Case 8- Acne and skin cancer Flashcards

Question

NMSC (non-melanoma skin cancer)

Answer 1

Refers to basal cell carcinoma, Actinic Keratosis and squamous cell carcinoma. Accounts for 90% of diagnosed skin cancers

Answer 2

Skin cancer is the most commonly diagnosed cancer in the UK and worldwide. There are more cases in hotter countries where the population have lower amounts of melanin i.e. Australia and USA.

Answer 3

95% of skin cancers are due to exposure to UV light and sunlight. The UV directly damages the DNA causing a thymidine dimer. In a thymidine dimer the T nucleotides join to each other forming kinks in the structure. The thymidine dimers cause DNA/DNA crosslinking. The UV can also indirectly damage DNA by damaging cells and creating free radicals which mediate oxidative DNA damage. This all leads to the activation of oncogenes and the inactivation of tumour suppressor genes. Leading to unregulated cell growth

Answer 4

Causes ageing and wrinkling, it is the longest wavelength and damages all layers of the skin (surface, epidermis and dermis)

Answer 5

Causes burning, it is medium wavelength and penetrates the skin surface and epidermis.

Answer 6

It rarely damages the skin, it is the shortest wavelength and is blocked by the ozone and lower atmosphere

Answer 7

A mutation in the BRAF oncogenes

Answer 8

Damage from UV exposure is cumulative and increases your skin cancer risk over time. While your body can repair some of the DNA damage in skin cells, it can’t repair all of it. The unrepaired damage builds up over time and triggers mutations that cause skin cells to multiply rapidly. That can lead to malignant tumours.

Answer 9

Rough scaly lesions. As the most prominent risk factor is chronic skin exposure they are found on places exposed to the sun. This could be the face, lips, ears, arms, neck and scalp. Common in older patients

Answer 10

99% of individuals can be cured using Imiquimod. It stimulates the immune system to become activated and remove the cancer cells. It is a topical skin ointment. The appearance of the lesions will appear worse as the skin becomes necrotic and scabs over, eventually it will return to healthy skin.

Answer 11

When left untreated only 0.5% per year progress to squamous cell carcinoma

Answer 12

Long term sun exposure and being immune-compromised

Answer 13

Leads to scaly outgrowths with an open sores, they can be elevated growths with a central depression. Can look like a wart. They are vascularised so can often bleed and become crusty.

Answer 14

98% of patients are cured with surgical incision, they remove the tumour and then sew the round up.

Answer 15

When left untreated about 0.5% a year become invasive and spread, eventually through the lymphatic and blood system. To these patients chemotherapy is offered, there is a 15% 5 year survival prognosis which is poor.

Answer 16

Intermittent sun exposure

Answer 17

There are 7 different types of basal cell carcinoma’s. There are 3 major types- Nodular BCC, Superficial BCC and infiltrative BCC.

Answer 18

The most common type, there is a single nodular growth which is either pink or flesh coloured. It has a pearly appearance and is slightly translucent. It may have overlying blood vessels, they can rupture leading to blooding and scabbing. Caused by the basal layer hyperproliferating. Forms a contained mass which doesn’t invade downwards into the skin. Good prognosis, removed through surgery (99%).

Answer 19

Can be locally destructive and cause disfigurement

Answer 20

It grows out, like a puddle and does not grow downwards into the skin. Is a red, scabby plaque which is either pink or inflamed. Misdiagnosed as eczema or psoriasis. Not itchy unlike eczema. As it grows horizontally it has a really good prognosis through surgery (99%).

Answer 21

The most severe and aggressive type. They spread over a large area. Hard to remove because they cant tell where the tumour starts and ends. Looks like a scar or tissue injury so is often under-reported. They are transparent with a depression and rolled border. They grow downwards and into the skin. They send out finger-like projections.

Answer 22

Require specialised surgical excision known as ‘Mo’s surgery,’ where both the pathology and surgical team to work out where the tumour is. They cut around the clear margin to make sure they remove all the tumour. This technique is 95-99% effective.

Answer 23

True invasion is extremely rare at less then 0.5%. They may not want surgery for infiltrative BBC on the face as it will lead to disfigurement. So, they may take a ‘Sonic Hedgehog’ inhibitor to slow the growth of the tumour and the activation of the smoothened receptor. It can be taken as a pill or a topical ointment. They can also remove some of the tumour and then take it.

