Pathology - Neoplasia 2

Question 1

What are the steps of malignant cells moving from a primary site to a secondary site?

Answer 1

1) growth and invading the primary site
2) entering the transport system and lodging at the secondary site
3) growing at the secondary site to form a new tumour (colonisation)

Immune attack occurs at all stages

Question 2

What are the three changes that allow a carcinoma cell to enter the surrounding tissue?

Answer 2

• altered adhesion
• stromal proteolysis
• motility

Question 3

What is epithelial-to-mesenchymal transition?

Answer 3

The changes that allow carcinoma cells to enter surrounding tissues can make them appear more like a mesenchymal cell than an epithelial cell

Question 4

How are the three changes of epithelial-to-mesenchymal transition carried out?

Answer 4

ALTERED ADHESION:
- reduction in E-cadherin expression
- changes in integrin expression
STROMAL PROTEOLYSIS:
- altered expression of matrix metalloproteinases which degrade basement membrane and stroma
MOTILITY:
- changes in actin cytoskeleton

Question 5

What is a cancer niche?

Answer 5

This occurs when malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases

Question 6

How do cancer cells signal each other?

Answer 6

Through integrins, using small G proteins such as members of the Rho family

Question 7

How can malignant cells reach distant sites?

Answer 7

• entering blood vessels via capillaries and venules
• entering lymphatic vessels
• entering fluid in body cavities (transcoelomic spread)

Question 8

What is a micrometastases?

Answer 8

A microscopic deposit of cells that made it to a secondary site but failed to grow. These may stay in the body for years without causing symptoms ‘tumour dormancy’)

Question 9

What factors can cause a tumour to fail to grow in a secondary location?

Answer 9

Immune attack, reduced angiogenesis, hostile site

Question 10

Why are we often able to predict the location of a secondary neoplasm?

Answer 10

• we can tell where the fluid that the cells are in is likely to go, eg lymphatic fluid goes to the regional lymph node.
• however, the ‘seed and soil’ effect (interactions of malignant cells and local tumour environment) can mess with our predictions

Question 11

Where do carcinomas typically spread first?

Answer 11

To draining lymph nodes, then to blood-borne distant sites such as lung, bone, liver and brain. These neoplasms frequently spread to bone - breast, bronchus, kidney, thyroid and prostate

Question 12

True or false - the size of the primary neoplasm does not affect the likelihood of metastasis?

Answer 12

False - it is directly related

Question 13

How are the effects that a neoplasm has on the host classified?

Answer 13

• those that are due to the direct local effects (primary and/or secondary neoplasm)
• those due to indirect systemic effects (effects of increasing tumour burden, secreted hormones, miscellaneous effects = ‘paraneoplastic syndromes’)

Question 14

What causes the local effects of primary and secondary neoplasms?

Answer 14

• direct invasion and destruction of normal tissue
• ulceration at a surface leading to bleeding
• compression of adjacent structures
• blocking tubes/orifaces

Question 15

What symptoms do increasing tumour burden and cytokines cause on the body?

Answer 15

Reduced appetite and weight loss, malaise, immunosuppression, thrombosis, neuropathies affecting brain and nerves, pruritus and abnormal pigmentation of skin, fever, finger clubbing and myositis

Question 16

Can benign neoplasms produce hormones?

Answer 16

Yes, if they are well differentiated eg a thyroid adenoma will produce thyroxine