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Y2 MCD Cancer > clinical oncology > Flashcards

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

1
Q

3 layers of skin (superficial to deep)

A

epidermis -> dermis -> hypodermis (contains subcutaneous fat and muscle)

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2
Q

structure of epidermis (from young at bottom, old at top)

A

dermis -> stratum basale -> stratum spinosum -> stratum granulosum -> stratum lucidum -> stratum corneum

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3
Q

what is present in dermis

A

sensory nerve ending

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4
Q

what is present in stratum basale

A

dividing keratinocyte (stem cell), tactile cell, melanocytes (sit on top of basement membrane)

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5
Q

what is present in stratum spinosum

A

dendritic cell, living keratinocytes

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6
Q

what is present in stratum corneum

A

dead keratinocytes (those on surface flake off)

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7
Q

examples of keratinocyte derived skin cancer (non-melanoma skin cancer - NMSC)

A

basal cell carcinoma, squamous cell carcinoma

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8
Q

example of melanocyte derived skin cancer

A

malignant melanoma

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9
Q

example of vasculature derived skin cancer (rarer)

A

Kaposi’s sarcoma (common in AIDS), angiosarcoma

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10
Q

example of lymphocyte derived skin cancer

A

mycosis fungoides

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11
Q

generic cause of skin cancer

A

accumulation of genetic mutations in key genes leading to uncontrolled cell proliferation

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12
Q

4 factors causing skin cancer

A

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)

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13
Q

UV spectrum from x-rays (low wavelength) to visible light (high wavelength)

A

UVC -> UVB -> UVA

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14
Q

perforation of UV spectrum

A

UVC to stratosphere, UVB to ground, UVA through water

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15
Q

4 effects of sunlight

A

photosynthesis, IR provides warmth, effect on human mood, stimulates vitamin D production in skin

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16
Q

what UV spectrum is most important wavelength in skin carcinogenesis

A

UVB

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17
Q

3 features of UVA concerning proportion, aging, skin carcinogenesis and PUVA therapy

A

100x more UVA penetrates surface than UVB, major cause of skin aging, contributes to skin carcinogenesis, used therapeutically in PUVA therapy for psoriasis

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18
Q

effect of UVB in DNA

A

induces photoproducts (mutations), causing cross-linking of pyrimidines (cytosine and thymine, causing e.g. thymine dimers)

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19
Q

what usually repairs UVB-induced photoproduct mutations

A

nucleotide excision repair

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20
Q

how does UVA promote skin carcinogenesis

A

DNA forms cyclobutane butane pyrimidine dimers (less efficiently than UVB), produces free radicals damage DNA and cell membrane

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21
Q

3 specific gene types involved in UV damage to DNA

A

cell division, DNA repair, cell cycle arrest

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22
Q

genetic condition with defective nucleotide excision repair (removes photoproducts)

A

xeroderma pigmentosum

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23
Q

presentation, diagnosis and treatment of xeroderma pigmentosum

A

before 10, extensive freckling, photosensitivity; genetic testing; remove skin cancers and strict sun protection

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24
Q

3 effects of mutations which cause cancer

A

stimulate uncontrolled cell proliferation (e.g. p53), alter responses to growth stimulating/repressing factors, inhibit apoptosis

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25
Q

what is sunburn and why

A

apoptotic ketatinocytes in UV overexposed skin (apoptosis removes UV damaged cells in skin which might otherwise become cancer cells)

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26
Q

describe 3 outcomes of photocarcinogenesis

A

UV -> DNA damage -> skin cancer / DNA repair / apoptosis of irrepairable DNA

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27
Q

what cells do UVA and UVB deplete in epidermis involved in skin immunity, and what they do

A

Langerhans cells (APCs which trigger immune response in malignant cell, causing cell death)

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28
Q

what is basis for UV phototherapy for e.g. psoriasis, and what is consequence of using phototherapy

A

reduced skin immunocompetence and immunosurveillance, however this further increases cancer causing potential of sun exposure

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29
Q

what determines host response to UV

A

genetic influences especially skin phototype

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30
Q

6 Fitzpatrick phototypes (I-IV) scale

A

always burns never tans -> never burns always tans

31
Q

6 Fitzpatrick phototypes (V) scale

A

moderate marked consitutive pigmentation - Asian

32
Q

6 Fitzpatrick phototypes (VI) scale

A

moderate marked consitutive pigmentation - Afrocaribbean

33
Q

what is responsible for skin colour and dictates skin sensitivity to UV damage

A

melanin pigmentation

34
Q

what produces melanin and where are they

A

melanocytes in basal layer of epidermis

35
Q

what does skin colour depend on

A

amount and type of melanin produced (not density of melanocytes as fairly constant)

