Cancer 15 Flashcards
what is the structure of the epidermis?
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
Come Lets Get Sun Burn
how do keratinocytes change throughout the layers of the skin?
- the basal layer of keratinocytes is resting on the basement membrane
- as keratinocytes proliferate they move up the layers of the epidermis, they differentiate and then end up in the stratum corneum
- the stratum corneum is a layer of keratinocytes that have lost their nuclei and mainly consist of keratin
- the stratum corneum provides the barrier function of the skin
what are the main cells in the epidermis?
- Keratinocytes
- Melanocytes - sits on the basement membrane and produces melanin
- Langerhans cells - APCs found within the epidermis
- Merkel cells - involved in sensation
what are the types of skin cancer?
- Keratinocyte derived
Basal cell carcinoma
Squamous cell carcinoma
- Melanocyte derived
Malignant melanoma
- Vasculature derived
Kaposi’s sarcoma = arises from the endothelium of the lymphatics
Angiosarcoma = arises from the endothelium of blood vessels
- Lymphocyte derived
Mycosis fungoides = lymphoma that is specific to the skin
what are examples of genetic syndromes causing skin cancer?
- Gorlin’s Syndrome
- Xeroderma pigmentosum
what is gorlins syndrome?
- Autosomal dominant condition where the individual has a defect in the PTCH gene
- germline condition so only requires one mutation to occur
- these patients have multiple basal cell carcinomas throughout their lives
what is xeroderma pigmentosum?
- rare condition caused by a mutation in a gene involved in DNA repair
- Nucleotide excision repair is faulty in these patients so they develop many skin cancers
what viral infections might cause skin cancer?
- human herpes virus 8 causes kaposis sarcoma
- HPV causes Squamous cell carcinoma
what skin cancer does UV light cause?
- Basal Cell Carcinoma
- Squamous Cell Carcinoma
- Malignant melanoma
what examples of immunosuppression might cause skin cancer?
- Drugs e.g. azathioprine, cyclosporin
- HIV
- Old age
- Leukaemia
who is skin cancer most prevalent in?
- in white people there is increase in prevalence
what are the features of Malignant Melanoma?
dark, lumpy, abnormal
what are the features of basal cell carcinoma?
- shiny and red
how far do the following wave lengths reach?
UVC
UVB
UVA
?
based on this which wavelength is most prevalent in skin cancer?
- UVC does not penetrate the atmosphere
- UVB will reach the sea level
- UVA will reach the dead sea level
UVB is most significant for skin cancer development
UVA is the second most significant for skin cancer development but less so than UVB
why is sunlight essential for life?
- Essential for photosynthesis
- Provides warmth
- Effect on human mood
- Stimulates the production of vitamin D in the skin
how does UVB cause skin carcinogenesis?
- UVB directly induces mutations in DNA
- Affects the pyridines and causes crosslinking producing Cyclobutane pyrimidine dimers and 6-4 pyrimidine pyrimidone photoproducts
- these are usually quickly repaired by nucleotide excision repair
how does UVA cause skin carcinogenesis?
- forms cyclobutane pyrimidine dimers but less effectively than UVB
- generates free radicals that damage the DNA
what genes does UV light damage?
- Cell division
- DNA repair
- Cell cycle arrest
however photoproducts (mutations) are normally removed by a process called nucleotide excision repair
what is Xeroderma pigmentosum?
- genetic condition with defective nucleotide excision repair
features of Xeroderma pigmentosum?
- patients with Xeroderma pigmentosum have defective nucleotide excision repair
- when the DNA is not being repaired properly patients develop cancer at a very young age
- they will develop BCCs, SCCs and melanomas
- they are also very photosensitive and have dry skin
- they sometimes also have ocular and neurological problems
Summarise the mutations that cause cancer?
- Mutations that stimulate uncontrolled cell proliferation
- Mutations that alter responses to growth stimulating/repressing factors
- Mutations that inhibit apoptosis
what happens in sunburn?
- UV leads to keratinocyte 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
explain Photocarcinogenesis:
- overexposure to UV radiation causes DNA damage in the keratinocytes
- the DNA can then get repaired and return to being a normal cell
- if the damage is very severe it might undergo apoptosis
- If this damage is accompanied by appropriate mutations in other cancer-promoting genes it might cause cancer
how does UV light affect the immunocompetence of the skin?
how might this be helpful?
