Skin Cancers

Question 1

What is a melanoma?

Answer 1

Malignant tumour arising from melanocytes

Question 2

Where can melanomas be found?

Answer 2

Skin and mucosal surfaces and within uveal tract of eye

Question 3

What are the genetic risk factors associated with melanoma

Answer 3

Family history - CNKN2A mutations, MC1R variants
DNA repair defects - xeroderma pigmentosum
Lightly pigmented skin
Red hair

Question 4

What are the environmental factors associated with melanoma?

Answer 4

Sun exposure
Sunbeds
Immunosupression

Question 5

In melanocytes how is cellular proliferation, growth and migration regulated?

Answer 5

Mitoses- activated protein kinase (MAPK) pathway

Question 6

What 4 mutations on a molecular level can lead to melanoma?

Answer 6

MAPK pathway
KIT mutations (receptor tyrosine kinase)
Activation mutations in NRAS
Activation mutations in BRAF

Question 7

Activation mutations in BRAF gene are high in melanomas of skin with _________

Answer 7

Intermittent UV exposure, yet low in melanomas of skin with high cumulative UV exposure

Question 8

Outline the host response to melanoma

Answer 8

CD8 T-cell recognise melanoma-specific antigens and if activated appropriately are able to kill tumour cells
Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) inhibits T-cell activation by removing the costimulatory signal

Question 9

Iplimumab immunotherapy for melanoma is based on what?

Answer 9

CTLA-4 blockade - blocks the blocker of immune response, allowing the immune system to attack the tumour

Question 10

What are the five subtypes of melanoma?

Answer 10

Superficial spreading, nodular, lentigo maligna, acran lentiginous, unclassifiable

Question 11

60-70% of all melanomas are of what type?

Answer 11

Superficial spreading

Question 12

Superficial spreading melanomas are found most frequently on what areas of men vs women?

Answer 12

Trunk of men
Legs of women

Question 13

What does regression of superficial spreading melanoma look like?

Answer 13

Grey, hypo- or depigmentation visible

Question 14

Generally, how do superficial spreading melanoma grow?

Answer 14

Horizontal growth then vertical growth

Question 15

15-30% of all melanomas are of what type?

Answer 15

Nodular

Question 16

Nodular melanomas are most commonly present on:

Answer 16

Trunk, head and neck

Question 17

What type of proliferation is most present in nodular melanomas?

Answer 17

Vertical

Question 18

Lentigo maligna is most commonly found in which age demographic?

Answer 18

> 60

Question 19

What do lentigo maligna look like?

Answer 19

Slow growing, asymmetric brown/ black macule with colour variation and an irregular indented border

Question 20

What is lentigo maligna called when in-situ vs when invasive?

Answer 20

In situ = lentigo maligna
Invasive = lentigo maligna melanoma

Question 21

Acral lentiginous is typically found on what areas of skin?

Answer 21

Palms and soles or in/ around nail apparatus

Question 22

What is the public awareness campaign for melanoma self detection?

Answer 22

ABCDE
Asymmetry, border, colour, diameter, evolution

Question 23

What are the three most common differential diagnosis for melanoma?

Answer 23

Basal cell carcinoma
Seborrhoeic keratosis
Dermatofibroma

Question 24

What are the features of a melanoma which are indicative of a poor prognosis?

Answer 24

Increased Breslow thickness > 1mm
Ulceration
Age
Male gender
Anatomical site - trunk, head, neck
Lymph node involvement

Question 25

What is breslow thickness?

Answer 25

Measurement from granular layer to bottom of tumour

Question 26

What investigations are conducted for melanoma?

Answer 26

Dermoscopy

Question 27

Outline how keratinocyte dysplasia/ carcinoma develops to invasive SCC

Answer 27

Actinic keratosis - dysplastic keratinocytes Bowmen’s disease - squamous cell carcinoma in situ Squamous cell carcinoma - potential for metastasis/ death

Question 28

How are melanomas staged?

Answer 28

Pathological TNM

Question 29

What is sentinel lymphoma node biopsy

Answer 29

Lymphatic drainage of finite regions of skin drain specifically to an initial node within a given nodal basin - the sentinel node Most likely nodes to contain metastatic disease

Question 30

What are the management options for unresectable or metastatic melanoma?

Answer 30

CTLA-4 inhibition (ipilmumab) PD-L1 inhibitors (nivolumab) Combination of BRAF inhibitors and MEK inhibitors

Question 31

Outline the pathogenesis of basal cell carcinoma?

Answer 31

Cross talk between tumour cells and mesenchymal cells of stroma Develops through addition of genetic alterations - alterations in p53 are most common CDKN2A, NOTCH1, NOTCH2

Question 32

What is the most common skin cancer?

Answer 32

Basal cell carcinoma

Question 33

What type of skin cancer virtually never metastasises?

Answer 33

Basal cell carcinoma

Question 34

What is actinic keratoses?

Answer 34

Atypical keratinocytes confined to epidermis Develop on sun-damaged skin Macules or papules

Question 35

What is bowens disease?

Answer 35

Squamous cell carcinoma in situ Erythematous scaly patch or slightly elevated plaque May arise de novo or from pre-existing AK

Question 36

What are the treatment options for actinic keratoses and bowens disease?

Answer 36

5-fluorouracil cream •Cryotherapy •Imiquimod cream •Photodynamic therapy •Curettage and cautery •Excision

Question 37

What are the high risk clinical features of squamous cell carcinoma?

Answer 37

Trunk and limbs > 2cm Head/ neck > 1cm

Question 38

What is a keratoacanthoma?

Answer 38

Rapidly enlarging papule that evolves into a sharply circumscribed, crateriform nodule with keratotic core •Resolves slowly over months •Most occur on head or neck / sun exposed areas •Difficult to distinguish clinically and histologically from squamous cell carcinoma