Skin Tumors

Front 1

Multi-step/”multi-hit” process

Back 1

accumulation of mutations
+
genomic “instability”
Less efficient DNA repair (bad helicases, etc)

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UVA

Back 2

penetrates to deep dermis
Not as effective as UVB in causing biological change
Immediate tanning (b/c the melanocytes release all their melanin to protect the skin)

Photoaging

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UVB

Back 3

penetrates epidermis to upper dermis
Responsible for most biological effects
Reddens skin in ~6 hrs
Delayed Tanning
48–72 hrs

Carcinogenesis

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Pyrimidine dimers

Back 4

cyclobutane and 3,4-photoproducts (the result of UVB)

Front 5

Indirect DNA damage (UVA)

Back 5

Reactive oxygen species created(H2O2, O)
Guanine most susceptible

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p53

Back 6

Key tumor suppressor
Halts progression into S phase of damaged cells
Promotes proofreading of damaged DNA
Most commonly mutated gene in human cancer
Expression elevated in Caucasians with chronic sun exposure
70% have p53 clones with missense mutation
Severe DNA damage=apoptosis
Mutated p53 clones are resistant to apoptosis

Front 7

Patched - Hedgehog Signaling

Back 7

Important in embryogenesis and many tumors (BCC, esp.)
Patched, Sonic Hedgehog and Smoothened
Highly conserved (studied in Drosophila sp.)

Front 8

Gorlin’s syndrome

Back 8

(Basal Cell Nevus Syndrome)
Palmoplantar pits, odontogenic keratocysts, calcification of the falx cerebri, bifid ribs, meduloblastoma, macrocephaly, frontal bossing/wide nasal root/coarse facies

Front 9

What is the most common mutation in basal cell cancers?

Back 9

Patched -Hedgehog signaling

Front 10

Actinic Keratoses

Back 10

Pink, relatively poorly demarcated, scaly patches & plaques on the sun-exposed skin
Symptomatic at times
Increasing prevalence with age (>80% over 60yo)

Front 11

Actinic Keratoses (prognosis)

Back 11

Spontaneous regression
Persistence
Evolve into SCC
1-3% chance progression to invasive SCC

Front 12

What does actininc keratoses progress to?

Back 12

squamous cell cancer

Front 13

AK treatment

Back 13

Cryotherapy for an isolated AK
Field treatment:
-topical 5-fluorouracil cream
-Aldara (imiquimod)
TCA
-Photodynamic Tx
Broad spectrum sunscreens
Prevents and allows resolution of AKs
Surgery?

Front 14

Squamous Cell Carcinoma

Back 14

In-situ and invasive forms
Painful, erythematous keratotic plaques/ nodules sometimes with ulceration
Head, Neck, arms/hands of men
-Chronic ulcers
-HPV link (immunosuppressed)
65-fold increased risk in
OTR

Front 15

Risk Factors for Squamous Cell Carcinoma

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Skin type
UV or ionizing radiation
-Cumulative and recent sunlight (esp. AKs)
Heredity (genomics)
Smoking?
Arsenic exposure
HPV
-Immunosuppression & OTRs

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SCC risk for metastases

Back 16

> 2cm-->9% vs 30%
>4mm invasion
Anatomic location-->11% lip
Immunosuppression-->~6% of mortality in OTRs
Perineural involvement
Bad histology
Recurrence-->25-45%
Etiology-->~20% (Marjolin’s ulcer)

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SCC treatment

Back 17

Standard Excision
Curettage and Electrodesiccation
Mohs
Imiquimod
Cryosurgery
Radiation Therapy
PDT
Laser
5-FU

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Basal Cell

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Most common malignancy period
Incidence near 1 million annually
80% of all nonmelanoma skin cancer

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Basal Cell Risk Factors

Back 19

skin type, UV or ionizing radiation exposure, heredity, arsenic exposure, immunosuppression?

10 fold increase for 2ndy BCC

Front 20

Basal Cell descriptors of skin

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Erythematous pearly plaque
With central ulceration
Associated telentatasia (small dilated blood vessels)
Slowly progressing

Front 21

many flavors of Basal Cell Carcinoma

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*****nodular, pigmented, cystic, superficial, morpheaform

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BCC Treatment (and 5 year recurrence rates)

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Curettage and Electrodesiccation (7.7%)
Standard Excision (10.1%)
Mohs (1%)
Imiquimod
Cryosurgery(7.5%)
Radiation Therapy (8.7%)
PDT
Laser
5-FU
No Treatment

Front 23

Mohs Indications ****

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****Recurrent tumors
Location (peri-nasal, orbital, auricular, oral, hands, genitalia)
Indistinct margins
Aggressive histology (high recurrence risk)

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Mohs Micrographic Surgery

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Excision with margin control
99% cure long term
Tissue sparing
2 vs 4-6 mm margins
Abused?
Fellowship training

Front 25

ABCDE of Melanoma

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Asymmetry
Border Irregularity
Color variation
Diameter
Evolution

Front 26

****What is the most important prognostic sign for melanoma?

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Breslow's Thickness (mm)

<0.75 mm = 99% survival
>3 mm = 46% survival

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melanoma treatment

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surgery

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Surgical Treatment of Melanoma

