Review of Cutaneous Malignancies

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Review of Cutaneous Malignancies Tanya Nino, MD Department of Dermatology Did You Know? More than 3.

org/research/cancerfactsstatistics/cancerfactsfigures2014/index Rogers, HW, Weinstock, MA, Harris, AR, et al.

In 2015, it is estimated that 137,310 new melanomas will be diagnosed in the US and that 9,940 deaths will occur from melanoma Nearly every

1 Review of Cutaneous Malignancies Tanya Nino, MD Department of Dermatology Did You Know? More than 3.5 million skin cancers are diagnosed in the US annually Melanoma incidence rates have been increasing for at least 30 years 1 in 5 Americans will develop some form of skin cancer during their lifetime American Cancer Society. Cancer Facts and Figures org/research/cancerfactsstatistics/cancerfactsfigures2014/index Rogers, HW, Weinstock, MA, Harris, AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, Arch Dermatol 2010; 146(3): Why is this important? In 2015, it is estimated that 137,310 new melanomas will be diagnosed in the US and that 9,940 deaths will occur from melanoma Nearly every hour, an American dies from Melanoma. US melanoma incidence has increased approximately 15 fold in the past 50 years. This represents a substantial public health problem Bolognia JL, Jorizzo JL, Rapini RP, eds. Mosby:St. Louis, Dermatology, 2nd edition American Cancer Society. Cancer Facts and Figures org/research/cancerfactsstatistics/cancerfactsfigures2014/index 1

Melanoma affects all of us While people with darker skin are less likely to get melanoma, they are still at

Melanoma is curable if caught early and treated quickly.

Beautiful California Of all states, California will have the greatest number of new Melanoma cases Of all

and nearly tied with San Diego) National Cancer Institute, State Cancer Profiles. http://statecancerprofiles.

2 Melanoma affects all of us While people with darker skin are less likely to get melanoma, they are still at risk, and it may often be advanced, partly because of late detection. We all have loved ones and friends at risk. Melanoma is curable if caught early and treated quickly. Many melanoma deaths might have been prevented by education alone. Beautiful California Of all states, California will have the greatest number of new Melanoma cases Of all counties in California, Orange County has the third highest annual count of melanoma (surpassed by Los Angeles and nearly tied with San Diego) National Cancer Institute, State Cancer Profiles. Sunburn = Serious Sun Damage Having a blistering sunburn increases the lifetime risk of developing melanoma The chances of developing a sunburn are greatest between 10am and 2pm, when the sun s rays are strongest. 2

Sun Damage Wrinkles While wrinkles can occur

We get a great percentage of our lifetime sun

3 Sun Damage Wrinkles While wrinkles can occur naturally with age, they can appear earlier and be more severe because of sun exposure we get when we re young. We get a great percentage of our lifetime sun exposure before we are 18 years old. Anatomy of the skin Actinic Keratoses 3

Actinic Keratoses Pre-cancerous 1 AK will become SCC 10% of the

history of chronic sun exposure, head and neck location Rough

background solar damage: dyspigmentation, telangiectasias and

4 Actinic Keratoses Pre-cancerous 1 AK will become SCC 10% of the time over 10 years Increased Risk: Elderly patients, fair skin, history of chronic sun exposure, head and neck location Rough erythematous papule with white to yellow scale Look for background solar damage: dyspigmentation, telangiectasias and wrinkling Marker for increased risk of non-melanoma skin cancer Actinic Keratoses 4

5 AK Types Hyperkeratotic Lichenoid Atrophic Pigmented Acantholytic Bowenoid Actinic Cheilitis 5

Actinic Keratosis - Treatment Cryotherapy Quick and Easy Great

Hypertrophic scarring Post-inflammatory hyper-or

because of concealment by the fibrous scar tissue Actinic

Topical diclofenac (NSAID) Topical ingenol mebutate

6 Actinic Keratosis - Treatment Cryotherapy Quick and Easy Great for AKs Disadvantages Not as precise for larger, patch-like AKs Hypertrophic scarring Post-inflammatory hyper-or hypo-pigmentation Recurrent carcinoma can become extensive because of concealment by the fibrous scar tissue Actinic Keratosis - Treatment Topical 5-fluorouracil Topical Imiquimod Topical diclofenac (NSAID) Topical ingenol mebutate Photodynamic Therapy topical 5-aminolevulinic acid Am Fam Physician May 15;81(10):

