Session 9 - Neoplasm 2 Flashcards
What 3 steps are necessary for a tumour to metastasise?
1) Growth and invasion at the primary site
2) Enter a transport system and lodge at a secondary site
3) Grow at the secondary site to form a new tumour
What is colonisation?
-The growth of a new tumour into a clinical entity at a distal site to become a metastasis (otherwise micrometastasis)
Why is colonisation a difficult process?
- The malignant cells often get sheared and destroyed in BVs
- Tiny clusers of cells which do get lodged die or fail to grow into clinically detectable tumours
Malignant cells must evade…
…destruction by the immune system during metastasising
What three important alterations are required for invasion of carcinomas?
1) Altered adhesion
2) Stromal proteolysis
3) Motility
What are the most lethal features of a malignant neoplasm?
-Invasion and metastasis
What is epithelial to mesenchymal transition?
-The alterations in adhesion, stromal proteolysis and motility create a carcinoma cell phenotype that appears more like a mesenchymal cell
What are micrometastises?
-Surviving microscopic deposits which fail to grow
What are the most common entry routes of malignant cells into the bloodstream?
-Capillaries and veins as they have very thin walls
How is adhesion between malignant cells altered?
-Initial reduction in E-cadherin expression -> re-expression upon entering blood stream to make cells viable for travel-> down regulation at distal site
How do renal cell carcinomas pass into the right heart?
-Invades the renal vein, forma a plug which grows along the inferior vena cava into the right heart
How is adhesion altered between malignant cells and stromal proteins?
-Changes in integrin expression
How is proteolysis altered for invasion?
-Altered expression of protesases, specifically matric metalloproteases which degrade the basement membrane and stroma
Why do metastases often become necrotic in the centre?
-The rate of growth is rapid and a blood supply cannot be generated quick enough to supply the centre so it become necrotic
Why do metastases increase tumour burden?
- There are more malignant cells in the body
- Metastases can produces metastases
What is the primary site of metastases in organs drained by the portal system?
-Liver
Brochial carcinomas often metastasise in the…
…adrenal glands
What are kruckenberg tumours?
-Bilateral metatastic tumours of the ovaries
What is meant by the seed and the soil?
- The seed is the malignant cells which develop into a tumour/metastasis
- The soil is the secondary organ which favours the growth of particular seeds
What is the most common way of spread of carcinomas?
-Lymphatics to draining lymph nodes and then to blood-borne distal sites
What is a cancer niche?
-Forms when malignant cells take advantage of surrounding non-neoplastic cells for their growth factors and proteases
How is mobility altered for invasion in carcinoma cells?
- Changes in the actin cytoskeleton
- Glycoproteins interact with integrins to cause stromal re-arrangement
Is penetration of the lymphatics a destructive process?
-No, malignant cells penetrate without destroying the epithelium
What happens once carcinomas are in the lymphatics?
-They travel to the next lymph node where they settle and grow
What are the three modes of transport of malignant cells to distal sites?
- Bloodstream
- Lymphatics
- Fluid in body cavities
What is transcoelemic spread?
-Tumours invade body cavity eg peritoneum, pleura, and spreads to other sites within that space
Why do lymph nodes downstream from a tumour become swollen?
- Due to antigens and irritating material that leaches out of the tumour, especially if it is necrotic, ulcerated or infarcted
- Draining lymph nodes can then undergo hyperplasia (not due to metastases)
When does the peritoneum become seeded?
-Complication of malignancies in abdominal organs
Why does ascites develop with peritoneal seeding?
- Hundreds of metastatic nodules can develop
- Leakage of fluid from peritoneal membrane
What is the greatest barrier to successful formation of metastasis?
-Colonisation
What is tumour dormancy?
-When an apparently disease-free person harbours many micrometastases which causes a malignant neoplasm relapse years later as they have started to grow
What determines the secondary site of neoplasms?
- Regional drainage of blood, lymph or coelomic fluid
- Seed and the soil phenomenon
What is the most common secondary site for lymphatic drainage?