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-Early identification and COMPLETE REMOVAL WITH MARGINS are key
-Appropriate surgical margins determined by tumor thickness
-The thicker the tumor, the worse the prognosis
NO CONTROLLED STUDY HAS SHOWN ELECTIVE LYMPH NODE DISSECTION IMPROVES SURVIVAL
-Recurrence has been noted decades after removal

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Non-Melanoma Skin Cancer

Back 29

95%
Actinic Keratosis
Squamous Cell Carcinoma
Basal Cell Carcinoma

Front 30

UVA light spectrum

Back 30

320-400 nm

Front 31

UVB light spectrum

Back 31

280-320 nm

Front 32

UV light spectrum

Back 32

100-400 nm

Front 33

UV Radiation as Complete Carcinogen

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Initiation: (UVB) Direct DNA damage mutations (affect cell cycle and division)
Promotion: (UVA/UVB) Reactive Oxygen Species (Damages biological molecules)
Progression: (UVB) Additional mutation load (metastasis), loss of apoptosis

Front 34

Which stages of UV radiation lead to complete carcinogen

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All 3 stages:
initiation, promotion, progression

Front 35

What happens when Hedgehod is present?

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-Patched (PTCH1) is normally next to Smoothened (SMO)
-When Hedgehog is present, smoothened dissociates from Patched.
-Smoothened alone results in Nuclear Transcription (CI and GLI)

Front 36

Estimated melanoma in 2007

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~60,000 melanoma patients

>8,000 deaths

Front 37

What populations are most susceptible to skin CA?

Back 37

-Outdoor workers
-Organ Transplant Recipients (OTR) b/c ~6% die from cutaneous SCC

Front 38

Why does Skin Cancer Incidence increase with Age?

Back 38

1- increase sun exposure
2- less ability to rapair cells
3- more mutations

Front 39

What is a better sunscreen: sun resistant or sun proof?

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Proof is better because it is more resistant to being washed off.

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2 Types of Sunscreens

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Physical
Chemical

Front 41

Physical Sunscreens

Back 41

Titanium Dioxide and Zinc Oxide
- scatter, messy, less iritancy

Front 42

Until what age should children be kept inside?

Back 42

6 months old

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Chemical Sunscreens

Back 43

Avobenzone, Cinnamates, Salicylates
- absorb and dissociate...poor photostability (unless complexed)...studies may inaccurately suggest increase risk of skin cancer

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Ecamsule

Back 44

(Mexoryl SX)

Anthelios from L'Oreal

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MED

Back 45

minimum erythema dose

Front 46

SPF system

Back 46

based on ratio of MED in protected to unprotected skin

SPF only grades UVB...we don't currently advertise UVA protection

Front 47

SPF measures

Back 47

only erythema
not other deleterious effects (collagen, immunosuppression...)

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Bottom Line of Sunscreen

Back 48

Only works if applied properly

Front 49

Broad Spectrum labeling

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UVA scoreage currently not reported to general population

Front 50

"Restless Epithelium" Concept

Back 50

when you have actinic keratosis...it can either become normal skin or squamous cell carcinoma depending on skin reaction

Front 51

What are the benefits of Mohs Micrographic Surgery?

Back 51

smaller margins and better cure rate

(important if there is not a lot of extra skin)

Front 52

What is the difference between ephelides and lentigo?

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Ephelides disappear in the winter but Lentigos stay

Front 53

Ephelides

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freckles...yellowish/brown macules develop with sun exposure

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lentigo

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A benign, acquired brown macule resembling a freckle except that the border is usually regular and microscopic elongation of rete ridges is present, with increased melanocytes and melanin pigment in the basal cell layer

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spitz nevus

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uesd to be called a juvenille melanoma...but not related to melanoma

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Amelanotic melanoma

Back 56

melanoma without pigment

Front 57

Nail Bed Melanoma

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-Variant of acral-lentiginous melanoma
-Manifested by streaks of pigmentation on the nail as well as pigmentation emerging from under and around the nail

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Acral-Lentiginous Melanoma

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-Melanoma of the volar hands and feet
-Radial growth first

(usually pretty bad b/c they are deep)

Front 59

Nodular Melanoma

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-Isolated nodule without typical pigment spread
-Poor prognosis

Front 60

Superficial Spreading Melanoma

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Nevi may meet criteria
-History of change or symptom most important

Front 61

Lentigo Maligna Melanoma

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-Most occur on the face
-Usually start as a noninvasive process
-Any thickening suggests the progression to invasive melanoma

Front 62

Recommended Excision Margins for:
in situ
0-2 mm
>2 mm

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in situ = 0.5 cm
0-2 mm depth = 1 cm margins
> 2 mm depth = 2 cm margins

Front 63

Sentinel Lymph Node Biopsy for Melanoma

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-No overall survival benefit demonstrated
-May provide prognostic information
-Significant morbidity with basin dissection
-Less sensitive in H&N cases of melanoma
-In the end, a highly individual decision

...don't really say much...could get you in clinical trial

Front 64

What is the most common type of melanoma?

Back 64

Superficial Spreading Melanoma