Wee 3 - A - Melanoma (abcde/types/Breslow/b-raf) - Melanin (freckling/hair/actinic lentinges), moles(congenital/acquired)

Question 1

What is the most common and second most common type of skin cancers? - what cells do they arise from? What type of skin cancer has the highest mortality rate?

Answer 1

Both arise from keratinocytes

* Basal cell carcinomas are the most common type of skin cancer (roughly 75%)

* Squamous cell carcinomas are the second most common type of skin cancer (roughly 20%)

Malignant melanomas (arising from melanocytes) however make up a small percentage of skin cancers (less than 10%) yet account for the majority of skin cancer related deaths (roughly 75%)

Question 2

State which skin cancer type risk is increased based on the exposure Chronic/long term sun exposure eg outdoors worker Intense intermittent sun exposure Excess sun exposure eg Sun burning Artifical UV rays - sunbeds

Answer 2

Chronic/long term sun exposure eg outdoors workers - squamous cell carcinoma risk increased

Intense intermittent sun exposure / sun burning - melanoma and basal cell carcinoma

Artifical UV rays - SCC, BCC, MM

Question 3

What is a melanoma? How is the incidence of melanoma changing of the years?

Answer 3

A melanoma is a type of skin cancer caused by the melanocytes becoming cancerous

Melanoma incidence has been increasing over the past 20-30 years

Question 4

Which type of skin cancer is likely to spread?

Answer 4

Melanoma much more likely to spread (metastasize) than keratinocyte skin cancers

Once melanoma has spread it is difficult to treat Early diagnosis is essential

Question 5

Where are melanocytes found? Does black or white skin contain more melanocytes?

Answer 5

Melanocytes are found in the basal layer of the epidermis

They have the same number of melanocyes however in black skin, each melanocyte produces more melanin

Question 6

When melanocytes settle in the epidermis, where is most of their pigment transferred to and how? What is the gene that governs the type of melanin being produced by the melanocytes known as?

Answer 6

Melancoytes transfer the melanosomes (containing the pigment) to keratincoytes via dendritic processes

The gene that governs the type of melanin being produced by melanin is called melanocortin 1 receptor gene (MC1R) aka melanocyte stimulating hormone receptor

Question 7

What are the two different melanin pigments? - what colour are they? What does MC1R cause?

Answer 7

Two different melanin pigments

Eumelanin - brown or black

Phaeomelanin - red or yellow

MC1R turns phaemelanin into eumelanin

Question 8

Eumelanin causes hair colour other than red

Phaemelanin causes red hair

What does one defective copy of MC1R cause? What do two defective copies cause?

Answer 8

As melanocortin 1 receptor gene converts phaemelanin to eumelanin, defective copies of this gene will prevent this

One defective copy causes freckling two defective copies cause red hair and freckling (autosomal recessive)

Question 9

What is freckling also known as and in which individiuals is it more common? Why can UV exposure cause the numbers to increase?

Answer 9

Freckling is also known as ephilides

It is more common in fair skinned individuals

The numbers of freckles increased after UV exposure because UV exposure triggers melanogenesis - melanin production

Question 10

What is the condition related to UV exposure marked by small brown patches typically on the elderly known as? Where is typically affected?

Answer 10

Actinic (solar) lentigines - better known as age or liver spots

Benign lesions appearing on sunexposed area related to UV exposure and typically occurs in the elderly usually on the face, forearms and dorsum of hands

Question 11

What is the medical term for a mole? Describe the typical appearance of a mole?

Answer 11

Mole is better known as a melanocytic naevi

Typical appearance of a mole - Symmetrical with uniform colour and shape, less than 5mm and do not evolve in size

Question 12

Mealnocytic naevi may be congenital or acquired Which is more common?

Answer 12

About 1% of babies are born with a congenital naevus

Most naevi are acquired in the first 2 decades of life and are very common benign lesions - average person has 20-30 naevi

Question 13

What are the three different types of congenital melanocytic naevi? Which lesions have an increased risk of melanoma and may required surgical excision?

Answer 13

Small 2cm but 20cm diamter

Risk of melanoma increases with size

Giant hold the greastest risk (10-15%)

Due to the premalignant potential, it is acceptable clinical practice to remove congenital nevi electively in all patients

Question 14

The usual type of naevi is acquired How do the acquired naevi develop?

