Skin Cancer Flashcards
2 main types of skin cancer
Keratinocyte skin cancer - basal cell carcinoma and squamous cell carcinoma
Melanoma
Why may the incidence of non-melanoma skin cancer in Scotland be increasing?
Cheap air travel
More leisure time
Sun-seeking behaviour
Ageing population
What does melanoma arise from?
Melanocytes - pigment forming cells scattered along the basal layer
Which skin cancer is most likely to spread - keratinocyte skin cancer or melanoma?
Melanoma as melanocytes migrate into the skin from the neural crest and move around
What does melanoma survival depend on?
Breslow thickness
What is Breslow thickness?
The measurement of depth of the melanoma from the surface of the skin to the deepest point of the tumour
5 year survival of melanoma with:
- Breslow thickness <1mm
- Breslow thickness >4mm
- Metastases
<1mm = 95-100% >4mm = 50% Metastases = 5%
Diagnosis of melanoma
ABCDE rule
“ugly duckling” sign
Dermoscopy
ABCDE rule in diagnosis of melanoma
A = asymmetry B = border C = colour (change of colour or presence of 2/3 different) D = diameter (>0.7mm is likely to be melanoma) E = evolution (speed of change, changing over weeks/months)
“Ugly duckling sign”
The mole suspected as being a melanoma looks very different to all other moles
Why is dermoscopy useful in the diagnosis of melanoma?
It allows us to see a magnified view showing pigment pattern
Atypical mole syndrome
Genetic condition where patients have multiple atypical moles. These patients are more likely to develop melanoma but are harder to monitor as they have so many moles
Clinical presentation of basal cell carcinoma
Slow growing lumps or ulcers that are painless
‘Pearly’ or translucent
Visible, arborising blood vessels
Central ulceration
Locally invasive but rarely metastasise
Can look scar-like with ill-defined edges
Different types of basal cell carcinoma
May present as scaly plaque - superficial
Nodular or nodulystic
Infiltrative - “morphoeic”
Pigmented
Clinical presentation of squamous cell carcinoma
Hyperkeratotic (crusty) lump or ulcer
Arises on sun damaged skin - often seen in elderly
Grow fairly fast
May be painful and/or bleed
Risk of metastases of squamous cell carcinoma
3-5%
Common sites for squamous cell carcinoma (higher risk)
Ear, lip, scalp
Keratoacanthoma
Self resolving squamous cell carcinoma
Precursor lesions for squamous cell carcinoma
Actinic keratosis
Bowen’s disease - carcinoma in situ
Where to squamous cell carcinomas tend to spread to when they metastasise?
Lymph nodes and bone
Rarer sites for squamous cell carcinoma
Chronic ulceration/wounds/scarring
Actinic keratoses
Pre-cancerous skin lesions. Precursors for non-melanoma skin cancers
What do actinic keratoses tell us about the skin?
That the skin is damaged
Actinic keratoses are highly associated with the risk of developing what?
Squamous cell carcinoma or basal cell carcinoma
What is Bowen’s disease?
Carcinoma in situ
Which type of cancer is Bowen’s disease related to?
Squamous cell carcinoma
Risk factors for skin cancer
Sun exposure
Genetic predisposition
Immunosuppression
Other environmental
Genetic predisposition conditions that can cause increased risk for skin cancer
DNA repair syndromes
Albinism
Naevoid basal cell carcinoma syndrome
Epidermolysis bullosa
What is albinism?
A congenital absence of melanin.
