MoD S10 - Neoplasm II Flashcards
What is the most lethal feature of malignant neoplasms?
Their ability to invade and spread to distant sites leading to greatly increased tumour burden
Untreated this results in a vast amount of ‘parasitic malignancy’
Can benign tumours metastasise?
Nope
Describe the process of metastasis in brief
For malignant cells to travel to a secondary site they must:
- Grow and invade at primary site
- Enter a transport system and lodge at secondary site
- Grow at secondary site to form a new tumour
At all points must evade immune destruction
In what tumour types is metastasis studied (mainly)?
Carcinoma
What cell behaviour changes are necessary for invasion of a malignant cell into a tissue?
Invasion of carcinomas requires:
- Altered adhesion
- Stromal proteolysis
- Motility
- Angiogenesis
These cells appear more mesenchymal than epithelial now, so this is called the epithelial to mesenchymal transition (EMT)
What are the genetic causes of the epithelial to mesenchymal transition?
Altered adhesion:
- To other carcinoma cells via reduced E-cadherin expression
- To stromal proteins via altered integrin expression
Stromal proteolysis:
- Altered expression of proteases, notably matrix metalloproteinases
- MMPs digest collagen allowing metastatic cell to digest ECM and break through basement membrane
- MMP 1 = type I collagen
- MMP 2/9 = type IV
Motility:
- Changes in the actin cytoskeleton
Angiogenesis:
- Once a tumour reaches 1 - 2 mm3 it must form new blood vessels or will turn hypoxic, restricting growth
- Must upregulate pro-angiogenesis factors (E.g. angiopoietin, VEGF)
- Thin walled vessels created provide easy route for metastasis
What is a cancer niche?
How is it helpful to malignant cells?
Malignant cells and surrounding non-neoplastic cells form a cancer niche, a cancer permissive microenvironment
Malignant cells take advantage of other non-neoplastic cells in the niche to provide proteases and growth factors
What transport routes are available for metastasis?
Malignant cells enter:
- Blood vessels via capillaries and venules
- Lymphatic vessels
- Fluid in the body cavities (pleural, peritoneum, brain ventricles) this is also known as transcoelomic spread
What is colonisation in reference to malignancy?
At secondary sites where malignant cells grow, they colonise
What are the outcomes of malignant colonisation?
Growth of malignant cells at secondary site to form a metastases
Failure to grow or death
Failure to grow and survival, leading to small malignant cell deposits known as micrometasases
What is the consequence of micrometastases formation?
Tumour dormancy:
- An apparently disease free person may harbour many micrometastases
Malignant neoplasm can then relapse (even after years) when they start to grow
What does the site of secondary tumours depend on?
Regional drainage of blood, lymph or coelomic fluid:
- Blood borne most likely to lodge in next capillary bed
- Transcoelomic to other areas in coelom or adjacent organs
- Lymph borne drain into lymph nodes
Seed and soil phenomenon:
- Certain tumours ‘seed’ certain organs with micrometastases (organotropism)
- Must be a secondary site with favourable conditions (a suitable niche can then be set up)
Give an example of the seed and soil phenomenon
Stomach cancer often metastasises to the ovaries
Colon cancer often metastasises to the liver
By which routes do carcinoma and sarcoma typically spread?
Carcinoma
- First into lymphatics and lymph nodes
- Then turns blood borne and spreads to distant sites
Sarcoma:
- Spreads initially via blood
Where are some common sites of blood borne metastases?
Include the locations/tumour types the metastasis is commonly from at each site of metastasis
Lungs:
- Wide range of malignancies
- Sarcomas (osteosarcoma)
- Carcinomas (breast, stomach)
- Kidney
- Testis
Bone:
- Carcinomas (bronchial, breast, thyroid)
- Can cause dense bone (osteosclerosis)
Liver
- Common site of carcinomas from large intestine (portal vein)
- Carcinomas (bronchial, breast)
Brain:
- Cause wide range of neurological symptoms and act as space occupying lesions
- Metastasis common from bronchial, breast and testicular carcinoma as well as melanoma
What neoplasms most frequently spread to bone?
Breast Bronchus Kidney Thyroid Prostate
How do malignant tumours vary in ‘aggressiveness’?
Some metastasise early in their course:
- Small cell bronchial carcinoma
Others almost never metastasise:
- Basal cell carcinoma
What is likelihood of metastasis of a tumour related to?
Size of primary tumour
This is the basis of cancer staging
How can the effects of neoplasm on the host be classified?
Direct local effects:
- Due to primary or secondary tumours
Indirect systemic effects:
- E.g. Hormonal effects
These effects are sometimes referred to as paraneoplastic syndromes
For benign neoplasm, what effects on the host are most relevant?
Local effects
Hormonal effects
Give some of the causes of local effects of neoplasms
Direct invasion and destruction of tissue (malignant only)
Ulceration of surface and bleeding
Compression of adjacent structures (pressure atrophy)
Blocking of tubes and orifices
What are some of the systemic effects of neoplasm?
BIG card
Increasing tumour burden (Malignant specific):
- Cachexia (decreased appetite and weight loss)
- Malaise
- Immunosuppression (Can be due to direct bone marrow destruction)
Endocrine (commonly benign):
- Well differentiated so often produce hormones
- Thyroid adenoma = Thyroxine
- Bronchial small cell carcinoma = ACTH or ADH
Neuromuscular:
- Problems with balance
- Sensory/sensorimotor neuropathy
- Myopathy and myasthenia
Skin problems:
- Increased pigmentation
- Pruritis
- Herpes zoster
- Dermatomyositis
Pyrexia
Haemotological:
- Anaemia (bone marrow infiltration, leukaemia)
- Low WBC and platelets (BM infiltration + treatments)
- Thrombosis (pancreatic carcinoma)
Give an example of a benign and malignant tumour that can cause hypercalcaemia and include mechanism(s)
Benign = Parathyroid adenoma:
- Increased PTH production
- Increased Ca2+ release from bone
- Increased Ca2+ re-uptake from kidneys
- Increased Ca2+ absorption in intestines
Malignant = Bronchial squamous cell carcinoma
- Primary or secondary tumour causes osteolysis
- Increased Ca2+ release from bone into blood
- OR
- Humoral hypercalcaemia as above (PTH-rP more likely mediator)
Define Cachexia
Loss of weight, muscle atrophy, loss of appetite in someone not actively trying to lose weight
What factors are involved in the development of cancer cachexia?
TNF
IL-1
IL-6
No precise mechanism known.
How do neoplasms kill people?
Local effects:
- Raised intracranial pressure
- Perforation
- Haemorrhage
Systemic effects:
- Replacement of essential body organs (E.g. bone marrow, lung tissue, liver)
