15. Skin cancer Flashcards
What does the BM separate in the skin?
Epidermis and dermis
Which part of the skin do most cancers arise in?
Epidermis
Describe the structure of the epidermis (from the bottom up)?
- Keratinocytes sit on BM - differentiate as they move up
- Stratum basale
- Stratum spinosum
- Stratum granulosum
- Stratum corneum (dead cells without nuclei)
Which cells are found in the epidermis?
- Keratinocytes
- Melanocytes
- Merkel cells
- Langerhans cells (APCs)
What are the different types of skin cancer?
- Keratinocyte - basal cell carcinoma, squamous cell carcinoma
- Melanocyte - malignant melanoma
- Vasculature - Kaposi’s sarcoma, angiosarcoma
- Lymphocyte - mycosis fungoides
What are the 2 most common skin cancers?
1) Basal cell carcinoma
2) Squamous cell carcinoma
(both keratinocyte derived)
What are the causes of skin cancer?
- Genetic syndromes - Gorlin’s syndrome, Xeroderma pigmentosum (DNA repair disorder)
- Viral infections - HHV8, HPV
- UV light
- Immunosuppression
What does a malignant melanoma look like?
- Typically a pigmented lesion on the chest that stands out
- Irregular edge and eccentrically placed nodule
- Asymmetrical
- Thickness determines prognosis and treatment (looked at with dermatoscope)
How has the incidence of malignant melanoma changed over the last 40 years?
Increase - in white skinned people
How has the incidence of basal cell carcinoma changed over the last 40 years and why?
- Increased
- Dramatic increase in Britain
- Could be due to an ageing population, more holidays and behaviour to the sun/UV (sunbathing, sunbeds)
Which type of UV is filtered out by the ozone?
- UVC completely
* UVB partially
Which UV type can penetrate all the way below sea level?
UVA (100 times more than UVB)
Which UV is the most significant in skin carcinogenesis out of UVA and UVB?
UVB
How does UVB affect DNA?
• Induces photoproducts, which affects the pyrimidines (C and T)
• Cyclobutane pyrimidine dimers form e.g. T=T, T-C, C=C
• 6-4 pyrimidine-pyrmidine photoproducts
• Usually repaired quickly by nucleotide excision repair
- if it is not repaired, and occurs in a gene essential for control of cellular proliferation => tumour
How does UVA affect DNA?
- Also causes production of pyrimidine dimers like UVB, but less effectively
- Free radical production - causing damage to DNA can cell membrane
Why does Xeroderma pigmentosum cause skin cancer?
- Recessive genetic condition with defective nucleotide excision repair
- Development of multiple skin cancers
What happens to cells when sun burnt (i.e. severe UV damage)?
Apoptosis
How does UV affect skin immunity?
- Depletes Langerhans cells - removal of damaged cells and apoptosis doesn’t work very well
- Reduces skin immunocompetence and immunosurveillance
- Suppresses the inflammatory response
What are the Fitzpatrick phototypes?
How much melanin is in the skin
• 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 constitutive pigmentation (Afrocaribbean)
What are the dendritic cells of the epidermis?
Melanocytes and Langerhans cells
Where are melanocytes found?
On the BM
What is the ratio of melanocytes to keratinocytes?
1:5
How is melanin produced in response to increased UV exposure?
- Keratinocytes produce MSH
- Paracrine effect on melanocyte - melanin production
- Melanin packaged into melanosomes - travels down dendritic processes
- Melanosomes are taken up by the keratinocytes and positioned in front of their nuclei
How does the number of melanocytes compare in a light and dark-skinned person?
Same
What are the 2 types of melanin formed from tyrosine?
- Eumelanin - brown/black
* Phaeomelanin - yellow/reddish brown
Which gene determines the production of melanin, and the eumelanin:phaeomelanin variation?
MCR1
What is Lentigo Maligna?
- Malignant melanoma
- Restricted to epidermis
- No risk of metastasis
- Flat
- Usually on face
- Often occur in elderly patients
What is superficial spreading malignant melanoma?
- Atypical melanocytes in the epidermis
- Invaded the dermis
- Lateral and downwards proliferation
- Invasion of BM - risk of metastasis
- Regression possible - due to immune response
How is a superficial spreading malignant melanoma diagnosed?
- A - asymmetry
- B - border irregular
- C - colour variation (dark brown-black)
- D - diameter >0.7mm
- E - erythema (redness) or evolution (getting bigger)
What is a nodular melanoma arising within a superficial spreading MM?
- Type of malignant melanoma
- Downward proliferation of malignant melanocytes, following previous horizontal growth
- Nodule developing within an irregular plaque
- Worse prognosis
- Tumour may be erythematous - non-pigmented as tumour can’t make melanin
What is an acral lentiginous melanoma?
- Type of malignant melanoma on palms of hands and soles of feet
- More frequent in darker-skinned people
- Starts off flat, can develop lumps within it
What is an amelanotic melanoma?
- Type of malignant melanoma
* Lacks pigment
What determines whether a melanoma is superficial or deep?
- Less than 1mm - superficial
* More than 1mm - deep
Why can a squamous cell carcinoma lead to the formation of a ‘horn’?
- Derived from keratinocytes
* Can sometimes produce keratin
What is a keratoacanthoma?
Benign lesion that looks very similar to a squamous cell carcinoma
What causes squamous cell carcinomas?
- UV exposure
- HPV
- Immunosuppression
Why are the lips a common site for squamous cell carcinomas?
- High sun exposure
- Smoking and drinking
- Good blood supply => metastasis risk
Where is a more common sight for squamous cell carcinomas in men and women?
- Men - ears (no long hair)
* Women - legs (increased exposure)
Is the genital region a common area for squamous cell carcinoma?
Yes
Can basal cell carcinoma metastasise?
No (but can go into fat, muscle and bone)
Which part of the body do basal cell carcinomas commonly affect?
Eye lid
What is mycosis fungoides and the stages?
- Lymphomas occuring in the skin
- Patches of erythematous, scaly skin
- Patch stage, plaque stage and tumour stage
- Slowly progressive
What is Kaposi’s sarcoma?
- Tumour derived from lymph endothelium
- Related to HIV
- Driven by HHV8
- Looks like purple nodules on the skin
What is epidermodysplasia veruciformis?
- Predisposition of HPV induced warts and squamous cell carcinomas
- Rare autosomal recessive condition
- Can be covered in little, flat warts, or thick and keratotic warts
What is the main form of treatment for skin cancers?
Surgical
