Session 9 - Neoplasm 2 Flashcards by Jodie Murdoch

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

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What is colonisation?

-The growth of a new tumour into a clinical entity at a distal site to become a metastasis (otherwise micrometastasis)

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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

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Malignant cells must evade…

…destruction by the immune system during metastasising

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What three important alterations are required for invasion of carcinomas?

1) Altered adhesion
2) Stromal proteolysis
3) Motility

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What are the most lethal features of a malignant neoplasm?

-Invasion and metastasis

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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

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What are micrometastises?

-Surviving microscopic deposits which fail to grow

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What are the most common entry routes of malignant cells into the bloodstream?

-Capillaries and veins as they have very thin walls

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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

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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

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How is adhesion altered between malignant cells and stromal proteins?

-Changes in integrin expression

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How is proteolysis altered for invasion?

-Altered expression of protesases, specifically matric metalloproteases which degrade the basement membrane and stroma

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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

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Why do metastases increase tumour burden?

There are more malignant cells in the body

- Metastases can produces metastases

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What is the primary site of metastases in organs drained by the portal system?

-Liver

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Brochial carcinomas often metastasise in the…

…adrenal glands

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What are kruckenberg tumours?

-Bilateral metatastic tumours of the ovaries

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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

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What is the most common way of spread of carcinomas?

-Lymphatics to draining lymph nodes and then to blood-borne distal sites

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What is a cancer niche?

-Forms when malignant cells take advantage of surrounding non-neoplastic cells for their growth factors and proteases

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How is mobility altered for invasion in carcinoma cells?

Changes in the actin cytoskeleton

- Glycoproteins interact with integrins to cause stromal re-arrangement

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Is penetration of the lymphatics a destructive process?

-No, malignant cells penetrate without destroying the epithelium

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What happens once carcinomas are in the lymphatics?

-They travel to the next lymph node where they settle and grow

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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