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ESA2 LKM > MOD 9 > Flashcards

MOD 9 Flashcards

1
Q

What are the most lethal features of a malignant neoplasm and why?

A

The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden. Untreated, this results in vast numbers of “parasitic” metastasis.

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2
Q

Define tumour burden:

A

The total mass of tumour tissue carried by an individual with malignancy.

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3
Q

Describe the multi-step journey malignant cells take to get from their primary to secondary sites:

A
  1. Grow and invade at primary site
  2. Enter a transport system and lodge at a secondary site
  3. Grow at a the secondary site to form a new tumour (colonisation).
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4
Q

What do malignant cells need to evade throughout all steps in their invasion and metastatic journey?

A

Destruction by immune cells.

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5
Q

Why is invasion and metastasis by malignant cells inefficient?

A

Malignant cells often fail at:

  1. Entering a vessel and lodging at a secondary site
  2. Colonisation at the secondary site
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6
Q

How do benign tumours metastasise?

A

They don’t!

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7
Q

Which three important alterations does invasion require?

A
  1. Altered adhesion
  2. Stromal and basement membrane proteolysis
  3. Motility
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8
Q

What is the epitheilial-to-mesenchymal transition (EMT)?

A

The changes to the carcinomal cell phenotype (altered adhesion, stromal proteolysis and motility) that occur which make the epithelial cell appear more like a mesenchymal cell.

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9
Q

How is altered adhesion between malignant cells acheived?

A

Reduced expression of E-cadherin.

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10
Q

How is altered adhesion between malignant cells and stromal proteins achieved?

A

Changes in Integrin expression.

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11
Q

How is stromal proteolysis achieved?

A

Altered expression of proteases, notably: matrix metalloproteinases.

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12
Q

What is the cancer niche?

A

The microenvironment that neoplastic cells are in. They can take advantage of neighbouring non-neoplastic cells which provide some growth factors and proteases.

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13
Q

How is altered motility achieved?

A

Changes in the actin cytoskeleton. Important in this process is signalling through Integrins which use small G proteins such as members of the Rho family.

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14
Q

What are the three routes that malignant cells can use to transport themselves to distant sites?

A

They can enter:

  1. Blood vessels via capillaries and venules
  2. Lymphatic vessels
  3. Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricle) = transcoelomic spread.
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15
Q

How can malignant cell transport by blood vessels be facilitated by the malignant cells?

A

They can stimulate angiogenesis creating new larger blood vessel which can transport the cancer cells. These are new and leaky, facilitating spread.

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16
Q

What is the greatest barrier to successful formation of metastasis?

A

Failed colonisation. Many malignant cells lodge at distal sites but these tiny clusters die or fail to grow into clinically detectable tumours (micrometastases).

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17
Q

What are micrometastases?

A

These are surviving microscopic deposits of malignant cells that fail to grow.

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18
Q

What is tumour dormany?

A

A stage in cancer progression where the cells cease dividing but survive in a quiescent state as micrometastases (producing no symptoms) while waiting for appropriate environmental conditions to begin proliferation again. This is why malignant neoplasm can relapse years after an apparent cure - typically one or more micrometastases starting to grow.

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19
Q

What determines the site of a secondary tumour?

A
  1. Regional drainage of blood, lymph or coelomic fluid.

2. “seed and soil” phenomenon - microenviornment (niche) at secondary site.

20
Q

When malignant cell are transported by lymph vessels where do they tend to spread?

A

Predictably to draining lymph nodes.

21
Q

When malignant cell are transported by transcoelomic spread where do they tend to spread?

A

Other areas in the coelomic space or to adjacent organs.

22
Q

When malignant cell are transported by blood vessels where do they tend to spread?

A

Sometime (but not always) to the next capillary bed that cells encounter.

23
Q

What is the “seed and soil” phenomenon?

A

The interactions of some microenvironments (niche) at secondary sites with malignant cells may determine where blood-borne malignant cells spread to. This could explain the seemingly unpredictable distribution of blood-borne metastases.

