Melanoma

Question 1

What is the most common cancer in 15-24 year olds ?

Answer 1

Melanomas

Question 2

Define what a melanoma is

Answer 2

• It is a potentially serious type of skin cancer, in which there is uncontrolled growth of melanocytes (pigment cells).
• It is sometimes referred to as malignant melanoma.

Question 3

What is the function of melanocytes ?

Answer 3

To prpduce melanin, which protects the skin by absorbing UV radiation

Question 4

What do non-cancerous growths of melanocytes result in ?

Answer 4

Moles (properly called benign melanocytic naevi) and freckles (ephelides and lentigines).

Question 5

What do cancerous growths of melanocytes result in ?

Answer 5

Melanoma

Question 6

What are the risk factors for the development of melanoma ?

Answer 6

• Increasing age (see above)
• Previous invasive melanoma or melanoma in situ
• Previous basal or squamous cell carcinoma
• Many melanocytic naevi (moles)
• Multiple (>5) atypical naevi (large or histologically dysplastic moles)
• A strong family history of melanoma with 2 or more first-degree relatives affected
• White skin that burns easily
• History of excess sun exposure, sunbed use or multiple sunburns
• Parkinson disease.

Question 7

What is FAMMM?

Answer 7

• Familial atypical multiple mole melanoma syndrome.
• People who have FAMMM have > 50 moles and at least one close relative has been diagnosed with a melanoma. It increases your risk of developing melanoma

Question 8

What gene is known to cause FAMMM?

Answer 8

CDKN2A

Question 9

What do melanomas arise from ?

Answer 9

From otherwise normal-appearing skin (in about 75% of melanomas) or from within a mole or freckle, which starts to grow larger and change in appearance

Question 10

List the different precursor lesions of melanoma

Answer 10

• Benign melanocytic naevus (normal mole)
• Atypical or dysplastic naevus (funny-looking mole)
• Atypical lentiginous junctional naevus (flat naevus in heavily sun damaged skin) or atypical solar lentigo
• Large or giant-sized congenital melanocytic naevus (brown birthmark).

Question 11

Where on the body can melanomas develop?

Answer 11

• Can occur anywhere on the body but more common in areas that get a lot of sun
• Most common site in men is the back and women is the leg
• Rarely they grow on mucous membranes such as the lips or genitals & Occasionally it occurs in other parts of the body such as the eye, brain, mouth or vagina.

Question 12

What are the clinical features of a melanoma ?

Answer 12

• The first sign of a melanoma is usually an unusual looking freckle or mole.
• A melanoma may have a variety of colours including tan, dark brown, black, blue, red and, occasionally, light grey
• During its horizontal phase of growth, a melanoma is normally flat. As the vertical phase develops, the melanoma becomes thickened and raised.
• Some melanomas are itchy or tender. More advanced lesions may bleed easily or crust over.

Question 13

What are the 2 checklists which can be used to help identify if a lesion is a melanoma or not

Answer 13

The Glasgow 7-point checklist or the ABCDE criteria of melanoma.

Question 14

What is the criteria of the Glasgow 7-point checklist ?

Answer 14

Major features

• Change in size
• Irregular shape
• Irregular colour

Minor features

• Diameter >7 mm
• Inflammation
• Oozing
• Change in sensation

Question 15

What is the criteria of the ABCDE criteria of melanoma ?

Answer 15

• *A**symmetry - a melanocytic naevus (harmless mole) is usually symmetrical, whereas melanoma is often irregular or asymmetrical in shape.
• *B**order irregularity - a melanocytic naevus has smooth and even borders, whereas a melanoma often has irregular and hard-to-define borders.
• *C**olour variation - a melanocytic naevus usually has a single shade of colour or two shades of colour with one occurring inside the other or regularly repeated (generally pink, brown, or tan). Melanoma can be brown but can have as many as five or six colours (blue, black, brown, tan, grey, pink, and red). These colours are unevenly or irregularly distributed.
• *D**iameter larger than 6 mm
• *E**volving or changing - A melanocytic naevus is usually stable and does not change in size, shape, or colour, whereas a melanoma changes over time. Change in size, colour, shape, or structure may be noted over months to years.

Question 16

What are the 4 main sub-types of melanoma ?

Answer 16

1. Superficial spreading
2. Acral/mucosal lentiginous
3. Lentigo maligna-sun
4. Nodular

Question 17

Describe the typical growth pattern of superficial spreading, Acral/mucosal lentiginous & Lentigo maligna melanomas

Answer 17

• They first grow as macules (radial growth phase;RGP) i.e. their growth is in epidermis
• Eventually the neoplastic melanocytes invade into the dermis forming a lump (vertical growth phase;VGP)

Question 18

Describe the typical growth pattern of nodular melanomas

Answer 18

Vertical growth phase from the outset

Question 19

When can a melanoma metastasise ?

Answer 19

Only when it has entered the vertical growth phase i.e. invaded the dermis

Question 20

In who and where do superficial spreading melanomas typically arise ?

Answer 20

• Typically affects the arms, legs, back and chest of young people (think trunk & limbs)
• Appearance - A growing moles with diagnostic features listed in the glasgow 7-point checklist or ABCDE checklist

Note - Amelanotic melanomas are those that lacking pigment

Question 21

In who and where do Acral/mucosal lentiginous melanomas typically arise ?

