DD 03-07-14 09-10am Skin Cancer slides - Dunnick

Question 1

Skin cancer - prevalence

Answer 1

= most common form of cancer in US
Each year…
- >3.5 million skin cancers Dxed in >2 million ppl
- More new cases of skin cancer than combined incidence of breast, prostate, lung & colon cancers

Question 2

Common Skin Cancer Types

Answer 2

Basal cell
Squamous cell
Melanoma

Question 3

Non-melanoma Skin Cancer - Risk Factors

Answer 3

• Fair skin + geographic areas w/ high UV exposure
• UV radiation is most common cause of BCC
• Ionizing radiation, arsenic or polycyclic hydrocarbon exposure

Question 4

Basal Cell Carcinoma - prevalence, morbidity/mortality

Answer 4

= Most common malignancy in the US

• ~2.8 million are Dxed annually in US
• rarely fatal, but can be highly disfiguring if allowed to grow

Question 5

Basal Cell Carcinoma - Subtypes & prevalence

Answer 5

Superficial (15%)

Nodular (75%)

• Micronodular
• Pigmented (6%)

Infiltrative (5%)

Sclerosing / Morpheaform / Desmoplastic (3%)

Question 6

Superficial BCC

Answer 6

?

Question 7

Nodular BCC

Answer 7

?

Question 8

Desmoplastic/Sclerosing/Morpheaform BCC

Answer 8

?

Question 9

Pigmented BCC

Answer 9

?

Question 10

Hedgehog Alterations in BCC & Treatment

Answer 10

Most BCCs have loss of function of PTCH1
= normally acts to block smoothened (SMO), a transmembrane protein

Vismodegib
= inhibitor of smoothened
= approved in 2012 for treatment of advanced BCC

Question 11

Actinic Keratosis (AK) - defn., prevalence, lead to…

Answer 11

= Intraepidermal neoplasia
= most common pre-cancer affecting >58 million Americans
- ~65% of all squamous cell carcinomas & ~36% of all basal cell carcinomas arise in lesions previously Dxed as AKs

Question 12

Actinic Keratosis - Treatment

Answer 12

Cryosurgery
- Liquid nitrogen (boiling point of -196 C)

Topical…

• 5-fluoruracil
• Imiquimod
• Diclofenac

Photodynamic therapy

Sun protection

Question 13

Squamous cell carcinoma - prevalence

Answer 13

• 2nd most common cutaneous malignancy

- More common in immunosuppressed, esp. organ transplant pts

Question 14

Squamous cell carcinoma - Risk factors

Answer 14

• UV damage
• Thermal injury
• Radiation
• HPV
• Burn scars (Marjolin’s ulcer)
• Chronic injury (i.e. EB)

Question 15

Squamous cell carcinoma - Subtypes

Answer 15

• SCC in situ (Bowen’s disease)
• Keratoacanthoma
• Invasive SCC

Question 16

Keratoacanthoma - distribution, time of growth, appearance

Answer 16

= subtype of squamous cell carcinoma

Distribution- primarily sun-exposed skin

Rapid growth over 6-8 weeks

Size- 1-3 cm

Crateriform endophytic & exophytic nodule w/ central keratin plug

Question 17

Keratoacanthoma - Complications

Answer 17

Deep invasion w/out regression in 10-20%

Question 18

Squamous Cell Carcinoma - appearance & distribution

Answer 18

Hyperkeratotic papule w/ variable size & thickness

Typically found on chronically sun-damaged skin

Question 19

Squamous Cell Carcinoma - complications

Answer 19

Metastasis occurs in 0.3-5%

= more common in SCC of the lip (10-30%)

Question 20

Types of Skin Cancer & Transplant Pts Risks

Answer 20

Kaposi’s sarcoma = 84 fold risk
SCC = 65 fold risk
BCC = 10 fold risk
Melanoma = 3.4 fold risk

Question 21

Skin Cancer & Transplant Pts - Risk factors

Answer 21

Age, Skin type, UV radiation

Genetic Factors

HPV (in 65-90% of SCC)

Level of immunosuppression:

• CD4 count
• Medications
• Heart > Kidney > Liver

Question 22

Skin Cancer & Transplant Pts - Statistics

Answer 22

Non-transplant pts SCC:BCC = 1:4
Transplant pts SCC:BCC = 4:1

Incidence of skin cancer increases w/ # of years post-transplant:

• 0.2-7% after 1 yr
• 47-82% after 20 yrs

Question 23

Non-melanoma Skin Cancer - Treatment

Answer 23

Topical…

• 5-fluoruracil
• Imiquimod

Cryosurgery

Electrodessication & Curettage

Excision

Mohs micrographic surgery

Radiation

Question 24

Malignant Melanoma - ABCD(E) & Ugly Duckling Guidelines

Answer 24

A = Asymmetry
B = Border irregularity 
C = Color variegation 
D = Diameter greater 	than 6 mm
(E = Evolution or change)

Ugly Duckling = if it looks different than other moles on the pt’s body

Question 25

Stages of the Progression of Melanoma

Answer 25

1. Benign Nevus 2. Dysplastic Nevus 3. Radial-Growth Phase 4. Vertical-Growth Phase 5. Metastatic Melanoma

Question 26

Biologic Events & Molecular Changes in Progression of Melanoma - Benign Nevus Stage

Answer 26

- Benign limited growth | - BRAF mutation & Activation of mitogen-activated protein-kinase (MAPK) pathway

Question 27

Biologic Events & Molecular Changes in Progression of Melanoma - Dysplastic Nevus Stage

Answer 27

- Premalignant - Lesions may egress - Random atypia - CDKN2A loss (cyclin-dependent kinase inhibitor 2A) - PTEN loss (phosphatase & tensin homologue)

