Flashcards in Pathology - Neoplasia 2 Deck (16):
What are the steps of malignant cells moving from a primary site to a secondary site?
1) growth and invading the primary site
2) entering the transport system and lodging at the secondary site
3) growing at the secondary site to form a new tumour (colonisation)
Immune attack occurs at all stages
What are the three changes that allow a carcinoma cell to enter the surrounding tissue?
- altered adhesion
- stromal proteolysis
What is epithelial-to-mesenchymal transition?
The changes that allow carcinoma cells to enter surrounding tissues can make them appear more like a mesenchymal cell than an epithelial cell
How are the three changes of epithelial-to-mesenchymal transition carried out?
- reduction in E-cadherin expression
- changes in integrin expression
- altered expression of matrix metalloproteinases which degrade basement membrane and stroma
- changes in actin cytoskeleton
What is a cancer niche?
This occurs when malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases
How do cancer cells signal each other?
Through integrins, using small G proteins such as members of the Rho family
How can malignant cells reach distant sites?
- entering blood vessels via capillaries and venules
- entering lymphatic vessels
- entering fluid in body cavities (transcoelomic spread)
What is a micrometastases?
A microscopic deposit of cells that made it to a secondary site but failed to grow. These may stay in the body for years without causing symptoms 'tumour dormancy')
What factors can cause a tumour to fail to grow in a secondary location?
Immune attack, reduced angiogenesis, hostile site
Why are we often able to predict the location of a secondary neoplasm?
- we can tell where the fluid that the cells are in is likely to go, eg lymphatic fluid goes to the regional lymph node.
- however, the 'seed and soil' effect (interactions of malignant cells and local tumour environment) can mess with our predictions
Where do carcinomas typically spread first?
To draining lymph nodes, then to blood-borne distant sites such as lung, bone, liver and brain. These neoplasms frequently spread to bone - breast, bronchus, kidney, thyroid and prostate
True or false - the size of the primary neoplasm does not affect the likelihood of metastasis?
False - it is directly related
How are the effects that a neoplasm has on the host classified?
- those that are due to the direct local effects (primary and/or secondary neoplasm)
- those due to indirect systemic effects (effects of increasing tumour burden, secreted hormones, miscellaneous effects = 'paraneoplastic syndromes')
What causes the local effects of primary and secondary neoplasms?
- direct invasion and destruction of normal tissue
- ulceration at a surface leading to bleeding
- compression of adjacent structures
- blocking tubes/orifaces
What symptoms do increasing tumour burden and cytokines cause on the body?
Reduced appetite and weight loss, malaise, immunosuppression, thrombosis, neuropathies affecting brain and nerves, pruritus and abnormal pigmentation of skin, fever, finger clubbing and myositis