Skin Cancer

Question 1

What are the 2 main types of skin cancer?

Answer 1

Melanoma/non melanoma (BCC/SCC)

Question 2

What is a key factor in melanoma survival?

Answer 2

Tumour depth

Question 3

What are the Breslow Thickness’?

Answer 3

4mm=50%, Metastases = 5%

Question 4

What do you look for in melanoma diagnosis?

Answer 4

Asymmetry, Border, Colour, Diameter, Evolution

Question 5

What is a known sign of melanoma?

Answer 5

Ugly ducking sign

Question 6

What is the clinical presentation of BCC?

Answer 6

Slow growing lump or non healing ulcer. Painless. Translucent/pearly. Visible arborising blood vessels. Central ulceration (rodent), scaly plaque if superficial. If infiltrative morphoeic. Locally invasive, usually >40 yo but can be younger

Question 7

What is the clinical presentation of SCC?

Answer 7

Hyperkeratotic lump or ulcer, arises on sun damaged skin. Grows fast, can be painful &/or bleed. Majority-well differentiated low risk, minority opposite. Metastases : 5%, poor prognosis at this stage. Precursor lesions

Question 8

What are the precursor lesions of SCC?

Answer 8

Actinic keratoses and Bowen’s disease (carcinoma-in-situ)

Question 9

What is the self resolving skin lesion that can occur in SCC?

Answer 9

Keratoacanthoma

Question 10

What is required for a finding of Actinic Keratoses?

Answer 10

Multiple lesions- evidence for a field of abnormality

Question 11

What are high risk sites in SCC?

Answer 11

Ear, lip and scalp

Question 12

What are some risk factors for Skin cancer?

Answer 12

Sun exposure, genetic predisposition, immunosuppression, HPV infection, other environmental carcinogen - coal tar, smoking etc

Question 13

What are the 6 skin types?

Answer 13

Skin type I - always burns, never tans
Skin type II - usually burns, can tan
Skin type III - can burn, but usually tans
Skin type IV - always tans, never burns
Skin type V - ‘brown’ skin
Skin type VI - ‘black’ skin

Question 14

What sun exposure pattern is likely to be the cause of SCC?

Answer 14

Chronic, cumulative UV exposure

Question 15

What sun exposure pattern is likely to be the cause of BCC and Melanoma?

Answer 15

Intermittent, intense sunburn episodes

Question 16

What conditions can cause a genetic susceptibility to skin cancer?

Answer 16

DNA repair syndromes e.g. Xeroderma Pigmentosum, Albinism, Naevoid BCC (Gorlin’s) syndrome

Question 17

What environmental carcinogens are risk factors for skin cancer?

Answer 17

Ionising radiation, arsenic, coal tar, trauma, chronic ulceration etc

Question 18

What does Xeroderma Pigmentosum cause in relation to skin cancer?

Answer 18

photosensitivity  
 skin cancers on UV-exposed sites
 neurological degeneration
 Increased risk of other cancers
 Defect in one of seven Nucleotide 
Excision Repair (NER) genes (XPA - G)

Question 19

What is Naevoid BCC (Gorlin’s) Syndrome?

Answer 19

Autosomal dominant familial cancer syndrome

Question 20

What are the major features of Gorlin’s?

Answer 20

Major features
early onset/multiple BCCs
palmar pits
jaw cysts
ectopic calcification falx

Question 21

What are the minor features of Gorlin’s?

Answer 21

Minor features
skeletal abnormality
OFC >97th centile
cardiac/ovarian fibroma
medulloblastoma

Question 22

What level of risk are Hereditary Type VII collagen deficiency (RDEB) of developing skin cancer ?

Answer 22

High risk

Question 23

What are the hallmarks of cancer?

Answer 23

Autonomous growth signals
Insensitivity to anti-growth signals
Resist cell death (apoptosis)
Limitless potential to divide
Angiogenesis
Invasion and metastasis

Question 24

What are the emerging hallmarks and enabling characteristics of cancer?

Answer 24

Deregulating cellular energetics and avoiding immune destruction. Genome instability and mutation and tumour promoting inflammation

Question 25

What light causes sunburn and is stopped by window glass?

Answer 25

UVB

Question 26

What light is stopped by sunscreens, yet doesn’t usually cause sunburn?

Answer 26

UVA

Question 27

Describe the damage to DNA caused by UVA?

Answer 27

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

Question 28

Describe the damage to DNA caused by UVB?

Answer 28

Direct DNA damage-1000x more damaging than UVA, only when sun is directly overhead

Question 29

What are some types of DNA damage?

Answer 29

Altered or missing base, incorrect base, UV signature mutation: pyrimidine dimer, insertion/deletion, strand break, crosslinking

Question 30

What occurs in the formation of UV signature mutations?

Answer 30

UV light induces covalent linkages producing cyclobutane pyrimidine dimers (CPDs) and 6,4 photoproducts. The photoproducts interfere with pairing during replication and lead to mutations. CPDs are most common, 3x more frequent than 6,4s, but 6,4s are more mutagenic.

Question 31

What happens when a mutator phenotype is formed?

Answer 31

Cells accumulate further mutations at a greatly increased rate because of failure of DNA repair

Question 32

What types of DNA repair exist?

Answer 32

Nucleotide excision repair, base excision repair, double strand break repair, mismatch repair

Question 33

What is the principle carcinogen in photocarcinogenesis?

Answer 33

UVB 290-320nm

Question 34

What happens in UV induced immunosuppression?

Answer 34

Dendritic cells lose ability to present antigen
T cells switch from ‘helper’ to ‘suppressor’; regulatory T cells predominate
Keratinocytes & DCs secrete immunosuppressive cytokines

Question 35

Describe the TP53 mutation in skin cancer

Answer 35

TP53 mutation – found in AK, carcinoma-in-situ & SCC
very early event; clonal patches of aberrant p53-cells in normal SE skin
relationship to carcinogenesis not clear
protects cells from apoptosis, allowing accumulation of other mutations