Flashcards in Neoplasm 2 Deck (20):
Why do malignant neoplasms have an increase tumour burden?
The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden. Untreated, this results in a vast numbers of “parasitic” malignant cells.
What three steps occur allowing a malignant neoplasm to move from one place to another successfully?
1. Grow and invade at the primary site
2. Enter a transport system and lodge at a secondary site
3. Grow at the secondary site to form a new tumour - colonisation.
Why is very hard for malignant cells to spread generally?
The whole process is inefficient as the vast majority of cells fail at steps 2 and 3. Cancer cells are not very good at surviving high pressures in arteries and being squashed in capillaries.
What three transport mechanisms are there for malignant neoplasms?
1. Blood vessels via capillaries and venules
2. Lymphatic vessels
3. Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles), which is known as transcoelomic spread.
Which 3 alterations need to occur for invasion to take place?
Invasion involves three important alterations: altered adhesion, stromal proteolysis and motility. Together, these three changes create a carcinoma cell phenotype that appears more like a mesenchymal cell than an epithelial cell, hence this is called epithelial-to-mesenchymal transition (EMT).
Describe how altered adhesion usually works in EMT?
Altered adhesion between malignant cells involves a reduction in E-cadherin expression (re expressed later on at colonisation). Altered adhesion between malignant cells and stromal proteins involves changes in Integrin expression.
Describe how stromal proteolysis usually works in EMT?
The cells must degrade basement membrane and stroma to invade. This involves altered expression of proteases, notably matrix metalloproteinases (MMPs). Malignant cells take advantage of nearby non-neoplastic cells, which together form a cancer niche. These normal cells provide some growth factors and proteases.
Describe how altered motility usually works in EMT?
Altered motility involves changes in the actin cytoskeleton. Signalling through integrins is important and occurs via small G proteins such as members of Rho family.
Describe the three processes that occur upon arrive at the malignant neoplasm's destination?
Malignant cells must grow at a secondary site to form a clinical metastasis. At a secondary site malignant cells must get out of a vessel (extravasation) and then grow (colonisation).
What are micrometastases?
Failed colonisation is very common because many malignant cells lodge at secondary sites but these tiny cell clusters either die or fail to grow into clinically detectable tumours. Any surviving microscopic deposits that fail to grow are called micrometastases. An apparently disease-free person may harbour many micrometastases, a phenomenon known as tumour dormancy. When a malignant neoplasm relapses years after an apparent cure it is typically due to one or more micrometastases starting to grow.
Where are neoplasms likely to colonise next if they are transported through blood, lymph or coelomic fluid?
The site of a secondary neoplasm depends on regional drainage of blood, lymph or coelomic fluid. For lymphatic metastasis, this is the next lymph nodes. For transcoelomic spread this is predictably to other areas in the coelomic space or to adjacent organs. For blood-born metastasis this sometimes (but not always) to the next capillary bed that the cells encounter.
What is the seed and soil phenomenon
The seed and soil phenomenon, explains the seemingly unpredictable distribution of blood-born metastases. It may be due to interactions between malignant cells and the local tumour environment (i.e. the niche) at the secondary site.
What are the typical transport mechanisms used by sarcomas and carcinomas,
Sarcomas tend to spread via the blood stream: Carcinomas typically spread first to draining lymph nodes and then to blood-born distant sites.
If transport of a malignant neoplasm is by blood where are they usually deposited?
Common sites of blood borne metastasis are lung, bone, liver and brain. The neoplasms that most frequently spread to bone are breast, bronchus, kidney, thyroid and prostate.
Give an example of an aggressive malignant neoplasm?
Small cell bronchial carcinoma
Give an example of a passive malignant neoplasm?
Basal cell carcinoma of the skin
What are the two classification of effects that neoplasms have on the host?
The effects of a neoplasm on the host can be classified as those that are due to the direct local effects, which can be due to the primary neoplasm and/or the secondary neoplasm(s), and those due the indirect systemic effects. The latter include effects of increasing tumour burden and secreted hormones etc. These are sometimes referred to as paraneoplastic syndromes.
What local effects does a neoplasm ahve on the host?
1. Direct invasion and destruction of normal tissue
2. Ulceration at a surface leading to bleeding
3. Compression of adjacent structures
4. Blocking tubes and orifices.
What systemic effects can malignancies have on the host generally?
Increasing tumour burden leads to a parasitic effect on the host. Together with secreted factors such as cytokines this contributes to reduced appetite and weight loss (cachexia), malaise, immunosuppression (can also be due to direct bone marrow destruction) and thrombosis.