MoD Neoplasia 2

Question 1

What are the most lethal features of a malignant neoplasm?

Answer 1

Invasion and metastasis

Ability to spread to distant sites leads to an increased tumour burden

Question 2

What is the process that leads to metastasis?

Answer 2

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

At each step the cells must avoid destruction by immune cells so the process in inefficient

Question 3

What do carcinoma cells require in order to invade surrounding tissue?

Answer 3

Altered adhesion
Stromal proteolysis
Motility

These changes make the epithelial cells appear as mesenchymal cells so it is called epithelia-to-mesenchymal transition (EMT). They then reverse when they have invaded (mesenchymal to epithelia).

Question 4

What changes take place in order for malignant cells to invade?

Answer 4

Altered adhesion - between malignant cells required reduced E-cadherin expression
between malignant cells and stromal proteins involves changes to integrin expression

Stromal proteolysis - Basement membrane and stroma must be degraded by proteases eg MMPs (matrix metalloproteinases)

Altered motility - changes in actin cytoskeleton

Question 5

What is a cancer “niche”?

Answer 5

Nearby non-neoplastic cells which malignant cells take advantage of
They provide some growth factors and proteases

Question 6

What are the routes in which malignant cells travel to distant sites?

Answer 6

Travel in blood
Travel in lymph
Transcoelomic spread (travels in fluid in the coelomic spaces eg peritoneum, pleura etc)

Question 7

What are micrometastases?

Answer 7

Tiny clusters of malignant cells that lodge at a secondary site but fail to grow
A person may be disease free but have many micrometastases - know as tumour dormancy. When a malignant neoplasm relapses years later is is due to one of the micrometastases starting to grow.

Question 8

What must malignant cells do in order to be successful at a secondary site?

Answer 8

Leave the vessel - extravasation

Grow - colonisation

Question 9

What determines the site of a secondary tumour?

Answer 9

Very predictable:
For lymphatic metastasis it is draining lymph nodes
For transcoelomic spread it is other areas/organs in that space
For blood-borne metastasis it is usually the next capillary bed (often lung, bone, liver, brain)

The “seed and soil” phenomenon - needs a good cancer niche eg spleen and kidneys get very few metastasis

Question 10

What is unusual about metastasis of prostate cancers to bone?

Answer 10

Usually metastasis to bone results in ‘osteolytic metastasis’ which is the destruction of bone.
When malignancy metastasises to bone from the prostate is actually makes irregular bone

Question 11

What is the basis of cancer staging?

Answer 11

The likelihood of metastasis
Some hardly ever metastasise eg basal cell carcinoma
Some are aggressive and metastasise early eg small cell bronchial

Question 12

What are the local and systematic effects of neoplasms? give examples

Answer 12

Direct local effects causes by the primary and secondary neoplasms

• invasion and destruction of normal tissue
• ulceration leading to bleeding
• compression of adjacent structures
• blocking tubes and orifices

And indirect systemic effects

• increasing tumour burden
• secreted cytokines causes weight loss (cachexia), immunosuppression and thrombosis
• ectopic hormone production (esp in benign as they are well differentiated like parent tissue)
• neuropathies