clinical oncology Flashcards
skin cancer: summarise the epidemiology of skin cancer, define basal cell carcinoma, squamous cell carcinoma, melanoma and epidermodysplasia verruciformis; explain the role of UV light in the pathogenesis of skin cancer and the role of p53 in relation to this; summarise the role of human papilloma virus in the pathogenesis of squamous cell carcinoma
3 layers of skin (superficial to deep)
epidermis -> dermis -> hypodermis (contains subcutaneous fat and muscle)
structure of epidermis (from young at bottom, old at top)
dermis -> stratum basale -> stratum spinosum -> stratum granulosum -> stratum lucidum -> stratum corneum
what is present in dermis
sensory nerve ending
what is present in stratum basale
dividing keratinocyte (stem cell), tactile cell, melanocytes (sit on top of basement membrane)
what is present in stratum spinosum
dendritic cell, living keratinocytes
what is present in stratum corneum
dead keratinocytes (those on surface flake off)
examples of keratinocyte derived skin cancer (non-melanoma skin cancer - NMSC)
basal cell carcinoma, squamous cell carcinoma
example of melanocyte derived skin cancer
malignant melanoma
example of vasculature derived skin cancer (rarer)
Kaposi’s sarcoma (common in AIDS), angiosarcoma
example of lymphocyte derived skin cancer
mycosis fungoides
generic cause of skin cancer
accumulation of genetic mutations in key genes leading to uncontrolled cell proliferation
4 factors causing skin cancer
genetic syndromes (e.g. Gorlin’s causing basal cell carcinoma; xeroderma pigmentosum preventing DNA repair), viral infections (HHV8 causing Kaposi’s sarcoma; HPV causing squamous cell carcinoma), UV light (basal cell carcinoma, squamous cell carcinoma, malignant melanoma), immunosuppression (e.g. by drugs, HIV, old age, leukaemia)
UV spectrum from x-rays (low wavelength) to visible light (high wavelength)
UVC -> UVB -> UVA
perforation of UV spectrum
UVC to stratosphere, UVB to ground, UVA through water
4 effects of sunlight
photosynthesis, IR provides warmth, effect on human mood, stimulates vitamin D production in skin
what UV spectrum is most important wavelength in skin carcinogenesis
UVB
3 features of UVA concerning proportion, aging, skin carcinogenesis and PUVA therapy
100x more UVA penetrates surface than UVB, major cause of skin aging, contributes to skin carcinogenesis, used therapeutically in PUVA therapy for psoriasis
effect of UVB in DNA
induces photoproducts (mutations), causing cross-linking of pyrimidines (cytosine and thymine, causing e.g. thymine dimers)
what usually repairs UVB-induced photoproduct mutations
nucleotide excision repair
how does UVA promote skin carcinogenesis
DNA forms cyclobutane butane pyrimidine dimers (less efficiently than UVB), produces free radicals damage DNA and cell membrane
3 specific gene types involved in UV damage to DNA
cell division, DNA repair, cell cycle arrest
genetic condition with defective nucleotide excision repair (removes photoproducts)
xeroderma pigmentosum
presentation, diagnosis and treatment of xeroderma pigmentosum
before 10, extensive freckling, photosensitivity; genetic testing; remove skin cancers and strict sun protection
3 effects of mutations which cause cancer
stimulate uncontrolled cell proliferation (e.g. p53), alter responses to growth stimulating/repressing factors, inhibit apoptosis
what is sunburn and why
apoptotic ketatinocytes in UV overexposed skin (apoptosis removes UV damaged cells in skin which might otherwise become cancer cells)
describe 3 outcomes of photocarcinogenesis
UV -> DNA damage -> skin cancer / DNA repair / apoptosis of irrepairable DNA
what cells do UVA and UVB deplete in epidermis involved in skin immunity, and what they do
Langerhans cells (APCs which trigger immune response in malignant cell, causing cell death)
what is basis for UV phototherapy for e.g. psoriasis, and what is consequence of using phototherapy
reduced skin immunocompetence and immunosurveillance, however this further increases cancer causing potential of sun exposure
what determines host response to UV
genetic influences especially skin phototype
6 Fitzpatrick phototypes (I-IV) scale
always burns never tans -> never burns always tans
6 Fitzpatrick phototypes (V) scale
moderate marked consitutive pigmentation - Asian
6 Fitzpatrick phototypes (VI) scale
moderate marked consitutive pigmentation - Afrocaribbean
what is responsible for skin colour and dictates skin sensitivity to UV damage
melanin pigmentation
what produces melanin and where are they
melanocytes in basal layer of epidermis
what does skin colour depend on
amount and type of melanin produced (not density of melanocytes as fairly constant)
process of keratinocyte nucleus protection from UV light by melanocytes
