9. Neoplasms

Question 1

What increases tumour burden?

Answer 1

The ability of malignant cells to invade and spread to distant sites.

Question 2

How many cancer cells will be in 1kg of tumour?

Answer 2

1 trillion cells.

Question 3

What three steps are all required for malignant cells to get from a primary site to a secondary site?

Answer 3

1) grow and invade 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 (colonisation).

Question 4

What makes the process of invasion and metastasis of tumours inefficient?

Answer 4

All three steps - grow at primary site, enter transport system, and grow a secondary site, have to be successful whilst evading destruction by immune cells. The vast majority fail in transport or growing in the new secondary site conditions.

Question 5

What three alterations must carcinoma cells undergo to invade surrounding tissues?

Answer 5

Altered adhesion, altered stromal proteolysis and altered motility.

Question 6

What is epitehlial-to-mesenchymal transition?

Answer 6

When carcinoma cells undergo alterations to adhesion, stromal proteolysis, and motility so they become more like mesenchymal cells than epithelial cells.

Question 7

What does altered adhesion between malignant cells involve?

Answer 7

A reduction in E-cadherin expression.

Question 8

What does altered adhesion between malignant cells ad stromal proteins involve?

Answer 8

Changes in integrin expression. The cells must degrade the basement membrane of the stroma to invade.

Question 9

Why is matrix metalloproteinases important for invasion of carcinoma cells?

Answer 9

It’s expression must be altered to degrade the basement membrane or the stroma. It helps malignant cells take advantage of nearby non-neoplastic cells, to form a cancer niche.

Question 10

How is motility of carcinoma cells altered?

Answer 10

By changes to the actin cytoskeleton.

Question 11

What are members of the Rho family used for in motility changes?

Answer 11

Signalling through integrins occurs via small G proteins like members of the Rho family.

Question 12

What are the three options for transport for malignant cells?

Answer 12

Entering: the blood vessels via capillaries and venules, or the lymphatic vessels, or fluid in the body cavities (pleura, peritoneal, pericardial and brain ventricles) in transcoelomic spread.

Question 13

How can lymphangiogenesis be a useful indicator of?

Answer 13

Survival rate and metastasis of a tumour.

Question 14

What is a colonisation?

Answer 14

A secondary site where malignant cells grow.

Question 15

What is the greatest barrier to successful formation of metastasis?

Answer 15

Failed colonisation.

Question 16

What are micrometastases?

Answer 16

Surviving microscopic deposits that fail to grow.

Question 17

What is tumour dormancy?

Answer 17

Where a clinically ‘disease-free’ person harbours many micrometastases.

Question 18

What causes a malignant neoplasm to relapse, years after an apparent cure?

Answer 18

Typically one or two micrometastases start to grow.

Question 19

What causes dormancy?

Answer 19

The hostility of the secondary site the malignant tumour is trying to grow in. The metastases need to relearn how to undergo angiogenesis in the new site.

Question 20

What two factor determine where a metastases goes?

Answer 20

The regional drainage of the blood, lymph, or coelomic fluid, and the seed and soil phenomenon.

Question 21

Where will metastases move to in transcoelomic spread?

Answer 21

Predictably to other areas in the coelomic space or to adjacent organs.

Question 22

Where will metastases grow in blood-borne spread?

Answer 22

Sometimes, but not always, in the next capillary bed that the cells encounter.

Question 23

What can the seed and soil phenomenon explain?

Answer 23

The seemingly unpredictable distribution of blood-borne metastases.

Question 24

What is the seed and soil phenomenon?

Answer 24

The seed is the cancer cell and the soil is the organ or niche of the secondary site. The soil has to be right for the seed to grow, there needs to be successful interactions between malignant cells and the local tumour environment.

Question 25

What is the typical route of spread of carcinomas?

Answer 25

Spread to draining lymph nodes, and then to blood-borne distant sites.

Question 26

What are the common sites of blood borne metastasis?

Answer 26

The lungs, bone, liver, and brain.

Question 27

Which neoplasms most frequently spread to bone?

Answer 27

Breast, bronchus, kidney, thyroid, and prostate.

Question 28

What is a type of malignant neoplasm known for being aggressive and metastasising early in their course?

Answer 28

Small cell bronchial carcinoma.

Question 29

What is a type of malignant neoplasm known for being unlikely to ever metastasise?

Answer 29

Basal cell carcinoma of the skin.

Question 30

Why is basal cell carcinoma of the skin defined as malignant even though it’s unlikely to ever spread?

Answer 30

It can still spread if neglected, so malignant tendency just easier to stop this. Also the way it grows is malignant, it infiltrates and destroys surrounding tissues rather than growing with pushing outer margins like benign neoplasms.

Question 31

What are the two classifications of neoplasm effects?

Answer 31

Direct local effects - from the primary and/or secondary neoplasm, and indirect systemic effects - from increased tumour burden, secreted hormones, and/or miscellaneous effects.

Question 32

What are paraneoplastic syndromes?

Answer 32

The indirect systemic effects of a neoplasm.

Question 33

What are the local effects of primary and secondary neoplasms due to?

Answer 33

Direct invasion and destruction of normal tissue, ulceration at a surface leading to bleeding, compression of adjacent structures and blocking tubes and orifices.

Question 34

How do neoplasms cause systemic effects?

Answer 34

Increased tumour burden leads to a parasitic effect on the host. Secreted factors, like cytokines, contribute to reduced appetite and weight loss (cachexia), malaise, immunosuppression, and thrombosis. Producing hormones can cause throdositosis for example. Miscellaneous effects like neuropathies affecting the brain or peripheral nerves, skin problems etc.

Question 35

Why is cancer lethal?

Answer 35

The massive tumour burden of growing to 1kg of tumour tissue.