Invasion and Metastasis Flashcards
What is the role of the cell stroma
Provides:
- Mechanical support
- Intercellular signalling
- Nutrition to neoplastic cells
How does the stroma form
- Desmoplastic reaction caused by fibroblast proliferation
How does the storm assist in neoplasm formation
- Blood vessels contained in storm perfuse the tumour
What factor determines how quickly the neoplasm develops
Ability of blood vessels in the storm to persuade it
Why would neoplastic tumours be limited in growth If not vascularised properly
- Only relies on nutrient diffusion into it
When does a tumour stop expanding
Once it reaches 1-2 mm in diameter
When is angiogenesis induced
By VEGF
What factors oppose the effect of VEGF
Angiostatin and endostatin
What are the characteristics of tumours with a polypoid shape
Benign
HOW CAN ULCERATED TUMOURS BE DISTINGUISHED FROM NON-NEOPLASTIC UCLERS
THE FORMER HAS HEAPED-UP IRREGULAR EDGES
What are benign tumours capsulated by
Connective tissue
How does a polyp form
When a benign tumour arises in epithelial or mucosal surfaces, it grows away from the surface as it can’t invade
Define a sessile polyp
Sits on surface and is FLAT
Define a pedunculate polyp
When a poly grows away from mucosal surface to form a stalk structure
Why would a benign tumour still cause problems
- Pressure on adjacent tissues
- Obstruction of flow
- Production of a hormone
- Anxiety
What are patients with widespread metastases called
Carcinomatosis
Define an endophytic tumour
Inwards direction of growth into underlying tissue
Define histogenesis
Specific cell or tissue of origin of an individual tumour
What cells form sarcomas
Connective tissues
What cells form carcinomas
Epithelial cells
What cells form leukaemia
Lymphoid organs
What is the tumour grade
The extent to which the tumour resembles histologically to the tissue of origin (degree of differentiation)
Define dysplasia
Immature cells escape from basal cell layer
Define in situ carcinoma
Total loss of stratification, immature cells throughout + basement membrane intact
What is a cyst
Fluid-filled space lined by epithelium
What is a pleomorphic nuclei
Where nuclei can vary in shape and size
Define the three grades of malignant tumours
- Grade 1 - Well differentiated
- Grade 2 - Moderately differentiated
- Grade 3 - Poorly differentiated
Why do neoplastic cells proliferate so much
They are immortal due to:
Autocrine growth: Abnormal expression of oncogenes
Intracellular signalling proteins
Inactivation of genes (tumour suppressor genes) that inhibit growth pathways
Reduced apoptosis due to abnormal expression of apoptosis inhibiting genes
Telomerase prevents telomeric shortening
What are oncogenes
Genes capable of both initiation and continuation of malignant transformation of normal cells
Define carcinogens
An environmental agent participating in the causation of tumours
What are mutagenic
Acting on DNA
What favours viral oncogenesis
Immunosuppression
What aged people tend to be effected by viral tumours
Younger people
What is the most important criterion for malignancy
Invasion
Why do we take a wide margin around the tumour out as well during surgery
So that tumour cells do not remain there which can result in local recurrence
What three factors effect tumour invasion
- Decreased cellular adhesion
- Secretion of proteolytic enzymes
- Abnormal or increased cellular motility
How does gene expression play a role in metastasis
Altered expression of adhesion molecules can allows decreased cell-cell adhesion in carcinomas thereby allowing them to escape from sites of origin
How is cellular motility of neoplasms abnormal
They are more motile and show a loss of normal mechanism that arrests or reverses normal cellular migration
What proteinases are most important in neoplastic invasion
Matrix metalloproteinases
What secretes matrix metalloproteinases
Malignant neoplastic cells, enabling them to digest the surrounding connective tissues
What three major families of metalloproteinases are there
- Interstitial collagenases
Gelatinises
Stromelysins
Role of interstitial collagenases
Degrade types I, II and III collagen
Role of gelatinases
Degrade IV collagen and gelatin
Role of stromelysins
Degrade type IV collagen and proteoglycans
What are metalloproteinases inhibited by
TIMPs
How is the net effect of metalloproteinases determined
- Balance between metalloproteinases and their inhibitors
Where does invasion of metalloproteinases take place
Along tissue planes offering less resistance to tumour growth such as perineurial and vascular lamina
What tissues are extremely resistant to neoplastic invasion
Cartilage and fibrocartilage of intervertebral discs
Why is invasion easy to recognise in epithelial tumours
Because the basement membrane serves as a clear line of demarcation between tissue boundaries
Why is invasion less easy to recognise in connective tissue tumours
Because you need a clear evidence for vascular or lymphatic permeation OR histological features such as mitotic activity
Define metastases
Process where malignant tumours spread from their site of origin (primary tumours) to form other tumours (secondary tumours) at distant sites
What is carcinomatosis
Extensive metastatic disease
Does basal cell carcinoma metastasise
No
Where does liposarcoma tend to metastasise to
Lung
How is the survival rate of anapaestic carcinoma of the thyroid
LOW
What are the steps involved in forming a successful metastatic tumour
- Detachment of tumour cell from neighbours
- Invasion of surrounding connective tissue to reach conduits of metastasis (blood vessels or lymphatics)
- Intraasation into lumen of vessels
- Evasion of host defence mechanisms, such as natural killer cells in the blood
- Adherence to endothelium at a remote location
- Extravasation of cells from vessel lumen into surrounding tissue
- Angiogenesis of tumour
Describe haematogenous metastasis
- Blood stream to form secondary tumours in organs perfused by blood that has drained from a tumour
What carcinomas are favoured via bone in haematogenous metastases
- Lung
- Breats
- Kidney
- Thyroid
- Prostate
How common is metastases of solid tumours to skeletal muscle or spleen
RARE
How does metastases spread through the lymphatic system
1, Secondary tumours in regional lymph nodes
- Tumour cells reach the lymph nodes through afferent lymphatic channel
- Lymph nodes involved by metastatic tumours are firmer and larger than normal
- Lymph node metastases may interrupt lymphatic flow causing oedema in the territory they drain
How is transcoelomic metastases caused
- In pleural, pericardial and peritoneal cavities where this results in a neoplastic effusion
- Fluid is rich in protein and may contain fibrin
- Fluid also contains neoplastic cells causing effusion
- Peritoneal effusions may be due to involvement of any abdominal tumour
What is a neoplastic effusion
An abnormal amount of fluid collecting between pleura, caused by a tumour)
What organ carcinomas are pleural and pericardial effusions common consequences of
Breast and lung
Where do carcinomas tend to spread
Lymphatic over vessels
Where do sarcomas tend to spread
Vessels over lymphatics
