Pathogenesis of the Head and neck 1 Flashcards
What are the most common head and neck cancers?
Squamous cell carcinomas
Other common head and neck cancers aside from SCC?
Salivary glands e.g. polymorphous adenocarcinoma
Odontogenic epithelium e.g ameloblastic carcinoma
Less frequent malignant tumour example
rhabdomyosarcoma
Main aetiological factors for head and neck cancers
tobacco, alcohol, high risk HPV infection, EBV
Aetiology of most salivary gland tumours
Unknown.
Molecular alterations identified in some e.g. MAML2 rearrangements in mucoepidermoid carcinoma.
Neoplasia
Genetic disease
Tumour cells breed true (parent cells were already tumour cells meaning this has been inherited).
How would you describe the development of a cancer?
Multistep, progressive, cumulative process.
Multistep theory of carcinogenesis
- Initiation - DNA damage and mutation
- Promotion - clonal expansion of abnormal cells leading to cancer
Components of neoplasm
- Neoplastic cells
- Blood vessels
- Inflammatory cells (macrophages, lymphocytes, polymorphs)
- Fibroblasts
- Stroma
- Tumour growth (replication, escape from senescence, evasion of apoptosis, limitless replicative potential)
- Invasive growth
- Angiogenesis
- Metastasis
Key elements in cancer development (4)
- Tumour growth (replication, escape from senescence, evasion of apoptosis, limitless replicative potential)
- Invasive growth
- Angiogenesis
- Metastasis
Tumour growth
Commonly tumours are monoclonal (i.e. stem from one parent cell)
What is tumour heterogeny?
When there are differences of the same type of tumour shown in different patients.
What occurs during invasive growth?
- Reduction in cell-cell adhesion (e.g. reduced/loss of E-cadherin)
- Invasion of basement membrane and stroma (tumour cell attaches to BM and produce proteolytic enzymes to break up matrix)
- Tumour cells need to be motile (extrude pseudopodia which attach to stroll proteins, actin cytoskeleton enables movement).
How do groups of cells display invasive growth?
- Require cell-cell adhesion and communication
- Predominates in well differentiated carcinomas
- Inner cells protected from immunological assault
- High levels of autocrine pro-migratory factors and of proteolytic enzymes
- Heterogenous sets of cells invade together
Angiogenesis (5)
“formation of new blood vessels”
- Usually under tight physiological control however control is 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 tumour into a bigger one with metastatic potential.
- Stimulus is increased production of factors by tumour cells; VEGF, angiogenic, inhibition of angiogenesis anticancer therapy area
Does the dentist of tumour microvasculature correlate with prognosis?
No
What is often a pre-requisite for tumour progression?
angiogenesis
Metastasis
“cancer spread to other sites”
- Tumour implants that are discontinuous with the primary lesion “secondaries”
- Sinister event
- Non-random
- Affects tumour stage and has prognostic implications
Common sites of metastatic disease (7)
- Regional lymph nodes
- liver
- lung
- bone
- brain
- skin
- Unusual sites: renal cancer, thyroid cancer, melanoma
Routes of metastasis
- Lymphatics (carcinomas)
- Haematogenous (sarcomas)
- Across body cavities (serous cavities/meninges/ventricles/spinal canal)
- Direct implantation
Process of metastasis
- Tumour cells breach the basement membrane of vessel and enter vessel lumen
- Tumour cells carried to site of metastasis
- Bind to endothelial cells, penetrate BM, move out of vessel
- Establishment of metastasis, cell proliferation, angiogenesis
- Complex molecular interactions involved in these stages.
Describe metastatic disease profile
Circulatory patterns account for common metastatic profiles.
Lung and liver very effective at arresting circulating cancer cells.
What is the “seed and soil hypothesis” in metastasis?
The seed (cancer cell) is dependent on some property of the soil (the metastatic site).
Delivery of cancer cells to a potential metastatic site is primarily mechanical - but the growth of metastatic deposits is dependent upon compatibility with the “soil”.
Explained by target tissues possess appropriate extracellular matrix and cell adhesion molecules to allow tumour cells to stop and grow at a site.