Basal Cell Carcinoma Basal Cell Carcinoma Most common type of

Caused by a large amount of total accumulated lifetime sun

Carcinoma Most common skin cancer Many variants: >26 types

immunosuppression and aggressive subtype: Morpheaform,

7 Basal Cell Carcinoma Basal Cell Carcinoma Most common type of skin cancer Slow-growing, rarely fatal, but can be disfiguring Caused by a large amount of total accumulated lifetime sun exposure Photographs courtesy of Gary Cole, MD Basal Cell Carcinoma Most common skin cancer Many variants: >26 types Nodular most common Metastasis very rare, usually in setting of immunosuppression and aggressive subtype: Morpheaform, Infiltrating, Metatypical, Basosquamous Higher risk with intermittent intense episodes of sunburn 7

Nodular BCC 60% of all BCC Raised, Translucent papule/nodule with

thin plaque More common on trunk and extremities Younger age (57)

Morpheaform BCC Flat, atrophic lesion or illdefined plaque Scar-like

8 Nodular BCC 60% of all BCC Raised, Translucent papule/nodule with Telangiectasias Extend Locally Superficial BCC Erythematous macule or thin plaque More common on trunk and extremities Younger age (57) Growth pattern is horizontal, can have extensive lateral spread Morpheaform BCC Flat, atrophic lesion or illdefined plaque Scar-like lesion Indurated Frequently much more extensive tumor that clinically visualized 8

9 Micronodular Basal Cell Carcinoma Macules, papules or elevated plaques Very Destructive High Recurrence Rate Subclinical Spread Squamous Cell Caricinoma 9

10 Squamous Cell Carcinoma Second most common type of skin cancer If treated early, 100% curable If untreated, can metastasize: higher risk on lip, ear, genital mucosa Caused by large amount of total accumulated lifetime sun exposure SCC in situ (aka Bowen s Disease) Squamous Cell Carcinoma 10

Keratoacanthoma Variant of SCC Rapidly enlarging papule that evolves into a crateriform

Areas NMSC- Treatment - Curettage and electrodesiccation for small and superficial lesions

excision with 4-6 mm margins for low risk lesions - Standard excision with > 6 mm margins

11 Keratoacanthoma Variant of SCC Rapidly enlarging papule that evolves into a crateriform nodule with a keratotic core May spontaneously resolve with atrophic scarring Sun-Exposed Areas NMSC- Treatment - Curettage and electrodesiccation for small and superficial lesions cure rates as high as 97-98% have been reported for carefully selected lesions - Standard excision with 4-6 mm margins for low risk lesions - Standard excision with > 6 mm margins for high risk lesions - Mohs micrographic surgery - Radiation therapy for non-surgical candidates 11

Wide Local Excision With Margins Pathology Specimen Processing: Bread Loafing Technique Mohs surgery is indicated when: The edges of

cosmetically sensitive or functionally critical area of the body (such as eyelids, nose, ears, lips, fingers, toes, and genitals) The

12 Wide Local Excision With Margins Pathology Specimen Processing: Bread Loafing Technique Mohs surgery is indicated when: The edges of the cancer (clinical margins) cannot be clearly defined Prior treatment has failed, i.e. recurrent tumor The cancer is located in a cosmetically sensitive or functionally critical area of the body (such as eyelids, nose, ears, lips, fingers, toes, and genitals) The histologic pattern of the cancer is aggressive (e.g., morpheaform, infiltrative, metatypical BCC, anaplastic SCC) The patient is immunosuppressed The cancer is > 2cm on the trunk or extremities The patient has a genetic syndrome with high risk for skin cancer (i.e. XP, BCC nevus syndrome) Cancer arising in: prior radiated skin, traumatic scar, osteomyelitis, area of chronic inflammation/ulceration 12

