Skin cancer Flashcards
what are the 3 main layers of the skin?
epidermis (top)
dermis (middle)
hypodermis (bottom with subcutaneous tissue)
what are the layers of the epidermis (the top layer)?
what cells do they contain?
o Stratum corneum – dead keratinocytes. o Stratum lucidum. o Stratum granulosum. o Stratum spinosum – dendritic cells. o Stratum basale – melanocytes, merkel cells, dividing cells
what are the origins of skin cancers? [4]
- keratinocyte derived
- melanocytes derived
- vasculature derived
- lymphocyte derived
name the keratinocyte derived cancers
1) BCC
(Basal Cell Carcinoma)
- highest incidence, least aggressive
2) SCC
(Squamous Cell Carcinoma).
aka Non-Melanoma Skin Cancer (NMSC).
- second highest incidence, more aggressive
name a melanocyte derived cancer
malignant melanoma
low incidence
name the vasculature derived cancers
Kaposi’s sarcorma (lymphatic epithelial cell)
angiosarcoma
name the lymphocyte derived cancers
mycosis fungoides
T cell lymphoma
what are keratinocytes and melanocytes exposed to?
UV and genetic mutations
when they proliferate they move from the basement membrane level towards the top of the epidermis
what are the 4 causes of skin cancer?
- genetics syndromes
- viral infections
- UV light exposure
- immunosuppression
name conditions caused by genetic syndromes
Gorlin’s syndrome and xeroderma pigmentosum
name conditions caused by viral infections
Kaposi’s sarcoma (HHV8) - vasculature derived
SCC (HPV)- keratinocyte derived
name conditions caused by UV light exposure
BCC
SCC
malignant melanoma
(increase in aggressivesness, decrease in incidence)
name the immunosuppressive causes of skin cancers
drugs
age
HIV
leukaemia
who are mostly affected by malignant melanomas?
those with pale skin (caucasian)
highest in the south-west of England (more sunshine)
low among darker skins ethnicities
describe a malignant melanoma
irregular margin and is dark-coloured
describe a BCC
- pearly appearance, glistens, greyish
- has dilated small capillaries on the surface (telangiectasia)
what are the types of UV radiation
o UVA – 310-400nm. Penetrates to deep sea level
o UVB – 280-310nm. Penetrates to ground level.
o UVC – 100-280nm. Does not penetrate ozone.
which of the UV radiation types account for mutations in the skin
UVA>UVB
UVA 100x more penetrating than UVB.
what does UVA contribute to?
Major cause of skin ageing as it will reach the collagen in the skin
and contributes to skin carcinogenesis (not as much as UVB)
how does UVA contribute to carcinogenesis?
- Forms Cyclobutane pyrimidine dimers i.e. cross linking but less efficiently than UVB.
- Forms free radicals to damage DNA and cell membranes
how does UVB contribute to carcinogenesis?
MAJOR contributor:
- Induces direct abnormalities in skin DNA – e.g. mutations.
- Induces photoproducts – affects pyramidines (C, T) bases, e.g. cyclobutane pyrimidine dimers (e.g. T=T, T=C, C=C).
- 6-4 pyrimidine pyrimidine photoproducts.
how how photoproduct resulting from UVB damage, mainly, repaired?
nucleotide excision repair
how can UVA be used to treat psoriasis? what is the risk?
PUVA (+psoralens)
increased risk of skin cancer
what conditions is caused by defective nucleotide excision repair (genetic)?
xeroderma pigmentosum
they develop skin cancer pretty early with little UV exposure
what are the benefits of sunlight?
photosynthesis
warmth from IR
human mood effects
production of VitD
what is sun burn?
UV light causes keratinocyte cell apoptosis in the epidermis
histology- this shows up black
what are the immunomodulatory effects of UV light? this is the basis for the treatment for what condition?
