Skin cancer Flashcards
What are the 5 layers of epidermis?
Come let's get sun burn: Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale
Where is the basal layer of keratinocytes?
Resting on the basement membrane
What happens to keratinocytes?
They proliferate and as they move up through the layers of epidermis they differentiate and eventually end up in stratum corneum
What is the stratum corneum?
Layer of keratinocytes that have lost their nuclei and mainly consist of keratin- it forms the barrier function of the skin
What are the main cell types of the epidermis?
Keratinocytes
Melanocytes- sit on the basement membrane and produce melanin
Langerhans cells- APC’s found within the epidermis
Merkel cells- involved in sensation
What skin cancers are keratinocyte derived?
Basal cell carcinoma (BCC)
Squamous cell carcinoma (SCC)
Collectively known as non-melanoma skin cancer (NMSC)
What skin cancers are melanocyte derived?
Malignant melanoma
What skin cancers are vasculature derived?
Kaposi’s sarcoma- arises from the endothelium of the lymphatics
Angiosarcoma- arises from the endothelium of blood vessels
What skin cancers are lymphocyte derived?
Mycosis fungoides- lymphoma that is specific to the skin
What is Gorlin’s syndrome?
Autosomal dominant condition where the individual has a defect in the PTCH gene, they have a germline mutation in this gene so only require one more mutation to develop BCC. These patients have multiple BCC’s throughout their lives
What is xeroderma pigmentosum?
Rare condition caused by a mutation in a gene involved in DNA repair which leads to faulty nucleotide excision repair so they go on to develop multiple skin cancers
What viral infections cause cancer?
HHV8 in Kaposi’s sarcoma
HPV in SCC
What cancers does UV light cause?
BCC
SCC
Malignant melanoma
What causes immunosuppression which leads to skin cancer?
Drugs
HIV
Old age
Leukaemia
What is the incidence of melanoma like?
It has been rising in the white population but it has remained relatively stable in other populations
What are the three different types of UV light?
UVC- doesn’t penetrate stratosphere
UVB will reach sea level
UVA will teach dead sea level
Which type of UV light is more significant for skin cancer development?
UVB- dose of UVB that reaches the earth surface is much lower than UVA
What is the major cause of skin ageing?
UVA
What is UVA used therapeutically to treat?
Psoriasis with PUVA therapy
In what way is sunlight essential for life?
Photosynthesis
Infrared spectra provide warmth
Effect on human mood
Stimulates the production of vitamin D in the skin
What effects does UVB have in humans?
It directly induces abnormalities in DNA e.g. mutations
UVB induces the formation of photoproducts (mutations)
What does UVB particularly affect in DNA?
Pyrimidines (cytosine and thymine)- causes cross linking to form cyclobutane pyrimidine dimers
What normally repairs the damage in DNA caused by UVB (cyclobutane pyrimidine dimers)?
Nucleotide excision repair
Apart from UVB, what else can promote skin carcinogenesis?
UVA- forms cyclobutane pyrimidine dimers as well but less effectively than UVB- it also generates free radicals, which can damage DNA and the cell membrane
What specific genes does UV damage to DNA lead to damage in?
Cell division
DNA repair
Cell cycle arrest
What process normally removes photoproducts?
Nucleotide excision repair
What is xeroderma pigmentosum?
Genetic condition with defective nucleotide excision repair
What does poor DNA repair normally lead to?
Cancer development at a very young age and at a high frequency- they will develop BCCs, SCCs and melanomas
They are also photosensitive and skin gets very dry
Sometimes also have ocular and neurological problems
Which mutations cause cancer?
Mutations that stimulate uncontrolled cell proliferation
Mutations that alter responses to growth stimulating/repressing factors
Mutations that inhibit apoptosis
Describe the process of sun burn?
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
Give a brief summary of photocarcinogenesis
Overexposure to UV radiation causes DNA damage in the keratinocytes
It can then get repaired and return to being a normal cell. If the damage is too severe, it could undergo apoptosis. If this damage is accompanied by appropriate mutations in other cancer promoting genes, it can lead to skin cancer
What are the immunomodulatory effects of UV light?
UVA and UVB affect the expression of genes involved in skin immunity- it depletes Langerhan cells in the epidermis, this causes reduced skin immunocompetence and immunosurveillance.
What is UV used to treat?
Psoriasis- it immunocompromised the skin so inflammatory condition gets better. However this does further increase the cancer causing potential of sun exposure
How does UV therapy increase risk of skin cancer?
UV can act on keratinocytes and cause DNA damage that could lead to it becoming a malignant cell.
If Langerhans are working properly, they will induce an appropriate immune response and cause cell death in the damaged cell.
If the Langerhans have been depleted as a result of UV phototherapy, they will be unable to knock out the damaged cells and this could promote the development of cancer
What are the 6 different Fitzpatrick prototypes?
- Always burns, never tans
- Usually burns, sometimes tans
- Sometimes burns, usually tans
- Never burns, always tans
- Moderate constitutive pigmentation
- Marked constitutive pigmentation- Afrocarribean
What produces melanin?
Melanocytes in basal layer of epidermis
What does skin colour depend on?
Amount and type of melanin produced, NOT the density of melanocytes which is fairly constant
What are melanocytes like?
