Skin Cancers and Common Spots Common lesions Skin cancers Non - - PDF document

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Skin Cancers and Common Spots

Lindy P. Fox, MD

Associate Professor Director, Hospital Consultation Service Department of Dermatology University of California, San Francisco

lindy.fox@ucsf.edu

I have no conflicts of interest to disclose

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Outline

• Common lesions
• Skin cancers

– Non‐ melanoma – Melanoma

Common Skin Lesions

• Seborrheic keratosis
• Dermatofibroma
• Pyogenic granuloma
• Sebaceous hyperplasia

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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Dermatofibroma

• Firm, 3‐7 mm slightly rough surfaced, slightly elevated

papules

• Overlying hyperpigmentation
• Firm to palpation; Dimple sign
• Often at sites of minimal trauma

– Bug bite, ingrown hair, etc

• Treatment : Reassure, cryotherapy, removal
• Often recur after removal
• Association: Multiple (>15) of sudden onset may

rarely signal T cell dysregulation (Lupus, HIV)

Cherry Angioma

• Very Common
• Increases with age (senile angioma)
• F>M (?hormonal)
• 1‐5 mm bright red dome‐shaped papule
• Not easily compressible
• Association: None
• Complications: None

Pyogenic Granuloma

• Friable, 5‐10 mm papule
• Occurs after trauma
• Children and adults
• Biopsy: Excess granulation tissue
• Treatment: Surgical removal (curette),

electrodessication of base

• Complication: Rarely may recur and form satellites

Sebaceous Hyperplasia

• Common, benign
• Single or multiple pink to yellow papules on the face,
• ften with telangiectasias and central dell
• May mimic BCC
• Multiple associated with calcineurin inhibitors
• When associated with sebaceous adenoma or

sebaceous carcinoma, rule‐out Muir Torre (Lynch) syndromes

• Treatment‐ low dose isotretinoin, electrodessication,

laser, shave removal, PDT, cryotherapy

3 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

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%) (Efudex)
• 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 (Solareze)
• BID x 60‐90 days
• Long term treatment (>120 days), moderately effective, side

effects

• Picato (ingenol mebutate); 0.015%, 0.05%
• Face/scalp‐ 0.015% QD x 3d
• Trunk/extrem‐ 0.05% QD x 2d
• Photodynamic therapy

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http://www.crutchfielddermatology.com

AKs treated with 5-fluorouracil 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
• verexposure (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

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Basal Cell Carcinoma‐ Superficial

• Clinically pink, slightly scaly, slightly shiny

patch

• Looks like an actinic keratosis
• May be treated with imiquimod, ED+C

Basal Cell Carcinoma‐ Pigmented

• May be entirely pigmented or there may

be specks of pigment within what

• therwise 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‐ 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

6 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

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

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.

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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

• r biopsy

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

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

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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 – Voriconazole

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 – Switch from voriconazole to another antifungal

• Please refer your organ transplant patients to a

dermatologist for regular skin checks

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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

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

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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

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.

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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 - 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.

Malignant Melanoma

• Asymmetry
• Border
• Color
• Diameter
• Evolution

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Malignant Melanoma

• Asymmetry – Two halves of lesion not

the same

• Border
• Color
• Diameter
• Evolution

Malignant Melanoma

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

Malignant Melanoma

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

and blue

• Diameter
• Evolution

Malignant Melanoma

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

eraser)

• Evolution

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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

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

• BCC

– Vismodegib (Erivedge)

• Hedgehog signaling pathway inhibitor
• Metastatic, relapsed, inoperable, ornot amenable to radiation
• Melanoma
• BRAF inhibitors (V600E mutation)
• Vemurafenib (Zelboraf); Dabrafenib (Tafinlar); trametinib (Mekinist);

cobimetinib (Cotellic)

– Monoclonal Ab to CTLA4

• Ipilimumab (Yervoy)

– Monoclonal Ab to PD-1

• Pembrolizumab (Keytruda); Nivolumab (Opdivo)

– MEK inhibitor

• Trametinib (Mekinist)

NEW Systemic Therapies for the Treatment of Advanced Skin Cancer

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, 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

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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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17 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 50+ (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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Sunscreen Myths

• Antioxidants in sunscreens

– Vit E, Vit C, tea extract, etc – No SPF value, prob no beneficial effect

• Nanoparticles in sunscreens (e.g. zinc and titanium)

– Coated when in sunscreen, do not penetrate intact skin, remain on surface of the skin – No evidence of any consequences when used on intact skin, not sufficient data when there is barrier dysfunction

• 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

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

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Vitamin D

• Typical sunscreen use does not affect Vit D

levels

• Strict use will lead to low Vit D levels
• Supplement those at risk for osteoporosis who
• bey stringent sun-protections practices
• E.g. organ transplant patients

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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