MoD S10 - Neoplasm II Flashcards Preview

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Flashcards in MoD S10 - Neoplasm II Deck (26)
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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?



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)?



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

- Changes in the actin cytoskeleton

- 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?

- First into lymphatics and lymph nodes
- Then turns blood borne and spreads to distant sites

- 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

- Wide range of malignancies
- Sarcomas (osteosarcoma)
- Carcinomas (breast, stomach)
- Kidney
- Testis

- Carcinomas (bronchial, breast, thyroid)
- Can cause dense bone (osteosclerosis)

- Common site of carcinomas from large intestine (portal vein)
- Carcinomas (bronchial, breast)

- 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?



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

- Problems with balance
- Sensory/sensorimotor neuropathy
- Myopathy and myasthenia

Skin problems:
- Increased pigmentation
- Pruritis
- Herpes zoster
- Dermatomyositis


- 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?


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)