Question 28

Biologic Events & Molecular Changes in Progression of Melanoma - Radial Growth Phase

Answer 28

- Decrased differentiation - Unlimited hyperplasia - Cannot grown in soft agar - Clonal proliferation - Increased CD1

Question 29

Biologic Events & Molecular Changes in Progression of Melanoma - Vertical Growth Phase

Answer 29

- Continued decreased differentiation - Crosses basement membrane - Grows in soft agar - Forms tumor Loss of E-cadherin Reduction of Reduced TRPM1 (melastatin 1) = melanocyte specific gene Expression of: - N-cadherin - alphaVbeta3 integrin - MMP-2 - Survivin

Question 30

Biologic Events & Molecular Changes in Progression of Melanoma - Metastatic Melanoma Stage

Answer 30

- Continued decreased differentiation - Dissociation from primary tumor - Grows at distant sites - Absent TRPM1 ---> associated w/ metastatic properties

Question 31

Malignant Melanoma - Relative risk

Answer 31

``` Fair skin - 2-3 Excessive sun exposure - 3-5 Immunosuppression - 2-8 MM in 1st degree relative - 2-8 Whites - 12 Large congenital nevus - 17-21 Sporadic dysplastic nevus syndrome - 7-70 FAMMM - 148 ```

Question 32

Melanoma - Epidemiology

Answer 32

- ~76,100 new melanomas will be Dx - ~9,710 ppl expected to die of melanoma = most common form of cancer for young adults 25-29 years old - 2nd most common form of cancer for young people 15-29 years old - One person dies of melanoma every hour (every 57 minutes)

Question 33

Age-standardized death rates in Melanoma

Answer 33

?

Question 34

Malignant Melanoma - Statistics

Answer 34

- Rapidity of increase exceeds all malignancies except for lung cancer in women - Of 7 most common cancers in US, melanoma is only one whose incidence is increasing (1.9% annually)

Question 35

Colorado Cancers Statistics (Cases estimated for 2014)

Answer 35

``` All Cancer: 23,810 Female Breast: 3,780 Prostate: 3,680 Lung & Bronchus: 2,540 Colon & Rectum: 1,720 Melanoma: 1,400 ```

Question 36

Malignant Melanoma - Demographics

Answer 36

Affects all age groups - Median 53 yo Distribution: - Blacks- acral and mucosa - Men- back - Women- legs (torso in females age 15-29, perhaps due to tanning)

Question 37

Malignant Melanoma - Clinical Variants

Answer 37

Superficial spreading - 70% Nodular - 15-30% Lentigo maligna melanoma - 5% Acral lentiginous - 2-10%

Question 38

Breslow Depth

Answer 38

Tumor invasion in millimeters

Question 39

Clark Levels

Answer 39

``` I Epidermis II Papillary Dermis III Mid Dermis IV Reticular Dermis V SubQ fat ```

Question 40

Malignant Melanoma - Treatment

Answer 40

Surgical excision - MM in-situ: 0.5 cm w/ SubQ tissue - MM 1 mm: 1-2 cm margins to fascia w/ sentinel node biopsy

Question 41

Mutations in Melanoma

Answer 41

Frequency of Mutations in Melanoma: - BRAF 50% - NRAS 20% - Kit 2% - GNAQ 2% *Vemurafenib for BRAF V600E

Question 42

Vemurafenib

Answer 42

- BRAF inhibitor

Question 43

Malignant Melanomaand Tanning

Answer 43

- # of skin cancer cases due to tanning may be higher than # of lung cancer cases due to smoking - UV radiation (UVR) is a proven human carcinogen, put in Group 1 (includes plutonium & cigarettes) - Just one indoor tanning session increases risk of melanoma by 20% - Each additional session increases risk 2%  Of melanoma cases among 18-to-29-year-olds who had tanned indoors, 76% were attributable to tanning bed use.   HB1054 Calls for a ban on tanning in Colorado <18

Question 44

Skin Cancer Prevention

Answer 44

- Sun avoidance (Avoid mid-day sun) - Sun protective clothing (Long-sleeved shirt) - Shade - Sunscreen - Sombrero (Wide-brimmed Hat) - Sunglasses

Question 45

What is SPF?

Answer 45

= "Sun Protection Factor" = only reflects product’s screening ability for UVB rays Sunscreen w/ SPF 15 prolongs burning time by a factor of 15. - i.e., it would take 15x longer to develop sunburn than w/out sunscreen

Question 46

When should sunscreen be used?

Answer 46

- should be applied every day to sun exposed skin, not just if you are going out into the sun. - Windows protect against UVB, but not UVA - Even on cloudy days up to 80% of sun’s UV rays pass through clouds. - Sand reflects 25% of the sun’s UV rays - Snow reflects 80% of the sun’s UV rays

Question 47

How much sunscreen should be used and how often should it be applied?

Answer 47

- Apply to dry skin 15-30 mins before going outdoors. - 1 oz of sunscreen (shot glass) to cover exposed areas of body. - Reapply at least every 2 hours or after swimming or sweating heavily. - Even “water-resistant” sunscreens lose their effectiveness after 40 minutes in the water.

Question 48

Will sunscreens limit amount of vitamin D I get?

Answer 48

- Individuals concerned about not getting enough vitamin D should discuss with their doctor the options for obtaining vitamin D through foods and/or a vitamin supplement.

Question 49

Skin Cancer Prevention

Answer 49

Get Vitamin D safely through healthy diet - may include vitamin supplements Check your birthday suit on your birthday - Self skin examinations - See dermatologist if notice anything changing, growing or bleeding