36
Q

process of keratinocyte nucleus protection from UV light by melanocytes

A

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

37
Q

melanocytes: keratinocytes along basement membrane

38
Q

what is melanin formed from

A

tyrosine via series of enzymes

39
Q

2 types of melanin and colour

A

eumelanin (brown/black), phaeomelanin (yellowish/reddish brown)

40
Q

what gene produces melanin

41
Q

effect of polymorphisms in MCR1 gene

A

variation in ratio of melanin type produced, explaining variety of hair and skin colours

42
Q

what happens to melanocytes in malignant melanoma

A

become abnormal, with atypical cell and architecture (have risk of metastasis)

43
Q

2 causes of malignant melanomas

A

UV exposure, genetic factors

44
Q

pathological features of lentigo maligna (melanoma in situ)

A

proliferation of malignant melanocytes within epidermis, with no risk of metastasis; can be invasive, in which case termed “lentigo maligna melanoma”

45
Q

clinical features of lentigo maligna (melanoma in situ)

A

irregular flat shape, light and dark brown colours, usually >2cm; common in elderly

46
Q

pathological features of superficial spreading malignant melanoma

A

lateral proliferation of malignant melanocytes, invading basement membrane into dermis, with risk of metastasis

47
Q

clinical appearance of superficial spreading malignant melanoma

A

dark, irregular border, asymmetrical, lumpy, looks abnormal

48
Q

ABCDE rule of diagnosis of superficial spreading malignant melanomas

A

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

49
Q

pathological features of nodular malignant melanoma

A

vertical proliferation of malignant melanocytes (can have no previous horizontal growth), with risk of metastasis

50
Q

pathological features of nodular melanoma arising within superficial spreading melanoma

A

downward proliferation of malignant melanocytes, following previous horizontal growth

51
Q

clinical features of nodular melanoma arising within superficial spreading melanoma

A

nodule developing within irregular plaque, with prognosis becoming worse

52
Q

describe location and appearance of acral lentiginous melanoma

A

melanomas on palms or soles, appearing as flat pigmented plaques or lumps

53
Q

describe appearance of amelanotic melanoma

A

non-pigmented melanoma

54
Q

5 types of malignant melanoma

A

superficial spreading, nodular, lentigo maligna melanoma, acral lentiginous, amelanotic

55
Q

ABCD of melanoma recognition

A

asymmetry, border, colour, diameter

56
Q

what is prognosis of melanoma based on

A

Breslow thickness (depth of invasion): measurement from granular layer to bottom of tumour

57
Q

6 main risk factors for development of melanoma

A

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

58
Q

what is a keratoacanthoma and feature of growth

A

type of squamous cell carcinoma which grows rapidly but then shrinks

59
Q

what is a squamous cell carcinoma

A

malignant tumour of keratinocytes with risk of metastasis (less than malignant melanoma)

60
Q

3 causes of squamous cell carcinoma

A

UV exposure, HPV, immunosuppression

61
Q

where may squamous cell carcinomas occur

A

in scars/scarring processes, on lips, ears and legs

62
Q

what is a basal cell carcinoma

A

malignant tumour of keratinocytes arising from basal layer of epidermis

63
Q

2 causes of basal cell carcinomas

A

sun exposure, genetics

64
Q

3 features of basal cell carcinomas

A

slow growing, invades tissues, doesn’t metastasise

65
Q

where are basal cell carcinomas most common

A

on face (e.g. around eyes)

66
Q

types of basal cell carcinomas

A

nodular, superficial

67
Q

rare skin cancer: what is mycosis fungoides and how does it appear

A

slow progressing cutaneous T cell lymphoma, appearing like psoriasis (patchy -> plaques -> tumours)

68
Q

rare skin cancer: what is Kaposi’s sarcoma, appearance and what is it associated with

A

tumour arising from endothelial cells of lymphatics; appear as purple plaques, nodules and flat lesions going along skin lines; associated with HIV and HHV8

69
Q

rare skin cancer: what is epidermodysplasioa veruciformis

A

rare autosomal recessive condition causing predisposition to HPV induced warts and squamous cell carcinomas

70
Q

main treatment option for skin cancers

71
Q

which skin layer do most skin cancers arise from

72
Q

4 cell types in epidermis

A

keratinocytes, dendritic cells, Merkel cells, melanocytes

73
Q

clinical appearance of basal cell carcinoma

A

pearly (pink/grey and glistens) with branching dilated small capillary blood vessels

Y2 MCD Cancer (20 decks)

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