Session 8 ILO's Neoplasia 2

Question 1

Understand what is meant by invasion and metastasis

Answer 1

Invasion - Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues
Metastasis - spread of tumour from primary site to sites that are physically discontinuous from the primary tumour (marks a tumour as malignant)

Question 2

List the common sites of blood-borne metastases

Answer 2

Lung, bone, liver and brain

Question 3

Identify the neoplasms that most frequently spread to the bones and the difference between lytic and sclerotic lesions.

Answer 3

• Breast
• Bronchus
• Kidney
• Thyroid

Cause osteolytic lesions - destruction of bone tissue

• Prostate
  Cause osteoblastic lesions - increased production of disorganised abnormal bone:

Question 4

Describe the local and systemic effects of neoplasms

Answer 4

Local effects: (5)

• Direct invasion and destruction of normal tissue
• Ulceration at a surface leading to bleeding
• Compression of adjacent structures
• Blocking tubes and orifices
• Raised pressure (brain) due to tumour growth or swelling

Systemic effects: (7)

• Hormone production by tumours (benign tumours)
• Reduced appetite and weightloss = Cachexia (wasting away)
• Malaise
• Immunosuppression
• Hypercalcaemia (osteolytic lesions)
• Anaemia
• Thrombosis

Question 5

Describe the cellular alterations that are required for invasion to occur

Answer 5

3 cellular adaptations needed for a carcinoma cell:

1. Altered adhesion
   - Reduced E-cadherin expression (holds cells together)
   - Change integrin expression
2. Stromal proteolysis
   - Altered expression of proteases, notably matrix metalloproteinases
   - Leads to a degraded basement membrane and stroma = allows for invasion
3. Motility
   - Requires changes to occur in the actin cytoskeleton

Question 6

Understand the processes that determine the site of a metastasis

Answer 6

It depends on Regional drainage:
1. Lymphatic metastasis spread to draining lymph nodes

2. transcoelomic spread is to other areas in the coelomic space or to adjacent organs
3. blood-borne metastasis is sometimes (but not always) to the next capillary bed that the malignant cells encounter.

• Carcinomas tend to spread via lymphatics first
• Sarcomas spread via blood stream
• Common sites of blood borne metastasis are lung, bone, liver and brain

Seed and soil phenomenon:
Just because the cells get there, doesn’t mean they can survive - you need the right environment for them to do so.
May explain unpredictable distribution of blood borne metastases.
Due to Interaction of malignant cell and local tumour environment at secondary site (seed is malignant cell/tumour, soil is tumour environment)

Failure to grow = micrometastasis

Question 7

Describe and understand the processes of invasion and metastasis

Answer 7

The process of invasion and metastasis:

1) Grow and invade at primary site with breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues
2) Enter transport system to move/lodge to a secondary site
3) Grow at secondary site and form new tumour