Skin Cancer Flashcards
what are the 2 main types of skin cancer?
non-melanoma skin cancer & melanoma
where do the majority of non-melanoma skin cancers arise from?
keratinocytes in the epidermis
where do basal cell carcinomas (BCC) arise from?
keratinocytes within the basal layer
where do squamous cell carcinomas (SCC) arise from?
the supra basal layers
which is the most serious form of skin cancer?
melanoma
where do melanomas arise from?
melanocytes scattered along the basal layer of the epideris
what do BCCs usually present as?
painless, pearly/transluscent, slow-growing lump or non-healing ulcer, visible arborising blood vessels
how do SCCs present?
a number of ways including a warty or crusted growth or a non-healing ulcer (hyperkeratotic lump/ulcer)
where do SCCs usually arise?
on sun damaged skin
how do SCCs tend to grow?
fast & may be painful
do SCCs or BCCs spread around the body?
SCCs spread around the body with serious consequences
BCCs only spread locally
which is the most common cancer in 15-24 yr olds?
melanoma
are melanomas more common in men or women?
more common in women but more men die
what does melanoma survival depend on?
tumour depth
what is the ABCDE rule for diagnosing melanomas?
A - asymmetry B - border C - colour D - diameter E- evolution
what happens in a rodent ulcer presentation of BCC?
central ulceration
what happens in a superficial presentation of BCC?
scaly laque
what is an infiltrative BCC called?
morphoeic
what are the precursor lesions for SCCs & BCCs?
actinic keratoses (AK) & Bowen’s disease (carcinoma in-situ)
what is a keratocanthoma?
a self-resolving skin lesion that erupts in sun damaged skin, rather like a little volcano, usually has a central plaque
what is field cancerisation?
more severe field change
what are the risk factors for skin cancer?
- sun exposure
- genetic predisposition
- immunosuppression
- other environmental carcinogens (coal tar, smoking, ionising radiation, arsenic, trauma, chronic ulceration)
- age
- immunosuppression
- HPV
what sun exposure pattern would create a risk of SCC?
chronic, cumulative UV-exposure
what sun exposure pattern would create a risk of BCC?
intermittent, intense sunburn episodes
what sun exposure pattern would create a risk of melanoma?
intermittent, intense sunburn episodes
who are at risk of SCCs?
outdoor workers, famers, sailors, recreational & dedicated sunbathers
which genetic conditions increase your risk of skin cancer?
- xeroderma pigmentosum
- oculocutaenous albinism
- naevoid BCC (Gorlin’s) syndrome
- recessive dystrophic epidermolysis bullosa
what immunological factors can increase your risk of skin cancer?
- organ transplantation
what is carcinogenesis?
the process by which a normal cell becomes a malignant cancer cell
what is cancer?
an accumulation of abnormal cells that multiply through uncontrolled cell division & spread to other parts of the body by invasion &/or distant metastasis via the blood & lymphatic system
what does uncontrolled cell proliferation require in terms of genes?
multi-step gene damage
e.g. gain of function of oncogenes & loss of function of tumour suppressors
what is clonal evolution?
a series of mutations that accumulate in successive generations of the cell in a process
what are the 6 hallmarks of cancer?
- autonomous growth signals
- insensitivity to anti-growth signals
- resist cell death (apoptosis)
- limitless potential to divide
- angiogenesis
- invasion & metastasis
how can damage occur to our DNA causing cancer?
- natural accumulation of DNA damage (cancer is usually a disease of old age)
- carcinogens
- inherited defects
what does UV-A do to our DNA?
indirect DNA damage, much more prevalent, penetrates more deeply into skin
what does UV-B do to our DNA?
direct DNA damage, much more damaging than UVA, only when sun is directly overhead
what can mutations in genes involved in DNA repair lead to?
a mutator phenotype whereby cells accumulate further mutations at a greatly increased rate because of failure of DNA repair
what can damage to genes that control the ingrate of cell devision lead to?
chromosome instability & the accumulation of chromosome abnormalities
what does UVB generate?
DNA photoproducts
what does UVA induce?
guanine oxidation roduces in DNA
what does UV-induced immunosuppression lead to?
- dendritic cells lose the ability to present antigens
- T cells switch from helper to suppressor, regulatory T cells predominate
- keratinocytes & DCs secrete immunosuppressive cytokines
what happens in initiation of photocarcinogenesis & what does this form?
DNA damage forms photoproducts e.g. TP53, RAS mutations
what happens in promotion of photocarcinogenesis & what does this form?
activation of signal transduction pathways & inflammation/oxidative stress causes AK
what happens in progression of photocarcinogenesis & what does this form?
constitutive cell proliferation & survival. genetic instability. acquire hallmarks of cancer & causes SCC & metastases
what do freckles mean in terms of tanning?
you cannot tan & need to protect your skin from sun
which skin cancer do sunbeams increase the risk of?
melanomas
what are the molecular drivers of BCC?
- genetically homogenous tumour
- aberrant hedgehog signalling
- involvement of PTCH
what gene is TP53?
guardian of the genome
what does TP53 do?
protects cells from apoptosis, allowing accumulation of other mutations
what are the phototoxic drugs?
Voriconazole – antifungal agent Thiazide diuretics NSAIDs Anti-TNF Azathioprine
how might specific cutaneous HPVS contribute towards cancer development?
- inhibition of apoptosis
- delay DNA repair
- promote keratinocyte invasion
which virus increases the risk of skin cancer?
HPV
how can skin cancer be prevented?
- screening/surveillance
- treatment of premalignant conditions (cyrcotherapy/surgery)
- sunscreens
- UVA & UVB avoidance