- UVA and UVB affect the expression of genes involved in skin immunity
- they deplete Langerhans cells in the epidermis
- this causes reduced skin immunocompetence
( this is the basis of using UV phototherapy to treat psoriasis it immunocompromised the skin so the inflammatory condition gets better) but this does increase risk of skin cancer
The mechanism by which UV therapy increases the risk of skin cancer:
- UV light can act on keratinocytes and cause DNA damage that could lead to it becoming a malignant cell
- if the Langerhans cells were working properly they would induce an immune response and cause cell death in the damaged cell
- but if the Langerhans cells are not working properly they are unable to knock out the damaged cells and this might result in cancer
what are Fitzpatrick Phototypes?
- Always burns never tans
- Usually burns, sometimes tans
- Sometimes burns, usually tans
- Never burns, always tans
- Moderate constitutive pigmentation = Asian
- Marked constitutive pigmentation = Afrocaribean
what is the function of melanin?
- Responsible for skin color
- produced by melanocytes in the basal layer of the epidermis
- ones skin colour depends on the amount and type of melanin produced not the density
what is the structure and function of melanocytes?
what do the keratinocytes do?
- melanocytes are dendritic and they interlock with about 30 or so keratinocytes
- melanocytes produce melanin which is packed into melanosomes
- the melanosomes are passed down the process and are taken up by the keratinocytes
- The keratinocytes put the melanosomes around their nucleus, which protects it from UV damage
How does tanning work?
- in pale skin types under the influence of UV light keratinocytes make melanocyte-stimulating hormone
- this has paracrine effects on the melanocytes to make more melanin
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what are the two types of melanin that are formed?
- Eumelanin - produced by people with dark hair and dark skin
- Phaeomelanin - produced by those with red/light hair and fair skin
which gene controls melanin?
how is melanin formed?
- The amounts of melanin are regulated by the MCR1 gene
- Melanin is formed from tyrosine
how many polymorphisms in the melanin gene?
- >20 gene polymorphisms in this gene
what is malignant melanoma?
what might it be caused by?
mortality rate?
- Malignant tumor of melanocytes
- melanocytes become abnormal and have atypical cells and atypical architecture
- Can be caused by UV exposure or Genetic factors
- high risk of metastasis and highest mortality
what is Lentigo Maligna?
- Proliferation of malignant melanocytes within the epidermis
- no risk of metastasis
- considered to be a pre- melanoma state
- often has an irregular shape and border
what is lentigo maligna melanoma ?
- this is a large area of lentigo maligna
- that might become invasive
how does the malignant melanoma superficially spread?
- Lateral proliferation of malignant melanocytes
- They invade the basement membrane
- It is invasive and it grows outwards
- There is now a risk of metastasis as the melanoma is below the basement membrane
how might one diagnose a superficial spreading malignant melanoma?
ABCDE -
Asymmetry
Border irregularity
Colour variation (dark brown=black)
Diameter >0.7
Erythema
what are some features of superficial spreading malignant melanoma?
- sometimes has a pale patch in the middle called area of regression
- tumour might of disappeared because it has burned itself out or the immune system has destroyed it
- has a high association with metastasis
what are the main risk factors for Development of Melanoma ?
What is Acral Lentiginous Melanoma?
- melanomas that appear on
what is Amelanotic Melanoma?
- Sometimes melanomas don’t produce pigments so it appears pink
- might metastasis to the lymph nodes
what is a Keratoacanthoma?
- no risk of metastasis
- grows rapidly then disappears
- it is a benign version of SCC
what is Squamous Cell Carcinoma ?
what is it caused by?
- Malignant tumour of keratinocytes
- Risk of metastasis
- it is caused by Immunosuppression, May occur in scars or scarring processes , UV exposure, HPV
features of well-differentiated Squamous Cell Carcinoma?
- well-differentiated SCC might have a keratin horn which means it is producing keratin
where are common sites of Squamous Cell Carcinoma?
- lower legs are common due to sun exposure in women
- protruding ears
what is basal cell carcinoma?
- Malignant tumour arising from the basal layer of the epidermis
what are causes of basal cell carcinoma?
- Sun exposure
- Genetics
how do basal cell carcinomas grow?
- These are slow-growing
- they invade tissues but they do not metastasise
what are nodular BCCs?
- It is pearly, has a rolled edge and there is telangiectasia
- a localised collection of distended blood capillary vessels = a localised collection of distended blood capillary vessels
- telangiectasia looks branching
what is Mycosis Fungoides?
- This is a cutaneous T cell lymphoma
- affects the skin causing red patches
- very slowly progression
what is Kaposi’s Sarcoma?
- HIV and HHV8 associated
- tumour of the endothelium of the lymphatics
what is Epidermodysplasia Verruciformis?
- this is a rare autosomal recessive condition that predisposes to HPV induced warts and SCCs
- the pale areas are abnormal
