Cancer as a Disease – Skin Cancer Flashcards
(45 cards)
1
Q
Outline the basic micronanatomy of the skin - layer by layer
A
- Epidermis
- Basement Membrane
- Dermis
- Hypodermis
2
Q
What are the five layers of the epidermis starting from the bottom and going up?
A
- Stratum basale
- Stratum spinosum
- Stratum granulosum
- Stratum corneum
- Stracum lucidum
3
Q
What are the main cell types in the epidermis?
A
- 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
4
Q
State the different types of skin cancer and some examples that come under each of the following types:
A
- 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
5
Q
State two examples of genetic syndromes that massively increase the risk of getting skin cancer
A
- Gorlin’s Syndrome – regular BCCs
- Xeroderma Pigmentosum – increased risk of BCC, SCC and malignant melanoma
6
Q
Give 3 examples of viruses that can lead to skin cancer?
A
- HHV8 - Kaposi’s Sarcoma
- HIV - Kaposi’s Sarcoma
- HPV - SCC (squamous cell carcinoma)
7
Q
What are the 3 types of UV rays, and describe the difference between them, mention which ones are more siginificant in regards skin cancer?
A
- 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
8
Q
How does UVB cause mutations in DNA?
A
- 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
9
Q
How can UVA promote skin carcinogenesis?
A
- Forms cyclobutane pyrimidine dimers (but less effectively than UVB)
- Generates free radicals that can damage DNA
10
Q
How are mutations induced by UVB and UVA usually corrected?
A
- Nucleotide excision repair
11
Q
Name a condition that is caused by a defect in nucleotide excision repair
A
- Xeroderma pigmentosum
12
Q
Describe the pathophysiology, presentation and the management of Xeroderma Pigmentosum
A
- 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
13
Q
What happens to keratinocytes in sunburn?
A
- 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
14
Q
Describe the immunomodulatory effects of UV light
A
- 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
15
Q
What are the 3 fates of cells that are damaged by UV light and accumulate mutations?
A
- 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
16
Q
What are the consequences of UV therapy for psoriasis?
A
- 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
17
Q
Which system is used to categorise people based on their skin type and sensitivity to UV and what are the different categories?
A
- 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
18
Q
Where are melanocytes found within the epidermis?
A
- In the stratum basale
19
Q
What happens to melanin once it is produced by the melanocytes?
A
- 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
20
Q
What are the two types of melanin?
A
- Eumelanin – black/brown
- Phaeomelanin – yellowish or reddish-brown
21
Q
What is melanin formed from?
A
- Tyrosine
22
Q
What gene regulates the relative amounts of melanin produced, and what else does it deteremine?
A
- MC1R
- It also determines the ratio of eumelanin : phaeomelanin produced
- It therefore determines the hair and skin colour
23
Q
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?
A
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
24
Q
What is it the name given to a large area of lentigo maligna that has a smaller area within it that has become invasive?
A
- Lentigo maligna melanoma
25
1) What is a superficial spreading malignant melanoma?
2) Regression can be seen in superficial spreading malignant melanoma - what is this and what is happening in this?
1)
* Melanoma that originates in the epidermis but invades through the basement membrane and there is subsequent lateral and downward proliferation - there is a risk of metastasis
2)
* Regression - immune response causing destruction of melanocytes - this can be seen as a visible clear patch within the melanoma
26
What is the ABCDE for the diagnosis of superficial spreading malignant melanoma?
* Asymmetry
* Border irregularity
* Colour variation
* Diameter (\>0.7 mm and increasing)
* Erythema (reddening of skin due to dilatation of capillaries as a result of injury or irritation)
27
What is it called when a pale area appears in the middle of a melanoma?
* Area of regression – this is associated with higher risk of metastasis
28
What is it called when you get a vertical proliferation of malignant melanocytes?
Nodular malignant melanoma
29
Describe the pattern of growth when a nodular melanoma arises from a superficial spreading malignant melanoma
* Downward proliferation of malignant melanocytes that is following previous horizontal growth
30
1) What is the type of melanoma that occurs on the palms and soles?
2) What does it look like?
1)
* Acral lentiginous melanoma
2)
* Dark lesion which starts off flat but can develop lumps
31
What type of melanoma produces no melanin?
* Amelanotic melanoma
32
Summarise the different types of malignant melanoma
SALAN
1. Superficial spreading malignant melanoma
2. Acral lentiginous
3. Lentigno maligna (melanoma in situ)
4. Amelanotic
5. Nodular melanoma
33
What is the prognosis of melanoma based on?
* Breslow thickness – thickness from the top of the tumour (starting from the granular layer) to the bottom
* \< 1mm = superficial
* \> 1mm = deep
34
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
35
1) What do SCCs arise from and what can they produce?
2) What is there a risk of with SCCs?
1)
* SCCs arise from keratinocytes
* If they are functioning, they can produce keratin
2)
* Risk of metastasis
36
What can squamous cell carcinomas (SCCs) be caused by?
* UV exposure
* HPV
* Immunosuppression (main cancer in organ transplant patients)
37
How can you tell whether an SCC is well differentiated?
* If the lesion has a keratin horn then it shows that the keratinocytes can still produce keratin and so they must be well differentiated as they are still functional (keratin horns are like projections of the SCC caused by production of keratin causing expansion)
38
What is a basal cell carcinoma (BCC)?
* Malignant tumour arising from keratinocytes in the basal layer of the epidermis (stratum basale)
39
Describe the appearance of BCCs
* They are pearly, have a rolled edge and often have arborising telangiectasia
40
1) Name a cutaneous T-cell lymphoma
2) What does this look like?
1)
* Mycosis fungoides
2)
* Patches of erythematous skin
41
Name a disease that predisposes to SCCs and HPV induced warts (that can become incredibly keratotic)
Epidermodysplasia Veruciformis
42
What is the difference between a leukaemia and a lymphoma, and thus describe what mycosis fungoides is
* Cancerous lymphocytes in the blood = leukaemia
* Cancerous lymphocytes restricted to tissues (often within lymph nodes) = lymphoma
* Mycosis fungoides is a T-cell lymphoma where the cancerous lymphocytes are restricted to cutaneous tissue
43
What are the 3 stages of the progression of mycosis fungoides?
1. Patch
2. Plaque
3. Tumour
44
1) What is Kaposi's Sarcoma and what is it caused by?
2) What does it look like?
1)
* Tumour derived from the lymph endothelium associated with the following viruses:
1. HHV8
2. HIV
2)
* Purple nodules
45
What is Epidermodysplasia Veruciformis - including inheritance pattern, what it leads to, and what it looks like?
* Rare autosomal recessive condition
* Leads to predisposition to HPV warts and SCCs
* The patient will be covered in warts, which may be either flat or thick and keratotic
