Skin cancer Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

what is the most common human cancer?

A

Skin cancer

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2
Q

what are the risk factors for skin cancer?

A
genetic predisposition 
immunosuppression 
age 
sun exposure (UV radiation)
other environmental carcinogens
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3
Q

where on the body can skin cancer arise?

A

from basically every area of the skin most commonly from the epidermis and melanocytes

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4
Q

What is melanoma?

A

cancer which arises from melanocytes found in along the basal layer
more common in older people but can also occur in younger people - most common cancer in 16-25 yr olds

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5
Q

what is the general prognosis of melanoma?

A

They are much more likely to metastasis than BCC and SCC [keratinocyte skin cancers]
Generally has a bad prognosis, early diagnosis is essential as it’s difficult to treat once it has spread -
survival depends on tumour depth (i.e. prognosis is good if Breslow thickness is <1mm, prognosis is worse if >4mm), thin melanomas are cured

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6
Q

how is melanoma diagnosed?

A

Asymmetry,
Border,
Colour,
Diameter,
Evolution [i.e. speed of change - red flag e.g. getting darker],
ugly duckling sign - look for the one that looks different esp. in atypical mole syndrome

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7
Q

How is melanoma treated?

A

primary excision to give clear margins,
sometimes also a sentinel node biopsy -
if SN positive then do a regional lymphadenectomy,
immunotherapy/genetic therapies,
narrow complete excision for confirmation of diagnosis and assessment of breslow:
• If in-situ => 5mm clearance
• If invasive but < 1mm => 1cm clearance
• If invasive but > 1mm => 2cm clearance
• Do SNB (sentinel node biopsy) if > 1mm thick or thinner with mitoses

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8
Q

what are the 4 main types of melanoma?

A
  1. Superficial spreading (SSM) => commonly found on trunk and limbs
  2. Acral/mucosal lentiginous (A/MLM) => acral (toes/fingers etc.) and mucosal
  3. Lentigo maligna (LMM) => sun-damaged face/neck/scalp
  4. Nodular (NM) => varied sites but often trunk
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9
Q

SSM, A/MLM and LMM growth

A

These all grow as macules (radial growth phase [RGP] - either entirely in situ or with dermal micro-invasion) - width
Eventually these melanoma cells can invade the dermis forming an expansive mass with mitosis = vertical growth phase [VGP] - only VGP melanomas can metastasise - depth

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10
Q

NM growth

A

No RGP, this is a nodule of VGP tumour, may be more aggressive

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11
Q

what determines the prognosis of a melanoma?

A

the Breslow depth/thickness (= deepest tumour from granular layer [mm] - the thinner the better!)
ulceration [‘b’ = the suffix for ulceration],
adverse prognosis is also indicated by high mitotic rate,
lymphovascular invasion, satellites and sentinel (original cancer) lymph node involvement

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12
Q

what % of skin cancers are melanoma?

A

5-10% the rest are BCC and SCC

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13
Q

what is basal cell carcinoma BCC?

A
Very common (about 75% of skin cancers), usually on sun-exposed sites, in middle-aged and elderly (in the UK)
Pathogenesis: groups of basal cells (?) invade the dermis, there’s lots of mitosis and apoptosis (peripheral palisading)
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14
Q

How does basal cell carcinoma present?

A
slow growing lump OR non-healing ulcer, painless (so often ignored), 
pearly, 
translucent, 
visible arborising blood vessels, 
central ulceration (‘rodent ulcer’)
Locally invasive - does not spread
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15
Q

What are the different types of BCC?

A
scaly plaque (superficial), 
nodular/nodulocystic (most common), pigmented, 
infiltrative (morphoeic, prominent desmoplastic fibrous stroma, poorly defined, most aggressive, difficult to completely remove, may spread along nerves = difficult to resect)
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16
Q

How is basal cell carcinoma treated?

A

surgery can get really bad if left untreated

17
Q

What is the prognosis of basal cell carcinoma?

A

death is unlikely - maybe could occur if tumour invades the eye and brain etc.

18
Q

What is squamous cell carcinoma?

A

it is less common about 20% of skin cancers - usually in the elderly
Rare associations = xeroderma pigmentosum etc.

19
Q

Prognosis of SCC?