-Draining lymph nodes
What is the common secondary site for transcoelomic spread?
-Other areas in coelomic space or adjacent organs
What is the most common way sarcomas spread?
-Via blood stream
What are common sites of blood-borne metastases?
-Ling, bone, liver and brain
What is meant by osteolytic?
-Dissolution of bone
What is meant by osteosclerotic?
-Increase in bone density
What tumours commonly spread to bone?
-Breast, bronchus, kidney, thyroid and prostate
What correlates with the presence of metastases?
-The size of the primary tumour
Name a malignant tumour which almost never metastasises?
-Basal cell carcinoma
Is a small cell bronchial carcinoma aggressive?
-Yes it metastasises very early on in its course
What is cancer staging based on?
-The aggression and metastases of a tumour ie tumour burden
What are the two classification of effects which neoplasms can have?
- Direct local effects
- Indirect systemic effects
What are direct local effects of a neoplasm?
- Those effects which are due to the physical presence of the primary and/or secondary neoplasm
1) Direct invasion and destruction of normal tissue
2) Ulceration of the surface leading to bleeding
3) Compression of adjacent structures
4) Blocking of tubes or orifices
What are indirect systemic effects?
- Those effects caused by tumour burden, secreted hormones or miscellaneous effects
- Cachexia, malaise, immunosuppression, thrombosis
What are paraneoplastic syndromes?
-Symptom complexex that accompany tumours and concern distant targets whether the mechanisms be hormonal, immunologic or unknown
Provide an example of direct invasion of a tumour which destroys local tissue
-Osteosarcoma and the osteolytic lesions in young people
What can be the result of ulceration and bleeding of malignancies in the bowel?
-Perforation leading to peritonitis
What is cachexia?
-Reduced appetite and weghtloss due to fat and muscle wastage as body in catabolic state
Why can thromobosis occur due to malignant neoplasms?
- Irregular tubes
- Irregular constituents
- Irregular flow
Why do benign tumours of endocrine glands typically produce hormones?
-They are well differentiated
Provide an example of a benign endocrine tumour secreting a hormone
-Thyroid adenoma producing thyroxine
What hormone does bronchial small cell carcinoma often produce? What is the result of this?
- ACTH -> cushings
- ADH -> hyponatramia-> confusion, convulsion and coma
What hormones does bronchial squamous cell carcinoma produce? What is the result of this?
-PTH-like hormone -> hypercalcaemia-> constipation, polyuria, polydipsia, vomiting, phsycosis and coma
Name some miscellaneous effects of malignant neoplasms
- Neuropathies of brain and peripheral nerves
- Puritis (increased skin itching) and abnormal pigmentation
- Fever
- Finger clubbing
- Myositis
Briefly, what is the mechanism of invasion and metasasis?
- Alter adhesion and separate from tumour mass
- Digest intercellular martrix and basement membrane to enter lumen of vessel
- Evade the immune system during transport
- Embolise a small vessel and survive the impact and mechanical squeeze
- Penetrate the endothelium and basement mambrane -> further evasion of immune system
- Multiply, induce angiogenesis and establish as a tumour
Is the metastatic process an efficient one?
-No, only 0.1-0.01% of cells succeed
In which organ are direct local effects most critical?
-Brain -> SOL no room for compensation
What is different between benign tumour secreting hormones and malignant tumour secreting hormones?
- Malignant tumour often secrete hormones unrelated to the tissue of origin (ectopic hormone secretion)
- Benign tumours secrete origin-related hormones
Why do malignant tumours often cause a hypercoagulable state?
- Platelets can be activated by tumour products eg ADP
- Tumours can secrete procoagulants eg tissue factor
What is tumour lysis syndrome?
-Extensive necrosis of a tumour by chemotherapy releases toxic amounts of K or uric acid
What is the most common ways cancer kills?
- Infection
- Haemorrhage and thromboembolic phenomena
- Cachexia
- Respiratory failue
- Renal failure
