Neoplasia 2 - Invasion and Metastasis Flashcards
What is invasion?
The ability of cells to break through the basement and spread
What is tumour burden?
The total mass of tumour tissue in the body
- Greatly increased by the ability of malignant cells to invade and spread to distant sites
How can malignant cells get from a primary site to a secondary site?
- Grow and invade at the primary site
- Enter a transport system and lodge at a secondary site
- Grow at the secondary site to form a new tumour (colonisation)
What alterations are required for invasion into surrounding tissues by carcinoma cells?
- Altered adhesion
- – Between malignant cells: involves a reduction in E-cadherin expression
- – Between malignant cells and stromal proteins: involves changes in integrin expression
- Stromal proteolysis
- – 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 (together they form a cancer niche, the normal cells provide some growth factors and proteases)
- Altered motility
- – Involves changes in the actin cytoskeleton
- Together these 3 changes create a carcinoma cell phenotype that appears more like a mesenchymal cell than an epithelial cell
What can malignant cells enter for metastasis?
- Blood vessels, via capillaries and venues
- Lymphatic vessels
- Fluid in body cavities (transcoelomic spread)
What are micrometastases?
- Many malignant cells lodge at secondary sites
- These tiny cell clusters either die or fail to grow into clinically detectable tumours
- Surviving microscopic deposits that fail to grow are called micrometastases
- When a malignant neoplasm relapses years after an apparent cure, it is typically due to 1 or more micro metastases starting to grow
What determines the site of a secondary tumour?
- Regional drainage of blood, lymph, or coelomic fluid
- – For lymphatic metastasis this is very predictably to draining lymph nodes
- – For transcoelomic spread: to other areas in the coelomic space or to adjacent organs
- – For blood-borne metastasis: sometimes to the next capillary bed that the cells encounter
- The seed and soil phenomenon
- – Due to interactions between malignant cells and the local tumour environment at the secondary site
- – May explain the seemingly unpredictable distribution of blood-borne metastasis
How do carcinomas spread?
Typically:
- First to draining lymph nodes
- Then to blood-borne distant sites
What are the common sites for carcinoma metastasis?
- Lung
- Liver
- Bone
- Brain
Which malignant neoplasms commonly spread to the lungs?
- Sarcomas
- Carcinomas
- Kidney
- Testis
Which carcinomas commonly spread to the liver?
Carcinomas of the large intestine
What are the effects of a metastasis to bone?
- Can cause destruction of bone (osteolysis) leading to pathological fracture
- Can cause production of dense bone (osteosclerosis)
Where are brain metastases commonly from?
- Bronchial carcinoma
- Breast carcinoma
- Testicular carcinoma
- Malignant melanoma
What are the effects of a metastasis to the brain?
- Can cause a wide range of neurological symptoms
- Acts as a space-occupying lesion
What are the local effects of a benign neoplasm?
- Cause compression
- – Pressure atrophy
- – Altered function
- Cause partial/complete occlusion of tubes/orifices
- Ulceration of surface mucosa
- Space occupying lesion (brain)
