Skin Cancer

Question 1

what are the 2 main types of skin cancer?

Answer 1

non-melanoma skin cancer & melanoma

Question 2

where do the majority of non-melanoma skin cancers arise from?

Answer 2

keratinocytes in the epidermis

Question 3

where do basal cell carcinomas (BCC) arise from?

Answer 3

keratinocytes within the basal layer

Question 4

where do squamous cell carcinomas (SCC) arise from?

Answer 4

the supra basal layers

Question 5

which is the most serious form of skin cancer?

Answer 5

melanoma

Question 6

where do melanomas arise from?

Answer 6

melanocytes scattered along the basal layer of the epideris

Question 7

what do BCCs usually present as?

Answer 7

painless, pearly/transluscent, slow-growing lump or non-healing ulcer, visible arborising blood vessels

Question 8

how do SCCs present?

Answer 8

a number of ways including a warty or crusted growth or a non-healing ulcer (hyperkeratotic lump/ulcer)

Question 9

where do SCCs usually arise?

Answer 9

on sun damaged skin

Question 10

how do SCCs tend to grow?

Answer 10

fast & may be painful

Question 11

do SCCs or BCCs spread around the body?

Answer 11

SCCs spread around the body with serious consequences

BCCs only spread locally

Question 12

which is the most common cancer in 15-24 yr olds?

Answer 12

melanoma

Question 13

are melanomas more common in men or women?

Answer 13

more common in women but more men die

Question 14

what does melanoma survival depend on?

Answer 14

tumour depth

Question 15

what is the ABCDE rule for diagnosing melanomas?

Answer 15

A - asymmetry
B - border
C - colour 
D - diameter
E- evolution

Question 16

what happens in a rodent ulcer presentation of BCC?

Answer 16

central ulceration

Question 17

what happens in a superficial presentation of BCC?

Answer 17

scaly laque

Question 18

what is an infiltrative BCC called?

Answer 18

morphoeic

Question 19

what are the precursor lesions for SCCs & BCCs?

Answer 19

actinic keratoses (AK) & Bowen’s disease (carcinoma in-situ)

Question 20

what is a keratocanthoma?

Answer 20

a self-resolving skin lesion that erupts in sun damaged skin, rather like a little volcano, usually has a central plaque

Question 21

what is field cancerisation?

Answer 21

more severe field change

Question 22

what are the risk factors for skin cancer?

Answer 22

• sun exposure
• genetic predisposition
• immunosuppression
• other environmental carcinogens (coal tar, smoking, ionising radiation, arsenic, trauma, chronic ulceration)
• age
• immunosuppression
• HPV

Question 23

what sun exposure pattern would create a risk of SCC?

Answer 23

chronic, cumulative UV-exposure

Question 24

what sun exposure pattern would create a risk of BCC?

Answer 24

intermittent, intense sunburn episodes

Question 25

what sun exposure pattern would create a risk of melanoma?

Answer 25

intermittent, intense sunburn episodes

Question 26

who are at risk of SCCs?

Answer 26

outdoor workers, famers, sailors, recreational & dedicated sunbathers

Question 27

which genetic conditions increase your risk of skin cancer?

Answer 27

- xeroderma pigmentosum - oculocutaenous albinism - naevoid BCC (Gorlin's) syndrome - recessive dystrophic epidermolysis bullosa

Question 28

what immunological factors can increase your risk of skin cancer?

Answer 28

- organ transplantation

Question 29

what is carcinogenesis?

Answer 29

the process by which a normal cell becomes a malignant cancer cell

Question 30

what is cancer?

Answer 30

an accumulation of abnormal cells that multiply through uncontrolled cell division & spread to other parts of the body by invasion &/or distant metastasis via the blood & lymphatic system

Question 31

what does uncontrolled cell proliferation require in terms of genes?

Answer 31

multi-step gene damage | e.g. gain of function of oncogenes & loss of function of tumour suppressors

Question 32

what is clonal evolution?

Answer 32

a series of mutations that accumulate in successive generations of the cell in a process

Question 33

what are the 6 hallmarks of cancer?

Answer 33

1. autonomous growth signals 2. insensitivity to anti-growth signals 3. resist cell death (apoptosis) 4. limitless potential to divide 5. angiogenesis 6. invasion & metastasis

Question 34

how can damage occur to our DNA causing cancer?

Answer 34

- natural accumulation of DNA damage (cancer is usually a disease of old age) - carcinogens - inherited defects

Question 35

what does UV-A do to our DNA?

Answer 35

indirect DNA damage, much more prevalent, penetrates more deeply into skin

Question 36

what does UV-B do to our DNA?

Answer 36

direct DNA damage, much more damaging than UVA, only when sun is directly overhead

Question 37

what can mutations in genes involved in DNA repair lead to?

Answer 37

a mutator phenotype whereby cells accumulate further mutations at a greatly increased rate because of failure of DNA repair

Question 38

what can damage to genes that control the ingrate of cell devision lead to?

Answer 38

chromosome instability & the accumulation of chromosome abnormalities

Question 39

what does UVB generate?

Answer 39

DNA photoproducts

Question 40

what does UVA induce?

Answer 40

guanine oxidation roduces in DNA

Question 41

what does UV-induced immunosuppression lead to?

Answer 41

- dendritic cells lose the ability to present antigens - T cells switch from helper to suppressor, regulatory T cells predominate - keratinocytes & DCs secrete immunosuppressive cytokines

Question 42

what happens in initiation of photocarcinogenesis & what does this form?

Answer 42

DNA damage forms photoproducts e.g. TP53, RAS mutations

Question 43

what happens in promotion of photocarcinogenesis & what does this form?

Answer 43

activation of signal transduction pathways & inflammation/oxidative stress causes AK

Question 44

what happens in progression of photocarcinogenesis & what does this form?

Answer 44

constitutive cell proliferation & survival. genetic instability. acquire hallmarks of cancer & causes SCC & metastases

Question 45

what do freckles mean in terms of tanning?

Answer 45

you cannot tan & need to protect your skin from sun

Question 46

which skin cancer do sunbeams increase the risk of?

Answer 46

melanomas

Question 47

what are the molecular drivers of BCC?

Answer 47

- genetically homogenous tumour - aberrant hedgehog signalling - involvement of PTCH

Question 48

what gene is TP53?

Answer 48

guardian of the genome

Question 49

what does TP53 do?

Answer 49

protects cells from apoptosis, allowing accumulation of other mutations

Question 50

what are the phototoxic drugs?

Answer 50

``` Voriconazole – antifungal agent Thiazide diuretics NSAIDs Anti-TNF Azathioprine ```

Question 51

how might specific cutaneous HPVS contribute towards cancer development?

Answer 51

- inhibition of apoptosis - delay DNA repair - promote keratinocyte invasion

Question 52

which virus increases the risk of skin cancer?

Answer 52

HPV

Question 53

how can skin cancer be prevented?

Answer 53

- screening/surveillance - treatment of premalignant conditions (cyrcotherapy/surgery) - sunscreens - UVA & UVB avoidance