Wee 3 - A - Melanoma (abcde/types/Breslow/b-raf) - Melanin (freckling/hair/actinic lentinges), moles(congenital/acquired) Flashcards
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?
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%)
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
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
What is a melanoma? How is the incidence of melanoma changing of the years?
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
Which type of skin cancer is likely to spread?
Melanoma much more likely to spread (metastasize) than keratinocyte skin cancers
Once melanoma has spread it is difficult to treat Early diagnosis is essential
Where are melanocytes found? Does black or white skin contain more melanocytes?
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
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?
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
What are the two different melanin pigments? - what colour are they? What does MC1R cause?
Two different melanin pigments
Eumelanin - brown or black
Phaeomelanin - red or yellow
MC1R turns phaemelanin into eumelanin
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?
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)
What is freckling also known as and in which individiuals is it more common? Why can UV exposure cause the numbers to increase?
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
What is the condition related to UV exposure marked by small brown patches typically on the elderly known as? Where is typically affected?
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
What is the medical term for a mole? Describe the typical appearance of a mole?
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
Mealnocytic naevi may be congenital or acquired Which is more common?
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
What are the three different types of congenital melanocytic naevi? Which lesions have an increased risk of melanoma and may required surgical excision?
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
The usual type of naevi is acquired How do the acquired naevi develop?
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
Why do moles change?
Moles may change because they become malignant however change due to other benign reasons such as developing * psoriasis (top pic) or eczema (bottom pic)
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?
Junctional naevi - usually develops in childhood
Compound naevi - usually develops in adolescence/early adulthood
Intradermal naevi - adulthood
What is the differences in depth of the three simple acquired naevi?
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)
What is the difference in appearance of junctional, compound and intradermal naevi?
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
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?
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
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?
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
What are different risk factors for the development of melanoma?
Risk factors include
* ultraviolet light exposure
* History of excess sun exposure - sunburn
* Sunbed use
* fair complexion
* many moles
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?
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
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?
Major criteria
- * Change in shape
- * Change in size
- * Change in colour
Minor criteria
- * diameter >6mm
- * bleeding
- * sensory change eg pain or itching
- * inflammation
What is the usual colour of a melanoma?
Usually different shades of brown, tan or black
As it grows, colours such as red, white or blue may also appear
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?
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
What is Hutchinson’s sign that can occur in acral lentiginous melanoma?
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
How do the superficial spreading, acral/mucosal and lentigo malignant melanomas first grow? What is the type of growth phase here?
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
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?
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
What type of growth phase are nodular melanomas?
Nodular melanomas only have vertical growth phase and therefore are considered to be more aggressive as it can metastasise from the outset
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?
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
What is the usual initial treatment for a malignant melanoma? What does this initial treatment allow you to calculate?
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
How is a malignant’s melanomas prognosis evaluated?
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
What are the margins of clearance advised for the different Breslow’s thickness depth of malignant melanoma?
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
What are indications for sentinel node biopsy? * ie what breslow thickness? * what adverse prognostic indicators?
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
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?
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.
What is an important pathway seen in familial melanomas and in acral melanomas?
Familial melanomas - CDKN2A network
Acral melanomas - c-KIT pathways
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)
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
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?
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
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?
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
Mole on right arm, thinks its been present for 2 months Using the ABCDE rule describe this mole What would you do?
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
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?
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