There is absence or defect of tyrosinase
Albinism is autosomal dominant/recessive
Recessive
Other environmental factors that are risk factors for skin cancer
Coal tar Smoking Ionising radiation Arsenic Trauma Chronic ulceration
Skin cancer prevention
Behaviour
Clothing
Sunscreens
Regular self surveillance for early detection
Things that fall under behaviour modification in skin cancer prevention
Avoid sun in its height (11am-3pm)
Use shade where possible
Particular care of babies/children
Avoid sunbeds
Things that fall under clothing modification in skin cancer prevention
Tightly woven, loose fitting clothing (dark clothing)
Long sleeves, trousers, skirts, hat, sunglasses
Information you should give about sunscreens in skin cancer prevention
The sunscreen should be broad spectrum (SPF 30+) with UVA protection
You usually only get a 1/3rd of the protection it says
Application is important - apply twice in sufficient quantities, re-apply after swimming or towelling
Oncogene
An overactive form of a gene that regulates cell division and drives tumour formation when activity or copy number is increased
Proto-oncogene
The normal, not yet mutated form of oncogene
Tumour suppressor
Inactive or non functional form of a gene that negatively regulates cell division. It prevents the formation of a tumour when functioning normally
Wavelength of UVB radiation
290-320nm
What does UVB radiation cause direct damage to?
Causes direct DNA damage
When is UVB radiation more damaging than UVA radiation?
It is 1000x more damaging than UVA when the sun is directly overhead
Wavelength of UVA radiation
320-400nm
What does UVA radiation cause indirect damage to?
Causes indirect oxidative damage
True or false: UVB radiation penetrates more deeply into the skin than UVA
False - UVA penetrates more deeply into the skin than UVB
Why are those with skin type I unable to tan?
Pheomelanin is produced instead of eumelanin, and pheomelanin absorbs UV less efficiently. Those with skin type I are unable to tan in a protective way
Sun exposure patterns
> 90% on head, neck, ears, hands, forearms
Outdoor workers
Ageing population
Arises from lifetime cumulative UV exposure
What is melanoma and basal cell carcinoma associated with, relating to UV exposure?
Associated with intermittent burning episodes
Also associated with subbed use
When does up to 80% of sun damage occur?
In first 18 years of life
Childhood sunburn increases the risk of melanoma by how much?
4-fold
Pyrimidine dimers
UV induced DNA lesions
2 types of pyrimidine dimers
Cyclobutane pyrimidine dimers and pyrimidine-pyrimidone photo-products
Which type of pyrimidine dimer is more common and which is more mutagenic?
Cyclobutane pyrimidine dimers are more common
Pyrimidine-pyrimidone photo-products are more mutagenic
How are pyrimidine dimers formed?
By covalent bonding between adjacent pyrimidines on the same DNA strand
How are pyrimidine dimers removed?
Nucleotide excision repair
Steps of nucleotide excision repair
- Recognition of the damaged DNA
- Cleavage of the damaged DNA on the other side of the photoproduct
- DNA polymerase fills the gap, using the undamaged strand as a template
- DNA ligase seals the end
What happens in UV induced immunosuppression?
Regards to Langerhans cells, T cells and cytokines
Depletion of Langerhans cells in the skin and reduced ability to present antigen
Generation of UV induced regulatory T cells with immune suppressive activity
Secretion of anti-inflammatory cytokines by macrophages and keratinocytes
Risk factors for UV induced immunosuppression
Inflammatory or autoimmune conditions
Immunosuppressants
Organ transplant recipients
Which autoimmune conditions can increase risk of UV induced immunosuppression
UC - 23% higher risk of melanoma
Crohn’s - 80% higher risk of melanoma
Immunosuppressants that can cause IV induced immunosuppression
Azathioprine
Cyclosporine
Adalimumab
Exposure to which chemical materials can increase the risk of non-melanoma skin cancer?
Coal tar pitch Soot Creosote Petroleum products Shale oils Arsenic
Examples of drugs which are phototoxic
NSAIDs
Thiazide diuretics
Anti-TNF
Azathioprine
Management of skin cancer
Sun protection
Surgery main treatment for skin cancers
Hedgehog inhibitors for BCC
Targeted responses for melanoma
Examples of targeted therapies for melanoma
Vemurafenib, dabarefenib, MEK inhibitors
What is the target for vemurafenib and dabarefinib?
Mutated form of B-raf
