Skin Cancer Flashcards by Alexandra Chan

What are the 3 layers of the skin

Epidermis
Dermis
Hypodermis

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What are the layers of the epidermis (starting outside)

Stratum corneum
Stratum lucidum
Stratum granulosum
Stratum spinosum 
Stratum basale 
Dermis

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What are the types of skin cancer

Keratinocyte derived
Melanocyte derived
Vasculature derived
Lymphocyte derived

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Give examples of keratinocyte derived skin cancers

(aka Non melanoma skin cancer (NMSC))
basal cell carcinoma
squamous cell carcinoma

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Give examples of melanocyte, vasculature and lymphocyte derived skin cancers

melanocyte - Malignant melanoma
Vacsulature - Kaposi’s
Lymphocyte - mycosis fungoides

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Give examples of causes of skin cancer

Genetic syndrome - Gorlin’s, xeroderma pigmentosum
Viral - HHV8 in Kaposi’s, HPV in SCC
UV - BCC, SCC, malignant melanoma
Immunosuppression - drugs, HIV, old age, leukaemia

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Compare UVA to UVB

100x more UVA than UVB reaches the Earth’s surface
UVA can also penetrate glass whereas UVB can’t
UVA - skin ageing
UBV - cancer

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Describe UVC

Very little UVC penetrates the atmosphere, so even though it would be the most damaging, it is the least relevant.

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Describe the ionising effects of UV

UV is not outright ionising, but the UV photons can affect molecular bonds.

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What are the wavelengths of UVA, UVB, UVC

UVC = 100-280
UVB = 280-310
UVA = 310-400

(lower = x-rays, higher = visible)

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Explain how UVB affects DNA

UVB directly induces photoproducts (mutations)
DNA as a chromophore (target) for UVB
Affects pyrimidines (Cytosine and Thymine)

Usually repaired quickly by nucleotide excision repair

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What are the most common photoproducts of UVB and DNA

Cyclobutane pyrimidine dimers eg T=T, T=C, C=C

Thymine Dimers

6-4 pyrimidine pyrimidone photoproducts

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Compare 6-4 pyrimidine photoproducts

6-4 pyrimidine pyrimidone photoproducts are more mutagenic but have a much shorter half-life.

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Describe the repairing of UVB mutations and what occurs when this fails

photoproducts can be repaired using base/nucleotide excision repair.
If the damage is irreparable, the cell apoptoses (causing sunburn), mediated by the protein Bax.

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How does UVA exposure cause indirect DNA damage

formation of singlet oxygens and free radicals which damage DNA and the cell membrane.

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Give examples of mutations that cause cancer

Mutations that stimulate uncontrolled cell proliferation
Eg abolishing control of the normal cell cycle (p53 gene)

Mutations that alter responses to growth stimulating / repressing factors

Mutations that inhibit programmed cell death (apoptosis)

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What are the immunomodulatory effects of UV Light

Langerhans cell function decreases proportionally with UV exposure.

Reduced skin immunocompetence and immunosurveillance (Basis for UV phototherapy for eg psoriasis)

Further increases the cancer causing potential of sun exposure

What are the Fitzpatrick phototypes

I - Always burns, never tans
II - Usually burns, sometimes tans
III - Sometimes burns, usually tans
IV - Never burns, always tans
V - Moderate constitutive pigmentation - Asian
VI - Marked constitutive pigmentation - Afrocaribean

What is the role of melanin and what does its function depend on

Skin pigmentation/colour

Skin colour depends on the amount and type of melanin produced not the density of melanocytes (which is fairly constant)

How is Melanin produced

produced by melanocytes in the basal layer of the epidermis

produced from tyrosine via DOPA

What are the types of melanin

Eumelanin: black/brown, insoluble, useful
Phaeomelanin: yellowish-reddish brown, soluble in alkalis, useless (red-heads)

How does melanin contribute to skin cancer

Melanin is a chromophore for UV light, absorbing it and thus providing protection for the more sensitive layers of skin underneath.
Melanin also traps electrons and free radicals.

