skin cancer

Question 1

what is a melanoma

Answer 1

malignant tumour arising from melanocytes
leads >75% of skin cancer deaths
- can arise on mucosal surfaces e.g oral, conjunctival, vaginal and within uveal tract of eye
- rising incidence rates observed

Question 2

what are the genetic risk factors for melanoma

Answer 2

family history - cdkn2a mutations, mc1r variants
lightly pigmented skin
red hair
dna repair defects e.g xeroderma pigmentosum

Question 3

what are the environmental risk factors for melanoma

Answer 3

intense intermittent sun exposure
chronic sun exposure
residence in equatorial latitudes
sunbeds
immunosuppresion

Question 4

what is the molecular pathogenesis for melanoma

Answer 4

mitogen activated protein kinase {RAS-RAF-MEK-ERK} pathway regulates cellular proliferation, growth and migration

Question 5

what are kit mutations responsible for

Answer 5

30-40% of acral and mucosal melanomas

- also common in melanomas that arise from chronically sun exposed skin

Question 6

melanoma can arise if activation mutations are present in

Answer 6

NRAS (15-20% of melanomas)

BRAF (50-60%) - high in melanomas of skin with intermittent UV exposure

Question 7

what can inherited cdkn2a mutations cause

Answer 7

MAPK pathway activation

Question 8

what does cdkn2a encode for

Answer 8

p16 tumour supressor
Binds to CDK4/6, p16 prevents formation of cyclin D1-CDK4/6 complex which phosphorylates rB, inactivating it leading to E2F which promotes cell cycle progression

Question 9

what is the host response to melanomas

Answer 9

cd8+ t cells recognise melanoma specific antigens and if activated appropriately - are able to kill tumour cells
cd4+ helper t cells and antibodies plays critical role

Question 10

what is the role of cytotoxic t lymphocyte associated antigen

Answer 10

natural inhibitor of t cell activation by removing costimulatory signal (b7-apc)

Question 11

what immunotherapy is used for melanoma pathogenesis

Answer 11

based on ctla4 blockade - ipilimumab

also checkpoint inhibitors (PD1, PDL1)

Question 12

melanoma epidemiology

Answer 12

increasing worldwide

develops predominantly in caucasian populations

Question 13

what is superficial spreading melanoma

Answer 13

60-70% of melanomas
- most common in fair skinned individuals
most frequently seen on trunk of men and legs of women
can arise de novo/ pre existing nevus
in upto 2/3 tumours regression is visible as grey,hypo depigmentation, reflects interaction of host immune system with tumour

Question 14

what is a nevus

Answer 14

mole

Question 15

what does a pink nodule suggest in superficial spreading melanoma

Answer 15

melanoma is growing vertically

Question 16

what is a nodular melanoma

Answer 16

2nd most common type of melanoma in fair skinned individuals
- 15-30% of all melanomas
most commonly in trunk, head and neck
m>f
usually present blue to black, sometimes pink to red nodule - may be ulcerated,bleeding
develops rapidly