15: Skin Cancer Flashcards
Recall the gross anatomy of the skin
- Epidermis
- Dermis
- separated by BM
- Hypodermis
What are the differnet skin cancers that are derived from keratinoytes?
Overall called: Non-melanoma skin cancer
- Squamous Cell Carcinoma (SCC)
- Basal Cell Carcinoma (BCC)
What kind of cancer is Melanocyte derived?
Malignant Melanoma
Which types of skin cancers are vasculature derived?
Overall: rare
- Kaposi’s sarcoma, associated with HIV and HHV8
- angiosarcoma
Name a skin cancer that is lymphocyte derived
Mycosis fungoides
cutaneous T-cell lymphoma
Name different causes for skin cancer
-
Genetic mutations
- Gorlin’s syndrome
- increases the risk of basal cell carcinoma
- xeroderma pigmentosum
- mutation in DNA mismatch repair
- Gorlin’s syndrome
-
Viral infections
- HHV8 in Kaposi’s syndrome
- HPV in SCC
- UV light
- Immunosupression
What is the trend of the incidence of Malignantn melanoma?
It is increasing in the past years
- expecially in white people (small change in other ethnicities)
Explain the trend of the incidence of Basal cell carcinoma
Also increasing incidence
Differentiate between the different types of UV light
- UVA
- 100x higher exposure than UVB
- contributes to skin ageing
- might contribute to carcinogenesis
- but also exploited therapeutically because of immunosupressant effects
- UVB
- causes Cancer (most important in carcinogenesis)
- UVC
- absorbed in athmosphere
Explain how UVB radiation causes cancer
- Radiation directly causes mutations
- causes formation of base dimers (thymine or cytosine dimers)
- Normally repaired by nucleotide excision repair
Explain how UVA radiation might cause cancer
Also promotes skin cancer by
- formation of pyrimidine dimers (but less potentn than UVB)
- formation of free radicals
What kind of mutatins can cause skin cancer?
- Mutations that stimmulate uncontrolled proliferation
- P53 mutation leading to abolished control of normal cell cycle
- Mutations that alter responses to growth factors/stimmulation
- Mutation interferin with apoptosis
Explain the effect of sunburn on the skin
Sunburn causes Keratinocyte apoptosis –> release of inflammatory mediators
–> inflammation of the dermis
What are the possible outcomes to photodamaged cells?
- Apoptosis (e.g. in sunburn)
- DNA repair
- Carcinogenesis
Explain the effect of UV light on the immune system
Influence immunity (UV ligh supresses immmune system)
- Via:Change of immunoregulatory genes in epidermis
- Depleting Langerhans cells in the epidermis
- reduce immunocompetence and surveilance
- used therapeutically e.g. in psoriasis (schuppenflechte)
–> Further increase in cancer risk
What does the host response to UV light depend on?
Depeinging on different genetic influences, expecially skin phototype
Where do melanocytes sit?
What do they do?
They ususally sit at the basement membrane in the epidermis
- produce melanin as reaction to UV light exposure
Explain the production of Melanin
UV light exposure causes paracrine signaling from keratinocytes to melanocytes:
- They produce Melainin
- From tyrosine via a series of enzymes
- Accumulates intracellularly in the Keratinocytes to protect the nucleus
What are the different types of Melanin?
What determines which type you produce?
- Eumelanin – brown or black
- Phaeomelanin – yellowish or reddish brown
Dependant on present polymorphism on MCR1 gene
What are the ususal causes and risk factors of malignant melanomas?
Causes:
- UV exposure
- Genetic factors
Risk factors:
- family history
- personal history
- light skin type
- UV radiation
- sunburn durign childhood (burning is more critical than increased exposure to sun
What is the prognosis of someone with malignant melanoma?
Depending on the stage of the disease and spreading
- measurement of granular layer to bottom of layer
- <1mm: thin
- 1-4 intermediate
- >4mm thick
but overall:
possibility of metastasis
What is a Lentigo maligna?
How would it usually look like?
A melanoma in situ
- proliferation of melanocytes within the epidermis
- non-invasive –> no risk of metastisis
Presentation
- Irregular shape
- Light & dark brown colours
- Size usually >2.0 cm
How do you call an invasive form of a Lentigo Maligna?
Lentigo Maligna Melanoma
What are the characteristics of superficial spreading malignant melanoma?
- Lateral proliferation of malignant melanocytes
- Invade basement membrane
- Risk of metastasis
Can be diagnosed via ABCD(E)
- Asymmetry
- Border irregular
- Colour variation (dark, brown)
- Diameter >0.7mm and increasing
- Erythema
What are the characteristics of a nodular malignant melanoma?
•Vertical proliferation of malignant melanocytes
(no previous horizontal growth)
Risk of metastasis –> worst prognosis and most agressive form of melanoma
Name different types of malignant melanomas
- Lentigo Maligna (Melanoma
- Superficial spreading
- Nodular Melanoma
- Acral lentiginous
- slow horizontal growth
- often below feet
- Amelanotic
- no pigmentatin
What are different causes of Squamous cell carcinoma?
- UV exposure
- HPV
- Immunosuppression
- May occur in scars or scarring processes
What are squamous cell carcinomas?
What is its prognosis?
Malignant tumors of Keratinocytes
They might metastisis but lower risk than in melanomas
What are common sites for Squamous cell carcinomas to occur?
They commonly occur on
- generally sun-exposed skin
- lips (worsening with smoking)
- ears (expecially in men)
- and legs of women
What is a basal cell carcinoma?
What are its chracteristics, causes and usuall sites of occurence?
- Malignant tumour arising from basal layer of epidermis
- Caused
- sun exposure
- Genetics
- Caused
- Characteristics
- Slow growing
- Invades tissue, but does not metastasise
- Common on face
- offen appear “parly”: greyish, red colour with shiny and dialated capillary vessels on top
What is mycosis fungoidis?
It is a cutaneous T-cell lymphoma
- chronic disease, slow progression
What is a Kaposi’s sarcoma?
Cancer of the endothelial cells of lymphatics
Associated with infections of HIV (AIDS) and HHV8 (Human Herpes Virus 8)
- Form: nodules, plaques and flat lesions
What is Epidermodysplasia veruciformis?
Rare autosomal recessive condition predisposition to HPV induced warts and SCCs
What is the role of HPV in the development of SCC?
HPV infection is associated with increase in
- cervical cancers
- and caners in the head and neck region
- In squamous cell carcinomas (e.g. oral scc)