Dendritic and they interdigitate with about 30 or so keratinocytes
What is melanin packed into after production?
Melanosomes
Where do melanosomes go?
They pass down the processes and are taken up by keratinocytes
What do keratinocytes do with melanosomes?
They put them around their nucleus which protects it from UV damage
What happens in keratinocytes in paler skin types under the influence of UV light?
The keratinocytes will make melanocyte stimulating hormone, which will have a paracrine effect on the melanocytes to make more melanin
What are the two types of melanin?
Eumelanin- brown/black
Phaeomelanin- yellowish or reddish-brown
What is melanin formed from?
Tyrosine via the action of many enzymes
Which group have more phaeomelanin than others?
Red heads- this doesn’t protect effectively against sun exposure
What is the amount of melanin production regulated by?
The MCR1 gene
There are >20 polymorphisms in this gene
What does the polymorphism in the MCR1 gene determine?
Eumelanin:Phaeomelanin produced and quantities
What is a malignant melanoma?
Malignant tumour of melanocytes- melanocytes become abnormal and have atypical cells and atypical architecture
What causes malignant melanoma?
UV exposure
Genetic factors
Risk of metastasis
What is a lentigo maligna (melanoma in situ)?
Proliferation of malignant melanocytes within the epidermis- Normally melanocytes are found along the basal layer but here they are distributed throughout the epidermis.
No risk at metastasis and considered a premelanoma stage
What do lentigo maligna usually look like?
They normally have an irregular shape and irregular borders with light and dark brown colours
Usually >2cm
Sometimes you have a large of lentigo maligna and then can develop an area within it that becomes invasive- lentigo maligna melanoma
What is superficial spreading malignant melanoma?
Lateral proliferation of malignant melanocytes- they invade the basement membrane. It is invasive and it grows outwards
How is superficial spreading malignant melanoma diagnosed?
ABCDE Asymmetry Border irregularity Colour variation Diameter >0.7mm and increasing Erythema
What does it mean if there is a pale area in the middle of a superficial spreading malignant melanoma?
It is an area of regression so the tumour has disappeared either because it has burned itself out or immune system has got rid of it- sounds good but is actually associated with a higher risk of metastasis
What is a nodular malignant melanoma?
Vertical proliferation of malignant melanocytes- no previous horizontal growth
What is the risk of metastasis like in nodular malignant melanoma?
As it is growing downwards, there is high risk of metastasis. These can originate from pre-existing moles or can originate de novo
What is nodular melanoma arising within a superficial spreading malignant melanoma?
Downward proliferation of malignant melanocytes that is following previous horizontal growth
What are acral lentiginous melanomas?
Melanomas that occur on palms and soles- might occur in dark skin people
Give a summary of the different types of malignant melanoma?
Superficial spreading Nodular Lentigo maligna melanoma Aural lentiginous Amelanotic
What simple stages are used for melanoma recognition?
Asymmetry
Border
Colour
Diameter
How is prognosis of melanoma determined?
Using Breslow thickness- The thickness of the tumour from top to bottom, measured in millimetres
<1mm= superficial tumour
>1mm= intermediate or deep tumour. Determines how likely the tumour is to metastasis and cause death
What are the risk factors for development of melanoma?
Genetic markers Family history of dysplastic nevi or melanoma UV irradiation Sunburns during childhood Intermittent burning exposure in unacclimatised fair skin Number (50) and size (>5mm) of melanocytic nevi Congenital nevi Number of atypical nevi Atypical/dysplastic nevus syndrome Personal history of melanoma High socioeconomic status Skin type I Equatorial latitudes DNA repair defects Immunosuppression
What are dysplastic nevi?
Moles that are a little atypical but not melanomas
What is Keratoacanthoma?
Either a benign lesion or benign version of an SCC- grows rapidly but then disappears. It has no risk of metastasis
What is a squamous cell carcinoma?
Malignant tumour of keratinocytes
What causes squamous cell carcinoma?
UV exposure
HPV
Immunosuppression
May occur in scars
What is the risk of metastasis of SCC like?
High but not as high as in melanoma
Who are at high risk of SCCs?
People that are immunosuppressed- people who have organ transplants etc
What is the sign of a well differentiated SCC?
A keratin horn- shows keratinocytes still have ability to produce keratin
Where do women tend to get SCCs?
On lower legs- more sun exposure
What is a basal cell carcinoma?
Malignant tumour arising from basal layer of the epidermis
What are the causes of BCC?
Sun exposure
Genetics
What are general features of BCCs like?
Slow growing
Invade tissues but don’t metastasis
Common on the face
What is a key feature of BCC?
Arborising telangiectasia- telengiectasia (localised collection of distended blood capillary vessels) looks like branches of a tree
What is mycosis fungoides?
Cutaneous T cell lymphoma- specifically affects the skin
Red patches make it look like psoriasis but if a biopsy is taken, atypical lymphocytes can be seen. Slowly progressive over decades
What is Kapok’s sarcoma and what is it associated with?
It is a tumour of the endothelium of the lymphatics
HIV and HHV8 associated
What is epidermodysplace verruciformis?
Rare autosomal recessive condition that predisposes to HPV induced warts and SCCs. Patients can develop abnormal warts on hands and feet that become extremely keratotic
