Neoplasia 2

Question 1

invasion

Answer 1

breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues

Question 2

metastasis

Answer 2

spread of tumour to sites that are physically discontinuous from the primary tumour.

• Unequivocally marks a tumour as malignant
• Each metastasise can create their own metastasise

Question 3

benign tumours do not

Answer 3

invade or metastasise

Question 4

multi-step journey of invasion

Answer 4

1. Grow and invade at the primary site
2. Enter a transport system and lodge at a secondary site
3. Grow at the secondary site to form a new tumour (colonisation)

Question 6

what does a carcinoma cell need in order to invade?

Answer 6

• Altered adhesion
• Stomal proteolysis
• Motility

Question 7

adhesion

Answer 7

• Reduction in E-cadherin expression (these hold cells in their position next to other cells)
• Changes in Integrin expression (holds the cell to basement membrane)

Question 8

stromal proteolysis

Answer 8

• Altered expression of proteases, notably matrix metalloproteinases (MMPs)
• Degrade basement membrane and stroma to allow for invasion
• Malignant cells take advantage of nearby non-neoplastic cells, which provide GF and proteases

Question 10

Malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases… this is called a

Answer 10

NICHE

Question 11

motility- locomotion

Answer 11

1. Detachment from contiguous cells- loss of cadherin
2. Become loose from base- loss of integrin expression
3. Increase in actin

Question 12

How do carcinomas spread to distant sites?

Answer 12

• blood vessels
• lympathic vessels
• fluids in body cavities

Question 13

lympathics

Answer 13

• E.g. axillary lymph nodes
• Breast cancer- women present with palpable axillary lymph nodes- due to normal drainage

Question 14

fluid cavities - transcoelomic (across a cavity)

Answer 14

E.g. Ovarian cancer

If tumour invades through the ovarian wall it can seed itself of the peritoneal wall

Question 15

as tumorus grow they can no longer reply on diffusion of nutrient alone

Answer 15

need angiogenesis

Question 16

secondary site

Answer 16

• At the secondary site the malignant cells have to grow- colonisation
• Failed colonisation is considered to be the greatest barrier to successful metastasis
• Most malignant cells lodge at secondary sites as tiny clinically undetectable cell clusters that either die or fail to grow into detectable tumours
• Surviving microscopic deposits that fail to grow are called micro metastases

Question 17

what determiens the site of a secondary tumour?

Answer 17

Regional drainage of blood, lymph of caulomic fluid

• For lymphatic metastasis this is predictably draining lymph nodes
  
  • Breast cancer goes to the ipsilateral axillary lymph nodes
• For transcoelemic spread this is predictably to other areas in the coelomic space or to adjacent organs
• For blood-borne metastasis this sometimes (but not always) to the next capillary bed that the malignant cells encounter
  
  • Lung cancers love to metastise to the adrenal gland

Question 18

seed and soil phenomenon

Answer 18

A theory proposed to explain the metastatic preference of cancer cells for specific organs is called the “seed and soil” theory, the cancer cells being the “seeds” and the specific organ microenvironments being the “soil.” Interaction between the “seeds” and the “soil” determines the formation of a secondary tumor.

• May explain the unpredictable distribution of blood born metastases
• Due to interactions between malignant cells and the local tumour environment at the secondary site

Question 19

carcinomas tend to spread via ….. first

Answer 19

lympathics

Question 20

sarcomas

Answer 20

spread via blood stream

Question 21

common sites of blood borne metastasis

Answer 21

Lung

Bone

Liver

Brain

Question 22

Common neoplasms that spread to the bone that can be detected on plain film and be the presenting system

Answer 22

Breast

Bronchus

Kidney

Thyroid

Prostate

Question 23

Bone neoplasms

Answer 23

• Majority are osteolytic lesions due to destruction to the bone tissue
• Prostate cancer actually causes osteosclerotic metastases as it caused increased production of disorganised abnormal bone

Question 24

personalities of neoplasms

Answer 24

• Some malignant neoplasms are more aggressive and metastasise very early in their course
• Small cell carcinoma of the bronchus for example is very aggressive and presents early with widespread systemic metastases or is at the very least locally advanced
• Others almost never metastasise e.g. basal cell carcinoma of the skin

Question 25

basal cell carcinomas

Answer 25

wont metastasise- but may spread signific and become locally destructive

Question 27

Evasion of host defence

Answer 27

• Tumour cells can be recognised by the immune system as non self (presented on MHC I- CD* T cells
• This is mediated predominantly cell mediated mechanisms
• Immunosuppressed patients are at increased risk for the development of cancer
• However in immunocompetent patients tumours can avoid the immune system via several mechanisms
  
  • Loss or reduced expression of histocompatibility antigens
  • Expression of certain factors that suppresses the immune system
  • Failure to produce tumour antigen
• This is the current concepts behind immunotherapy agents

Question 28

effects of tumours

Answer 28

local and systemic

Question 29

local effects of neoplasm

Answer 29

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

Question 30

local effect of neoplasm int he brain

Answer 30

Brain starts to herniates (skull means nowhere else to go) through natural barriers and can be pushed down into the brainstem respiratory/ cardiac depression and death

Question 31

systemic effects of neoplasia

Answer 31

• Increased tumour burden results in a parasitic effect on the host
• Together with secreted factors such as cytokines
  
  • Reduced appetite and weight loss (Cachexia)
  • Malaise
  • Immunosuppression (as we get an increase in tumour burden)
  • Thrombosis
• Production of hormones
  
  • Usually benign tumours

Question 32

paraneoplastic syndrome

Answer 32

Some cancer bearing individuals develop signs and symptoms that cannot readily be explained by the anatomic distribution of the tumour or by the production of hormones from the tissue in which the tumour arose

• Affects approx. 10% of people with cancer
• Important because
  
  • May be the earliest manifestation of an occult neoplasm
  • Can case signif clinical problems and be fatal
  • Can mimic metastatic disease and confound treatment

Question 33

example of a paraneosplastic syndrome

Answer 33

hypercalcaemia

• most common cause
• 2 proceses:

1. Osteolysis- indcued by cancer due to either primary bone lesions such a myeloma or seocdnary metastases
2. Production of calcaemic humoral substance by extraosseous neoplasm (out of the bone- e.g. small cell in lungs)

Question 34

misc systemic effects of neoplasia

Answer 34

• Neuropathies affecting brain and peripheral nerves
• Skin problems e.g. pruritus and abnormal pigmentation
• Fever
• Clubbing
  
  • presenting sign of lung cancer
• Myositis