L15: Neoplasia 2

Question 1

Define invasion?

Answer 1

Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissue

Question 2

Define metastasis?

Answer 2

Spread of tumour to a site that is physically discontinuous from the primary tumour
Unequivocally marks a tumour as malignant

Question 3

Describe the multi-step journey required to colonise a secondary site?

Answer 3

1. Grow and invade the primary site
2. Enter a transport system and lodge at a secondary site
3. Grow at a secondary site (colonisation)
   At all points it has to evade destruction by immune cells
   Process is inefficient

Question 4

What needs to happen to a carcinoma cell for it to invade a new site?

Answer 4

Requires altered adhesion
Stromal proteolysis
Motility

Question 5

What is the phenotype of these new carcinoma cells?

Answer 5

More like a mesenchymal cell (more unspecialised)

Epithelial to mesenchymal transition

Question 6

What happens to the cells during altered adhesion?

Answer 6

Reduction in E cadherin –> loose adhesion between the cells
Changes to intergrin expression –> keep it attached to BM

Question 7

What is meant by stromal proteolysis?

Answer 7

Degradation of the basement membrane and stroma
Happens through altered expression of proteases, matrix metalloproteinases (MMPs)
Take advantage of nearby non-neoplastic cells which provide growth factors and proteases –> niche

Question 8

What allows the cells to move?

Answer 8

Changes to the actin cytoskeleton

Signalling through integrins is important and occurs via small G proteins–> Rho family

Question 9

How do malignant cells travel to distant sites?

Answer 9

Blood vessels via capillaries and venules
Lymphatics
Fluid in body cavities –> pleura, peritoneal, pericardial and brain ventricles–> transcoelomic spread

Question 10

What has to happen at the secondary site for the formation of a clinical metastasis?

Answer 10

Colonisation–> growth of the cells

Question 11

Why do most metastasis fail to develop?

Answer 11

Unable to colonise
Lodge a secondary site forming undetectable cell clusters
Die or fail to grow into detectable tumour

Question 12

What are metastasis that manage to survive but fail to grow called?

Answer 12

Micrometastases

Can habour many micrometastases and be disease-free–> called tumour dormancy

Question 13

Why do apparently cured malignant neoplasms relapse?

Answer 13

Thought to be due to one or more micrometastases that start to grow

Question 14

What determines the site of a secondary tumour?

Answer 14

1) The regional drainage of blood, lymph or coelomic fluid
- -> Blood-borne metastases–> next capillary bed (not always)
- -> Lymph–> lymph node
- -> Transcoelomic spread–> other areas in coelomic space or to adjacent organs
2) ‘Soil and seed’ phenomenon
- -> interactions between malignant cells and the local tumour environment at the secondary site
- -> ?Explains the unpredictable distribution of blood-borne metastases

Question 15

What is the difference in spread between carcinomas and sacromas?

Answer 15

Carcinomas (epithelial) –> lymphatics

Sarcomas (stromal) –> blood stream

Question 16

What are the common sites for blood-borne metastasis

Answer 16

Lung, bone, liver and brain

Question 17

Which neoplasms commonly spread to bone?

Answer 17

Breast, bronchus, kidney, thyroid and prostate
Majority–> osteolytic lesions–> destruction of bone tissue
Prostate–> osteosclerotic lesion–> increased bone production, disorganised abnormal bone

Question 18

What do we mean by personalities of malignant tumours?

Answer 18

Some neoplasms are very aggressive and metastasise early on, some almost never metastasise
Small carcinoma of bronchus–> aggressive–> widespread systemic metastases or locally advanced
Basal cell carcinoma–> rarely
Likelihood related to size of primary neoplasm

Question 19

What do we mean by evasion of the host defence?

Answer 19

Tumour cells recognised by immune system as non-self and destroyed
Mediated by predominantly cell mediated mechanisms
Tumour antigens on MHC –> CD8+ cytotoxic T cells recognise
Immunosupressed patient&raquo_space;cancer risk
Immunocompetent patients–> tumours can avoid the immune system–> via several mechanisms

Question 20

In immunocompetent patients how do tumour cells avoid the immune system?

Answer 20

Loss or reduced expression of histocompatibility antigens
Expression of certain factors that suppress the immune system
Failure to produce tumour antigen

Question 21

What is the concept behind immunotherapy agents?

Answer 21

Drugs optimise immune system

Immune system can help clear cancers

Question 22

What are the classes of effects that neoplasms can have on the host?

Answer 22

Direct local effects –> due to primary or secondary neoplasm
Indirect systemic effect–> increasing tumour burden, secreted hormones and/or miscellaneous effects –> paraneoplastic syndrome

Benign tumours–> local effects from primary and hormonal effect most relevant

Question 23

What are the local effect of neoplasms?

Answer 23

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

Question 24

What are the systemic effects of neoplasia?

Answer 24

Increasing tumour burden–> parasitic effect on host
Secreted factors such as cytokines:
–> Reduce appetite and weight loss (cachexia)
–> Malaise
–> Immunosuppression (can be due to direct bone marrow destruction)
–> Thrombosis
Production of hormones
–> Usually benign tumours that are well differentiated

Question 25

What are the paraneoplastic syndromes?

Answer 25

Signs and symptoms that cannot be explained by the anatomical distribution of the tumour or by the hormones produced
Occurs in approximately 10% of people with cancers

Question 26

Why are paraneoplastic syndromes important?

Answer 26

Can be earliest presentation of occult neoplasm
Can cause significant clinical problems and be fatal
Can mimic metastatic disease and confound treatment

Question 27

What is hypercalcaemia?

Answer 27

High plasma calcium
Most common symptom
2 process
–> osteolysis (bone breakdown)–> primary myeloma or secondary metastases
OR
–> production of calcaemic humoral substances by extraosseous neoplasms

Question 28

What is meant by miscellaneous systemic effects?

Answer 28

Neuropathies affecting the brain and peripheral nerves
Skin problems such as pruritus and abnormal pigmentation –> increased production of hormones
Fever –> not septic but just get fever
FInger clubbing–> overgrown nail bed
Myositis –> weakness
Many others–> pathogenesis is poorly understood