Cancer 15: Skin cancer Flashcards
Outline the microanatomy of the skin
Epidermis:
- stratum corenum
- stratum granulosum
- stratum spinosum
- stratum basale
Dermis (contains glands and hair follices)
Hypodermis (blood vessels)
Where do most cancers aruse from in the skin
Epidermis
Which cells are present in the epidermis
Keratinoytes… prolferate and move up the epidermis until they become the stratum corneum- so stem cells in stratum basale
Melanocytes
Merkel cells (mecahnoceptors detecting light touch)
Langerhans cells (dendritic cells- prominent in stratum spinosum)
Outline the cancers derived from keratinocytes
Non-melanocyte skin cancer:
basal cell carcinoma
squamous cell carcinoma
Outline melanocyte derived cancer
Malignant melanoma
List vasculature derived tumours
Kaposi’s sarcoma, angiosarcoma
List a type of lymphocyte derived cancer
Mycosis fungoides
NOT fungal infection (a skin lymphoma)
Cause of skin cancer
Accumulation of genetic mutations
leads to
uncontrolled cell proliferation
Examples of causes of skin cancer
Genetic syndromes
Viral infection
UV light
Immunosuppression
Examples of genetic syndromes leading to skin cancer
Gorlin’s syndrome (Basal cell)
xeroderma pigmentosum (DNA repair system malfunction)
Examples of viruses leading to skin cancer
HHV8 in Kaposi’s sarcoma
HPV in SCC
Examples of UV light causing skin cancer
BCC, SCC, malignant melanoma
Examples of immnosuppression causing skin cancer
drugs, HIV, old age, leukaemia
Look at malignant melaona
Compare to squamous cell
Malignant melanoma (streaks/different coloured areas)
Swuamous cell pearly and veins on surface
What skin type is malignant melanoma most common in
White people and increasing
What is happenng t BCC
Increasing
Common on face
Has increased since people stopped wearing hats
Which UV rays are we exposed to
UVA and UVB
UVA most penetrative can go down to sea level
UVB most important for for skin cancer
UVC filtered out by the ozone layer
What is the spectrum of visible light
400-700
Why is UV essential for life
Essential for photosynthesis (plants)
Infrared spectra provide warmth
Effect on human mood
Stimulates the production of vitamin D in the skin
Why are UVB and UVA important
UVB:
most important wavelength in skin carcinogenesis
UVA:major cause of skin ageing
contributes to skin carcinogenesis
used therapeutically in PUVA therapy
How does UVB usually affect DNA
UVB directly induces abnormalities in DNA eg mutations
UVB induces photoproducts (mutations)
-Affects pyrimidines ie Cytosine (C) and Thymine (T) bases
cyclobutane pyrimidine dimers eg T=T, T=C, C=C
-6-4 pyrimidine pyrimidone photoproducts
Why is UVB normally not a problem for DNA
The damage is usually repaired quickly by nucleotide excision repair
Outline affect of UVA on skin carcinogenesis
Also promotes skin carcinogenesis
DNA forming cyclobutane butane pyrimidine dimers but less efficiently than UVB
free radicals which damage DNA and cell membrane (including langerhans)
How can the UV damage to DNA lead to cancer i.e. which specific genes
UV damage to DNA leads to mutations in specific genes
cell division
DNA repair
cell cycle arrest
How can the UV damage to DNA lead to cancer
UV damage to DNA leads to mutations in specific genes
cell division
DNA repair
cell cycle arrest
Photoproducts are removed by what. When is this a problem
Photoproducts are removed by a process called Nucleotide Excision Repair
Xeroderma pigmentosum
=Genetic condition with defective Nucleotide Excision Repair
Mutations causing skin cancer more generally (i,e not just in UV)
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)
What happens in sun burn
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
Outline photocarcinogenesis
Usually skin cell with DNA damage due to UV rays will have DNA repaired, so it dosn’t develop cancer phenotype
If the damage is too severe it will apoptose,
in a p53 mutation, there is inactivated wild type
Skin cancer
As well as directly inducing DNA mutations, what other effect of UV light in the skin
IMMUNOMODULATORY
Outline the immunomodulatory effect of UV light
UVA and UVB effect the expression of genes involved in skin immunity
Depletes Langerhans cells in the epidermis
Reduced skin immunocompetence and immunosurveillance
Basis for UV phototherapy for eg psoriasis
Further increases the cancer causing potential of sun exposure
What is the use of UV light in psoriasis
Down regulating langerhans cells reduces skin immunocompetence and immunosurveilance (UV A and UVB)
And this will reduce the inflammatory response
