Neoplasms-invasion, Metastasis And Effects Flashcards
What leads to a greatly increased tumour burden?
The ability of malignant cells to invade and spread to distant sites
Can a metastasises cause further problems? How?
Yes, by metastasising further
How do neoplasms metastasise?
1) grow at the primary site (need a big enough tumour)
2) invade at the primary site (need a big enough tumour)
3) enter a transport system and lodge at a secondary site (at this moment, not causing any clinal disease)
4) grow at the secondary site to form a new tumour (colonisation)
** at all points the cells must evade destruction by immune cells
Name a problem with the process of neoplasm metastases?
It is a very inefficient process.
Most cells are destroyed by mechanical trauma- sheered and broken.
Many cells get to the secondary sites but dont grow.
This is why we often need a substantially sized primary tumour in order to produce enough cells to metastasise.
What does invasion into surrounding tissues by carcinoma cells require?
- altered adhesion
- stromal proteolysis
- motility
What are the three routes that cells can take in order to metastasise?
Malignant cells can reach distant sites by entering;
1) blood vessels via capillaries and venules
2) lymphatic vessels
3) fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles) - transcoelomic spread
Spread of malignant cells via the fluid in the body cavities is known as what?
Transcoelomic spread
Because they’re using coelomic spaces
What is the growth of a malignant cell at a secondary site called?
Colonisation
What do you call a surviving microscopic deposit of malignant cells that fails to grow at a secondary site ?
Micrometastases
(An apparently disease free person may harbour many micrometastases, a phenomenon known as tumour dormancy- relapses can occur if these dormant micrometastases suddenly colonises)
What determines the site of a secondary tumour?
The site depend on:
1) regional drainage of blood, lymph and coelomic fluid (for blood-borne metastasis sometimes to the next capillary bed that the cells encounter/ for lymphatic metastasis this is very predictably to draining lymph nodes/for transcoelomic spread this is predictably to other areas in the coelomic space or adjacent organs
2) the ‘sees and soil’ phenomenon, is due to interactions between malignant cells and the local tumour environment (ie the niche) at the secondary site. Tumours find the areas that are better for growth, therefore it is more likely that cancer will metastasise in specific organs (ie lungs)
How do carcinomas spread typically?
Via lymphatics first and then Blood-borne distant sites
What are the typical blood-borne metastasis sites?
Blood Borne metastasis are lung, bone, liver and brain
What type of neoplasms most frequently spread to the bone?
Breast, bronchus, kidney, thyroid and prostate
How do sarcomas tend to spread?
Via the blood stream
The likelihood of a malignant neoplasm metastasising is related to what?
The size of the primary neoplasm (this is the basis of cancer staging)
What are the local effects of primary and secondary neoplasms due to?
1) direct invasion and destruction of normal tissue
2) ulceration at the surface leading to bleeding (may lead to infection and inflammation)
3) compression of adjacent structures
4) blocking tubes and orifices
What 3 things need to happen to allow invasion by a carcinoma cell?
- Altered adhesion
- Stromal proteolysis
- Motility
During the process by which carcinoma cells invade other sites, they begin to appear more like mesenchymal cells rather than epithelial cells, what is this change called?
Epithelial-to-mesenchymal transition (EMT)
What occurs to allow altered adhesion in carcinoma cells so that they can invade other sites?
Between malignant cells: reduced production of E-Cadherin
Between cells and stromal proteins: changes in integrin expression
What occurs to allow stromal proteolysis of carcinoma cells that aids them to invade other sites? Give an example
In order to access other sites, the cells need to be able to break down the stroma and basement membranes. To do this they alter the expression of proteases.
Eg matrix metalloproteinases (MMPs)
How do carcinoma cells alter their motility in order to help them invade other sites?
There are changes made to the actin cytoskeleton
How is the actin cytoskeleton of a carcinoma cell changed, in order that it might invade other sites?
This is done by signalling through integrins via small G proteins (eg members of the Rho family)
What is the typical cause of someone who has a malignant neoplasm relapse years after an apparent cure?
The micrometastases which were dormant, have now started to grow
What sort of things will prevent colonisation of malignant cells?
- Immune attack
- Reduced angiogenesis
- Hostile secondary site
How do sarcomas tend to spread?
Via blood stream
What are the classification of effects that can be seen with neoplasms?
Local and systemic
Local: direct physical effects of the benign/malignant tumours at the primary sites, direct physical effects of malignant tumours at the secondary sites
Systemic: tumour burden (Mass), hormones, misc.
What are the systemic effects of neoplasms sometimes called?
Paraneoplastic syndrome
What effects are most relevant for benign neoplasms?
Local effect from the primary site
And hormonal systemic effects
What are the systemic effects of a neoplasm in regards to tumour burden?
In a tumour there are many highly metabolically active cells that are having a parasitic effect on the host and producing cytokines.
The combination of these things will cause:
1. Reduced appetite
2. Weight loss (cachexia)
3. Malaise
4. Immunosuppression (May also be due to direct bone marrow destruction)
5. Thrombosis
What are the systemic effect of a neoplasm in regards to the hormonal secretions? Give examples
Benign tumours: these are often functional tissues and so usually produce hormones (if it is a tumour of a hormone secreting tissue, ie thyroid adenoma secreting thyroxine)
Malignant tumours: it is less likely but still possible for these neoplasms to produce hormones eg bronchial small cell carcinoma producing ACTH or ADH
What are some of the misc. systemic effects seen with neoplasms?
- Neuropathies affecting the brain and peripheral nerves
- Skin problems eg pruritis (itching a lot, can get it with lymphomas)
- Abnormal pigmentation
- Fever (due to cytokines)
- Myositis
- Finger clubbing (distorted angle of nail beds)
