Melanoma

Question 1

Epidermis layers

Answer 1

Stratum corneum
Stratum lucidum
Stratum Granulosum

Question 2

Stratum corneum

Answer 2

15-30 layers of dry, dead cells
•Continuously shed and replaced from deeper strata, takes approx. 4 weeks to replace entire layer
•Helps to prevent penetration by microbes and dehydration of underlying tissues, mechanical protection from abrasion
•Callus formation due to constant friction

Question 3

Stratum lucidum

Answer 3

Only in thicker skin
•3-5 layers of clear, dead keratinocytes
•Large amounts of keratin and thickened plasma membranes

Question 4

Stratum granlosum

Answer 4

Transition between active and “dead” strata
•Middle layer of epidermis

Question 5

Keratinocytes

Answer 5

90% of epidermis
Produces protein keratin.

Transition between active and “dead” strata
•Middle layer of epidermis

Question 6

Melanocytes

Answer 6

8%
Produces pigment melanin

Produce melanin, a yellow/red, black/brown pigment that contributes to skin colour and absorbs UV light
•Long slender projections between melanocyte and keratinocytes transfers melanin
•Melanin granules cluster inside keratinocytes to form a protective layer over the nucleus at the skin side, shielding nucleus from UV damage
•Melanin protects from UV damage but Melanocytes are susceptible to damage by UV light!

Question 7

Langerhans cells

Answer 7

Arise from bone marrow

Question 8

Key melanoma mutations

Answer 8

BRAF → In 50% of melanomas
Lead to alteration in a cell protein that regulates and controls cell growth
Found in benign Levi
Not sufficient to cause melanoma

Question 9

CDKN2A

Answer 9

Loss of or inactivation of the gene CDKN2A.
•This point of the gene is responsible for encoding tumour suppressor proteins P16 and P14, this leads to uncontrolled cell proliferation
•Loss of genetic material at this point is seen in familial melanoma and in up to 40% of sporadic melanomas

Question 10

Key pathways

Answer 10

MAPK/MEK signalling
•This is a chain of proteins in the cell. These communicate signals from the cell surface to the DNA in the cell nucleus
•This signal is initiated by tyrosine kinases. The pathway is responsible for regulating cell growth, proliferation, differentiation, migration and apoptosis
•A mutation along this pathway leads to an increase in cell proliferation

Question 11

Melanoma epidemiology

Answer 11

16,700 new melanoma cases per year in UK= 46 every day
•5th most common cancer, 4% of all new cancer diagnoses
•8,400 new cases in females
•8,400 new cases in males!!
•Incidence rates highest in 85–89-year-olds, with peak age group in the over 75’s
•In the last decade, rate have increased by 27% in females and 38% in males
•Most melanomas are on the trunk or legs
•52% lower rate in females from the most deprived areas and 54% lower in males from most deprived areas

Question 12

Melanoma management → stage 0

Answer 12

Surgical excision
•Margin of 0.5 cm to be used
•Further management to be discussed if margins not adequate
•Imiquimod cream (Aldara)
•Modifies immune response
•Binds to cell surface receptors and induced apoptosis
•Used if 0.5cm margins are not appropriate due to disfigurement
•Repeated skin biopsy required to check effectiveness of treatment

Question 13

Stage 1

Answer 13

Surgical excision
•Margin of 1cm to be used for stage 1

•Stage 2
•Surgical excision
•Margin of 2cm to be used for stage 2 tumours

•Sentinel lymph node biopsy
•This may be offered to those diagnoses with stage 1B to 2C melanoma
•Completed at the same time as surgical excision

Question 14

Follow up

Answer 14

Tests will be conducted to check for
•Signs of recurrence of original tumour
•Signs of spread
•Development of further melanomas
•Stage 0- discharge following treatment completion
•Stage1A- 2-4 visits in first 12 months- discharge after 1 year
•Stage 1B-2C- follow up every 3 months for first 3 years then 6 months for next 2 years, discharge after 5 years. No routine screening investigations completed.

Question 15

Stage 3

Answer 15

Tumour has spread to 1-3 nearby lymph nodes
•Surgery
•Tumour removal
•Lymph node removal
•Radiotherapy
•Adjuvant radiotherapy not recommended for stage 3A
•Stage 3B-C, adjuvant radiotherapy not recommended unless the reduction of local recurrence is seen to outweigh the side effects and reactions from RT
•MAB therapy, for untreated stage IV or unresectable stage III
•Nivolumab plus ipilimumab

Question 16

Ipilimumab (Yervoy)

Answer 16

•A MAB therapy that is used as a “checkpoint inhibitor”
•It works by stopping the cancer cell from suppressing the body’s immune system
•The immune system is then able to destroy the cancer cell
•A molecule, CTLA-4, acts as a stopping mechanism for immune response. It is important in stopping the bodies response to stimuli
•Ipilimumab blocks the activity of CTLA-4, allowing the immune response to be increased and T-cells to be activated

Question 17

Melanoma stage 3

Answer 17

Intralesional treatment: Talimogene laherparepvec (T-VEC)
•Recommended in adults for treatment of; unresectable, regionally or distantly metastasised melanoma (stage 3B, 3C or 4) if there is no spread to bone, brain, lung or internal organs.
•Used if systemically administered immunotherapies are not suitable

Question 18

Melanoma stage 3→ pt 2

Answer 18

T-VEC
•2nd method of action- as the infected cell ruptures, due to replication of the modified virus, more viral particles are released. These new particles and their release into the blood stream allows continued infection of tumour cells.
•Immune response is also stimulated by the release of GM-CSF. This release then activates the body’s immune response to the melanoma cells- allowing for a more systemic reaction.