Answer 24

Neural crest cells

Answer 25

Moles occur when melanocytes group together. Melanomas arise 50% from existing moles and 50% from normal skin.

Answer 26

Through EMT (Epithelial mesenchymal transition)

Answer 27

Fair skin (low melanin levels), many/atypical moles (increased concentration of Melanocytes) and family history (mutations on CDKN2A- p16 tumour suppressor gene).

Answer 28

1) Mutations on CDKN2A- p16 tumour suppressor gene 2) 50% of the metastatic melanoma’s caused have the B-RAF gene mutation. 3) Mutations in the mitogen-activated protein kinase (MAPK) pathway which is used in cancer cell growth, differentiation and survival.

Answer 29

The mutations in B-RAF and MEK in this cycle leads to uncontrolled proliferation, survival, invasion and metastasis. Clinicians target this pathway to treat advanced melanomas.

Answer 30

* Asymmetry- will look like its grown at an uneven rate, a normal healthy mole is round. * Border- melanoma’s have a ragged or blurred border or edges. * Colour- A mole has uniform colour whilst melanoma’s are uneven in their colour. * Diameter- melanomas are often larger than 6mm * Evolution- a melanoma may physically change and get bigger and more raised. Other new symptom such as inflammation, swelling, bleeding, itching or crusting are also indicative of melanoma progression

Answer 31

All suspicious pigmented skin lesions scoring 3 points or more should be referred urgently

Answer 32

Major feature of the lesion (2 points each) • Change in shape • Irregular shape • Irregular colour

Answer 33

``` Minor feature of the lesion (1 point each) • Largest diameter of 7mm or more • Inflammation • Oozing • Change in sensation ```

Answer 34

A referral should be considered for a pigmented or non-pigmented skin lesion if it is suggestive of nodular melanoma, and is more likely to spread (endophytic)

Answer 35

Most common type of melanoma, primarily grows horizontally like a 'puddle'. It can invade and spread. Risk factor is intermittent sun exposure

Answer 36

Primarily grows vertically, it is a burrowing mole which frequently invades and spreads. Most likely to cause invasion and metastasis

Answer 37

Within the nail. It grows both horizontally and vertically, appears brown. It is frequently ignored by patients and invades and spreads.

Answer 38

Grows mainly vertically, frequently ignored by patients. Often invades and spreads

Answer 39

Benign mole / melanocyte growth

Answer 40

Waxy, scaly, slightly elevated appearance. The cause is not fully known. Not thought to be sun induced

Answer 41

Harmless patch of darkened skin due to excessive melanin

Answer 42

Benign fibrous nodule. Reaction to insect bites etc

Answer 43

Can be removed by surgical excision which has an excellent 98% curative prognosis. They would perform a football incision, cutting around the melanoma and the safe margin, which is skin that does not contain melanoma.

Answer 44

Invasive melanoma is when the melanocytes have gone through the basement membrane and spread throughout the body. This has a 18% 5 year survival. Patients are offered radiotherapy and then chemotherapy. You do not die from the original tumour but from when it spreads through your body as melanocytes are mobile cells

Answer 45

Fluorouracil (5fu) and Iminoquinone or SHH inhibitor (VISMODEGIB in BCC)

Answer 46

B-raf inhibitor or PD-1 inhibitor

Answer 47

It has a V600E mutation which keeps B-raf’s active site exposed so the cell continually goes through the cell cycle without its DNA being checked.

Answer 48

Normally growth factors induce a confirmational change in B-raf exposing it active site. The active site can bind to ATP, the ATP then phosphorylates a series of transcription factors which are responsible for the transcription and translation of G1 checkpoint proteins. The cell can then undergo DNA replication and enter the cell cycle.

Answer 49

The drug Zelboraf binds to B-raf and prevents it from being turned on, preventing hyperproliferation. You give it to the patient after they have had the V600E mutation. After 6-9 moths this treatment no longer works as it undergoes molecular compensation. Instead of using B-raf it uses the sister enzyme C-raf. This is acquired resistance.

Answer 50

1) B-raf mutations make the cell divide inappropriately as it bypasses the g1-s checkpont 2) B-raf inhibitor blocks this action 3) But B-raf is a scaffold for C-raf 4) B-raf recruits and scaffolds C-raf and drives the cell progression through G1-S 5) The tumour comes back because the inhibitor does not effect C-raf, lots of B-raf is expressed to scaffold C-raf