What are the 2 main types of skin cancer?
Melanoma/non melanoma (BCC/SCC)
What is a key factor in melanoma survival?
Tumour depth
What are the Breslow Thickness’?
4mm=50%, Metastases = 5%
What do you look for in melanoma diagnosis?
Asymmetry, Border, Colour, Diameter, Evolution
What is a known sign of melanoma?
Ugly ducking sign
What is the clinical presentation of BCC?
Slow growing lump or non healing ulcer. Painless. Translucent/pearly. Visible arborising blood vessels. Central ulceration (rodent), scaly plaque if superficial. If infiltrative morphoeic. Locally invasive, usually >40 yo but can be younger
What is the clinical presentation of SCC?
Hyperkeratotic lump or ulcer, arises on sun damaged skin. Grows fast, can be painful &/or bleed. Majority-well differentiated low risk, minority opposite. Metastases : 5%, poor prognosis at this stage. Precursor lesions
What are the precursor lesions of SCC?
Actinic keratoses and Bowen’s disease (carcinoma-in-situ)
What is the self resolving skin lesion that can occur in SCC?
Keratoacanthoma
What is required for a finding of Actinic Keratoses?
Multiple lesions- evidence for a field of abnormality
What are high risk sites in SCC?
Ear, lip and scalp
What are some risk factors for Skin cancer?
Sun exposure, genetic predisposition, immunosuppression, HPV infection, other environmental carcinogen - coal tar, smoking etc
What are the 6 skin types?
Skin type I - always burns, never tans Skin type II - usually burns, can tan Skin type III - can burn, but usually tans Skin type IV - always tans, never burns Skin type V - ‘brown’ skin Skin type VI - ‘black’ skin
What sun exposure pattern is likely to be the cause of SCC?
Chronic, cumulative UV exposure
What sun exposure pattern is likely to be the cause of BCC and Melanoma?
Intermittent, intense sunburn episodes
What conditions can cause a genetic susceptibility to skin cancer?
DNA repair syndromes e.g. Xeroderma Pigmentosum, Albinism, Naevoid BCC (Gorlin’s) syndrome
What environmental carcinogens are risk factors for skin cancer?
Ionising radiation, arsenic, coal tar, trauma, chronic ulceration etc
What does Xeroderma Pigmentosum cause in relation to skin cancer?
photosensitivity skin cancers on UV-exposed sites neurological degeneration Increased risk of other cancers Defect in one of seven Nucleotide Excision Repair (NER) genes (XPA - G)
What is Naevoid BCC (Gorlin’s) Syndrome?
Autosomal dominant familial cancer syndrome
What are the major features of Gorlin’s?
Major features early onset/multiple BCCs palmar pits jaw cysts ectopic calcification falx
What are the minor features of Gorlin’s?
Minor features skeletal abnormality OFC >97th centile cardiac/ovarian fibroma medulloblastoma
What level of risk are Hereditary Type VII collagen deficiency (RDEB) of developing skin cancer ?
High risk
What are the hallmarks of cancer?
Autonomous growth signals Insensitivity to anti-growth signals Resist cell death (apoptosis) Limitless potential to divide Angiogenesis Invasion and metastasis
What are the emerging hallmarks and enabling characteristics of cancer?
Deregulating cellular energetics and avoiding immune destruction. Genome instability and mutation and tumour promoting inflammation
What light causes sunburn and is stopped by window glass?
UVB
What light is stopped by sunscreens, yet doesn’t usually cause sunburn?
UVA
Describe the damage to DNA caused by UVA?
Indirect DNA damage, much more prevalent, penetrates more deeply into skin
Describe the damage to DNA caused by UVB?
Direct DNA damage-1000x more damaging than UVA, only when sun is directly overhead
What are some types of DNA damage?
Altered or missing base, incorrect base, UV signature mutation: pyrimidine dimer, insertion/deletion, strand break, crosslinking
What occurs in the formation of UV signature mutations?
UV light induces covalent linkages producing cyclobutane pyrimidine dimers (CPDs) and 6,4 photoproducts. The photoproducts interfere with pairing during replication and lead to mutations. CPDs are most common, 3x more frequent than 6,4s, but 6,4s are more mutagenic.
What happens when a mutator phenotype is formed?
Cells accumulate further mutations at a greatly increased rate because of failure of DNA repair
What types of DNA repair exist?
Nucleotide excision repair, base excision repair, double strand break repair, mismatch repair
What is the principle carcinogen in photocarcinogenesis?
UVB 290-320nm
What happens in UV induced immunosuppression?
Dendritic cells lose ability to present antigen
T cells switch from ‘helper’ to ‘suppressor’; regulatory T cells predominate
Keratinocytes & DCs secrete immunosuppressive cytokines
Describe the TP53 mutation in skin cancer
TP53 mutation – found in AK, carcinoma-in-situ & SCC
very early event; clonal patches of aberrant p53-cells in normal SE skin
relationship to carcinogenesis not clear
protects cells from apoptosis, allowing accumulation of other mutations