Describe the melanocortin-I receptor (MCIR) gene

Highly polymorphic, and regulates the skin and hair pigmentation phenotype.
MC1R promotes a switch from phaeomelanin to eumelanin production, and thus MC1R alleles which work worse are associated with being a ginger and hence skin cancer.

Explain how sunburn can be thought of as protective

UV leads to keratinocyte cell apoptosis

‘Sun burn’ cells are apoptotic cells in UV overexposed skin

Apoptosis removes UV damaged cells in the skin which might otherwise become cancer cells

What are the 3 most common skin cancers

Basal cell carcinoma (most common, least deadly) Squamous cell carcinoma Melanoma (least common, most deadly)

Describe Basal Cell Carcinomas (who it affects, what it arises from, where it is found, metastatic characteristics, what affects histological subtype)

generally tumour of the elderly Arises from pluripotent stem cells in the basal layer of the epidermis Found on sun-exposed body parts e.g. face Locally destructive (invasive) but rarely metastatic Underlying stroma affects histological subtype

Describe squamous cell carcinomas (what it develops from, who it affects, metastatic characteristics, spread, what it can arise from)

Malignant tumour of basal keratinocytes Tumours of the elderly, occurring on sun-exposed areas Tumours are metastatic Spreads to regional lymph nodes and spreads particularly to the lungs Can arise form other lesions e.g. solar keratoses

Describe melanomas (who it affects, what it arises form, what its associated with, metastatic characteristics)

Tumour of young age Arises from epidermal melanocytes (may be from dermal melanocytes) Associated with intermittent intense sun exposure and systemic immunosuppression Highly metastatic, spreading to lymph nodes, lungs, liver, and brain

What are the risk factors for melanoma

Family history Presence of dysplastic naevae (abnormal moles) or >50 total naevae Burning Exposure on unacclimatised fair skin Childhood radiotherapy Higher socioeconomic group (more sunny holidays) Other cancers

What are the 4 clinical subtypes of melanoma

Superficial spreading Nodular Lentigo maligna Acrolentigenous

Describe superficial spreading melanoma

a horizontal growth phase through the epidermis is followed by vertical invasion (affects younger people and 30% arise from a “mole that has changed”)

Describe nodular melanoma

more aggressive, no horizontal growth phase (patients tend to be older)

Describe lentigo maligna melanoma

``` Proliferation of malignant melanocytes within the epidermis No metastasis risk Irregular shape Light & dark brown colours Size usually >2.0 cm ```

Describe acrolentigenous melanoma

start on feet or hands, sometimes under nails, tends to be due to trauma - not sun exposure (most common type in Afrocarribeans as melanoma is extremely rare)

Describe the genetics of Gorlin's syndrome

Autosomal dominant Caused by a mutation of both alleles of the Patched gene -> Loss of suppression of the smoothened gene (transcription factor that causes cell proliferation) Epidermodysplasia verruciformis

Describe the genetics of xeroderma pigmentosum

Autosomal or sex-linked recessive condition Caused by defective base excision repair Very early solar ageing BCCs, SCCs and melanomas before 10 Death at 10-30yrs

Describe Epidermodysplasia verruciformis

Associated with mild immunodeficiency Skin is infected with opportunistic HPV, causing thousands of warts before 10yrs UV exposure -> SCC

Describe the genetics of Epidermodysplasia verruciformis

Autosomal recessive | The opportunistic HPV’s E6 protein disrupts DNA repair following UV exposure and inactivates p53.

What is epithelium caniculatum

``` Transplant patients (immunosuppressed) are 10x more likely to get an SCC than a BCC, thanks to EV-causing HPV strains. virions can be seen within. ```

Describe the epidemiology of skin cancer

Increase in incidence of malignant melanoma, particularly in the white-skin population (very little in those of darker skin) Higher incidence in areas with greater sun exposure