L15: Neoplasia 2 Flashcards Preview

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Flashcards in L15: Neoplasia 2 Deck (28)
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1
Q

Define invasion?

A

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

2
Q

Define metastasis?

A

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

3
Q

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

A
  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
4
Q

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

A

Requires altered adhesion
Stromal proteolysis
Motility

5
Q

What is the phenotype of these new carcinoma cells?

A

More like a mesenchymal cell (more unspecialised)

Epithelial to mesenchymal transition

6
Q

What happens to the cells during altered adhesion?

A

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

7
Q

What is meant by stromal proteolysis?

A

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

8
Q

What allows the cells to move?

A

Changes to the actin cytoskeleton

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

9
Q

How do malignant cells travel to distant sites?

A

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

10
Q

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

A

Colonisation–> growth of the cells

11
Q

Why do most metastasis fail to develop?

A

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

12
Q

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

A

Micrometastases

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

13
Q

Why do apparently cured malignant neoplasms relapse?

A

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

14
Q

What determines the site of a secondary tumour?

A

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

15
Q

What is the difference in spread between carcinomas and sacromas?

A

Carcinomas (epithelial) –> lymphatics

Sarcomas (stromal) –> blood stream

16
Q

What are the common sites for blood-borne metastasis

A

Lung, bone, liver and brain

17
Q

Which neoplasms commonly spread to bone?

A

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

18
Q

What do we mean by personalities of malignant tumours?

A

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

19
Q

What do we mean by evasion of the host defence?

A

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

20
Q

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

A

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

21
Q

What is the concept behind immunotherapy agents?

A

Drugs optimise immune system

Immune system can help clear cancers

22
Q

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

A

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

23
Q

What are the local effect of neoplasms?

A
  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)
24
Q

What are the systemic effects of neoplasia?

A

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

25
Q

What are the paraneoplastic syndromes?

A

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

26
Q

Why are paraneoplastic syndromes important?

A

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

27
Q

What is hypercalcaemia?

A

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

28
Q

What is meant by miscellaneous systemic effects?

A

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