A

more likely to cause death than BCC
Low risk SCC: majority, well-differentiated cancer cells
High risk SCC: poorly-differentiated, cutaneous horn
Keratoacanthoma = self-limiting form of SCC
If neglected, may spread - the risk of mets is only 3-5% but once it happens = poor prognosis
Occassionally may get chronic leg ulcers (e.g. stasis ulcers), sites of burns (e.g. sinuses e.g. chronic osteomyelitis), chronic lupis vulgaris

20
Q

Who gets SCC?

A
Usually sun-damaged skin (chronic, long-term, UV)
Precursor lesions (squamous dysplasia): actinic keratosis, Bowen’s disease, viral lesions (more on all these later)
High risk sites for SCC: ear, lip, scalp
21
Q

how does SCC present?

A

warty/crusted (hyperkeratoic) lump or ulcer,
grows fast,
may be painful,
may bleed

22
Q

the types of UV light

A

UVB (290-320nm) causes direct DNA damage, it is more damaging than UVA when the sun is directly overhead, it can cause sunburn
UVA (320-400nm) causes indirect oxidative damage, it penetrates more deeply into the skin than UVB
UVB and UVA can be blocked by sunscreen, and they can both cause pigmentation and skin cancer/ageing
UVC is blocked by window glass and atmospheric ozone

23
Q

what is normal cutaneous photosensitivity?

A

normal sunburn

24
Q

What is abnormal cutaneous photosensitivity?

A

abnormal cutaneous response to UV radiation and, in some people, visible light.

25
Q

DNA damage by UVB light

A

UVB can lead to direct damage
UVB-induced DNA lesions:
- Cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) [these are both formed by covalent bonding between adjacent pyrimidines on the same DNA strand]
This is repaired by nucleotide excision repair
CC -> TT = ‘UVB-signature mutation’

26
Q

DNA damage by UVA light

A

causes indirect DNA damage
it does this by the oxidation of deoxyguanosine forming 8-oxo-deoxyguanosine
repaired by base excision repair
C - A (point mutation)

27
Q

what elso other than cancer can UV induced DNA damage lead to?

A

immunosuppression
• Decreased langerhans cells in the skin and decreased ability to present antigens
• There is the production of UV induced regulatory T cells (T-reg) which have immune suppressive activity
• Macrophages and keratinocytes secrete anti-inflammatory cytokines (e.g. IL-10)

28
Q

Mutations in the DNA caused by UV light which lead to BCC?

A

Mutations in PTCH1 (associated with nevoid basal cell carcinoma syndrome) are linked with BCC development.
PTCH1 is a key component of the hedgehog signalling pathway - hedgehog signalling activates transcription factors, this leads to cell proliferation and angiogenesis.
Vismodegib is an example of a hedgehog inhibitor.

29
Q

mutations caused by UV damage which lead to melanoma?

A

Mutations of CDKN2A and CDK4 (genes) are linked to familial melanoma.
• CDK2NA prevents cells from replicating when there’s DNA damage
• CDK4 [cyclin dependent kinase 4] permits cell cycle progression by the phosphorylation of Rb [retinoblastoma]
Mutations in BRAF, Ras, Raf or MAPK can also cause melanoma

30
Q

targeted melanoma drugs

dasatinib and Imatinib

A

target - c-Kit and prevent cell growth

31
Q

targeted melanoma drugs Ipilimumab and Pembrolizumab

A

Ipilimumab: CTLA-4 on T cells
Pembrolizumab: PD-1 on T cells
they are involved in T cell activation to enable tumour cell killing

32
Q

targeted melanoma drugs Trametinib

A

target - MEK and prevents cell growth

33
Q

targeted melanoma drugs vemurafenib and dabrofenib

A

target B-raf they prevent cell growth

- resistance to B-raf inhibitors is quick so they are used in combo with trametinib

34
Q

Phototoxic drugs

A
variconazole (antifungal agent), 
thiazide diuretics, 
NSAIDs, 
anti-TNF, 
azathioprine (immunosuppressant, may cause photosensitivity of skin to UVA)
35
Q

how do you manage phototoxic drugs?

A
sun protection (esp. if on azathioprine/variconazole) - must be ‘day long-year round’, 
increased skin surveillance (if high risk patient)
36
Q

what are freckles?

A

AKA ephelides
due to 1 defective copy of MC1R,
there is a patchy increase in melanin pigmentation,
occurs after UV exposure,
most common in fair skinned and red heads,
islands with most melanocytes tan

37
Q

what are actinic lentigines/ solar lentigines

A

also known as age/liver spots,
related to UV exposure,
usually on face, forearms and dorsal hands, due to increased melanin and increased basal melanocytes,
causes elongated rete ridges in the epidermis