24
Q

Where do carcinomas tend to spread to first?

A

Typically spread via lymphatics first to lymph nodes and then to blood-borne distant sites.

25
Q

Where do sarcomas tend to spread to first?

A

Tend to spread through bloodstream.

26
Q

What are common sites of blood-borne metastases?

A

Lung, bone, liver and brain.

27
Q

Which neoplasms most frequently spread to bone?

A

Breast, bronchus, kidney, thyroid and prostate.

28
Q

What is meant by malignant tumours having “personalities”?

A

Some malignant neoplasms are more aggressive and metastasise very early in their course (e.g. small cell bronchiomal carcinoma). Others almost never metastasise (basal cell carcinoma of the skin).

29
Q

How is the likelihood of metastasis (e.g. staging of a cancer) determined?

A

It is related to the size of the primary neoplasm.

30
Q

Why are organ transplants from individuals with a known history of cancer not accepted?

A

Because their organs may contain undetectable micrometastases which could cause cancer in their organ recipients - especially as the recipients will be on immunosupressives.

31
Q

Why is basal cell carcinoma considered as malignant when it almost never metastasises?

A

Because if it is neglected it infiltrates and invades tissue (nibbles away at it which is why it is nicknamed the rodent ulcer).

32
Q

What are paraneoplastic syndromes?

A

Clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease as a result of tumour burden, secreted hormones and/or miscellaenous effects. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature. The most common presentation is fever.

33
Q

What causes the local effects of primary and secondary neoplasms?

A
  1. Direct invasion and destruction of normal tissue
  2. Ulceration at the surface leading to bleeding
  3. Compression of adjacent structures
  4. Blocking tubes and orifices
34
Q

What causes superior vena cava syndome?

A

It is caused obstruction to the superior vena cava and is commonly caused by malignancy within the thorax (85% by lung cancer). It can cause oedema of the neck and face as well as respiratory distress.

35
Q

What causes the systemic effects of neoplasms?

A

The parasitic effect of an increasing tumour burden coupled with secreted factors such as cytokines.

36
Q

List some systemic effects of neoplasms:

A
  1. Reduced appetite and weight loss (cachexia)
  2. Malaise
  3. Immunosupression (can also be due to direct bone marrow destruction)
  4. Thrombosis
37
Q

Why do benign neoplasms of endocrine glands typically produce hormones?

A

Because the tumour cells are well differentiated and therefore retain the local tissue functions e.g. Thyroid adenoma secretes thryroxine.

38
Q

What hormones can bronchial small cell carcinomas secrete?

A

ACTH or ADH.

39
Q

What hormones can bronchial squamous cell carcinoma secrete?

A

PTH-like hormone (this can lead to hypercalcaemia).

40
Q

List some of the many miscellaenous sytemic effects of cancer:

A
  1. Neuropathies affecting the brain and peripheral nerves
  2. Skin problems such as pruritis
  3. Abnormal pigmentation
  4. Fever
  5. Finger clubbing
  6. Myositis
41
Q

Which type of cancer is finger clubbing particularly associated with?

A

Small cell carcinoma of bronchus.

42
Q

List some cells and constituents that may be part of the cancer niche:

A
  1. Stroma
  2. Fibroblasts
  3. Endothelial cells
  4. Inflammatory cells
43
Q

What is extravasation?

A

The movement of cells out of a vessel into the surrounding tissue.

44
Q

Which factors may contribute to tumour dormancy during remission?

A
  1. Immune attack
  2. Reduced angiogenesis
  3. Hostile secondary site
45
Q

What is often the first capillary bed that blood borne metastases reach?

A

Lung and liver.

46
Q

In the “seed and soil” phenomenon, what is the seed and what is the soil?

A

Seed: malignant cells
Soil: niche (stroma, fibroblasts, endothelial cells and inflammatory cells that create the microenvironment that interacts with the “seed”.

47
Q

What are the most relevant effects of benign neoplasms?

A

Local effects and hormonal effects.

ESA2 LKM (45 decks)

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