Neoplasia 2

Question 0

Describe the process that leads to metastasis

Answer 0

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)
   The cells must evade by destruction of immune cells

Question 1

Define the terms ‘invasion’ and ‘metastasis’

Answer 1

Invasion - the ability of cells to break through the basement membrane and spread
Metastasis - the spread of a malignant tumour to a distant site
Leads to a greatly increased tumour burden

Question 2

Describe the alterations needed for invasion

Answer 2

Altered adhesion - reduction in E-cadherin and integrin expression
Altered proteolysis - matrix metalloproteinases digest ECM
Altered motility - changes in actin cytoskeleton
Angiogenesis
Epithelial-to-mesenchymal-transition (EMT)
Malignant cells form a cancer niche (stroma, fibroblasts, endothelial, inflammatory) that provide some growth factors and proteases.

Question 3

Describe the routes and common sites of metastasis

Answer 3

Blood vessels:
Capillaries, venules, no muscle coat, leaky vessels
Common sites - lung, liver, bone, brain
Lymphatic vessels:
Basement membrane not well formed, spread to local and distant lymph nodes, frequent route of spread of carcinomas, can involve lymphatics of lung
Fluid in body cavities:
Pleura, peritoneal, pericardial, cerebrospinal, transcoelomic spread

Question 4

Describe the local effects of benign and malignant neoplasms

Answer 4

Benign:
Compression of adjacent structures
Blocking tubes and orifices (obstruction)
Ulceration of surface mucosa
Space occupying lesion (brain)
Malignant:
Direct invasion and destruction of normal tissue
Blocking tubes and orifices (obstruction)
Ulceration at a surface leading to bleeding –> anaemia
Infiltration around and into nerves, blood vessels, lymphatics
Space occupying lesions (brain)

Question 5

Describe the systemic effects of benign and malignant neoplasms (paraneoplastic)

Answer 5

Increasing tumour burden leads to a parasitic effect on the host, metabolic burden. Cytokines may contribute to reduced appetite, weight loss, malaise, immunosuppresion and thrombosis.
Haematological - anaemia, low white cells and platelets, thrombosis
Endocrine - excessive secretion of hormones, ectopic hormone secretion
Skin - increased pigmentation, pruritis (itching), herpes zoster,
Neuromuscular - problems with balance, sensory neuropathies, myopathy, myasthenia

Question 6

Explain micrometastasis and what determines the site of a tumour

Answer 6

Micrometastasis - malignant cells lodge at a secondary site but fail to grow into clinically detectable tumours, due to immune attack, reduced angiogenesis or a hostile secondary site. An apparently disease free person may harbour many micrometastasis (dormancy).
The site of a secondary neoplasm depends on regional drainage and the local tumour environment (seed and soil)