melanocytes have a baseline production of melanin, but upon UV exposure they secrete MSH which causes adjacent melanocytes to produce more melanin, which is uptaken by keratinocytes via dendritic processes of melanocyte, and surrounds nucleus to protect from UV
melanocytes: keratinocytes along basement membrane
1:5
what is melanin formed from
tyrosine via series of enzymes
2 types of melanin and colour
eumelanin (brown/black), phaeomelanin (yellowish/reddish brown)
what gene produces melanin
MCR1
effect of polymorphisms in MCR1 gene
variation in ratio of melanin type produced, explaining variety of hair and skin colours
what happens to melanocytes in malignant melanoma
become abnormal, with atypical cell and architecture (have risk of metastasis)
2 causes of malignant melanomas
UV exposure, genetic factors
pathological features of lentigo maligna (melanoma in situ)
proliferation of malignant melanocytes within epidermis, with no risk of metastasis; can be invasive, in which case termed “lentigo maligna melanoma”
clinical features of lentigo maligna (melanoma in situ)
irregular flat shape, light and dark brown colours, usually >2cm; common in elderly
pathological features of superficial spreading malignant melanoma
lateral proliferation of malignant melanocytes, invading basement membrane into dermis, with risk of metastasis
clinical appearance of superficial spreading malignant melanoma
dark, irregular border, asymmetrical, lumpy, looks abnormal
ABCDE rule of diagnosis of superficial spreading malignant melanomas
asymmetry, border irregularity, colour variation (dark brown-black; if loses pigmentation indicates regression due to immune response - may have metastasised already), diameter (>7mm and increasing), erythema
pathological features of nodular malignant melanoma
vertical proliferation of malignant melanocytes (can have no previous horizontal growth), with risk of metastasis
pathological features of nodular melanoma arising within superficial spreading melanoma
downward proliferation of malignant melanocytes, following previous horizontal growth
clinical features of nodular melanoma arising within superficial spreading melanoma
nodule developing within irregular plaque, with prognosis becoming worse
describe location and appearance of acral lentiginous melanoma
melanomas on palms or soles, appearing as flat pigmented plaques or lumps
describe appearance of amelanotic melanoma
non-pigmented melanoma
5 types of malignant melanoma
superficial spreading, nodular, lentigo maligna melanoma, acral lentiginous, amelanotic
ABCD of melanoma recognition
asymmetry, border, colour, diameter
what is prognosis of melanoma based on
Breslow thickness (depth of invasion): measurement from granular layer to bottom of tumour
6 main risk factors for development of melanoma
family history of dysplastic nevi or melanoma, UV irradiation, sunburns during childhood, intermittent burning exposure in unacclimatised fair skin, atypical/dysplastic nevus syndrome, personal history or melanoma, skin type I or II
what is a keratoacanthoma and feature of growth
type of squamous cell carcinoma which grows rapidly but then shrinks
what is a squamous cell carcinoma
malignant tumour of keratinocytes with risk of metastasis (less than malignant melanoma)
3 causes of squamous cell carcinoma
UV exposure, HPV, immunosuppression
where may squamous cell carcinomas occur
in scars/scarring processes, on lips, ears and legs
what is a basal cell carcinoma
malignant tumour of keratinocytes arising from basal layer of epidermis
2 causes of basal cell carcinomas
sun exposure, genetics
3 features of basal cell carcinomas
slow growing, invades tissues, doesn’t metastasise
where are basal cell carcinomas most common
on face (e.g. around eyes)
types of basal cell carcinomas
nodular, superficial
rare skin cancer: what is mycosis fungoides and how does it appear
slow progressing cutaneous T cell lymphoma, appearing like psoriasis (patchy -> plaques -> tumours)
rare skin cancer: what is Kaposi’s sarcoma, appearance and what is it associated with
tumour arising from endothelial cells of lymphatics; appear as purple plaques, nodules and flat lesions going along skin lines; associated with HIV and HHV8
rare skin cancer: what is epidermodysplasioa veruciformis
rare autosomal recessive condition causing predisposition to HPV induced warts and squamous cell carcinomas
main treatment option for skin cancers
surgical
which skin layer do most skin cancers arise from
epidermis
4 cell types in epidermis
keratinocytes, dendritic cells, Merkel cells, melanocytes
clinical appearance of basal cell carcinoma
pearly (pink/grey and glistens) with branching dilated small capillary blood vessels