MOD 9 Flashcards
What are the most lethal features of a malignant neoplasm and why?
The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden. Untreated, this results in vast numbers of “parasitic” metastasis.
Define tumour burden:
The total mass of tumour tissue carried by an individual with malignancy.
Describe the multi-step journey malignant cells take to get from their primary to secondary sites:
- Grow and invade at primary site
- Enter a transport system and lodge at a secondary site
- Grow at a the secondary site to form a new tumour (colonisation).
What do malignant cells need to evade throughout all steps in their invasion and metastatic journey?
Destruction by immune cells.
Why is invasion and metastasis by malignant cells inefficient?
Malignant cells often fail at:
- Entering a vessel and lodging at a secondary site
- Colonisation at the secondary site
How do benign tumours metastasise?
They don’t!
Which three important alterations does invasion require?
- Altered adhesion
- Stromal and basement membrane proteolysis
- Motility
What is the epitheilial-to-mesenchymal transition (EMT)?
The changes to the carcinomal cell phenotype (altered adhesion, stromal proteolysis and motility) that occur which make the epithelial cell appear more like a mesenchymal cell.
How is altered adhesion between malignant cells acheived?
Reduced expression of E-cadherin.
How is altered adhesion between malignant cells and stromal proteins achieved?
Changes in Integrin expression.
How is stromal proteolysis achieved?
Altered expression of proteases, notably: matrix metalloproteinases.
What is the cancer niche?
The microenvironment that neoplastic cells are in. They can take advantage of neighbouring non-neoplastic cells which provide some growth factors and proteases.
How is altered motility achieved?
Changes in the actin cytoskeleton. Important in this process is signalling through Integrins which use small G proteins such as members of the Rho family.
What are the three routes that malignant cells can use to transport themselves to distant sites?
They can enter:
- Blood vessels via capillaries and venules
- Lymphatic vessels
- Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricle) = transcoelomic spread.
How can malignant cell transport by blood vessels be facilitated by the malignant cells?
They can stimulate angiogenesis creating new larger blood vessel which can transport the cancer cells. These are new and leaky, facilitating spread.
What is the greatest barrier to successful formation of metastasis?
Failed colonisation. Many malignant cells lodge at distal sites but these tiny clusters die or fail to grow into clinically detectable tumours (micrometastases).
What are micrometastases?
These are surviving microscopic deposits of malignant cells that fail to grow.
What is tumour dormany?
A stage in cancer progression where the cells cease dividing but survive in a quiescent state as micrometastases (producing no symptoms) while waiting for appropriate environmental conditions to begin proliferation again. This is why malignant neoplasm can relapse years after an apparent cure - typically one or more micrometastases starting to grow.
What determines the site of a secondary tumour?
- Regional drainage of blood, lymph or coelomic fluid.
2. “seed and soil” phenomenon - microenviornment (niche) at secondary site.
When malignant cell are transported by lymph vessels where do they tend to spread?
Predictably to draining lymph nodes.
When malignant cell are transported by transcoelomic spread where do they tend to spread?
Other areas in the coelomic space or to adjacent organs.
When malignant cell are transported by blood vessels where do they tend to spread?
Sometime (but not always) to the next capillary bed that cells encounter.
What is the “seed and soil” phenomenon?
The interactions of some microenvironments (niche) at secondary sites with malignant cells may determine where blood-borne malignant cells spread to. This could explain the seemingly unpredictable distribution of blood-borne metastases.
Where do carcinomas tend to spread to first?
Typically spread via lymphatics first to lymph nodes and then to blood-borne distant sites.
Where do sarcomas tend to spread to first?
Tend to spread through bloodstream.
What are common sites of blood-borne metastases?
Lung, bone, liver and brain.
Which neoplasms most frequently spread to bone?
Breast, bronchus, kidney, thyroid and prostate.
What is meant by malignant tumours having “personalities”?
Some malignant neoplasms are more aggressive and metastasise very early in their course (e.g. small cell bronchiomal carcinoma). Others almost never metastasise (basal cell carcinoma of the skin).
How is the likelihood of metastasis (e.g. staging of a cancer) determined?
It is related to the size of the primary neoplasm.
Why are organ transplants from individuals with a known history of cancer not accepted?
Because their organs may contain undetectable micrometastases which could cause cancer in their organ recipients - especially as the recipients will be on immunosupressives.
Why is basal cell carcinoma considered as malignant when it almost never metastasises?
Because if it is neglected it infiltrates and invades tissue (nibbles away at it which is why it is nicknamed the rodent ulcer).
What are paraneoplastic syndromes?
Clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease as a result of tumour burden, secreted hormones and/or miscellaenous effects. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature. The most common presentation is fever.
What causes the local effects of primary and secondary neoplasms?
- Direct invasion and destruction of normal tissue
- Ulceration at the surface leading to bleeding
- Compression of adjacent structures
- Blocking tubes and orifices
What causes superior vena cava syndome?
It is caused obstruction to the superior vena cava and is commonly caused by malignancy within the thorax (85% by lung cancer). It can cause oedema of the neck and face as well as respiratory distress.
What causes the systemic effects of neoplasms?
The parasitic effect of an increasing tumour burden coupled with secreted factors such as cytokines.
List some systemic effects of neoplasms:
- Reduced appetite and weight loss (cachexia)
- Malaise
- Immunosupression (can also be due to direct bone marrow destruction)
- Thrombosis
Why do benign neoplasms of endocrine glands typically produce hormones?
Because the tumour cells are well differentiated and therefore retain the local tissue functions e.g. Thyroid adenoma secretes thryroxine.
What hormones can bronchial small cell carcinomas secrete?
ACTH or ADH.
What hormones can bronchial squamous cell carcinoma secrete?
PTH-like hormone (this can lead to hypercalcaemia).
List some of the many miscellaenous sytemic effects of cancer:
- Neuropathies affecting the brain and peripheral nerves
- Skin problems such as pruritis
- Abnormal pigmentation
- Fever
- Finger clubbing
- Myositis
Which type of cancer is finger clubbing particularly associated with?
Small cell carcinoma of bronchus.
List some cells and constituents that may be part of the cancer niche:
- Stroma
- Fibroblasts
- Endothelial cells
- Inflammatory cells
What is extravasation?
The movement of cells out of a vessel into the surrounding tissue.
Which factors may contribute to tumour dormancy during remission?
- Immune attack
- Reduced angiogenesis
- Hostile secondary site
What is often the first capillary bed that blood borne metastases reach?
Lung and liver.
In the “seed and soil” phenomenon, what is the seed and what is the soil?
Seed: malignant cells
Soil: niche (stroma, fibroblasts, endothelial cells and inflammatory cells that create the microenvironment that interacts with the “seed”.
What are the most relevant effects of benign neoplasms?
Local effects and hormonal effects.
