Skin Cancer Flashcards
State five factors that portray the impact of skin cancer on the population
- size of problem
- demographic/behavioural
- cost of the problem
- morbidity & mortality
- lack of effective therapy
Name three types of skin cancer
Melanoma, squamous cell carcinoma, basal cell carcinoma
State four key risk factors for skin cancer
- Sun exposure
- Genetic susceptibility
- Immunosuppression
- Environmental factors
What conditions make a person more susceptible to skin cancer?
- DNA repair syndromes
- Albinism
- Naevoid basal cell carcinoma (Gorlin’s)
- Epidermolysis Bullosa (butterfly disease)
- Collagen deficiency
Give an example of a DNA repair syndrome that is a risk factor for skin cancer
Xeroderma Pigmentosum
What patient groups are at increased risk of skin cancer?
Organ transplant recipients
Haematological malignancy
Specific drugs
HIV/AIDs
What environmental factors lead to an increased risk of skin cancer?
Ionising radiation
Arsenic, coal tar
Trauma, chronic wound
How does a skin cancer arise due to genetics?
Cancers originate from a single cell, genetic mutations contribute to the emergence of a cancer cell. A series of mutations accumulate in successive generations, eventually there are enough mutations for the cell to become cancerous
What are a series of mutations accumulating in successive generations known as?
Clonal evolution
What is an oncogene?
over-active form of a gene positively regulates cell division
Give an example of an oncogene
Ras, Raf
What is a proto-oncogene?
Normal not yet mutated form of an oncogene
What is a tumour suppressor?
Inactive/non-functional form of a gene that negatively regulated cell division
Give an example of a tumour suppressor
Rb, p53
Describe the impact of p53 on sun exposure
Tp53 prevents cancer by ‘fixing problems’ but damage by sun exposure results in p53 mutations leading to lack of cancer control
Describe the mechanism by which p53 mutations arise
Cancer cell UVB specific damage Residual lesion Evasion of apoptosis by mutant p53 UV driven clonal expansion leads to further mutations & thus proliferation Tumour formation
Describe how different doses/patterns of exposure often lead to different cancers
Chronic/long term = SCC
Recreational/burning = Melanoma/BCC
Artificial UV = SCC/BCC/Melanoma
What type of skin cancer does chemical exposure increase your risk for?
Non-melanoma
Describe the damage caused by UVB and what it looks like
Direct DNA damage to the epidermis leading to sunburn
Describe the damage caused by UVA and what it looks like
Indirect oxidative damage of DNA bases in collagen leading to ageing
What happens when UBV is absorbed by DNA? How does this occur?
Absorbed to the double helix it causes
- CPDs
- 6-4 photo-products
Both occur by the formation of coolant bonds between adjacent pyrimidines on the same DNA strand
How does DNA repair itself after UVB forming CPDs and 6-4PPs?
- Recognition of damaged DNA
- Cleavage of damaged DNA on either side of photoproduct
- DNA polymerase fills in the gap
- DNA ligase seals the end
What happens when UVA causes oxidative damage?
8 oxo dG mispairs form leading to a GC to AT point mutation
How does DNA repair itself when bases are oxidised?
- Recognition and cleavage by DNA glycosylase
- Cleavage of deoxyribose by endonuclease
- DNA polymerase fills gap
- DNA ligase seals the ends
How does UV cause immunosuppression?
- depletion of langerhans
- generation of UV induced T cells with immune suppressive activity
- secretion of anti-inflammatory cytokines
What mutations are associated with BCC development?
PTCH1 mutations active hedgehog signalling to cause cell proliferation & angiogenesis
Name the drug that targets the hedgehog signalling pathway and can be used to treat BCC
Vismodegib
Mutations in what genes predispose to melanoma?
CDKN2A - prevents cells with damaged DNA replicating
CDK4 - permits cell cycle acting mutations to accelerate cell cycle
Where are melanocytes derived from?
Neural crest
What is the purpose of the MC1R protein?
Sits on cell surface and determines the balance of pigment in the skin and hair
Name the two main types of melanin
Eumelanin
Phaeomelanin
What is eumelanin responsible for?
Hair colour other than red
What is phaeomelanin responsible for?
Red hair
Name the portion that turns phaeomelanin to eumelanin
MCR1
What will on defective copy in MCR1 result in?
Freckles
What will two defective copies of MCR1 result in?`
Freckles and red hair
State another name for freckles
Ephilides
What are freckles?
