Pathogenesis of Head and Neck Cancer

Question 1

How does cancer develop?

What are key elements in cancer development?

Answer 1

• multistep, progressive, cumulative process
  1. Initiation - DNA damage and mutation
  2. Promotion - clonal expansion of abnormal cells leading to cancer

Tmuour growth:

• replication
• escape from senescence
• evasion of apoptosis
• limitless replicative potential
• invasive growth
• angiogenesis
• metastasis

Question 2

What are the components of a neoplasm?

Answer 2

• neoplastic cells
• blood vessels
• inflammatory cells: macrophages, lymphocytes, polymorphs
• fibroblasts
• stroma

Question 3

How do tumours grow?

Answer 3

• most tumours are monoclonal (all cells appear to arise from one parent cell) which has undergone genetic change
• this is then passed on to all the progeny
• tumour cells lack normal control mechanisms thus the clone expands due to uncontrolled proliferation

Question 4

What does invasive growth display?

Answer 4

• reduction in cell-cell adhesion
• invasion of basement membrane and stroma
• tumour cells need to be motile

Question 5

What is angiogenesis?

Answer 5

• formation of new blood vessels
• usually under tight physiological control, but control lost in tumours - the angiogenic switch - development of rich blood supply around tumour
• vessels formed are abnormal
• new blood vessels formed by outgrowth of endothelial cells from post capillary venules into tumour mass
• critical step in progression of small localised tumours to a big one with metastatic potential

Question 6

What is metastasis?

Answer 6

Metastasis: tumour implants that are discontinuous with the primary lesion (secondaries)

• sinister event
• non-random
• affects tumour stage and has prognostic implications

Question 7

List some common sites of metastatic disease:

What are some routes of metastasis?

Answer 7

• regional lymph nodes
• liver
• lung
• bone
• brain
• skin

Routes:

• lymphatic - carcinomas
• haematogenous - sarcomas
• across body cavities (serous cavities, meninges/ventricles/spinal canal)
• direct implantation

Question 8

What is epithelial dysplasia?

Answer 8

• a pre-malignant process - indicates a risk of developing carcinoma
• atypical epithelial alterations limited to the surface squamous epithelium

Architectural changes - maturation and differentiation

Cytological changes - changes in cells

Cells show abnormal features, also seen in cancer cells, but do not yet possess the bility to invade adjacent normal tissues

Question 9

How is epithelial dysplasia graded using WHO 2017 classification?

Answer 9

Based on 1/3 of epithelium

• mild: disorganisation, increased proliferation and atypia of basal cells
• moderate: more layers of disorganised basaloid cells, atypia, suprabasal mitoses
• severe: very abnormal, affects full thickness of epithelium