 50 12
Question: The most important prognostic indicator in melanoma is: 1. Duration of lesion before diagnosis 2. Depth of lesion 3. Presence of ulceration 4. Size of radial growth phase 5. Location of lesion Question: The most important prognostic indicator in melanoma is: 1. Duration of lesion before diagnosis 2. Depth of lesion 3. Presence of ulceration 4. Size of radial growth phase 5. Location of lesion Malignant Melanoma Most frequent cause of death from skin cancer Frequently occurs in young adults #1 cause of cancer death in women age 30-35 Intermittent, intense sun exposure (sunburns) Certain genetic mutations explain melanoma in non sun-exposed sites 13
Lifetime Risk of Melanoma 1935: 1 in 1,500 1980: 1 in 250 1991: 1 in 105 2000: 1 in 75 Malignant Melanoma Current lifetime risk of melanoma in US 1.94% males, 1.30% females Current lifetime risk of dying of melanoma in US 0.35% males, 0.20% females 2/3 of melanomas diagnosed bet 1988-99 <1mm in depth (thin) Proportion of thick melanomas ( 2mm) stayed the same (14.4-15.5%) KEY- know who is at risk and what to look for and diagnose early J Am Acad Dermatol. 2007 Oct;57(4):555-72 Ann Int Med. 2009; 150: 188-93 Malignant Melanoma 85% are cured by early diagnosis. This has been increased from 65% 30 years ago by educating MD s and patients. Advanced lesions are virtually always fatal The goal of all physicians is to recognize melanomas EARLY when curable. Diagnosis of Melanoma The prognosis is DEPENDENT on the depth of lesion (Breslow s classification) and lymph node status Melanoma of < 1mm in thickness is low risk Sentinel lymph node biopsy is recommended for melanoma > 1mm (controversial) If melanoma is on the differential, complete excision or full thickness incisional biopsy is indicated 14
Risk factors for melanoma M oles - atypical M oles - typical > 50 R ed hair and freckling I nability to tan skin types 1 and 2 S evere childhood sunburns K indred - first degree relatives with melanoma; genetic mutations: CDKN2A, CDK4, others Melanoma and Sunscreen Use Sunscreen use does decrease the risk of melanoma 1621 patients Regular sunscreen vs. discretionary sunscreen use 11 melanomas in sunscreen group vs 22 in discretionary group Fewer invasive melanomas in sunscreen group Green et al. J Clin Oncol 2011. 15
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Acral Melanoma Malignant Melanoma Asymmetry Border Color Diameter Evolution Suspect in African American, Latino, Asian patients Malignant Melanoma Asymmetry Two halves of lesion not the same Border Color Diameter Evolution 17
Malignant Melanoma Malignant Melanoma Asymmetry Border Irregular, notched, vague Color Diameter Evolution Asymmetry Border Color - Variations in color: red, white and blue Diameter Evolution Malignant Melanoma Asymmetry Border Color Diameter - Approximately 6mm (pencil eraser) Evolution 18
Malignant Melanoma Asymmetry Border Color Diameter Evolution - Changing Amelanotic Melanoma Form of melanoma that lacks pigment Must THINK about it in order to make the diagnosis 19
Melanoma and Imiquimod Lentigo maligna (LM) = in situ melanoma in sun exposed areas Lentigo maligna melanoma (LMM)- when LM becomes invasive melanoma www.meddean.luc.edu Melanoma and Pregnancy In pregnant patients Biopsy suspicious lesions Localized melanoma does not change prognosis Treatment with wide local excision is safe SLN mapping/ biopsy controversial in pregnancy Pregnancy before or after melanoma does not change prognosis No absolute contraindication to OCPs or HRT in patient with history of melanoma with no reasonable alternative NEW Therapies in the Treatment of Skin Cancer Vismodegib (Erivedge) Hedgehog signaling pathway inhibitor Indicated for metastatic, relapsed, inoperable BCC or BCC not amenable to radiation Vemurafenib (Zelboraf) BRAF inhibitor (V600E mutation) Melanoma (late stage) Ipilimumab (Yervoy) Inhibits CTLA4 Melanoma (late stage) Clin Dermatol. 2009 Jan-Feb;27(1):116-21 20
Why Sunscreens? Prevention of skin cancer Prevention of photosensitivity (UVA) Medications Diseases: e.g. lupus erythematosus Prevention of skin aging 81 82 UV-B and UV-A UVB (290 320nm) Burning rays of the sun Filtered by the ozone layer Most carcinogenic Primary target of sunscreens SPF refers only to UVB blockade UVA (320 400nm) Tanning rays Aging rays a complete UVA blocker = anti-aging cream Cause of medication related photosensitivity (e.g. HCTZ) Harder to block Sunscreen 101 SPF refers ONLY to UVB blockage There is no standardized measure of UVA blockade (yet) Water resistant Maintain SPF after 40 minutes of immersion in water Water proof Maintain SPF after 80 minutes of immersion in water 83 84 21
New Sunscreen Labeling (Summer 2012) Broad spectrum = blocks UVA and UVB SPF= UVB blockade For sunscreen to say can prevent skin cancer AND sunburn, must 1. be broad spectrum 2. SPF 15 Water resistant for 40 min or 80 min No more water proof, sweat proof Suggests that always need to re-apply every 2h Chemical vs Physical Sunscreens Chemical sunscreens have UV absorbing chemicals Benzophenone, Parsol 1789, Mexoryl, etc Chemical UVA blockers are photo-unstable (degrade) Stabilizers are now common (e.g. Helioplex) Physical sunscreens scatter or block UV rays Zinc and titanium are physical blockers More photostable Block UVA well Inelegant (white film) 85 86 What Sunscreen Should I Buy? SPF must be double digits (preferably 30) Broad spectrum (UVA AND UVB protection) UVA blockade does not parallel SPF on the label Best UVA protection in US: TiO 2, ZnO, Mexoryl, or Parsol 1789 with Helioplex Examples: Neutrogena Ultrasheer SPF 85 (Parsol 1789 with helioplex) Anthelios XL 50+ (Mexoryl) (now approved in US as SPF 40) How to Apply Sunscreen Put it on every morning before leaving the house at least 20 min before sun exposure For heavy sun exposure: reapply 20 minutes after exposure begins Reapply every 2 hours or after swimming/sweating/towel-drying Apply liberally 1oz application= shot glass = covers the body 87 88 22
What to Tell Your Patients Use sunscreen, SPF 30 EVERYDAY Avoid mid-day sun/short Shadow Seek Shade Wear protective clothing (hats) Put sunscreen on your children Ask your doctor to check your skin lesions (most persons with melanoma have been seeing doctors regularly for years) Vitamin D Supplement for those at risk for osteoporosis who obey stringent sunprotections practices E.g. organ transplant patients 89 The American Academy of Dermatology recommends that an adequate amount of vitamin D should be obtained from a healthy diet that includes foods naturally rich in vitamin D, foods/beverages fortified with vitamin D, and/or vitamin D supplements. Vitamin D should not be obtained from unprotected exposure to ultraviolet (UV) radiation. Unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk. To protect against skin cancer, a comprehensive photoprotective regimen, including the regular use and proper use of a broadspectrum sunscreen, is recommended Taken from: American Academy of Dermatology website, 1/25/11 90 Summary The FOX family Look at the skin during routine exams If you suspect melanoma, try to perform an excisional biopsy UVA and UVB exposure are implicated in skin disease Broad spectrum sunscreens required to block both Dermatologists do not recommend UV exposure as vitamin D supplementation 92 23