Pathology of pigmented lesions

Question 1

How can melanomas of odd body sites (e.g the liver) be explained?

Answer 1

Melanocytes become lost during migration from the neural crest and later become cancerous

Question 2

What is the function of the melanocortin 1 receptor (MC1R) gene?

Answer 2

Production of the melanocortin 1 protein which is involved in the conversion of phaeomelanin into eumelanin (controls pigmentation of hair & skin)

Question 3

What happens when there are mutations in the MC1R gene?

Answer 3

Freckling (one defective copy) and red-hair (two defective copies)

Question 4

What is another name for freckles? What are freckles?

Answer 4

Ephilides. Patchy increases in melanin pigment

Question 5

What are actinic/solar lentingines? How do they occur?

Answer 5

Age/liver spots. UV exposure causes changes within the epidermis (elongated rete ridges, increased melanocytes & pigment)

Question 6

Where are actinic lentingines typically found?

Answer 6

Dorsal hands, face & forearms

Question 7

What are melanocytic naevi? How are they acquired?

Answer 7

A broad catagory of moles/raised skin lesions. Congenital or developing over time (often within the first two decades of life)

Question 8

How are congenital melanocytic naevi classified?

Answer 8

Small - 2cm but 20cm

Question 9

What is the risk of progression to cancer with congenital melanocytic naevi?

Answer 9

Giant melanocytic naevi has a 10-20% risk of progression to melanoma

Question 10

How are congenital melanocytic naevi treated?

Answer 10

Small lesions are generally left along while larger lesions may be surgically excised (may need to be a staged excision)

Question 11

How are simple naevi acquired?

Answer 11

Melanocyte : keratinocyte ratio breaks down at specific cutaneous sites during childhood > simple naevus forms

Question 12

What is the risk of progression to cancer with simple naevi?

Answer 12

Minimal

Question 13

What is the relation to simple naevi and the immune system?

Answer 13

Immunosuppressed children develop more naevi

Question 14

How do simple naevi develop?

Answer 14

Melanocytes proliferate creating a junctional naevi > compound naevi form as clusters of melanocytes form in the DEJ and dermis > intradermal naevi form when DEJ melanocyte clusters disappear and the naevi is entirely dermal

Question 15

What is the presentation of dysplastic naevi?

Answer 15

Asymmetrical border, variegated pigment & generally >6mm diameter

Question 16

What are the features of sporadic dysplastic naevi?

Answer 16

Not inherited, generally only a few naevi, slightly increased risk of progression to melanoma

Question 17

What are the features of inherited dysplastic naevi?

Answer 17

Family history of melanoma (autosomal inheritance), high penetrance, many atypical naevi, high risk of progression to melanoma

Question 18

What differentiates dysplastic naevi from typical naevi in terms of architecture and histology?

Answer 18

Dysplastic naevi is architecturally AND histologically abnormal (with evidence of inflammation and fibrosis)

Question 19

What is the main distinguishing feature between melanoma and dysplastic naevi?

Answer 19

The epidermis is not effaced in cases of dysplastic naevi

Question 20

What are halo naevi? Why does this occur?

Answer 20

A naevi surrounded by a ring of depigmentation. The body is attacking the melanocytes of the naevi and surrounding skin to cause regression

Question 21

What are blue naevi?

Answer 21

Dermal proliferations of pigment rich dendritic spindle cells (may mimic melanoma)

Question 22

At what age is halo naevi most common?

Answer 22

Late teens/early twenties

Question 23

What is a spitz naevi?

Answer 23

A (commonly) benign skin tumour composed of large spindle and/or epithelioid cells which may resembled melanoma

Question 24

Which age group most commonly develops spitz naevi?

Question 25

Spitz naevi with prominent vasculature are commonly red in colour. T/F

Answer 25

True

Question 26

How are malignant melanomas acquired?

Answer 26

De novo or transformation from a dysplastic naevi

Question 27

What is the sex distribution of malignant melanoma?

Answer 27

More common in females

Question 28

Which age groups most commonly develop malignant melanoma?

Answer 28

Middle aged (rare in children)

Question 29

What is the aetiology of malignant melanoma?

Answer 29

Childhood sunburn, UV exposure, genetic risk, dysplastic naevi, skin type

Question 30

When should malignant melanoma be suspected?

Answer 30

Change in shape of existing naevi, irregularly pigmented lesion, bleeding lesion, development of satellite nodules, ulceration, new pigmented lesion developing in adulthood

Question 31

What are the four main types of malignant melanoma?

Answer 31

Superficial spreading, acral/mucosal lentiginous, lentigo maligna, nodular

Question 32

What the the most common type of melanoma and where is it most commonly found?

Answer 32

Superficial spreading & on the arms and trunk

Question 33

What is the second most common type of melanoma and where is it most commonly found?

Answer 33

Lentigo maligna & on sun-damaged skin of the face, scalp and neck

Question 34

Where is nodular melanoma most commonly found?

Answer 34

Trunk

Question 35

A mole which shows some patchy regression is typical of what?

Answer 35

Malignant melanoma

Question 36

What are acral melanomas commonly misdiagnosed as?

Answer 36

Trauma related

Question 37

What is the pathogenesis of non-nodular malignant melanomas?

Answer 37

Grow as macules in situ or with microinvasion (radio growth phase) > melanoma invades dermis forming expansile mass with mitoses (vertical growth phase) > metastases

Question 38

RGP and VGP melanomas can both metastasise. T/F

Answer 38

False - only VGP melanomas can metastasise

Question 39

Nodular melanomas have both a RGP and VGP. T/F

Answer 39

False - they do not have a RGP and instead present as nodules of VGP tumour

Question 40

Which is the most aggressive form of melanoma?

Answer 40

Nodular

Question 41

Describe Breslow classification of melanoma

Answer 41

``` pTis = melanoma in situ pT1 = tumour 4mm ```

Question 42

What are the adverse prognostic factors of melanoma?

Answer 42

Increasing breslow classification, ulceration (suffix b), high mitotic rate, lymphovascular invasion, satellite lesions, sentinel lymph node involvement

Question 43

How does melanoma spread?

Answer 43

- local dermal lymphatics (satellite deposits) - regional lymph node metastases - blood spread

Question 44

How is melanoma treated?

Answer 44

Primary excision with clear markings, sentinal node biopsy, regional lymphadenectomy (questionable), chemotherapy, immunotherapy, genetic therapies

Question 45

What is the process for excision of suspected melanoma?

Answer 45

Narrow excision (confirms diagnosis & breslow thickness) > re-excision margins based on breslow thickness ``` pTis = 5mm clearance pT1 = 1cm clearance pT2,3,4 = 2cm clearance & SNB ```

Question 46

How may acral melanomas with c-kit mutations be treated?

Answer 46

Imatinib

Question 47

When might BRAF-inhibitors be particularly useful in melanoma treatment?

Answer 47

Melanomas on intermittently sun exposed skin

Question 48

What is BRAF? What happens when it mutates?

Answer 48

Weak cytosolic proto-oncogene. Drives cell proliferation via MEK and ERK

Question 49

Name 2 BRAF inhibitors

Answer 49

Dabrafenib & vemurafenib