Answer 21

• Acral - Nails, palms or soles, African Americans or Asians
• Appearance - Subungual pigmentation (Hutchinson’s sign) or on palms or feet

Question 22

In who and where do lentingo maligna melanomas typically arise ?

Answer 22

• Chronically sun-exposed skin (face, neck, scalp) in older people
• Appearance - A growing mole with diagnostic features listed in Glasgow 7-point checklist or ABCDE checklist

Question 23

In who and where do nodular melanomas typically arise & what are the characteristic features of it?

Answer 23

• Site varies but often sun exposed skin esp trunk & in middle-aged people
• Appearance - Red or black lump or lump which bleeds or oozes

Question 24

What is the most likely type of melanoma shown due to where the lesion is situated ?

Answer 24

Acral melanoma of the heel

Question 25

What is the most likely type of melanoma shown due to where it is situated ?

Answer 25

Subungual type of acral melanoma

Question 26

What is the most likely type of melanoma shown due to where it is situated ?

Answer 26

Lentigo maligna melanoma

Question 27

How are melanomas diagnosed ?

Answer 27

1st line = assess using dermoscopy * 2nd line If clinically atypical melanocytic lesion that does not need excision at 1st presentation = baseline photography (dermoscopic) followed by review of appearance & comparision to baseline images after 3 months. Then may have exicision or not. * 2nd line otherwise = surgical excision with a 2-3mm clinical margin & sample sent to pathology.

Question 28

What is the typical dermoscopical appearance of melanomas ?

Answer 28

* Atypical pigment network, black dots, irregular streaks, * Focally a blue-whitish veil and a white regression zone with hairpin vessels (atypical blood vessels that double back on themselves)

Question 29

Following pathological diagnosis of melanoma what is the most important aspects from the pathology report ?

Answer 29

The stage & breslow thickness

Question 30

Define what is meant by breslow thickness

Answer 30

It is measured vertically in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement

Question 31

Describe the different stages of melanoma

Answer 31

* Stage 0 = In situ melanoma * Stage 1 = melanoma \< 2mm thickness * Stage II = melanoma \> 2mm thickness or \> 1mm + ulceration * Stage III = melanoma spread to local lymph nodes * Stage IV = distant metastases

Question 32

Define what a melanoma in situ is

Answer 32

It is an early form of primary melanoma in which the malignant cells are confined to the tissue of origin, the epidermis.

Question 33

Why is it so essential to catch melanomas at any early stage ?

Answer 33

Because it is a cancer which spreads at an early stage and the prognosis once it has started to invade deeper drops dramatically: * If the tumour depth is less than 1mm, the 5 year survival is excellent. However, if the tumour depth is greater than 4mm, only half of the patients will survive … * And if there is evidence of distant spread only 5% will survive 5 years.

Question 34

For stage III or suspected stage IV melanoma what imaging is done to help stage it ?

Answer 34

CT staging for adults or whole body MRI for children & young people (0-24 years old)

Question 35

What is measured in all people diagnosed with melanoma ?

Answer 35

Vit D levels

Question 36

If someone diagnosed with melanoma is found to have low Vit D levels what is done ?

Answer 36

Vit D supplementation

Question 37

What is the treatment of melanoma ?

Answer 37

Wide local excision +/- sentinel lymph node biopsy +/- lymph node dissection

Question 38

What is the criteria for when a sentinel lymph node biopsy is done in the treatment of melanoma ?

Answer 38

Offer it as a staging procedure in people with stage IB-II melanoma

Question 39

If micrometastases are seen on analysis of the sentinel lymph node biopsy what is then done ?

Answer 39

Completion lymphadenectomy

Question 40

Instead of lymph node biopsy what is done for patients with stage III melanoma ?

Answer 40

Lymph node dissection

Question 41

When doing wide local excision what margin of clearance is needed ?

Answer 41

* Stage 0 ≥ 0.5cm clearance * Stage 1 ≥ 1cm clearance * Stage 2 ≥ 2cm clearance

Question 42

What alternative treatment can be used for stage 0 melanoma in adults if surgery to mremove lesion with ≥ 0.5cm clear margins would lead to unacceptable disfigurment or morbidity ?

Answer 42

Topical Imiquimod

Question 43

What palliative treatment is used for superficial melanoma skin metastases ?

Answer 43

Topical Imiquimod

Question 44

What is the general management of stage IV melanoma ?

Answer 44

* Refer for specalist MDT * Consider surgical or ablative treatments to prevent & control **symptoms**

Question 45

What is the breslow thickness of a melanoma directly proportional to ?

Answer 45

Prognosis

Question 46

What targeted drug may some acral melanomas be treated with and why ?

Answer 46

May have c-kit mutation and therefore may be treated with imatinib

Question 47

What targeted drug(s) may BRAF mutated melanomas be treated with and why ?

Answer 47

* BRAF inhibitor dabrafenib or vemurafenib * Melanomas commonly develop resistance to these inhibitors so they may be used in conjunction with MEK inhibtor trametinib or cobimetinib