Neoplasia 2

Question 1

Invasion define

Answer 1

breach of basement membrane

progressive infiltration and destruction of surrounding tissues

Question 2

3 step journey for metastasis

Answer 2

Grow and invade at primary site
Enter transport system (lodge at secondary)
Grow at secondary site and form new tumour

Question 3

Invasion needs (3 things)

Answer 3

Altered adhesion
Stromal proteolysis
Motility

(epithelial to mesenchymal transition) - change of phenotype

Question 4

How is altered adhesion achieved?

Answer 4

Reduced E-cadherin expression (looser attachments to eachother)
Changes to integrin expression (looser attachments to basement membrane)

Question 5

How is stromal proteolysis achieved?

Answer 5

Altered expression of proteases - MATRIX METALLOPROTEINASES

= degrading stroma and basement membrane allows invasion

Question 6

What is the ‘niche’?

Answer 6

Stroma, fibroblasts, endothelial cells and inflammatory cells present - non neoplastic cells

Malignant cells take advantage and use GF and proteases

Question 7

How is motility achieved?

Answer 7

Changes in cytoskeleton

Question 8

How does neoplasm spread to second site?

Answer 8

Blood vessels (haematogenous spread)
Lymphatic vessels
Fluid in body cavities (transcoelomic spread)

Question 9

Barrier to successful metastasis

Answer 9

Failed colonisation

Instead lodge at secondary sites as tiny clinically undetectable cell clusters

Question 10

What are micrometastases?

Answer 10

Microscopic deposits of tumours that fail to grow

Question 11

What determines site of secondary tumours?

Answer 11

Regional drainage (blood, lymph or coelomic fluid)

eg breast cancer can cause enlarged axillary lymph nodes

Question 12

Transcoelemic spread determined by

Answer 12

Other areas in coelemic space (eg within pleural sac) or adjacent organs

Question 13

Blood borne metastasis spread

Answer 13

next capillary bed (lungs and liver common)

Question 14

What is seed and soil phenomenon

Answer 14

Explains unpredictable distribution of blood borne metastases
Interaction of malignant cell and tumour environment (seed is tumour, niche is soil)

Question 15

Which cancers spread via which routes?

Answer 15

Carcinoma = lymphatics first
Sarcomas = blood stream first 

(common sites - lung, bone, liver and brain)

Question 16

What should you think if there is malignant tumour found in bone?

Answer 16

Usually as a result of metastasis (from breast, prostate, bronchus, kidney or thyroid)

Question 17

Metastases to bone features

Answer 17

Haematogenous spread usually
Axial skeleton (skull, spine, pelvis)
Asymptomatic or pain is only symptom
Pathological fractures seen

Question 18

What do most cancers cause in bone?

Answer 18

Osteolytic lesions - destruction of bone tissue

Question 19

What cancer has opposite effects and causes osteosclerotic metastases due to increase production of bone?

Answer 19

Prostate cancer

very white blobby x ray

Question 20

Personalities of malignant neoplasms

Answer 20

Small cell carcinoma of bronchus - very aggressive
Basal cell carcinoma of skin - often does not metastasise

Benign neoplasms often slow growing, chilled

Question 21

How does body protect against tumour cells?

Answer 21

Recognised by immune system as non-self (cell mediated mechanism)
Tumour antigens presented by MHC to CD8+ cytotoxic T cells

Question 22

Problems with immunity protection against tumours

Answer 22

Immunosuppressed more at risk (transplant patients)

Tumours can avoid immune system

Question 23

How can tumours avoid immune system?

Answer 23

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

Question 24

Effects of neoplasms

Answer 24

direct local
Systemic effects:
Increase tumour burden (metabolism increased)
Secretion of hormones
Unexplained effects

Question 25

Local effects neoplasm

Answer 25

Direct invasion and destruction of tissue Ulceration --> bleeding Compression of adjacent structures Blocking tubes/orifices Raised pressure due to tumour growth/swelling (brain)

Question 26

Systemic effects neoplasia

Answer 26

Parasitic effect on host ``` Secreted cytokines and tumour: Reduce appetite and weight loss Malaise Immunosuppression Thrombosis (hypercoagulative state) ``` Production of hormones (usually benign)

Question 27

What are paraneoplastic syndromes?

Answer 27

Development of signs/symptoms that cannot be explained by distribution of tumour or by production of hormones from tissue that tumour arose from (bodies response to tumour)

Question 28

Why is paraneoplastic syndrome important?

Answer 28

Earliest sign Significant clinical problems/fatal Affect treatment

Question 29

Paraneoplastic examples

Answer 29

Hypercalcaemia | Syndrome of inappropriate ADH secretion

Question 30

Hypercalcaemia (why?)

Answer 30

Osteolysis (cancer induces via primary bone lesions or secondary) Production of calcaemic humoral substances (PTHrP)

Question 31

SIADH

Answer 31

``` Small cell lung cancer Causes hyponatraemia (sodium diluted with lots of water) ```

Question 32

Micellanoeus neoplastic symptoms

Answer 32

Neuropathies (CNS and PNS) Skin problems (pruritus, abnormal pigmentation) Fever Clubbing Myositis (muscle inflammation = weak tired and painful) Hypoglycaemia (some secrete insulin?)