13 Pathology Specimen Processing: Mohs Technique 13

14 14

NMSC - Treatment Radiation Use if surgery is

procedure Disadvantages: Lack of margin control

time, unlike surgery) Prolonged course of therapy

15 NMSC - Treatment Radiation Use if surgery is contraindicated Advantages: avoidance of invasive procedure Disadvantages: Lack of margin control Poor cosmesis in some patients (scars worsen with time, unlike surgery) Prolonged course of therapy Increased risk for future skin cancers Higher recurrence rates 15

NMSC Medical management Topical 5-fluorouracil for AKs, superficial BCCs, and selected SCCs in situ Topical imiquimod induces interferon-alpha and other cytokines, promotes Th1-type immunity Cure

Used for KA rather than for BCC or other forms of invasive SCC Oral retinoid prophylaxis Usually for multiple KAs Risk Factors for Non-Melanoma Skin Cancer Fair skin, freckling, red hair, always

16 NMSC Medical management Topical 5-fluorouracil for AKs, superficial BCCs, and selected SCCs in situ Topical imiquimod induces interferon-alpha and other cytokines, promotes Th1-type immunity Cure rates for nodular BCC range from 53-75%, higher cure rates for superficial BCC NMSC - Medical Management Intralesional interferon-α-2b 3x weekly for 3 weeks Intralesional fluorouracil or methotrexate Used for KA rather than for BCC or other forms of invasive SCC Oral retinoid prophylaxis Usually for multiple KAs Risk Factors for Non-Melanoma Skin Cancer Fair skin, freckling, red hair, always burns/never tans Environmental exposures: Sun exposure, tanning beds, ionizing radiation, chemicals (arsenic), human papillomavirus, cigarette smoking Chronic, non-healing wounds, DLE, LP, LSA Organ transplantation 16

17 Melanoma Melanoma Malignant tumor arising from melanocytes Majority are brown-black due to melanin deposition, but some are skin-colored to pinkred (i.e. amelanotic) Photographs courtesy of Kenneth Linden, MD,PhD Melanoma 17

Melanoma The ABCDE s of Melanoma ASSYMETRY: -If you were to

BORDER IRREGULARITY: -Jagged or blurred edges rather than

COLOR VARIATION: -Two or more different colors are present.

18 Melanoma The ABCDE s of Melanoma ASSYMETRY: -If you were to fold it in half, the two sides wouldn t match up. BORDER IRREGULARITY: -Jagged or blurred edges rather than smooth, continuous line. COLOR VARIATION: -Two or more different colors are present. DIAMETER: -Any sudden or continuing growth -Any mole larger than 6mm (pencil-top eraser) EVOLUTION: -Change over time Melanoma 18

19 Melanoma Superficial Spreading Melanoma Most common type Age Trunk of men, legs of women 50% arise de novo and 50% arise in a pre-existing nevus Can be < 5mm 19

Nodular Melanoma Arises as a de novo vertical

Lentigo Maligna Melanoma Chronically sun

In situ precursor to invasive lentigo maligna

20 Nodular Melanoma Arises as a de novo vertical growth phase tumor without the pre-existing horizontal growth phase Diagnosed at a thicker, more advanced stage Poorer prognosis Lentigo Maligna Melanoma Chronically sun damaged skin Mostly on the face Slow growing In situ precursor to invasive lentigo maligna melanoma Acral Lentiginous Melanoma Palms, soles, around nails 20

Pigmented nail streaks Possibility of melanoma should be considered for all pigmented nail bands in fairskinned

the periungual tissues and valuable clue to diagnosis of subungual melanoma If melanoma is suspected: Excisional

lesion Saucerization biopsy thick disc of tissue removed with a curved blade Incisional biopsy if: Impractical to

21 Pigmented nail streaks Possibility of melanoma should be considered for all pigmented nail bands in fairskinned individuals, especially if darkly pigmented, irregularly pigmented, or width > 3mm Hutchinson sign: Pigmentation of the periungual tissues and valuable clue to diagnosis of subungual melanoma If melanoma is suspected: Excisional biopsy with 1-2mm margins is best Prevents sampling error Enables pathologist to assess overall architecture of the lesion Saucerization biopsy thick disc of tissue removed with a curved blade Incisional biopsy if: Impractical to perform a full excision (i.e. tumor is too large to be excised, sensitive location) Urgent Derm Referral if uncomfortable doing biopsy 21

