Skin cancer Flashcards
Skin microanatomy
/
Structure of the epidermis
/
Types of skin cancer
- Keratinocyte derived (eg: BCC, SCC)
- Melanocyte derived (eg: malignant melanoma)
- Vasculature derived (eg: Kaposi’s sarcoma)
- Lymphocyte derived (eg: mycosis fungoides)
Causes of skin cancer
ACCUMULATION OF GENETIC MUTATIONS LEADS TO UNCONTROLLED CELL PROLIFERATION
- Genetic syndromes (Gorlin’s syndrome)
- Viral infections (HHV8 in Kaposi’s sarcoma)
- UV light (BCC,SCC)
- Immunosuppression (drugs, HIV etc)
Malignant melanoma
MALIGNANT TUMOUR OF MELANOCYTES
- melanocytes become abnormal
- atypical cells and architecture
- risk of metastasis
Causes:
- UV exposure
- genetic factors
UV spectrum
/
UVB
- most important wavelength in skin carcinogenesis
- directly induces DNA abnormalities
- induces photoproducts
UVA
- 100x more UVA penetrates Earth surface than UVB
- major cause of skin ageing
- skin carcinogenesis contribution
- used therapeutically in PUVA therapy
UV induced skin carcinogenesis
-UV damage to DNA leads to mutations in specific genes (cell division, DNA repair, cell cycle arrest)
Repair of UV induced DNA damage
- photoproducts removed by nucleotide excision repair
- xeroderma pigmentosum=genetic condition with defective nucleotide excision repair
Mutations causing cancer
- mutations stimulating uncontrolled cell proliferation
- mutations altering responses to growth stimulating/repressing factors
- mutations that inhibit apoptosis
Sunburn
- UV light leads to keratinocyte cell apoptosis
- ‘sunburn’ cells are apoptotic cells in UV overexposed skin
- apoptosis removes UV damaged cells in skin which might otherwise become cancer cells
Photocarcinogenesis
/
Immunomodulatory effects of UV light
- UVA and UVB effect gene expression in skin immunity (deplete Langerhans cells in epidermis)
- reduced skin immunocompetence and immunosurveillance (UV phototherapy basis) but further increases cancer causing potential of sun exposure
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=moderate constitutive pigmentation (afrocaribbean)
Melanin
- melanin pigmentation responsible for skin colour=dependent on amount and type of melanin produced, not melanocyte density (fairly constant density)
- produced by melanocytes within basal layer of epidermis
- dictates skin sensitivity to UV damage
Types of melanin
MELANIN FORMED FROM TYROSINE VIA ENZYME SERIES
- Eumelanin=brown or black
- Phaeomelanin=yellowish or reddish brown
MCR1 gene
- > 20 polymorphisms
- variation in eumelanin:phaeomelanin produced
- explains different hair colour and skin types
Lentigo maligna
- ‘in situ melanoma’
- proliferation of malignant melanocytes within epidermis
- no risk of metastasis
Features:
- irregular shape
- light and dark brown colours
- size usually >2 cm
Superficial spreading malignant melanoma
- lateral proliferation of malignant melanocytes
- invade basement membrane
- risk of metastasis
Superficial spreading malignant melanoma diagnosis
ABCD rule A=asymmetry B=border irregular C=colour variation (dark brown-black) D= >0.7mm diameter and increasing E=erythema
Nodular malignant melanoma
- vertical proliferation of malignant melanocytes with no previous horizontal growth
- risk of metastasis
- much darker appearance
Nodular melanoma arising with superficial spreading melanoma
- downward proliferation of malignant melanocytes following previous horizontal growth
- nodule developing within irregular plaque
- prognosis worsens
Acral lentiginous melanoma
/
Amelanotic melanoma
/
Types of malignant melanoma
- superficial spreading
- nodular
- lentigo maligna melanoma
- acral lentiginous
- amelanotic
Breslow thickness
- measurement from granular layer to bottom of tumour
- used for melanoma prognosis
Risk factors for melanoma development
- family history of dysplastic nevi or melanoma
- UV irradiation
- sunburns during childhood
- intermittent burning exposure in unacclimatised fair skin
- atypical/dysplastic nevus syndrome
- personal melanoma history
- skin types 1,2
Squamous cell carcinoma (SCC)
- malignant tumour of keratinocytes
- risk of metastasis
Causes:
- UV exposure
- HPV
- Immunosuppression
- scars or scarring processes
Basal cell carcinoma (BCC)
- malignant tumour arising from basal layer of epidermis
- slow growing
- invades tissue but does not metastasise
- common on face
- can be nodular of superficial
Causes:
- Sun exposure
- Genetics
Mycosis fungoides
/
Kaposi’s sarcoma
-HIV and HHV8 associated
Epidermodysplasia verruciformis
- ‘treeman syndrome’
- rare autosomal recessive condition
- gives predisposition to HPV-induced warts and SCC
Importance of sunlight
- essential for photosynthesis (plants)
- infrared spectra provide warmth
- effect on human mood
- stimulates vitamin D production in skin
Photoproducts induced by UVB
- affects pyrimidines (cytosine and thymine bases)
- cyclobutane pyrimidine dimers
- 6-4 pyrimidone photoproducts
- usually quick repair by nucleotide excision repair
Skin carcinogenesis and UVA
- UVA promotes skin carcinogenesis
- DNA forming cyclobutane pyrimidine dimers but less efficiently than with UVB
- free radicals damage DNA and cell membrane
Host response to UV light
Determined by genetic influences (especially skin phototype)
Malignant melanoma incidence
/
Basal cell carcinoma incidence
/
Melanoma recognition
A=asymmetry
B=border
C=colour
D=diameter
