Cancer 14 - Skin Cancer Flashcards
Most skin cancers arise from cells in the?
Epidermis
Describe the structure of the epidermis
Keratinocytes above Basement membrane —> differentiate as they move up.
Layers of epidermis =Stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, stratum basale
Blood = leukaemia Tissue = ?
(for lymphocyte derived carcinomas)
Lymphomas
What are the different types of skin cancer
- Keratinocyte derived - basal cell carcinoma, squamous cell carcinoma
- Melanocyte derived - malignant melanoma
- Vasculature derived - Kaposi’s sarcoma, angiosarcoma
- Lymphocyte derived - mycosis fungoides
What is the cause of skin cancer
Accumulation of genetic mutations leading to uncontrolled cell proliferation
Give examples of causes of skin cancer
- Genetic syndromes - e.g. Gorlins syndrome, xeroderma pigmentosum (problem with DNA repair mechanism)
- Viral infections - HHV8 in Kaposis sarcoma, HPV in Squamous cell carcinoma
- UV light - BCC, SCC, malignant melanomas
- Immunosuppression - Drugs, HIV, old age, leukaemia
Why is the incidence of basal cell carcinomas increasing
More sun exposure, behavioural changes e.g. not wearing hats
UV light is separated into 3 wavebands
UVA = 310-400nm (most penetrative - major cause of skin aging) UVB = 280-310nm (most important wavelength in skin carcinogenesis) UVC = 100-280nm (blocked out by ozone layer)
How do UVB (and UVA) cause DNA damage
UVB does it more than UVA
They induce photoproducts (mutations) in DNA by causing cross linking of pyrimidines - may cause 6-4 pyrimidine pyrimidine photoproduct
Normally, these mutations are repaired via nucleotide excision repair
How may UV induce skin carcinogenesis
UV damage to DNA –> mutations in specific genes. If these genes are genes for cell division, DNA repair, cell cycle arrest, could lead to skin carcinogenesis
e.g. xeroderma pigmentosum, genetic condition with defective nucleotide excision repair
Which mutations can cause cancer
- Mutations stimulating uncontrolled cell proliferation (e.g. P53 gene)
- Mutations altering responses to growth stimulating/repressing factors
- Mutations inhibiting apoptosis
Describe sunburn
UV exposure –> leads to keratinocyte apoptosis
Sunburn cells = apoptotic cells in UV overexposed skin
Apoptosis removes UV damaged cells in skin - which might otherwise become cancer cells
Explain the processes that may occur regarding photocarcinogenesis
- Keratinocyte exposed to UV
Either:
- skin cancer occurs as UV mutates p53
- DNA damage occurs but DNA repaired
- DNA damaged beyond repair –> apoptosis
What are the immunomodulatory effects of UV light
- UVA and UVB affect expression of genes involved in skin immunity - depletes Langerhans cells in the epidermis
- Reduced skin immunocompetence and immunosurveillance - basis for IV phototherapy e.g. for psoriasis
- Further increases cancer causing potential of sun exposure
How many Fitzpatrick phototypes are there
6
1-6, gradually getting darker. Reflects melanin levels
Where is melanin produced?
What does skin colour depend on?
Melanin produced by melanocytes within basal layer of epidermis
Skin colour - depends on amount and type of melanin produced - not density of melanocytes (fairly constant)
How does melanin production work
After sun exposure, keratinocytes produce MSH. Melanocytes produce melanin, packaged in melanosomes and sent via dendritic processes into keratinocytes
What are the 2 types of melanin formed
- Eumelanin = brown/black
- Phaeomelanin - yellowish/reddish brown
Melanin = formed from tyrosine via series of enzymes
The variation in eumelanin : phaeomelanin is coded by MCR1 gene
Melanin = dictates skin sensitivity to UV damage
Describe malignant melanoma
Malignant tumour of melanocytes - melanocytes become abnormal - atypical cells and architecture
Caused by UV exposure and genetic factors. Risk of metastasis
Describe the types of melanoma
- Lentigo maligna (melanoma in situ) - proliferation of malignant melanocytes within epidermis - no risk of metastasis. (Lentigo maligna melanoma (if INVASIVE)
- Superficial spreading malignant melanoma - lateral proliferation of malignant melanocytes + invade basement membrane, risk of metastasis
- Nodular melanoma - vertical proliferation of malignant melanocytes (no previous horizontal growth) - risk of metastasis. (THERE IS ALSO NODULAR MELANOMA ARISING FROM SUPERFICIAL SPREADING MELANOMA)
- Acral lentiginous melanoma
- Amelanotic melanoma - no melanin produced, difficult to diagnose
What is the ABCD(E) rule of diagnosing superficial spreading malignant melanoma
- Asymmetry
- Irregular border
- Colour variation
- Diameter >0.7mm and increasing
- Erythema
Nodular malignant melanoma may arise from?
Superficial spreading melanoma
This is the case if:
Downward proliferation of malignant melanocytes, following previous horizontal growth
Describe acral lentiginous melanoma
May occur in palms/soles (more likely in darker skin types)
What does melanoma prognosis depend on?
The thickness/how deep the melanoma goes, aka Breslow thickness (mm from top to bottom of melanoma)
What are the risk factors for melanoma development
- Family history of dysplastic nevi/melanoma
- UV radition
- Sunburns during childhood
- Intermittent burning exposure in unacclimatised fair skin
- Atypical/dysplastic nevus syndrome
- Personal history of melanoma
- Skin type 1/2
Squamous cell carcinomas are bad - they also happen to look like?
Keratoacanthomas (benign)
Describe squamous cell carcinoma
- Malignant tumour of keratinocytes
Caused by:
UV exposure, HPV, Immunosuppression, may occur in scars or scarring process
Risk of metastasis/spreading
Growing a horn = well differentiated - SCC
(no horn = poorly differentiated)
SCC on the lip has a high risk of metastasis. Why?
Lips have rich blood supply
High risk of SCC = ears, lips and genital region
Describe basal cell carcinomas
Malignant tumour arising from Basal layer of epidermis
Caused by sun exposure and genetics
SLOW GROWING, invades tissue but does not metastasise
Common on face
Dont make keratin so not rough and horny (unlike SCC)
Seeing tree-like blood vessels (aborising) = giveaway for BCC
Flat appearance of basal cell carcinoma is aka
Superficial BCC
Describe mycosis fungoides
Lymphoma - lymphocyte derived.
Plaques/patches of erythematous scaly skin. Can metastasise slowly.
Patches —> plaques –> tumour
Describe Kaposis sarcoma
Tumour of endothelial cells of lymphatics
HIV and HHV8 associated - moley, purpley plaques on skin
Describe epidermodysplasia veruciformis
Rare, autosomal recessive condition
Predisposition to HPV induced warts and SCCs
