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Melanoma and Non‐melanoma Skin Cancer: What You Need to Know

Lindy P. Fox, MDAssociate Professor

Director, Hospital Consultation Service  Department of Dermatology

University of California, San Franciscofoxli@derm.ucsf.edu

Disclosures

• I have no conflicts of interest to disclose

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• 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

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• 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

Derm Speak

• 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

• Caused primarily by ultraviolet radiation• SCC and Actinic Keratoses

– P53 tumor suppression gene mutated by UV• BCC

– PTCH gene

Diagnosis of Skin Cancer

• Recognize the suspicious lesion• BIOPSY TO CONFIRM YOUR DX

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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- 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

http://www.crutchfielddermatology.com

AKs treated with 5-fluorouracil

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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

• Nodular (classic) 

• Superficial

• Pigmented

• Morpheaform (scar‐like)

• Clinical subtypes have different biologic behavior

• Histologic subtypes also influence behavior

Basal Cell Carcinoma‐ Superficial

• Clinically pink, slightly scaly, slightly shiny patch

• Looks like an actinic keratosis

• May be treated with imiquimod, ED+C

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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

Basal Cell Carcinoma‐ TreatmentLocation, 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

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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‐ TreatmentMohs 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

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

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Keratoacanthoma

• Rapidly growing (1month)• Dome-shaped nodule with central core of keratin• May spontaneously regress, but treat as an SCC

Squamous Cell Carcinoma Treatment

• SCC in situ– 5FU, imiquimod, liquid nitrogen,

electrodesiccation and curettage

• Invasive SCC– Excision with 4 mm margins

– Mohs micrographic surgery

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Squamous Cell Carcinoma‐ TreatmentMohs 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.

Case

• 64 year old man with psoriasis, hypertension, s/p renal transplant

• 3 months of ulceration of medial aspect of left lower leg, thought to be due to venous insufficiency 

• 3 months of topical treatment fails to improve ulceration

• Skin Biopsy = Squamous Cell Carcinoma

• Chronic phototherapy and immunosuppressive treatments have led to skin cancer

• If leg ulcer doesn’t heal with appropriate treatment—refer or biopsy

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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 fatal5. Skin cancers are the most common

type of malignancy in this group

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: SCC>BCC– Squamous cell carcinoma (SCC)

• 65 X the incidence in the general population

– Basal cell carcinoma• 10 X 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

Traywick and O’Rielly. Derm Therapy. 2005; 18: 12-18

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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

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

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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

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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

Dermatol Clin. 2012 Jul;30(3):363-8

Lifetime Risk of Invasive Melanoma in US

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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):555-72Ann 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

Risk factors for melanoma

M oles - atypicalM oles - typical > 50R ed hair and frecklingI nability to tan – skin types 1 and 2

S evere childhood sunburns K indred - first degree relatives with

melanoma; genetic mutations: CDKN2A, CDK4, others

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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.

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Acral Melanoma

Suspect in African American, Latino, Asian patients

Malignant Melanoma

• Asymmetry

• Border

• Color

• Diameter

• Evolution

Malignant Melanoma

• Asymmetry – Two halves of lesion not the same

• Border• Color• Diameter• Evolution

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Malignant Melanoma

• Asymmetry • Border – Irregular, notched, vague• Color• Diameter• Evolution

Malignant Melanoma

• Asymmetry • Border • Color - Variations in color: red, white

and blue• Diameter• Evolution

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Malignant Melanoma

• Asymmetry • Border • Color• Diameter - Approximately 6mm (pencil

eraser)• Evolution

Malignant Melanoma

• Asymmetry • Border • Color• Diameter• Evolution - Changing

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Amelanotic Melanoma

• Form of melanoma that lacks pigment

• Must THINK about it in order to make the diagnosis

www.meddean.luc.edu

Melanoma and Imiquimod

• Lentigo maligna (LM) = in situ melanoma in sun exposed areas

• Lentigo maligna melanoma (LMM)- when LM becomes invasive melanoma

Reports in literature supporting treatment of LM with imiquimod

CONTROVERSIAL, more studies needed, I don’t recommend

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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

Clin Dermatol. 2009 Jan-Feb;27(1):116-21

NEW Systemic Therapies for the Treatment of Advanced Skin Cancer

• Vismodegib (Erivedge)– Hedgehog signaling pathway inhibitor– Indicated for metastatic, relapsed, inoperable BCC or BCC

not amenable to radiation

• Vemurafenib (Zelboraf) and Dabrafenib (Tafinlar)– BRAF inhibitor (V600E mutation)– Melanoma (late stage)

• Ipilimumab (Yervoy)– Inhibits CTLA4– Melanoma (late stage)

• Trametinib (Mekinist)– MEK inhibitor– Melanoma (late stage)

Sunscreens 101

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Why Sunscreens?

• Prevention of skin cancer

• Prevention of photosensitivity (UVA)– Medications

– Diseases: e.g. lupus erythematosus

• Prevention of skin aging

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UV-B and UV-A

• Burning rays of the sun

• Filtered by the ozone layer

• Most carcinogenic • Primary target of

sunscreens

• SPF refers only to UVB blockade

• Tanning rays• Aging rays

– a complete UVA blocker = anti-aging cream

• Cause of medication related photosensitivity (e.g. HCTZ)

• Harder to block

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UVB (290‐320nm) UVA (320‐400nm)

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

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New Sunscreen Labeling (Summer 2012)

• Broad spectrum = blocks UVA and UVB

• SPF= UVB blockade

• For sunscreen to say can prevent skin cancer AND sunburn, must1. 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

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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)

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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:

• TiO2, 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)– Vanicream 55+ (Zinc and titanium)

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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

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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 sun-protections practices • E.g. organ transplant patients

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• 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 broad-spectrum sunscreen, is recommended

84Taken from: American Academy of Dermatology website, 1/25/11

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Summary

• Look at the skin during routine exams

• If you suspect invasive melanoma, try to perform an excisional biopsy, if not saucerization OK

• 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

The FOX family

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