Cancer as a disease - Skin cancer Flashcards
What are the five layers of the epidermis? (superficial to deep)
Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale
Then have a basement membrane to separate the underlying dermis
What are the main cell types in the epidermis?
Keratinocytes
Melanocytes
Langerhans Cells (dendritic)
Merkel Cells
State the types of skin cancer that come under each of the following types:
a. Keratinocyte derived
b. Melanocyte derived
c. Vasculature derived
d. Lymphocyte derived
a. Keratinocyte derived Basal Cell Carcinoma Squamous Cell Carcinoma b. Melanocyte derived Malignant Melanoma c. Vasculature derived Kaposi Sarcoma – endothelium of lymphatics Angiosarcoma – endothelium of blood vessels d. Lymphocyte derived Mycosis fungoides
State two examples of genetic syndromes that massively increase the risk of getting skin cancer. Which ones?
Gorlin’s Syndrome – regular BCCs
Xeroderma Pigmentosum – increased risk of BCC, SCC and malignant melanoma
Give two examples of viruses that can lead to skin cancer?
HHV8 in Kaposi’s sarcoma
HPV in SCC
State two other known causes of skin cancer
UV light => BCC, SCC, MM
Immunosuppression
What is the difference between the depth reached by UVB radiation and UVA radiation?
UVB – reaches sea level
UVA – reaches dead sea level
What is the most important wavelength category of UV in skin carcinogenesis?
UVB
note that UVA also contributes to skin carcinogenesis
Which wavelength category of UV is the major cause of skin ageing?
UVA
How is UVA radiation used therapeutically?
used therapeutically in PUVA therapy (psoralen and ultraviolet A)
How does UVB cause mutations in DNA?
UVB induces photoproducts, specifically pyrimidine dimers (normally repaired by nucleotide excision repair)
How can UVA promote skin carcinogenesis?
- Forms cyclobutane pyrimidine dimers (but less effectively than UVB)
- Generates free radicals that can damage DNA and cell membrane
Name a genetic condition with defective Nucleotide Excision Repair
Xeroderma pigmentosum
patients develop skin cancers at a very young age with minimal sun exposure
What are the features of XP?
Increased risk of BCCs, SCCs and melanoma
Photosensitivity and dry skin
What happens to keratinocytes in sunburn? What does this prevent?
The UV damage leads to keratinocyte apoptosis (the apoptotic cells are called ‘sunburn’ cells).
Apoptosis removes UV damaged cells in the skin which might otherwise become cancer cells.
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
How may the immunomodulatory effects of UV light be used therapeutically?
What are the potential negative consequences?
UV phototherapy for e.g. psoriasis
UV can act on keratinocytes and cause DNA damage; Langerhans cells have been depleted and so they will be unable to knock out the damaged cells, which could then persist and become cancerous
Which system is used to categorise people based on their skin type and hence sensitivity to UV?
Fitzpatrick Phenotypes
Which epidermal cell produces melanin? What layer of epidermis is it found in?
Hence state what skin colour depends on?
Produced by melanocytes within the basal layer (stratum basale) of the epidermis.
Skin colour depends on the amount and type of melanin produced not the density of melanocytes (which is fairly constant).
What happens to melanin once it is produced by the melanocytes?
How does UV exposure cause more melanin to be produced?
- It is packaged into melanosomes and it travels down the dendritic 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
- UV exposure causes the keratinocytes to release melanocyte stimulating hormone which will make adjacent melanocytes produce more melanin (paracrine signalling)
What are the two types of melanin? What are their colours?
Eumelanin – black/brown
Phaeomelanin – yellowish or reddish-brown
What is melanin formed from?
formed from tryosine via a series of enzymes
What gene encodes for the production of melanin?
Explain the variation in eumelanin:phaeomelanin produced.
MCR1 gene
> 20 gene polymorphisms of the gene explains the different hair colours and skin types
What is malignant melanoma? What is the major risk?
Malignant tumour of melanocytes; melanocytes become abnormal
What is Lentigo Maligna? aka? treated by?
Melanocytes exhibit Pagetoid spread which is defined as individual cell proliferation in the upper levels of the epidermis.
- There is no risk of metastasis
- Irregular light/dark brown patch
- Also called melanoma in situ
- Treated by excision
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
Describe superficial spreading malignant melanoma?
Lateral proliferation of malignant melanocytes (also proliferates upwards and downwards)
They invade the basement membrane so there is a risk of metastasis
What is the ABCDE rule for the diagnosis of superficial spreading malignant melanoma?
Asymmetry Border irregularity Colour variation Diameter (>7 mm and increasing) Erythema
What is it called when a pale area appears in the middle of a melanoma? What does it mean?
Area of regression
- there’s been an immune response against the melanoma cells
- usually represents an area of the melanoma that has already metastasised
What is it called when you get a vertical proliferation (up and down) of malignant melanocytes?
Nodular malignant melanoma
risk of metastasis
Describe the pattern of growth when a nodular melanoma arises from a superficial spreading malignant melanoma.
Downward proliferation of malignant melanocytes following previous horizontal growth
State the the type of melanoma that occurs on the palms and soles?
Acral lentiginous melanoma
What type of melanoma is non-pigmented (no melanin produced)?
Amelanotic melanoma
What is the prognosis of melanoma based on?
Breslow thickness = measurement from the top of the granular layer of the epidermis to the bottom of tumour i.e. depth of invasion
State the major risk factors for the development of melanoma
Family history Personal history Skin type 1, 2 Sunburns during childhood Intermittent burning exposure
What is a keratoacanthoma?
It is either a benign lesion or a benign version of an SCC
It grows rapidly but then disappears
There is no risk of metastasis
What is a squamous cell carcinoma described as?
What can squamous cell carcinomas (SCCs) be caused by?
= Malignant tumour of keratinocytes
- UV exposure
- HPV
- Immunosuppression (main cancer in organ transplant patients)
- May occur in scars
How can you tell whether an SCC is well differentiated?
If it has a keratin horn then it shows that the malignant keratinocytes can still produce keratin and so they are well differentiated
What is a basal cell carcinoma (BCC)? Characterise it?
Malignant tumour arising from keratinocytes in the basal layer of the epidermis.
- Slow growing
- Invades tissue, but DOES NOT metastasise
- Common on face
Describe the general appearance of BCCs
They glisten, have a rolled edge and often have arborising telangiectasia
What is mycosis fungoides also known as?
cutaneous T-cell lymphoma
appears as pink scaly plaques
Which viruses are associated with Kaposi sarcoma?
HHV8
HIV
What kind of disease is Epidermodysplasia Veruciformis?
Rare autosomal recessive condition that predisposes to SCCs and HPV induced warts (that can become incredibly keratotic).
