Cancer as a Disease – Skin Cancer

Question 1

What are the five layers of the epidermis?

Answer 1

Stratum corneum 
Stracum lucidum 
Stratum granulosum 
Stratum spinosum 
Stratum basale

Question 2

What are the main cell types in the epidermis?

Answer 2

Keratinocytes
Melanocytes
Langerhans Cells
Merkel Cells

Question 3

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

Answer 3

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

Question 4

State two examples of genetic syndromes that massively increase the risk of getting skin cancer.

Answer 4

1. Gorlin’s Syndrome – regular BCCs

2. Xeroderma Pigmentosum – increased risk of BCC, SCC and malignant melanoma

Question 5

Give two examples of viruses that can lead to skin cancer?

Answer 5

HHV8 in Kaposi’s sarcoma

HPV in SCC

Question 6

What is the difference between the depth reached by UVB, UVC radiation and UVA radiation?

Answer 6

UVB – reaches sea level
UVA – reaches dead sea leve
UVC- doesn’t penetrate ozone

Question 7

How does UVB cause mutations in DNA?

Answer 7

Induces the formation of photoproducts
Particularly affects pyrimidines – causing cross-linking
Formation of cyclobutane pyrimidine dimers and 6-4 pyrimidine pyrimidone photoproducts

Question 8

How are these mutations usually corrected?

Answer 8

Nucleotide excision repair

Question 9

How can UVA promote skin carcinogenesis?

Answer 9

Forms cyclobutane pyrimidine dimers (but less effectively than UVB)
Also generates free radicals that can damage DNA

Question 10

Name a condition that is caused by a defect in nucleotide excision repair.

Answer 10

Xeroderma pigementosum

Question 11

What are the features of Xeroderma pigementosum condition?

Answer 11

Increased risk of BCCs, SCCs and melanoma

Photosensitivity and dry skin

Question 12

What happens to keratinocytes in sunburn?

Answer 12

The UV damage leads to keratinocyte apoptosis

The apoptotic cells in UV overexposed skin are called sun burn cells

Question 13

Describe the immunomodulatory effects of UV light.

Answer 13

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

Question 14

What are the consequences of UV therapy for psoriasis?

Answer 14

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

Question 15

Which system is used to categorise people based on their skin type and sensitivity to UV?

Answer 15

Fitzpatrick Phenotypes

Question 16

Where are melanocytes found within the epidermis?

Answer 16

In the basal layer

Question 17

What happens to melanin once it is produced by the melanocytes?

Answer 17

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

Question 18

What are the two types of melanin?

Answer 18

Eumelanin – black/brown

Phaeomelanin – yellowish or reddish-brown

Question 19

What is melanin formed from?

Answer 19

Tyrosine

Question 20

What gene regulates the relative amounts of melanin produced?

Answer 20

MC1R

Question 21

What is Lentigo Maligna?

Answer 21

Proliferation of malignant melanocytes within the epidermis
There is no risk of metastasis
This is also called melanoma in situ

Question 22

What is it the name given to a large area of lentigo maligna that has a smaller area within it that has become invasive?

Answer 22

Lentigo maligna melanoma

Question 23

What is a superficial spreading malignant melanoma?

Answer 23

Lateral proliferation of malignant melanocytes

They invade the basement membrane so there is a risk of metastasis

Question 24

What is the ABCDE for the diagnosis of superficial spreading malignant melanoma?

Answer 24

Asymmetry 
Border irregularity  
Colour variation  
Diameter (>0.7 mm and increasing) 
Erythema

Question 25

What is it called when a pale area appears in the middle of a melanoma?

Answer 25

Area of regression – this is associated with higher risk of metastasis

Question 26

What is it called when you get a vertical proliferation of malignant melanocytes?

Answer 26

Nodular malignant melanoma

-risk of metastasis

Question 27

Describe the pattern of growth when a nodular melanoma arises from a superficial spreading malignant melanoma. What happens to the prognosis now?

Answer 27

Downward proliferation of malignant melanocytes that is following previous horizontal growth
-prognosis gets worse

Question 28

What is the type of melanoma that occurs on the palms and soles?

Answer 28

Acral lentiginous melanoma

Question 29

What type of melanoma produced no melanin?

Answer 29

Amelanotic melanoma

Question 30

What is the prognosis of melanoma based on?

Answer 30

Breslow thickness – thickness from the top of the tumour to the bottom
-deeper the melanoma, the worse the prognosis

Question 31

What is a keratoacanthoma?

Answer 31

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

Question 32

What can squamous cell carcinomas (SCCs) be caused by? Does it have a risk of metastasis?

Answer 32

UV exposure
HPV
Immunosuppression (main cancer in organ transplant patients)
-risk of metastasis

Question 33

How can you tell whether an SCC is well differentiated?

Answer 33

If the lesion has a keratin horn then it shows that the keratinocytes can still produce keratin and so they are well differentiated

Question 34

What is a basal cell carcinoma (BCC)? Does it metastasise?

Answer 34

Malignant tumour arising from keratinocytes in the basal layer of the epidermis
- does not metastasise but does invade tissue

Question 35

Describe the appearance of BCCs

Answer 35

They are pearly, have a rolled edge and often have arborising telangiectasia
-common on face

Question 36

Name a cutaneous T cell lymphoma.

Answer 36

Mycosis fungoides

Question 37

Which viruses are associated with Kaposi sarcoma?

Answer 37

HHV8

HIV

Question 38

Name a disease that predisposes to SCCs and HPV induced warts (that can become incredibly keratotic).

Answer 38

Epidermodysplasia Veruciformis

Question 39

Which wavelength of sunlight is most important in skin carciogenesis?

Answer 39

UVB

Question 40

Which wavelength of sunlight is most important in skin AGEING ?

Answer 40

UVA

100x more penetrates to earth surface than UVB

Question 41

What is the pathway for the formation of melanin?

Answer 41

Tyrosine
DOPA
Dopaquinone 
Eumelanin or Phaemelanin
Melanin

Question 42

What are malignant melanoma caused by?

Answer 42

UV exposure
Genetic factors
- there is a risk of metastasis

Question 43

What are the types of malignant melanoma?

Answer 43

1. Superficial spreading
2. Nodular
3. Lentigo maligna melanoma
4. Acral lentiginous
5. Amelanotic

Question 44

List the features of the 6 Fitzpatrick phototypes

Answer 44

1 - 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 constitutive pigmentation - Afrocaribean