22 Surgical Excision How big do the margins need to be? Who gets a Sentinel Lymph Node Biopsy? Primary melanomas > 0.75mm Breslow Depth Reasons to proceed with SLN biopsy Obtain most complete and accurate diagnostic and staging information Institute early therapeutic complete lymph node dissection Impacts disease-free survival but not overall survival Institute adjuvant therapy Gain entry into clinical trial for new adjuvant therapies Disadvantage of SLN biopsy Morbidity from completion lymphadenectomy chronic lymphedema Treatments for metastatic melanoma Chemotherapy i.e. interferon, dacarbazine Immunotherapy IL-2 CTLA-4 blockade PD-1 inhibition Molecularly targeted therapy targeting the cell signaling pathways involved in melanoma progression BRAF/MEK inhibitors 22

carcinoma Merkel cell carcinoma Dermatofibromasarcoma protuberans Undifferentiated pleomorphic sarcoma

23 Prognosis Patients with Stage IA melanoma have 10 year survival expectancy of > 95% Median survival time for stage IV patients is 9 months Other Types of Skin Cancer Atypical fibroxanthoma Microcystic adnexal carcinoma Merkel cell carcinoma Dermatofibromasarcoma protuberans Undifferentiated pleomorphic sarcoma Sebaceous carcinoma And many more.. Encourage self skin exams (Images and text from the American Academy of Dermatology) 23

Encourage self skin exams (Images and text from the American Academy of Dermatology) Ultraviolet Radiation Sunlight consists of two types of harmful ultraviolet (UV) rays that

In addition to causing skin cancer: UVA rays can prematurely age your skin, causing wrinkles and age spots and can pass through window glass.

Even on cloudy days, UV rays can penetrate the skin.

24 Encourage self skin exams (Images and text from the American Academy of Dermatology) Ultraviolet Radiation Sunlight consists of two types of harmful ultraviolet (UV) rays that reach the earth ultraviolet A (UVA) rays and ultraviolet B (UVB) rays. Exposure to either can lead to skin cancer. In addition to causing skin cancer: UVA rays can prematurely age your skin, causing wrinkles and age spots and can pass through window glass. UVB rays are the primary cause of sunburn and are blocked by window glass. Ultraviolet Radiation The sun emits harmful UV rays year round. Even on cloudy days, UV rays can penetrate the skin. The United States Department of Health & Human Services and the International Agency of Research on Cancer have declared ultraviolet (UV) radiation from the sun and artificial sources, such as tanning beds and sun lamps, as a known carcinogen (cancer causing substance). There is no safe way to tan. Every time you tan, you damage your skin. As this damage builds, you speed up the aging of your skin and increase your risk for all types of skin cancer. 24

erythema dose (MED) in protected and unprotected skin SPF = MED (protected) MED (unprotected) Is SPF 100 better than SPF 30?

25 What is SPF? DETERMINATION OF THE SUN PROTECTION FACTOR: 20 human subjects Skin type I or II Instrumentation: light source which mimics solar spectrum Procedure: determine minimal erythema dose (MED) in protected and unprotected skin SPF = MED (protected) MED (unprotected) Is SPF 100 better than SPF 30? How to Select A Sunscreen The best sunscreen is the one that you will actually use again and again! Creams are best for dry skin and face Sticks are good to use around the eyes Combination products: cosmetics and moisturizers Avoid combination sunscreens/insect repellants Sprays current FDA regulations on testing and standardization do not pertain to spray sunscreens 25

Water resistance. Sunscreen helps to protect your skin from sunburn, early skin aging, and skin cancer.

