Neoplasia 2 Flashcards
invasion
breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues
metastasis
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
benign tumours do not
invade or metastasise
multi-step journey of invasion
- Grow and invade at the primary site
- Enter a transport system and lodge at a secondary site
- Grow at the secondary site to form a new tumour (colonisation)
what does a carcinoma cell need in order to invade?
- Altered adhesion
- Stomal proteolysis
- Motility
adhesion
- 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)
stromal proteolysis
- 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
Malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases… this is called a
NICHE
motility- locomotion
- Detachment from contiguous cells- loss of cadherin
- Become loose from base- loss of integrin expression
- Increase in actin
How do carcinomas spread to distant sites?
- blood vessels
- lympathic vessels
- fluids in body cavities
lympathics
- E.g. axillary lymph nodes
- Breast cancer- women present with palpable axillary lymph nodes- due to normal drainage
fluid cavities - transcoelomic (across a cavity)
E.g. Ovarian cancer
If tumour invades through the ovarian wall it can seed itself of the peritoneal wall
as tumorus grow they can no longer reply on diffusion of nutrient alone
need angiogenesis
secondary site
- 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
what determiens the site of a secondary tumour?
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
seed and soil phenomenon
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
carcinomas tend to spread via ….. first
lympathics
sarcomas
spread via blood stream
common sites of blood borne metastasis
Lung
Bone
Liver
Brain
Common neoplasms that spread to the bone that can be detected on plain film and be the presenting system
Breast
Bronchus
Kidney
Thyroid
Prostate
Bone neoplasms
- 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
personalities of neoplasms
- 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
basal cell carcinomas
wont metastasise- but may spread signific and become locally destructive
Evasion of host defence
- 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
effects of tumours
local and systemic
local effects of neoplasm
- 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)
local effect of neoplasm int he brain
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
systemic effects of neoplasia
- 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
paraneoplastic syndrome
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
example of a paraneosplastic syndrome
hypercalcaemia
- most common cause
- 2 proceses:
- Osteolysis- indcued by cancer due to either primary bone lesions such a myeloma or seocdnary metastases
- Production of calcaemic humoral substance by extraosseous neoplasm (out of the bone- e.g. small cell in lungs)
misc systemic effects of neoplasia
- Neuropathies affecting brain and peripheral nerves
- Skin problems e.g. pruritus and abnormal pigmentation
- Fever
- Clubbing
- presenting sign of lung cancer
- Myositis
