Neoplasms 2 Flashcards
What does the ability of malignant cels to invade and spread to distant sites lead to?
Greatly increased tumour burden
What does increased tumour burden cause if untreated?
A vast number of ‘parasitic’ malignant tumours
Can a patient develop metastases if they are clinically tumour free?
Yes
What must happen for malignant cells to get from a primary site to a secondary site?
They must grow and invade at the primary site, enter a transport system and lodge at a secondary site and grow at the secondary site to form a new tumour
What are micrometasteses?
Microscopic tumour deposits that are clinically undetectable
What is it called when a tumour grows at a second site to form a new tumour?
Colonisation
What must happen at all points if a tumour is to metastasise?
It must evade destruction by immune cells
Why is the process of tumour metastasis inefficient?
As it needs to do all three steps
How do the vast majority of attempted tumour metastasis fail?
Due to difficulty transporting and difficulty growing at a secondary site
What have the steps of metastasis be studied in?
Mainly carcinomas rather than other types of malignant neoplasms
What does invasion into surrounding tissue by carcinoma cells require?
Altered adhesion
Stomal proteolysis
Motility
What are the changes undergone by carcinoma cells when invading surround tissues called?
Epithelial-to-mesenchymal transition (EMT)
What does EMT create?
A carcinoma cell phenotype that appears more like a mesenchymal cell than an epithelial cell
What does altered cell adhesion between malignant cells involve?
A reduction in E-cadherin expression
What does altered adhesion between malignant cells and stromal proteins involve?
Changes in Integrin expression
What must cells be able to degrade in order to invade?
The basement membrane and stroma
What does invasion degradation of the basement membrane and stoma involve?
Altered expression of proteases, notably matrix metalloproteinases (MMPs)
What do malignant cells take advantage of?
Nearby non-neoplastic cells
What do malignant cells and nearby non-neoplastic cells together form?
A cancer niche
What do the normal cells in a cancer niche do?
Provide some growth factors and proteases
What does altered mobility involve?
Changes in the actin cytoskeleton
How does signalling through integrins occur?
Via small G proteins such as members of the Rho family
What can malignant cells enter?
Blood vessels via capillaries and venules
Lymphatic vessels
Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles)
What is metastasis caused by malignant cells entering fluid in body cavities called?
Transcoelomic spread
When do malignant cells need to metastasise by entering blood vessels?
If bigger than 1mm
What helps malignant cells travel by the blood stream?
The cancer niche
What must happen to malignant cells at a secondary site?
They must grow
What is the growing of malignant cells at a secondary site called?
Colonisation
How can organ donation cause cancer?
Micrometastases can transfer through organ donations, even if the donor never officially had cancer- could still have deposits, which then developed in the immunosuppressed organ receivers
What is failed colonisation considered to be?
The greatest barrier to successful formation of metastasis
Why is colonisation considered to be the greatest barrier to successful formation of metastases?
Because many malignant cells lodge at secondary sites, but these tiny cell clusters either die or fail to grow into clinically detectable tumours
What are surviving microscopic deposits that fail to grow called?
Micrometastases
What is tumour dormancy?
When an apparently disease-free person may harbour micrometastases
What is a malignant neoplasm relapse after many years typically due to?
One or more micrometastases starting to grow
What does the site of a secondary neoplasm depend on?
Regional drainage of blood, lymph and coelomic fluid
The ‘seed and soil’ phenomenon
Where do lymphatic metastases spread to?
Draining lymph nodes
Where do tumours that spread by transcoelomic spread go to?
Other areas in the coelomic space or to adjacent organs
Where do blood-borne metastases go?
Sometimes (but not always) to the next capillary bed that the cells encounter, often the liver and lung
What may the ‘seed and soil’ phenomenon explain?
The seemingly unpredictable distribution of blood-bourne metastases
What is the seed and soil phenomenon due to?
Interactions between malignant cells and the local tumour environment (the niche) at the secondary site
Where do carcinomas typically spread to first?
Draining lymph nodes
Where do carcinomas typically spread to after lymph nodes?
Distant blood-borne sites
What are the common sites of blood borne metastasis?
Lung, bone, liver and brain
What neoplams are more frequently spread to bone?
Breast, bronchus, thyroid and prostate
What is meant by malignant tumours having ‘personalities’?
Some malignant neoplasms are more aggressive and metastasise very early in their course
Give an example of an aggressive tumour?
Small cell bronchial carcinoma
Give an example of a tumour that almost never metastasises?
Basal cell carcinoma in the skin
What is the likelihood of metastases related to?
The size of the primary neoplasm
What is the size of the likelihood of metastasis the basis for?
Cancer staging
How can the effects of a neoplasm on the host be classified?
Those that are due to direct local effects
Those that can be due to the primary neoplasms and/or the secondary neoplasms
Those due to indirect systemic effects
What do indirect systemic effects include?
Effects of increasing tumour burden, secreted hormones and/or miscellaneous effects
What are indirect systemic effects sometimes referred to as?
Paraneoplastic syndromes
What are the most relevant effects for benign neoplasms?
Local effects from the primary and hormonal effects
What are the local effects of primary and secondary neoplasms due to?
Direct invasion and destruction of normal tissue
Ulceration at surface leading to bleeding
Compression of adjacent structures
Blocking tubes and orifices
What does increasing tumour burden lead to?
A parasitic effect on the host
What does the parasitic effect of increasing tumour burden work with to produce symptoms?
Secreted factors such as cytokines
What does the parasitic effect of the increased tumour burden have on the host?
Reduced appetite and weight loss (cachexia)
Malaise
Immunosupression
Thrombosis
Other than increased tumour burden, how can a cancer cause immunosuppression?
Due to direct bone marrow destruction
What happens in benign neoplasms of the endocrine glands?
They are well differentiated, and so typically produce hormones
Give an example of a benign neoplasm of an endocrine gland
A thyroid adenoma, which produces thyroxine
Can malignant tumours produce hormones?
Sometimes
Give two examples of a malignant tumour that can produce hormones?
Bronchial small cell carcinoma can produce ACTH or ADH
Bronchial squamous cell carcinoma can produce PTH-like hormone
What are the miscellaneous systemic effects of neoplasms?
Neuropathies affecting the brain and peripheral nerves
Skin problems such as pruritus and abnormal pigmentation
Fever
Finger clubbing
Myositis