26 Sunscreen Recommendations The American Academy of Dermatology recommends everyone use sunscreen that offers the following: Broad-spectrum protection (protects against UVA and UVB rays). Sun Protection Factor (SPF) 30 or greater. Water resistance. Sunscreen helps to protect your skin from sunburn, early skin aging, and skin cancer. Seek shade when your shadow is shorter than you are Wear sleeves, pants, a wide-brimmed hat, and sunglasses whenever possible. 26

When should patients use sunscreen? Every day. The sun emits harmful ultraviolet (UV) rays year round.

On a cloudy day, up to 80 percent of the sun s UV rays can pass through the clouds.

Snow reflects 80 percent of the sun s rays, and sand reflects 25 percent of the sun s rays.

Use enough sunscreen to generously coat all skin that will be not be covered by clothing.

To be sure you use enough, follow this guideline: One ounce, enough to fill a shot glass, is considered the amount

27 When should patients use sunscreen? Every day. The sun emits harmful ultraviolet (UV) rays year round. Even on cloudy days, harmful UV rays can penetrate your skin. On a cloudy day, up to 80 percent of the sun s UV rays can pass through the clouds. Snow and sand increase the need for sunscreen. Snow reflects 80 percent of the sun s rays, and sand reflects 25 percent of the sun s rays. How much suncreen should be used? Use enough sunscreen to generously coat all skin that will be not be covered by clothing. Ask yourself, Will my face, ears, arms, or hands be covered by clothing? If not, apply sunscreen. To be sure you use enough, follow this guideline: One ounce, enough to fill a shot glass, is considered the amount needed to cover the exposed areas of the body. Adjust the amount of sunscreen applied depending on your body size. Most people only apply percent of the recommended amount of sunscreen. Apply the sunscreen to dry skin 15 minutes BEFORE going outdoors. To protect your lips, apply a lip balm or lipstick that contains sunscreen with an SPF of 30 or higher. Re-apply sunscreen approximately every two hours or after swimming or sweating heavily 27

Sunscreen manufacturers will no longer claim that a sunscreen is waterproof or sweat proof. This is not possible because all sunscreen eventually washes off.

28 New FDA Sunscreen Regulations On the label, you ll see whether the sunscreen: Protects against UVB and/or UVA rays. Reduces the risk of skin cancer and early skin aging in addition to helping prevent sunburn, or just protects against sunburn alone. Is water-resistant up to 40 or 80 minutes. Sunscreen manufacturers will no longer claim that a sunscreen is waterproof or sweat proof. This is not possible because all sunscreen eventually washes off. In order to reduce the risk of skin cancer and early skin aging, the sunscreen must offer two things: broad-spectrum protection (protects against UVA and UVB rays) and an SPF of 30 or higher. Without both, the sunscreen only helps prevent sunburn. Will using sunscreen limit levels of Vitamin D? Using sunscreen may decrease skin s production of vitamin D. Vitamin D in sunscreen users vs. non-users Vitamin D in dark-skinned individuals, women, and people in northern climates in winter Controversy about Vitamin D optimum levels, health benefits Tanning salon industry Nevertheless: Adequate vitamin D should be obtained from diet and supplements, NOT UV radiation More on Vitamin D Many people can get the vitamin D they need from foods and/or vitamin supplements. This approach gives you the vitamin D you need without increasing your risk for skin cancer. 28

cancer Many skin cancers are curable if diagnosed and treated early Remember the ABCDEs of Melanoma Encourage

29 Foods rich in Vitamin D Fish oils (salmon, mackerel, tuna) Fortified milk/yogurt Egg yolks Cheese Beef or calf liver Mushrooms exposed to UV light Conclusion Exposure to UV light is the most preventable risk factor for skin cancer Many skin cancers are curable if diagnosed and treated early Remember the ABCDEs of Melanoma Encourage patients to use sunscreen/sun protective clothing regularly Incorporate a skin exam in your routine when possible 29

Cutaneous Malignancies: A Primer COPYRIGHT. Marissa Heller, M.D.

Cutaneous Malignancies: A Primer Marissa Heller, M.D. Associate Director of Dermatologic Surgery Department of Dermatology Beth Israel Deaconess Medical Center December 10, 2016 Skin Cancer Non-melanoma