MoD 10 Neoplasia 2 Flashcards
What are the most lethal features of malignant neoplasms?
Ability to metastasise and invade distant sites as this greatly increases tumour burden. Benign tumours dont metastasise
What three steps need to occur for malignant cells to get from a primary site to a secondary site? What must the cells evade at all points?
- cells must grow and invade at primary site
- cells must enter a transport system and lodge at a secondary site
- COLONISATION- cells must grow at the secondary site to form a new tumour
Immune destruction by immune cells
Do cancer cells always succeed in metastasising?
No, it is a very inefficient process, sometimes cells woll fai lto enter a vessel and lodge at a secondary site, some cells will fail to grow at the secondary site
What 3 alterations are needed for carcinoma cells to invade surrounding tissue?
Altered adhesion
Stromal proteolysis
Motility
What do the alterations in invasion make the phenotype of the cancer cells appear like? What is this transition called?
Like a mesenchymal cell
Epithelial to mesenchymal transition (EMT)
The changes in expression of which two proteins alters adhesion in malignant cells?
E-cadherin
Integrin
What do cancer cells break down to invade? What performs this proteolysis?
Basement membrane and stroma
Altered expression of matrix metalloproteinases (MMPs)
What forms a cancer niche?
The nearby non-neoplastic cells that malignant cells take advantage of Stroma Fibroblasts Endothelial cells Inflammatory cells
What changes to alter motility of invading cells?
Actin cytoskeleton changes
Signalling through integrins important (via G proteins in Rho family)
In what 3 ways can malignant cells spread to distant sites?
- Through blood vessels via capillaries and venules
- Through the lymphatic vessels
- Through fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles), known as TRANSCOELOMIC SPREAD
What two things must happen at the secondary site for a clinical tumour to form?
Malignant cells must get out of vessel (extravasation)
Malignant cells must colonise
What are micrometastases?
Microscopic tumour cell deposits at secondary sites that survive but fail to grow into clinically detectable tumours
Explain tumour dormancy
When an apparently disease free person harbours micrometastases they have no symptoms until a time after when/if these metastases then start to grow
What factors can cause tumour dormancy?
Immune attack
Reduced angiogenesis
Hostile secondary site
What does secondary site of neoplasm depend on?
Regoinal drainage of lymph (regional lymph node) blood(next capillary bed enters) or coelomic fluid (elsewhere in coelomic space or adjacent organs)
Where are the most likely metastases of each type of transport system?
Lymphatic: regional lymph node
Coelom: elsewhere in coelom
Blood: lung and liver (first capillary beds encountered) bone, brain
Why do the sites of blood borne metastases often seem unpredictable?
“seed and soil” phenomenon, due to interactions between malignant cells and niche at secondary site. Niche might not suit those malignant cells so they dont grown there etc.
What neoplasms most frequently spread to bone?
breast, bronchus, kidney, thyroid and prostate
Do all malignant neoplasms metastasise?
No, some are aggressive and metastasise early and others almost never metastasise. Likelihood of metastasis is related to the size of the primary neoplasm
What is the basis of cancer staging?
The size of the primary neoplasm as this relates to likelihood of metastasis
Give an example of an aggressive malignant neoplasm that metastasises early and one that almost never metastasises
aggressive- small cell bronchial carcinoma
rarely metastasises- basal cell carcinoma
What two types of effects can neoplasms have?
Local in areas of primary and secondary tumours
Systemic from increased tumour burden, secreted hormones and misc. effects
What are having systemic effects of neoplasms called?
Paraneoplastic syndrome
What effects are most relevant in benign tumours?
Local effects from primary and hormonal effects
What are some local effects of tumours?
Direct invasion and destruction of normal tissue
Ulceration at a surface leading to bleeding
Compression of adjacent structures which can block vessels
Blockage of tubes and orifices from the inside
What symptoms can increasing tumour burden give?
Reduced appetite and weight loss (cachexia), malaise (feeling generally unwell), immunosupression (can also be due to BM destruction) and thrombosis
Why do benign endocrine tumours typically secrete hormones?
They are well differentiated
What hormone can squamous cell carcinoma produce?
PTH-like hormone
What hormones can bronchial small cell carcinoma produce?
ACTH or ADH
Give some examples of miscellaneous systemic effects that can be caused by neoplasms
Neuropathoes affecting the brain and peripheral nerves, skin problems e.g pruritis (itching) and abnormal pigmentation, fever, myositis(muscle inflammation)
