Melanoma

Question 1

What are the three types of skin cancers?

Answer 1

Basal cell carcinoma (BCC)
- Most common, 80% skin cancers
- Low metastatic potential, but locally
destructive

Squamous cell carcinoma (SCC)
- 20% skin cancers
- Can develop in sites of chronic wounds,
inflammation, or scarring

Melanoma

Question 2

Risk factors for melanoma

Answer 2

Non-melanoma
- UV exposure (especially early childhood)
- Male > female

Melanoma
- UV
-Fair skin type
- Multiple atypical moles
- Family history of melanoma

Question 3

prevention of BCC/ SCC

Answer 3

Sun protection
Oral nicotinamide (Vit B3) 500mg bd (NOT nicotinic acid/niacin)
Topical Fluorouracil bd 4 weeks

Question 4

Treatment of BCC/ SCC

Answer 4

Surgical excision
Mohs surgery
Curettage and electrodesiccation
Photodynamic therapy (PDT)
Cryosurgery
Topical Fluorouracil/ Imiquimod
Radiation

Question 5

Melanoma Pathophysiology

Answer 5

Melanoma begins when mutations in the BRAF gene lead to uncontrolled cell growth, by continuously activating the MAPK pathway, forming benign moles. As it progresses, further mutations, like those in the TERT promoter, boost telomerase activity, which helps early-stage melanoma cells survive longer. Over time, mutations in the CDKN2A gene disrupt normal cell-cycle regulation, allowing the tumour to invade deeper layers of the skin and spread.

Additional mutations, such as in NF1, PTEN, or p53 genes, further accelerate tumour growth and promote metastasis. Targeted therapies, including BRAF and MEK inhibitors, aim to block these overactive pathways, slowing down or stopping the progression of melanoma.

Question 6

Target Therapy C-KIT

Answer 6

Some melanomas involve mutations in the C-KIT gene, which is more common in melanomas originating in specific areas like the palms of the hands, soles of the feet, under the nails, or mucosal surfaces. These mutations can drive tumour growth in these unique locations, making them a distinct subset of melanomas that may require different therapeutic approaches.

Question 7

Pathophysiology- Adaptive Immune Resistance of melanoma cells

Answer 7

When melanoma cells are detected, the body’s immune system, specifically T cells release interferons to alert the immune system. However, melanoma cells can defend themselves by producing a protein called PD-L1 on their surface. PD-L1 binds to a receptor on T cells called PD-1. When this binding happens, it essentially “turns off” the T cells, stopping them from attacking the melanoma cells. This is how the tumour evades the immune system—it uses this interaction to hide and continue growing.

Immunotherapy targets this trick used by melanoma cells. MABs are designed to block PD-1 or PD-L1, preventing them from binding together. By blocking this interaction, T cells are reactivated and can resume attacking the melanoma cells, allowing the immune system to fight the cancer more effectively.

Question 8

Melanoma Treatment By Stage

Answer 8

Treating stage 0- I melanoma (no lymph node)
Surgery to remove the melanoma and a small margin of normal skin around it. The removed sample is then sent to a lab to be looked at with a microscope to assess if a wider excision is required.
For melanomas in sensitive areas on the face→ Mohs surgery/ imiquimod cream if surgery might be disfiguring.

Treating stage II or above melanoma
surgery+ lymph node biopsy.
If lymph nodes are positive then target therapy and/ or immunotherapy.