Outline photocarcinogenesis with regard to UV
So we had that UV induces mutations in key regions such as p53 and the other types of genes (cell division, DNA repair
, cell cycle arrest)
But normally and immune reponse would be mounted against this skin cancer
But if there is UV damage to langer hans cells this will not happen so no cell death
What determines the host response to UV
Phototype
Fitzpatrick (1-6) depends how dark you are
What determiens skin colour
Amount of melanin and the type of melanin
How is melanin produced
By melanocute in the stratum basale (dendritic cell)
….. FINISH
What happens in th eevent of sun exposure
Keratinocytes release MSH
Stimuates melanocytes to release melanin from melanosomes wich then are released from dendrtic process of the melanocyte
T/F there is difference in the meanocyte number between light and dark skinned people
F
What are the two types of melanin
Eumelanin – brown or black
Phaeomelanin – yellowish or reddish brown
What affects the expression of eumelanin or phaeomelanin
MCR1 gene
>20 gene polymorphisms
Variation in eumelanin : phaeomelanin produced
Explains different hair colour and skin types
How is melanin produced
Melanin is formed from tryosine via a series of enzymes
what dictates skin sensitivity to UV damage
MELANIN
Outline malignant melanoma
Melanocytes become abnormal
Atypical cells and architecture
by UV exposure
Genetic factors
Risk of metastasis
What is lentigo maligna
Melanoma in situ
Proliferation of malignant melanocytes within the epidermis
No risk of metastasis
Usually flat and dark
What is it called if lengigo is malignant FNISH
Lentigo maligna melanoma
What is a superficial spreading malignant melaonma
Lateral proliferation of malignant melanocytes
Invade basement membrane
Risk of metastasis
What is ABCDE rule
Asymmetry Border irregular Colour variation (dark brown-black) Diameter >0.7mm and increasing Erythema
Why can there be a white patch in the middle of the lesion…. good or bad
Immune response has been mounted against it
Good bcause there is a immune response
Bad because it might mean the melanoma has gone deeper
What is a nodular melanoma
Vertical proliferation of malignant melanocytes
(no previous horizontal growth)
Risk of metastasis
When is prognosis worse with malignant melaonma
Nodule developing within irregular plaque (i,e, nodular within superifical spreadng)
Prognosis will become WORSE
Why could you get erythema in malingnat melanoma
……
What is acral lentiginous melanoma
Acral lentiginous melanoma (ALM) is a specific type of melanoma that appears on the palms of the hands, the soles of the feet, or under the nails
What is amelanotic melanoma
Amelanotic melanoma
When the migantn cells lose ability to make melanin
Types of malignant melanoma
Superficial spreading Nodular Lentigo maligna melanoma Acral lentiginous Amelanotic
What is breslow thickness
How far down the melanoma goes affects the prognosis
Important risk factors for melanoma developent
Family hisotry Personal hostry Skin type I,II Sunburns during childhood Do they have lots of moles (atypical nervus syndrome)
What is keratocanthoma
Lumps which grow quickly and then fall off
Benign
What could keratocanthoma look like SCC
…..
When is SCC worse
When worse differentiated (when the lump doesn’t have a core)
Having a horn or core is good
What us SCC
Malignant tumour of keratinocytes
Case of SCC
UV exposure
HPV
Immunosuppression
May occur in scars or scarring processes
High risk site for SCC
Ears for men (not covered by hair)
Lips
Genital regions
What is a commons site of SCC for women
Legs (low risk malingancy)
What SCC is worse
If just a lump not horns or a core
What is basal cell carcinoma and cause, compare to SCC
Malignant tumour arising from basal layer of epidermis
Sun exposure and genetics
BCC invades tissue but DOES NOT METASTASISE, relatively slow growing
Why are basal cell carcinoma not havig horns or a core
Don’t make keratin so not rough or horny
Where do basal cell carcinomas commonly occur
On the eye (incluidng eye lashes)
Outline the vascularitsation on basal cell carcinoma
Looks like a tree
Arbarising telangiotectasia
T/f BCC can incade
Invades tissue, but does not metastasise
Slow growing
Where are BCC common
Common on face
What will be seen under microscpe in mycosis fungoides
Lymphocytes in the dermis and epidermis….
CHECK
slow progressive disease
What kaposis sarcoma
HIV and HHV8 associated
Spread to gut liver and lung
What is epidermodysplasia veruciformis
Rare autosomal recessive condition
predisposition to HPV induced warts and SCCs