Patchy increase in melanin - melanosomes produce increased melanin in response to sun exposure.
What are letingines?
Small pigmented macules as a result of increased melanocytes in the basal layer but does not darker after sun exposure - often found on sun exposed skin
Describe the histological finding of lentigines
Elongated rete pegs
What are the three common types of acquired melanocytic nave?
- Junctional
- Compound
- Intradermal
What type of melanocytes give a navei their colour?
Junctional melanocytes
What type of melanocyte cause a naevi to be raised?
Dermal melanocytes
Describe a junctional naevus
Melanocytes are at DEJ only so appear dark but flat, appear in childhood
Describe a compound naevus
Melanocytes at DEJ and in dermis so appears dark and raised, appear in adolescence
Describe a intradermal naevus
Melanocytes are in the dermis only so appears raised but not dark
Can melanocytic naevi be congenital?
Yes in 1% of babies usually large lesions which have up to 15% risk of melanoma therefore may need excised
What are dysplastic naevi?
> 6mm diameter, variegated pigment, asymmetrical
State two causes of dysplastic naevi
sporadic or familial
Describe sporadic dysplastic naevi
Not inherited, risk of melanoma increased, number of atypical naevi
Describe familial dysplastic naevi
Family history of melanoma, autosomal inheritance, high penetrance, 100% risk of melanoma
State the histological appearance of dysplastic naevi
Architectural and cellular atypia
Fibrosis and inflammation
Epidermis not effaced
Name three rare types of naevi
- halo naevi
- blue naevi
- spitz naevi
Describe a halo naevi
Peripheral halo of depigmentation due to lymphocytes & inflammatory regression
Describe blue naevi
Entirely dermal, consists of melanin producing dendritic cells
Describe spitz naevi
<20 year olds, most are benign but mimic melanoma with large spindle/epitheloid cells presents as a small red bump on face
What are the signs of a malignant melanoma?
Change in shape, bleeding, ulceration, new lesion, irregular pigmentation, satellite nodules
What do each of the letters in ABCD stand for in skin cancer diagnosis?
Asymmetry
Border
Colours
Diameter >6mm
Name the instrument used to inspect a mole more closely
Dermatoscope
Name four types of melanoma
- superficial spreading melanoma (trunk and limbs)
- Acral/mucosal lentiginous melanoma
- Letting maligna melanoma (sun exposed sites)
- Nodular melanoma
What are the two growth phases of an melanoma?
Radial Growth Phase
Vertical Growth Phase
What is the radial growth phase?
Macule, entirely in situ/dermal micro-invasion, no lymphatic involvement and curable
What is the vertical growth phase?
Invasion of dermis to form an expansile mass, can metastasise.
What type of melanoma only goes through VGP?
Nodular
Define satellite nodules
Group of tumour cells near primary tumour
What is used to predict the prognosis for a melanoma?
Breslow Depth
What is Breslow depth?
Depth of tumour from granular layer
State the categories and corresponding percentage survival of melanoma prognosis
pTis - in situ 100% pT1 <1mm 90% pT2 1-2mm 80% pT3 2-4mm 55% pT4 >4mm 20% 'b' added if ulceration occurs
How will melanomas appear on histological stain?
Pagetoid (upward spread)
Mitosis
Melanin pigments
Melanocytes with nuclear atypia
How will melanomas spread?
Local - satellite nodules
Lymphatic - lymph nodes
Blood - heart, lungs, GI tract, liver, brain
How does melanomas be initially managed?
Primary excision with 2mm margin followed by wide local excision to reduce recurrence, sample should be sent for biopsy
If lymph node spread has occurred due to melanoma what treatment is indicated?
Sentinel Node Biopsy
What can be done in advanced malignant melanoma?
BRAF/MEK inhibitors
Systemic treatments (chemo/radiotherapy)
Immunotherapy
Name the monoclonal antibody that can increase survival in patients with advanced melanoma
Ipilimumab
What are seborrhoeic keratoses also known as?
Basal cell papilloma
Warts
Who are where are seborrhoeic keratosis found?
Elderly patients on their trunk
How do seborrhoeic keratosis present?
Superficial lesions appear greasy & stuck on, usually asymptomatic but can be itchy/inflamed/irritated after trauma
Describe the histology of seborrhoeic keratosis
Proliferation of keratinocytes, acanthosis, hyperkeratosis
What is done to manage seborrhoeic keratosis?