UVA/B affect expression of genes:
- deplete Langerhans cells in the epidermis
- decreased skin immunocompetance
- UV phototherapy for psoriasis BUT also further increases cancer chances.
what mutation can lead to photocarcinogenesis?
p53 mutations leads to defective repair and apoptosis
how does the response to UV differ with host?
o 1 – always burns, never tans.
o 2 – usually burns, sometimes tans.
o 3 – sometimes burns, usually tans.
o 4 – never burns, always tans.
o 5 – moderate constitutive pigmentation – Asian.
o 6 – moderate constitutive pigmentation – Afrocaribean.
what produces melanin and what is it derived from?
melanosomes in melanocytes ,in the basal layer of the epidermis, produce melanin
melanin is derived from tyrosine
why does pigmentation differ among ethnicities?
people have roughly the same amount of melanocytes in the skin but darker people just produce more melanin with their cells than fairer people
people also produce different types of melanin
i.e. a different amount and type of melanin is produced among people
how is melanin made use of when produced by melanocytes?
once produced in the basal layer it is transported (melanosome transfer) up spines that go the keratinocytes
they pass into the cells and coat the nuclei within so the protect it from UV damage
what gene encodes melanin?
MCR1 gene
what are the types of melanin and what enables these types of be derived?
> 20 polymorphisms in the MC1R gene exist, enabling the 2 types of melanin to exist
Eumelanin
– brown or black.
Phaeomelanin
– yellowish or reddish.
the type of melanin expressed depends on the polymorphism
what is the biochemical pathway in melanin production?
Tyrosine –>DOPA –> Dopaquinone –> Eumelanin or Phaeomelanin –> melanin
what is the difference between a malignant melanoma and lentigo maligna?
malignant melanoma has a risk of metastasis
lentigo maligna has no risk of metastasis (confined to epidermis)
what is the cause of malignant melanoma?
UV and genetic risk factors
what is a hallmark of melanoma?
abnormal melanocyte position
they should be at the basal layer but in melanoma they travel upwards and in other directions
describe lentigo maligna
o Irregular shape.
o Light & dark colours.
o Size usually >2.0cm.
what happens when the malignant melanocytes proliferate laterally? can they metastasise?
superficial spreading malignant melanoma
this has a risk of metastasis as it invades the basement membrane
how are malignant melanomas diagnosed?
o A – Asymmetry. o B – Border irregularity. o C – Colour variation. o D – Diameter >0.7mm (?) and increasing. o (E – Erythema).
what does a patchy melanoma indicate?
immune response has occurred so the melanoma has regressed but this could also mean that it has metastasised
what happens when malignant melanocytes proliferate vertically? can they metastasise?
Nodular Malignant Melanoma (darker in appearance)
this is with no previous horizontal growth
risk of metastasis
what happens when the malignant melanocytes proliferate vertically WITH previous horizontal growth?
Nodular Melanoma arising within superficially spreading malignant melanoma
here the prognosis becomes worse
what is aural lentiginous melanoma?
- A malignant melanoma affecting the palms and soles of the feet.
- Occur in darker skinned people more often than lighter coloured skin people.
what is amelanotic melanoma?
A melanoma where the cancer cells have lost the ability to create melanin.
how is prognosis of a melanoma assessed? what does it measure and therefore indicate?
Breslow thickness:
- measured from granular layer to bottom of tumour
- states that the deeper the melanoma, the worse the prognosis.
what are there risk factors that contribute to the development of a melanoma?
- Family history
- Intermittent burning exposure to unacclimatised skin
- Skin types 1, 2.
- UV light exposure
- Atypical nevus syndrome.
- Sunburns during childhood
- Personal melanoma history.
what are the 7 types of malignant melanomas?
1- Malignant Melanoma
2- Lentigo Meligna (Melanoma in situ)
3- Superficial Spreading Malignant Melanoma (horizontal)
4- Nodular Malignant Melanoma (vertical)
5- Nodular Melanoma arising within SSMM (vertical and horizontal)
6- Acral Lentiginous Melanoma (darker skinned people)
7- Amelanotic Melanoma (no melanin produced)
what is SCC?
Malignant tumour of keratinocytes
can metastasise
what causes SCC? [4]
UV
HPV
immunosuppression
scarring processes.
name a variant of SCC
keratoacanthoma
what is the feature that define differentiation level in SCC
keratin horns: indicates well differentiated carcinoma
absence of keratin indicates poor differentiation (keratinocytes no longer identifiable)
what is BCC?
Malignant tumour arising from the basal layer of the epidermis which normally produces other skin cells
Locally destructive but not metastatic
what are the causes of BCC?
- sun exposure
- genetics.
what are the features of BCC?
o Slow growing. o Invades but does not metastasise. o Common on the face. - nodular or superficial - glistens with telangiectasia
what is mycosis fungoides?
NOT a fungal condition as it was misclassified
its actually a T cell lymphoma of the skin which can take decades to progress
can be fatal and has internal organ involvement
what are the associated causes of Kaposi’s sarcoma?