Answer 14

During infancy the melanocyte:keratinocyte ratio breaks down at a number of cutaenous sites allowing for the formation of simple naevi

The average person has 20-30 naevi

Question 15

Why do moles change?

Answer 15

Moles may change because they become malignant however change due to other benign reasons such as developing * psoriasis (top pic) or eczema (bottom pic)

Question 16

Simple Acquired naevi develop along a well defined path and have differences in where the groups of melanocytes are in the skin and how they appear What are the three types of simple acquired naevi?

Answer 16

Junctional naevi - usually develops in childhood

Compound naevi - usually develops in adolescence/early adulthood

Intradermal naevi - adulthood

Question 17

What is the differences in depth of the three simple acquired naevi?

Answer 17

Junctional naevi - clusters of melanocytes at the dermo-erpidermal junction (flat, brown-black)

Compound naevi - junctional clusters + groups of cells in the dermis (slightly elevated, light-dark brown)

Intradermal naevi - all junctional activity has ceased, entirely dermal (looks like a lump under skin, little colour)

Question 18

What is the difference in appearance of junctional, compound and intradermal naevi?

Answer 18

Junctional naevi - pigmented flat/slightly raised (maculopapule) during childhood

Compound naevi - pigmented slightly raised mole (papule) during adolescence

Intradermal naevi - faint pigmented raised mole (nodule) during adulthood

Question 19

Change is very important in moles It is important to realise that some moles may look unusual but are actually benign What are moles that broadly do not change in shape, size or colour however fulfill the ABCD criteria for a melanoma? What is advised?

Answer 19

These are known as atypical or dysplastic naevi

Generally asymmetrical border

Variegated pigment

Generally >6mm in diamter

Close watching of these moles is advised as it increse the lifetime risk of melanoma

Question 20

What is the type of mole known as that occurs most often on the back of patients with a white area around the mole? What causes this white area?

Answer 20

These moles are known as haelo naevi due to the bright white halo around the mole

Haelo nevi are often multiple are represent an immune response where there is a loss of melanocytes due to lymphocyte action

Question 21

What are different risk factors for the development of melanoma?

Answer 21

Risk factors include

* ultraviolet light exposure

* History of excess sun exposure - sunburn

* Sunbed use

* fair complexion

* many moles

Question 22

Examining the significance of moles seen on patients usually uses the ABCDE rule to check for potential melaoma What do each if these stand for?

Answer 22

A - asymmetry within the lesion - shape or colour

B - border irregular

C - colour irregularity - usually 2 or more colours

D - diameter >6mm

E - evolving over time

Question 23

What are the major and minor criteria for thinking about possible melanoma formation from a changing mole? When would you consider referring a patient after assessing their mole?

Answer 23

Major criteria

• * Change in shape
• * Change in size
• * Change in colour

Minor criteria

• * diameter >6mm
• * bleeding
• * sensory change eg pain or itching
• * inflammation

Question 24

What is the usual colour of a melanoma?

Answer 24

Usually different shades of brown, tan or black

As it grows, colours such as red, white or blue may also appear

Question 25

There are four main types of melanoma and tends to be defined clinically by what it looks like and how it presents What are the 4 main types? - which is most common? Where are they usually found?

Answer 25

Maligno-melanoma types Superficial spreading - commonest types - trunks and limbs Acral/mucosal lentiginous - mucosae and acral referring to extremities eg palms and soles, nailbeds Lentigo - sun damaged face/neck/scalp Nodular - varied sites but often trunk

Question 26

What is Hutchinson's sign that can occur in acral lentiginous melanoma?

Answer 26

Hutchinson's sign --\> subungual pigmentation It is the periungual extension of brown-black pigment from the nail bed and nail matrix onto the surrounding tissues, which usually occurs during the radial growth phase of subungual melanoma

Question 27

How do the superficial spreading, acral/mucosal and lentigo malignant melanomas first grow? What is the type of growth phase here?

Answer 27

The superficial spreading, acral/mucosal and lentigo malignant melanomas inititally grow as flat macules and tend to spread with a radial growth phase (ie enlarge horizontally) - growth is centered on the epidermis

Question 28

Eventually the malignant cells of superficial spreading, acral/mucosal and lentigo malignant melanomas will invade the dermis forming a nodule or lump What is this known as? What can happen now?

