Skin cancer Flashcards
What are the different types of skin cancer?
Keratinocyte derived, e.g. basal cell carcinoma, squamous cell carcinoma (non-melanoma skin cancer)
Melanocyte derived, e.g. malignant melanoma
Vasculature derived, e.g. Kaposi’s sarcoma, angiosarcoma
Lymphocyte derived, e.g. mycosis fungoides
What are the different causes of skin cancer?
Genetic syndromes: Gorlin’s syndrome, xeroderma pigmentosum.
Viral infections: HHV8 in Kaposi’s sarcoma, HPV in SCC.
UV light: BCC, SCC, malignant melanoma.
Immunosuppression: drugs, HIV, old age, leukaemia.
What is the most important wavelength of light in skin carcinogenesis?
UVB (280-315)
What is the significance of UVB light in skin cancer?
Risk factor.
Directly induces abnormalities in DNA, e.g. mutations.
Induces photoproducts (mutations).
Affects pyrimidines, i.e. cytosine and thymine bases.
- cyclobutane pyrimidine dimers, e.g. T=T, T=C, C=C.
- 6-4 pyrimidine pyrimidone photoproducts.
Usually repaired quickly by nucleotide excision repair.
What is the significance of UVA in skin cancer?
Promotes skin carcinogenesis.
DNA forming cyclobutane butane pyrimidine dimers but less efficiently than UVB.
Free radicals which damage DNA and cell membrane.
How may UV-induced DNA damage be repaired?
Photoproducts are removed by nucleotide excision repair.
What is xeroderma pigmentosum?
Genetic condition with defective nucleotide excision repair.
Photosensitivity, early development of skin cancers.
What types of mutations can cause cancer?
Mutations that stimulate uncontrolled cell proliferation, e.g. 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).
What is sunburn?
UV leads to keratinocyte cell apoptosis.
‘Sunburn’ 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 immunomodulatory effects of UV light?
UVA and UVB affect the expression of genes involved in skin immunity.
Depletes Langerhans cells in the epidermis.
Reduced skin immunocompetence and immunosurveillance- basis for UV phototherapy for e.g. psoriasis.
Further increases the cancer causing potential of sun exposure.
What determines the host response to UV?
Genetic influences, especially skin phototype.
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- Afro-Caribbean.
What is melanin?
Melanin pigmentation is responsible for skin colour.
Produced by melanocytes within the basal layer of the epidermis.
Skin colour depends on the amount and type of melanin produced not the density of melanocytes (which is fairly constant).
What are the 2 types of melanin?
Eumelanin- brown or black.
Phaeomelanin- yellowish or reddish brown.
Melanin is formed from tyrosine via a series of enzymes.
What is the significance of the MCR1 gene?
>20 gene polymorphisms.
Variation in eumelanin:phaeomelanin produced.
Explains different hair colour and skin types.
What is malignant melanoma?
Malignant tumour of melanocytes.
Melanocytes become abnormal.
Atypical cells and architecture.
Risk of metastasis.
What causes malignant melanoma?
UV exposure
Genetic factors
What is lentigo maligna?
Melanoma in situ
Proliferation of malignant melanocytes within the epidermis
No risk of metastasis
Irregular shape
Light and dark brown colours
Size usually >2cm
What is superficial spreading malignant melanoma?
Lateral proliferation of malignant melanocytes
Invade basement membrane
Risk of metastasis
How is the ABCD rule used in the diagnosis of melanoma?
ABCDE rule
Asymmetry
Border irregular
Colour variation (dark brown-black)
Diameter >0.7mm and increasing
Erythema
What is nodular malignant melanoma?
Vertical proliferation of malignant melanocytes (no previous horizontal growth)
Risk of metastasis
Nodular melanoma may arise within a superficial spreading melanoma:
- downward proliferation of malignant melanocytes
- following previous horizontal growth
- nodule developing within irregular plaque- prognosis will become worse
What is acral lentiginous melanoma?
Occur on soles of feet and palms of hands.
Occur in darker skinned people.
Often darkly pigmented lesion that starts off flat and can develop lumps within it.
What is amelanotic melanoma?
Melanomas lose ability to make melanin.
Lesion lacks pigment.
What are the different types of malignant melanoma?
Superficial spreading
Nodular
Lentigo maligna melanoma
Acral lentiginous
Amelanotic
How is the prognosis of melanoma determined?
Breslow thickness- measurement from granular layer to bottom of tumour, in mm.
<1mm = superficial
>1mm = deep, high risk of metastasis
What are the main risk factors for the development of melanoma?
Personal history of melanoma
Family history of dysplastic nevi or melanoma
Skin type I, II
Ultraviolet radiation
Sunburns during childhood
Intermittent burning exposure in unacclimatised fair skin
Atypical/dysplastic nevus syndrome
What is squamous cell carcinoma?
Malignant tumour of keratinocytes.
Risk of metastasis.
What are the causes of squamous cell carcinoma?
UV exposure
HPV
Immunosuppression
May occur in scars or scarring processes
What is basal cell carcinoma?
Malignant tumour arising from basal layer of epidermis.
Slow growing.
Invades tissue, but does not metastasise.
Common on face.
What are the causes of basal cell carcinoma?
Sun exposure
Genetics
What is epidermodysplasia veruciformis?
Rare autosomal recessive condition.
Predisposition to HPV induced warts and squamous cell carcinomas.
What is mycosis fungoides?
Lymphoma occurring in the skin.
(not caused by fungus)
Present with plaques and patches of erythematous scaly skin, which can turn into thick lesions (tumours).
Often spreads to lymph nodes and other organs.
Slowly progressive condition.
What is Kaposi’s sarcoma?
Derived from the lymph endothelium.
HIV and HHV8 associated.
Purple papules and nodules.
