Skin Cancer Flashcards by Jane Keery

What behavioural methods should be used in the prevention of skin cancer?

Avoid the sun at peak times, use shade, avoid sunbeds

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What clothing is best to prevent skin cancer?

Tightly woven, loose fitting, dark clothing

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NON MELANOMA SKIN CANCER

What types of skin cancer come under this category?

What proporation of skin cancers do these make up?

Where do they arise from?

SCC and BCC

90-95%

Arise from the keratinocytes in the epidermis; BCC = basal layer, SCC = supra-basal

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With regards to the non melanoma skin cancers:

Which is the most common?

Which is more serious?

BCC

SCC

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Where do melanomas arise from?

Melanocytes which are scattered along the basal layer of the epidermis

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EPIDEMIOLOGY

Which type of skin cancer is most common in the elderly group?

Which type of skin cancer is most common aeged 25-45?

Which sex is more at risk of melanoma?

Which sex is more likely to die from melanoma?

BCC

Melanoma

Females (2:1)

Males

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PROGNOSIS OF MELANOMA

What is the 5 year survival for a tumour that is:

< 1mm?

> 4mm?

Metastasised?

95-100%

50%

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TYPES OF MELANOMA

Describe a superficial spreading melanoma?

Describe a nodular melanoma?

Melanoma spreads horizontally through the epidermis first

Melanoma spreads vertically into the dermis where it can metastasise

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What are some presenting features of a BCC?

Slow growing lump or non-healing ulcer

Painless

Pearly or translucent

Telangectasia

Scaly plaque

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Are BCCs locally invasive?

Do BCCs metastasise?

How fast do BCCs grow?

The cells involved in a BCC are mainly found where?

The biggest problem with BCCs is when they arise where?

Yes

Rarely

Very slowly

Papillary dermis

On the central facial region

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How may an SCC present?

Where do SCCs tend to present?

Are they painful?

Do they metastasise?

Warty/crusted growth or a non-helaing ulcer

Sun exposed skin

Yes, and can bleed

Yes

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What is a keratoacanthoma?

A type of SCC which erupts suddenly on a sun exposed site.

May need excised or may resolve on its own.

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What is the risk of metastases of an SCC?

If a patient survives an SCC, what is their chance of recurrence at 5 years?

What are some examples of precursor lesions?

SCC has associations with sites of longstanding what?

5%, but poor prognosis once this occurs

50% recurrence of a non-melanoma cancer

Actinic keratosis, Bowen’s disease (erythematous plaque)

Venous ulceration, burns or lupus vulgaris

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What are some risk factors for skin cancer?

SUN EXPOSURE

Genetic predisposition (DNA repair syndromes)

Immunosuppressed

HPV infection

Enironmental carcinogens e.g. tar, smoking, radiation

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What are DNA repair syndromes?

What are some examples?

Which patients are the biggest at risk group for getting and dying from SCC?

The inability to repair skin sites which have been damaged by UV light

Xeroderma pigmentosum, albinism, naevoid BCC syndrome

Transplant patients

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Xeroderma pigmentosum is a DNA repair syndrome which increases the risk of skin cancers. What are some features of this?

Causes photosensitivity

Skin cancers on UV exposed sites and increased risk of other cancers

Neurological degeneration

Defect in NER genes

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What is naevoid BCC syndrome?

What are some features?

An autosomal dominant familial cancer syndrome

Early onset/multiple BCCs

Palmar pits, jaw cysts, ectopic calcification

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Does smoking cause cancer directly or indirectly?

How?

Indirectly

It causes genetic damage which then increases mutations and hence cancer

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What is a particularly important cytokine which is very prone to causing cancer if inhibited?

TNF alpha

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What is an oncogene?

Give examples?

An over-active form of a gene which positively regulates cell division

Ras, Raf

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What is a proto-oncogene?

What happens once these are switched on by a mutation?

The normal, not yet mutated, form of an oncogene.

They cannot be switched off, causing cancer

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What is a tumour suppressor?

Give examples?

An inactive or non-functional form of a gene which negatively regulates cell division

Rb, p53

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What type of skin cancers will each of the following be more prone to getting:

Chronic/long-term sun exposure e.g. outdoor worker?

Intense intermittent and recreational sun exposure?

Frequent burning?

Artificial UV (i.e. sunbed)?

SCC

Melanoma and BCC

Melanoma, BCC and SCC

In terms of skin type, who are more likely to get cancer?

Why are darker skin types more protected against cancer?

Types 1-3, particularly fair skinned with fair hair and eyes, and those more prone to burning

Increased production of eumelanin

Occupational exposure to chemicals such as coal tar, soot, petroleum and arsenic increases the risk of which types of skin cancer? Immunosuppression increases the risk of all types of skin cancer but which in particular? Out of ulcerative colitis and Crohn's, which has a higher risk of melanoma?