Answer 28

Eventually they will invade the dermis forming a nodule or lump and this is called the vertical growth phase Only vertical growth phase melanomas can metastasise

Question 29

What type of growth phase are nodular melanomas?

Answer 29

Nodular melanomas only have vertical growth phase and therefore are considered to be more aggressive as it can metastasise from the outset

Question 30

What is a melanoma known as if confined to the epidermis?? What is it called when it spreads to the dermis? What is it known as if it spreads to other tissues?

Answer 30

When a melanoma is confined to the epidermis - melanoma in-situ When a melanoma spreads to the dermis - invasive melanoma When it spreads to other tissues - metastatic melanoma

Question 31

What is the usual initial treatment for a malignant melanoma? What does this initial treatment allow you to calculate?

Answer 31

A primary eliptical excision is the usual initial treatment for a malignant melanoma Evaluation of the tumour biopsy allows for confirmation of diagnosis and evaluation of Breslow thickness

Question 32

How is a malignant's melanomas prognosis evaluated?

Answer 32

Malignant melanomas prognosis is evaluated by measuring the breslow thickness after excising the mole from the patient Breslow thickness is defined as the granular to the deepest point of invasion (deepest cancerous cell) and is examined under a microscope

Question 33

What are the margins of clearance advised for the different Breslow's thickness depth of malignant melanoma?

Answer 33

If in-situ -confined to epidermis - clear by circa 5mm If invasive - 1cm margin of normal skin around the lesion for every mm of depth (up to 3cm) If invasive and \>1mm thick - 2cm clearance

Question 34

What are indications for sentinel node biopsy? \* ie what breslow thickness? \* what adverse prognostic indicators?

Answer 34

Carry out sentinal node biopsy if Breslow thickness \>1mm Can carry out if less than 1mm if there are adverse prognostic factors such as \* Ulceration \* High mitotic rate

Question 35

Molecular analysis of tumours now enables targeted treatments at tumours in patients when surgical excision does not suffice What is the most common mutation seen in patients with melanoma?

Answer 35

B-raf - a proto-oncgene is commonly seen in patients with melanoma Proto-oncogene: A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer.

Question 36

What is an important pathway seen in familial melanomas and in acral melanomas?

Answer 36

Familial melanomas - CDKN2A network Acral melanomas - c-KIT pathways

Question 37

Image shows melanoma pathways for which targeted drug treatment is being developed Name a drug that can treat BRAF+ melanomas? BRAF inhibitors can be given in conjunction with MEK inhibitors -drug? Give a C-kit inhibitor example? (acral MM)

Answer 37

Vemurafenib has a UK marketing authorisation for 'the treatment of adult patients with BRAF mutation-positive unresectable or metastatic melanoma'. - BRAF inhibitor MEK inhibitor - trametinib C-kit inhibitor - imatinib

Question 38

21y/o female presented to GP with a new mole on her left arm Was not aware of any change in shape, size or colour Using the ABCDE rule describe this mole What would you do?

Answer 38

Asymmetrical? - it is symmetrical Border irregular - the border is regular Colour irregularity - colour is even- two colours brown and orange Diameter - mole diamater is 5mm E - patient history said it has not evlolved Reassure patient that you think it is a benign naevus (mole) -give advice on mole-watching and sun protection

Question 39

Patient presented Did not think there was a change in size shape or colour Using the ABCDE rule describe this mole What would you do?

Answer 39

A - slight degree of asymmetry B - fairly even border C - one or two colours D - max 6 or 7mm E - not evolved from history Likely to be a benign naevus however if there is any doubt, it may be wise to excise the lesion Advice patient to keep a close eye and take a clinical photograph

Question 40

Mole on right arm, thinks its been present for 2 months Using the ABCDE rule describe this mole What would you do?

Answer 40

A - asymmetrical B - irregular border C - 2or3 colours D - diameter \>1cm E - unsure if evolved from history Best advice would be to excise the mole as highly suspicous of early melanoma and biopsy

Question 41

Patient presented with a mole that had been present on left shoulder for many years. Patient indicated that it had been around 1mm in diameter and had grown over 8 weeks Using the ABCDE rule describe this mole What would you do?

Answer 41

A - degree of asymmetry of colour B - slight irregularity in the bordr (1 and 6 oclock) C - 2or3 colours D - diameter of 1cm E - has evolved over last 8 weeks Highly suspicious of malignant melanoma, would most likely carry out an excisional node biopsy