Reassurance
What is the name given to a SCC in situ?
Bowen’s Disease
Describe the appearance of Bowen’s Disease
Well defined inflamed scaly patch on lower limbs, irregular border looks like eczema
What does bowen’s look like histologically?
Full thickness dysplasia but no dermal invasion
How is Bownen’s disease treated?
Surgery if SCC suspected
Liquid nitrogen cryotherapy
Topical 5-fluorouracil
Imiquimod
Describe actinic keratosis
Pre-Malignant lesions occurring on chronic light exposed skin common in fair skin individuals
How can actinic keratosis present?
Usually asymptomatic but may cause an itch on be present as a cutaneous horn
What does actinic keratosis look like and why?
Crumbly yellow-white scaly crusts due to dysplastic epidermal proliferation of atypical keratinocytes
How is actinic keratosis managed?
Any chance in size or inflammation warrants biopsy
Surgery if SSC suspected
Cryotherpay
Topical - fluorouracil, diclofenac, imiquimod
Most commonly left and sun protection advised
Describe viral precursors of skin cancer
Viral genital lesions are often dysplastic and associated with HPV
Type 1-4 common warts
Type 16 associated with dysplasia
How can viral skin cancer precursors be treated?
Cryotherapy or imiquimod cream
What is a dermatofibroma?
Proliferation of fibroblasts in the dermis often due to an insect bite
How does a dermatofibroma present?
Firm hard nodule - may be itchy dimples when pressure exerted laterally
Which gender is dermatofibroma more common in?
Females
What is a epidermoid cyst?
Cysts derived from the pilar unit. Epidermal wall surrounding a core of keratin common in young to middle aged adults usually asymptomatic
When to epidermoid cysts require treatment?
If they become inflamed or infected - often found on scalp
Where are basal cell carcinomas generally found?
Sun-exposed sites (head and neck)
What are the three main subtypes of basal cell carcinoma?
- nodular
- superficial
- infiltrative/morphoeic
Describe a nodular BCC
Most common type, pearly translucent papule/nodule with telangiectasia and rolled edge. Ulceration, bleeding and crusting may occur. May be pigmented causing confusion with melanoma.
Describe a superficial BCC
Usually found on trunk, scaly pink - red/brown patches/papules with a pearly border
Describe a infiltrative/morphoeic BCC
Scar-like waxy plaque/papule, ill defined edges. May spread along nerves with tumour extension beyond the observed clinical margins. Usually occur on the face and can have ulceration bleeding and crusting.
What is the histological appearance of basal cell carcinomas?
Basal cells sprout from epidermis, groups of cells invade dermis. More dense at the periphery (palisading).
Describe the progression of a BCC
Slow growing and locally destructive rarely metastases unless they invade eye and into the brain
How is a BCC diagnosed?
Usually clinical diagnosis is sufficient but if doubt a biopsy is required - superficial shave is best
What is the treatment pathway for a BCC?
Surgical excision is the most appropriate may require a skin graft or flap
Low risk sites can be treated by curettage or cautery
Radiotherapy for larger tumour’s
Topical therapy - cryotherapy, imiquimod or fluorouracil
Photodynamic therapy
What surgery is indicated in morpheoic BCC?
Moh’s micrographic surgery
State the risk factors for squamous cell carcinoma
Long term skin exposure, age (old), having fair skin
What autoimmune condition can be associated with squamous cell carcinoma?
Lupus
Where do SCCs occur?
Ear, lip, hands and scalp
What do SCCs look like?
> 4mm indurated crusted or nodular ulcerated lesions
Describe the histology of SCC
Irregular nests of epidermal cells with normal and atypical dysplastic squamous cells, keratinisation, perituoral inflammation
How are SCCs managed?
Excision with 3-5mm margin or 1mm in larger lesions
Low risk can be treated with curettage or cautery
Radio or cryotherapy may also be used
Moh’s surgery may be required in high risk lesions
What is the prognosis for SCC?
No mets - 30% risk of second primary SCC in 5 years
Regional lymphadenopathy <20% 10 year survival
Distant mets <10% 10 year survival
State six complications of biopsy
- Bleeding
- Wound dehiscence
- Infection
- Scarring
- Motor/Sensory nerve damage
- Loss of function
What is Moh’s micrographic surgery ?
Bulk of tumour is removed by curettage to create a saucer like defect, a further margin is removed from sides and base to work out if there is further excision required
