Pathogenesis Of BCC/SCC/MM

Question 1

BCC

Answer 1

• sun exposure = cumulative UV radiation is significant risk factor & anatomic site
• restricted to skin = pilosebaceous units
  — face (nose)
  — contain higher number of target progenitor cells NB role
• initiate growth (spontaneous regression not a feature)
• never metastasize
• develop as monoclonal proliferation consistent with unicellular origin
• gene most altered = PTCH 1 gene - chromosome 9q
• second most common genetic alteration found in BCC = point mutations in TP53 gene
• intact DNA repair genes
• detrimental effect of insufficient repair of UV induced DNA damage = pt with xeroderma pigmentosum = numerous BCC at early age
• stroma dependent for growth, arises without precursors & show continuous growth without progression to metastatic disease

Question 2

BCC growth characteristics

Answer 2

• dependent on specific loose connective tissue stroma = growth
• lose connective tissue stroma surrounds nests of BCC cells consists of dermal fibroblasts & thin collagen fibers
• cross talk between tumor cells & mesenchymal cells of stroma = epithelial stromal interactions found in normal developing & adult cycling hair follicles

Question 3

BCC progression

Answer 3

Nodular & ulcerating
Pearly surface = stretching of overlying epidermal layer
Arborizing telangiectasia = uncontrolled & disharmonious neoangiogenesis in tumour tissue
Palisades = reproduction of abnormal palisades in tumour
Central ulceration = tissue ischemia & necrosis in central tumour
Rolled edges = peripheral tumour maintains blood supply from neighboring tissues

Question 4

SCC

Answer 4

• UV solar radiation (cumulative dose) factor = cutaneous SCC
  1. Precursor lesions
  2. Tumour progression
  3. Potential = metastatic disease
• different regions & other sites lined with squamous epithelium (mouth, esophagus, vagina)
• secondary risk factors for metastasis = immunosuppression & location on lips/ear

Question 5

SCC - clinical

Answer 5

• precursor lesion associated with cutaneous SCC = actinic keratoses & Bowen disease (in situ)
  — microscopically actinic keratoses = chronic sun damage
  Eg: solar elastoses & SC dysplasia within epidermis
  Bowmen’s disease displays SC dysplasia = full thickness & high grade
  Actinic keratoses common of older caucasions
• lesions primarily on face, hairless scalp, dorsal aspects of hands & forearms & helices of ears

Question 6

Development of SCC

Answer 6

1. UV-induced DNA damage manifests a mutation on normal skin
   (TP53 mutation)
2. Resistance to UV-induced apoptosis — clinal expansion
   (Second TP53 mutation)
3. Additional mutations — selection for growth advantage (actinic keratoses)
4. Additional genetic alterations — proliferation of neoplasticism clone & genomic instability
5. Invasive — additional genetic alterations — acquisition of invasive capacity
6. Tumor progression metastatic properties
7. Metastasis
8. Additional genetic alterations — acquision of metastatic capacity

Question 7

Malignant melanoma

Answer 7

• genetic risk factors = Fitzpatrick 1 & 2, multiple nevi on skin surface, extreme sun hypersensitivity
  (Fitzpatrick 4-6 = Acral Melanoma)
• intermittent intense sun exposure & sunburn in childhood
• no/minimal sunscreen use/ protective clothing
• location
• tanning beds
  (Increased UVA/B)

Question 8

Formation of cyclobutene pyrimidine diners in melanocytes

Answer 8

• melanin & ROS activation in melanocytes = oxidative DNA damage in melanocytes
• mutation in tumor protein 53
• Accelerated proto-oncogene (BRAF)
  = increased cell division of mutated melanocytes = MELANOMA

Question 9

What is true pertaining to BCCs?
a) most common anatomical site for BCC to develop on the face is the cheek
b) specific areas of skin that contain a low number of target progenitor cells plays NB role
c) BCCs do not have autonomous growth
d) intermittent, recreational sun exposure more so than cumulative UV radiation is significant risk factor

Answer 9

D)

Question 10

The development of BCCs is restricted to skin containing
a) melanocytes
b) pilosebaceous units
c) ceramides
d) specialised cell junctions

Answer 10

B)

Question 11

The most striking feature of BCCs is that
a) superficial & nodular BCC cannot develop de novo
b) Tumors virtually never develop metastasis
c) BCCs arise from precursors
d) BCCs are fairly uncommon

Answer 11

B)