Skin cancers and malignant melanoma

1. What are the most common types of skin cancers?

1. Basal cell carcinoma- arise from epidermal basal cells

2. Squamous cell carcinoma- arise from keratinocytes- cells of epidermis
3. Melanoma – arise from melanocytes - cells of epidermis (5% of all cancer, but 70% of skin
cancer deaths)

2. What are the risks of developing cancers of the skin?

 UV exposure
 Familial history
 Age
 Redheads, light skins, freckles and those who hardly tan
 Sex
 Immunosupression
 Race

3. Where can melanoma first appear?

> 90% of melanomas arise from melanocytes in the skin, however it can appear in the eye, mucous
membranes, and other areas.

4. What is the “ABCD” rule for melanoma and what is the “ugly duckling sign”?

A= asymmetry, B= borders irregular, C= color not uniform, D= diameter>5mm, E= evolution of lesion.

The ugly duckling sign= A spot that deviates from the typical appearance of spots on an individual's
body.

5. How is melanoma diagnosed?

1. Dermatoscopy by an experienced physician

2. Followed by full thickness excision, processed by an experienced pathology institute.
6. What are the Clinical subtypes of melanomas?

 Non-CSD: no sun induced damage

 CSD: marked by presence of solar elastosis
 Acral: melanomas on the soles, palms, or sub-ungual sites

7.What are the prognostic factors in metastatic melanoma?

 Elevated LDH levels

 Age
 ECOG performance
 Metastasis sites
 BRAF and NRAS mutations
 Tumor burden
 Disease stage

8. What is the melanoma microstage Clark’s classification?

Level 1: lesion remains in epidermis

Level 2: lesion goes to papillary dermis

Level 3: lesion goes to papillary dermis

Level 4: lesion spreads to reticular dermis

Level 5: lesion spreads to subcutaneous tissue

9. What is the most common genomic subtype of cutaneous melanoma?

The BRAF mutation type.

NRAS and BRAF mutations are considered driver mutations, which means that
they occur early and contribute to melanoma pathogenesis.

10. What are the features of BRAF mutations?

11. What is the difference in OS between patients with BRAF and inhibitor therapy and BRAF wt?

Patients with BRAF-mutant melanoma receiving targeted therapy had similar survival outcomes vs
patients with BRAF-WT melanoma.

12. How do BRAF mutations and alterations in MAPK pathways allow melanoma to progress?

 BRAF mutations increase PD-L 1 and 2 expression, thus inhibiting CD8+ cell death
 BRAF mutations increase IL-1, which supresses the immune system through fibroblasts
 BRAF mutations activate (IL-6, IL-10, and VEGF), all which recruit suppressor T-cells to inhibit
lymphocyte immune activity.
 BRAF mutations cause a decreased expression of melanoma antigens and lower MHC-1
expressio, thus evading immune destruction
 MAPK upregulation causes an immunosuppressive environment, that favors tumor growth.

13. Which patients should be tested for BRAF mutations?

 Mandatory for patients with advanced disease (unresectable stage III or stage IV)
 Highly recommended for patients with high-risk resected disease (stage IIC, stage IIIB-IIIC)

14. What are the testing methods available for mutational testing of BRAF mutations?
15. What are the treatment options for melanoma?

16. What should be done before agressive resection?

Imaging in order to determine if there are DISTANT METASTASIS.