Cancer as a Disease – Skin Cancer Flashcards
(45 cards)
Outline the basic micronanatomy of the skin - layer by layer
- Epidermis
- Basement Membrane
- Dermis
- Hypodermis
What are the five layers of the epidermis starting from the bottom and going up?
- Stratum basale
- Stratum spinosum
- Stratum granulosum
- Stratum corneum
- Stracum lucidum
What are the main cell types in the epidermis?
- Keratinocytes - these are the main cells which begin at the basement membrane and stratum basale level and then differentiate as they go up the layers of the epidermis
- Melanocytes
- Langerhans Cells
- Merkel Cells
State the different types of skin cancer and some examples that come under each of the following types:
- Keratinocyte derived - Basal Cell Carcinoma, Squamous Cell Carcinoma
- Melanocyte derived - Malignant Melanoma
- Vasculature derived - Kaposi Sarcoma (endothelium of lymphatics), Angiosarcoma (endothelium of blood vessels)
- Lymphocyte derived - Mycosis fungoides
State two examples of genetic syndromes that massively increase the risk of getting skin cancer
- Gorlin’s Syndrome – regular BCCs
- Xeroderma Pigmentosum – increased risk of BCC, SCC and malignant melanoma
Give 3 examples of viruses that can lead to skin cancer?
- HHV8 - Kaposi’s Sarcoma
- HIV - Kaposi’s Sarcoma
- HPV - SCC (squamous cell carcinoma)
What are the 3 types of UV rays, and describe the difference between them, mention which ones are more siginificant in regards skin cancer?
- UVC is completely filtered out by the ozone
- UVB – reaches sea level but partially filtered out by the ozone, however it is still the most significant in regards skin cancer
- UVA – reaches dead sea level - penetrates the furthest and is not really filtered by the ozone layer - also relevant in regards skin cancer
How does UVB cause mutations in DNA?
- Induces the formation of photoproducts (mutations)
- Particularly affects pyrimidines (cytosine and thymine) – causing cross-linking
- Formation of….
- Cyclobutane pyrimidine dimers (e.g. T–T, T–C, C–C)
- 6-4 pyrimidine-pyrimidine photoproducts
How can UVA promote skin carcinogenesis?
- Forms cyclobutane pyrimidine dimers (but less effectively than UVB)
- Generates free radicals that can damage DNA
How are mutations induced by UVB and UVA usually corrected?
- Nucleotide excision repair
Name a condition that is caused by a defect in nucleotide excision repair
- Xeroderma pigmentosum
Describe the pathophysiology, presentation and the management of Xeroderma Pigmentosum
- Recessive defect in genes encoding proteins which carry out nucleotide excision repair which normally correct mutations induced by UV light that are carcinogenic
- Therefore increased risk of BCCs, SCCs and melanoma
- Photosensitivity and dry skin
- The condition is managed by reducing exposure to UV light
What happens to keratinocytes in sunburn?
- The keratinocytes are over-exposed to UV, causing damage to DNA and therefore accumulation of mutations which leads to keratinocyte apoptosis as a protective mechanism
- Sunburn cells - keratinocyte cells that undergo apoptosis as a result of UV-over exposure
Describe the immunomodulatory effects of UV light
- UVA and UVB affect the expression of genes involved in skin immunity
- It depletes Langerhans cells in the epidermis
- This reduces skin immunocompetence and immunosurveillance
What are the 3 fates of cells that are damaged by UV light and accumulate mutations?
- Skin cancer due to accumulation of mutations including in genes to do with stimulating uncontrolled proliferation, altering responses to growth stimulating / repressing factors and to do with apoptosis
- Apoptosis as a protective mechanism due to the mutations
- DNA repair of the mutations by nucleotide excision repair
What are the consequences of UV therapy for psoriasis?
- Increased risk of skin cancer
- UV can act on keratinocytes and cause DNA damage
- If the Langerhans cells have been depleted then they will be unable to knock out the damaged cells so they could persist and become cancerous
Which system is used to categorise people based on their skin type and sensitivity to UV and what are the different categories?
- Fitzpatrick Phenotypes
- I - Always burns, never tans
- II - Usually burns, sometimes tans
- III - Sometimes burns, usually tans
- IV - Never burns, always tans
- V - Moderate constitutive pigmentation - Asian
- VI - Marked constutive pigmentation - Afrocarribean
Where are melanocytes found within the epidermis?
- In the stratum basale
What happens to melanin once it is produced by the melanocytes?
- It is packaged into melanosomes and it passes along the processes of the melanocytes and is taken up by the keratinocytes
- The keratinocytes put the melanosomes around their nuclei, which protects the nuclei from DNA damage
What are the two types of melanin?
- Eumelanin – black/brown
- Phaeomelanin – yellowish or reddish-brown
What is melanin formed from?
- Tyrosine
What gene regulates the relative amounts of melanin produced, and what else does it deteremine?
- MC1R
- It also determines the ratio of eumelanin : phaeomelanin produced
- It therefore determines the hair and skin colour
1) Describe what Lentigo Maligna is, and give another name for it
2) What does Lentigo Maligna look like and where do they usually occur?
3) What is Lentigo Maligna Melanoma?
1)
- Proliferation of malignant melanocytes within the epidermis
- There is no risk of metastasis
- This is also called melanoma in situ
2)
- Light or dark brown
- Irregular shape
- Small
- Flat
- Usually on the face
3)
- Invasion within the Lentigo Maligna
What is it the name given to a large area of lentigo maligna that has a smaller area within it that has become invasive?
- Lentigo maligna melanoma