Non-melanoma skin cancers Melanoma Crohn's

Which has a shorter wavelength, UVA or UVB? Which causes direct DNA damage? Which causes indirect DNA damage? How? Which penetrates deeper into the skin?

UVB UVB UVA- oxidative damage UVA

What are some features of UV induced immunosuppression?

Depletion of Langerhans cells and hence reduced antigen presentation Generation of T cells with immunosuppressive activity Secretion of anti-inflammatory cytokines

UVB light will cause DNA damage by forming what?

Pyramidine dimers (two thymine or cytosine bases which are next to each other in the chain join with a double bond)

What are the two major types of UVB induced DNA lesions?

Cyclobutane pirimidine dimers Pirimidine-pirimidone 6-4 photo products

How is DNA damage induced by UVB removed? Complete the following: 1) Recognition of damaged DNA 2) Cleavage of the damaged DNA on either side of the photoproduct 3) ? fills the gap, using the undamaged strand as a template 4) ? seals the end

Nucleotide excision repair DNA polymerase DNA ligase

UVA causes DNA damage by indirect mechanisms of oxidation of DNA bases. What is the most common oxidation reaction to occur?

Deoxyguanosine to 8-oxo-deoxyguanosine

The 8-oxo-deoxyguanosine which is produced as a result of UVA damage should normally bind with deoxycytosine. In the case of damaged DNA, what does it bind with instead?

Deoxyadenosine

How is indirect damage from UVA repaired? Complete the following: 1) Recognition of the chemically altered base causes slight helix distorsion 2) Cleavage of the altered base from the deoxyribose by ? 3) Base free deoxyribose cleared away by ? 4) Single nucleotide gap filled by ? 5) ? seals the end

Base excision repair DNA glycosylase Endonuclease DNA polymerase beta DNA ligase

What is the most likely mutation in UVB sun damage? What is the most likely mutation in UVA sun damage?

TT --\> CC signature mutation C --\> A point mutation

Mutations in PTCH1 are associated with the development of which type of skin cancer? This is involved in what signalling pathway?

BCC Hedgehog signalling pathway

Mutations in the Ras/Raf/MAPK signalling pathways commonly cause what type of skin cancer? \> 50% of melanomas have what type of mutation? How are these mutations acquired?

Melanomas B-raf Sun damage

What two genes have been linked to familial melanoma?

CDKN2A CDK4

What is the normal function of CDKN2A?

Prevents cells from replicating when they contain damaged DNA

Mutations in CDK4 have what effect?

Acceleration of the cell cycle

What is the target of dasatinib and imatinib? What is the function of this?

c-Kit Prevent cell growth

What is the target of vemurafenib and dabrafenib? What is the function of this?

B-Raf Prevent cell growth

What is the target of trametinib? What is the function of this?

MEK Prevent cell growth

What are the targets of ipilimumab, tremelimumab and prembrolizumab? What is the function of this?

CTLA-4 on T cells and PD-1 on T cells T cell activation to enable tumour cell killing

What is the purpose of a biopsy for skin rashes? What is the purpose of a biopsy for skin tumours?

Assist in diagnosis Assist in diagnosis, remove malignanies and unwanted growths

What is seen in the image? How will it feel to touch? It can be hard to distinguish from what?

Dermatofibroma Firm BCC

What is imiquimod cream?

A new treatment option for non-melanoma skin cancers in patients who do not want to have surgery

What are some complications of skin biopsy?

Bleeding Non-healing wound Infection Scarring Nerve damage Loss of function

What are some adverse effects of a patient being on steroid treatment at the time of a skin biopsy?

Takes the wound longer to heal It is also an immunosuppressant which predisposes the patient to infection

What is the treatment plan for a melanoma?

Surgery Possibly further surgery Follow up radio/chemotherapy

What are the treatment options for non-melanoma skin cancer?

Usually surgery Some new upcoming non-surgical procedures

If a patient undergoes excision of a skin cancer of the face, what nerve is most likely to be affected?

Branches of the trigeminal nerve

What are some methods of anaesthesia for the removal of a skin cancer?

Topical Local infiltration Nerve block Field block

What is the maximal safe dose of lignocaine?

50ml 1% lignocaine with adrenaline

What is the purpose of giving adrenaline with an anaesthetic? Where and when should adrenaline not be given?

Prolongs the anaesthesia and reduces bleeding Fingers and toes, patients with cardiac disease or on psychotropic drugs

Grasping the lesion with a hook and cutting across the base of the lesion describes what type of skin surgery? What is the standard method of removal of most small skin tumours? Describe the above procedure?

Snip excision Elliptical excision Take off an area of normal skin along with the abnormal area, the scalpel blade should be at 90 degrees to the skin