HVV8 and HIV
can occur in non-HIV patients
what is Kaposi’s sarcoma?
A tumour of the endothelial cells of the lymphatics.
what is epidermodysplasia verruciformis?
Rare autosomal condition.
Gives a predisposition to HPV-induced warts and SCCs.
what is the main treatment for skin cancers?
surgery
what is the main aetiological agent of skin cancer?
sunlight
others:
- ionising radiation
- viruses
- tissue scarring
which carcinoma type has the highest incidence?
basal cell carcinoma
which carcinoma type has the lowest incidence?
how aggressive?
melanoma
the aggressiveness increases with decreasing incidence
3 main types of skin cancer
basal cell carcinoma
squamous cell carcinoma
melanoma
which type of skin is sensitive to sun light and have high incidence of skin cancer?
Fitzpatrick Skin Type 1
what are the Fitzpatrick phenotypes for skin?
1-6 I – Always burns, never tans II – Usually burns, sometimes tans III – Sometimes burns, usually tans IV – Never burns, always tans V – Moderate constitutive pigmentation VI – Marked constitutive pigmentation
Fitzpatrick type I
always burns
never tans
Fitzpatrick type II
usually burns
sometimes tans
Fitzpatrick type III
sometimes burns
usually tans
Fitzpatrick type IV
never burns
always tans
Fitzpatrick type V
moderate constitutive pigmentation
Fitzpatrick type VI
marked constitutive pigmentation
what is the wavelength range of UVA?
310-400nm
what is the wavelength range of UVB?
280-310nm
which UV type will reach the earth’s surface more?
UVA
(100 times more)
therefore major cause of ageing and contributor to carcinogenesis
how does UVA damage the skin?
- free radical generation
- T –> G transversions
- membrane damage
which wavelength is the major contributor to carcinogenesis?
UVB
most important
how does UVB contribute to carcinogenesis?
forms pyrimidine dimers (using adjacent thymidine residues)
they covalently link when exposed
e.g. cyclobutane-butane dimers
what is the wavelength range of UVC?
100-280 nm
filtered out by ozone
what is the relationship between carcinogenicity and wavelength
the lower the wavelength, the closer to X-ray, the higher the carcinogenicity
the higher the wavelength, the closer to visible spectrum, the lower the carcinogenicity
which chromosome is p53 coded on?
17q
what role does p53 have in skin cancer?
UV sensitive
one mutated p53 is enough, even though it is a TSG, to have mutagenic effect
binds to DNA as tetramer regulating other genes
what immune cells normally presents antigens to T cells for the destruction of tumour cells?
Langerhans cells (dendritic cells)
what role do Langerhan cells have in skin cancer?
they are sensitive to UV and therefore their density is decreased so their APC role is compromised
who and where is basal cell carcinoma most common?
in the elderly
seen on head and neck (areas of sun exposure)
main feature of basal cell carcinoma
pearly appearance with telangiectasia
what is squamous cell carcinoma?
- metastatic?
malignancy of epidermal keratinocytes due to UV
this one is metastatic unlike basal cell carcinoma
spreads to lymph nodes and other organs like the lung
[remember the lower the incidence, the higher the aggressiveness; BCC is higher in incidence than SCC]
who and where is SCC most common?
the elderly
head and neck
main features of SCC
- may be ulcerated
- hyperkeratotic (keratin horn–> well differentiated)
- crusty or scaly
- non-healing
what is a melanoma?
- metastatic?
arises from melanocytes
highly metastatic: lymph nodes and organs (lung, brain, liver)
in which people can melanoma occur?
in all even younger people
what are the risk factors for melanoma?
- Dysplastic naevae (moles)
- Family history
- Tanning beds
- Intermittent, intense, early age sun exposure.
how is epidermodysplasia verruciformis inherited?
aka Treeman syndrome
autosomal recessive
which viral infection does epidermo. v predispose you to?
what does it do?
HPV
what cancer can arise from epidermo.v?
squamous cell carcinoma
how does HPV deactivate p53 in epidermodysplasia verruciformis?
E6 protein deactivates p53
how does HPV infection in epidermodysplasia verruciformis lead to squamous cell carcinoma?
- mild immunodeficiency leads to multiple viral warts
- they become oncogenic in the sun
- keratinocytes become infected
- E6 deactivates p53
