13.6.2 BCC/SCC/MM

Question 1

Basal Cell Carcinoma

Answer 1

• Sun exposure and anatomic site = of etiologic importance in development of BCC
• Intermittent, recreational sun exposure, more than cumulative UV radiation is a significant risk factor
• development restricted to skin containing pilosebaceous units
  ➢ commonly develop in the face (particularly the nose) suggests that anatomic site i.e. specific areas of skin that contain a higher number of target progenitor cells plays an important role
• capacity to initiate growth
  ➢spontaneous regression is not a feature
• usually never metastasize
• Has unique growth characteristics
  ➢ dependent on a specific loose connective tissue stroma for its continued growth
  ➢The loose connective tissue stroma that characteristically surrounds nests of BCC cells consists of dermal fibroblasts and thin collagen fibres
  ➢The cross talk between tumour cells and mesenchymal cells of the stroma stimulates the epithelial stromal interactions found in normal developing and adult cycling hair follicles
• develop as a monoclonal proliferation consistent with a unicellular origin
• The gene most often altered in BCCs is the PTCH 1 gene which is located on chromosome 9q
• second most common genetic alteration found in BCC is point mutations in the TP53 gene
• Presence of intact DNA repair genes is of importance
• The detrimental effect of insufficient repair of UV-induced DNA damage is well illustrated in patients with xeroderma pigmentosum who develop numerous BCCs at an early age
• BCC is stroma dependent for its growth, arises without precursors and shows continuous growth without progression to metastatic disease

Question 2

Squamous cell carcinoma

Answer 2

• UV solar radiation is a major etiologic factor in the development of cutaneous SCC
• The cumulative dose of UV radiation received over time is a significant risk factor (not intermittent radiation)
• SCC of the skin is a ‘classic cancer’ as it has:
  ➢precursor lesions
  ➢tumour progression
  ➢potential to develop metastatic disease
• SCC can develop in different regions of the skin as well as other sites lined by squamous epithelium e.g. mouth, esophagus, vagina
• Secondary risk factors for metastasis include immunosuppression and location on the lips or the ear
• Clinical precursor lesions associated with cutaneous SCC include actinic keratoses and Bowen disease
  ➢Microscopically, actinic keratoses display signs of chronic sun damage
  ❖i.e. solar elastoses and squamous cell dysplasia within the epidermis
  ❖Bowens disease also displays squamous cell dysplasia which is full thickness and often high grade
• Actinic keratoses are common in chronically sun exposed skin of older caucasions
  ➢Lesions occur primarily on the face, hairless scalp, dorsal aspects of hands and forearms and helices of the ears

Question 3

Multistep development of SCC

Answer 3

• UV-induced DNA damage manifests a mutation on normal skin
• TP53 mutation
• Resistance to UV-induced apoptosis – clonal expansion
• Second TP53 mutation
• Additional mutations – selection for growth advantage (actinic keratoses)
• Additional genetic alterations – proliferation of neoplastic clone and genomic instability
• Invasive Squamous Cell Cancer – additional genetic alterations – acquisition of invasive capacity
• Tumour progression metastatic properties
• Metastasis of squamous cell cancer
• Additional genetic alterations – acquision of metastatic capacity

Question 4

Malignant Melanoma

Answer 4

• Genetic risk factors – Fitzpatrick 1 and 2, multiple nevi on skin surface, extreme sun hypersensitivity (NB to note that Fitzpatrick 4-6 can also get Acral Melanoma)
• Intermittent intense sun exposure and sunburn in childhood
• No/minimal sunscreen use
• Minimal protective clothing (hats, sunglasses etc)
• Geographic location –Australia
• Tanning beds
  ALL THE ABOVE ↑UVA/B
• Formation of cyclobutene pyrimidine dimers in melanocytes ➢Melanin and ROS activation in melanocytes → Oxidative DNA damage in melanocytes
  ➢Mutation in tumour protein 53 ➢Accelerated proto-oncogene (BRAF)
  = ↑ Cell division of Mutated melanocytes → MELANOMA

Question 5

What is true pertaining to BCCs?
- The most common anatomical site for a BCC to develop on the face is the cheek
- Specific areas of the skin that contain a low number of target progenitor cells plays an important role
- BCCs do not have autonomous growth
- Intermittent, recreational sun exposure more so than cumulative UV radiation is a significant risk factor

Answer 5

Intermittent, recreational sun exposure more so than cumulative UV radiation is a significant risk factor

Question 6

The development of BCCs is restricted to skin containing:
- Melanocytes
- Pilosebaceous units
- Ceramides
- Specialised cell junctions

Answer 6

Pilosebaceous units

Question 7

The most striking feature of BCCs is that:
- Superficial and nodular BCC can not develop de novo
- Tumours virtually never develop metastasis
- BCCs arise with precursors
- BCCs are fairly uncommon

Answer 7

Tumours virtually never develop metastasis