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What are the most lethal features of a malignant neoplasm

What do they lead to

Invasion and metastasis, lead to increased tumour burden


Define Invasion and Metastasis

Invasion: Breach of 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


What are the 3 steps taken by a tumour in the process of Invasion and Metastasis

What must the cell do at all points?

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

Cells must evade immune destruction


What 3 things must be altered for Invasion to occur?

What happens to the cell as it makes these alterations?

- Adhesion
- Stromal Proteolysis
- Motility

Epithelial to mesenchymal transition (takes on a phenotype more akin to a mesenchymal/ stromal cell than an epithelial cell)


Describe how Adhesion is altered for Invasion of a tumour to occur in 2 ways

1. Reduction in E-Cadherin expression
2. Changes in Integrin expression


Describe how Stromal Proteolysis is altered for Invasion of a tumour to occur in 2 ways?

What happens to nearby non-neoplastic cells? What do these cells form?

- Altered expressions of proteases, mainly MMPs (Matrix metalloproteinases)

- Degrade basement membrane and stroma to allow for invasion

- Malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases

Non-neoplastic cells form a Cancer Niche


Describe how Motility is altered for Invasion of a tumour to occur in 1 way?

Changes in actin cytoskeleton


By what 3 routes does a tumour spread to distant sites?

- Blood
- Lymph
- Transcoelomic (Fluid in body cavities)


What is the greatest barrier to successful metastasis?

Failed colonisation of tumour at secondary site

(Most malignant cells lodge at secondary sites as tiny clinically undetectable cell clusters that either die or fail to grow into detectable tumours)


What are Micrometastases?
What do they cause?

Surviving microscopic deposits of malignant cells lodged at secondary sites, that fail to grow

Cause relapse of a malignant neoplasm


What is Tumour Dormancy?

The presence of many metastases in an apparently disease-free person


What 2 things determine the site of a metastasis

- Regional drainage of blood/ lymph or coelomic fluid
- ‘Seed and soil’ phenomenon


What is the “Seed and soil phenomenon’?

What can it explain?

The interactions between malignant cells and local tumour environment (the niche) at the secondary site

May explain the unpredictable distribution of blood-borne metastases


How do Carcinomas and Sarcomas spread to distant sites?

- Via Lymphatics first
- Via blood

- Via blood


What are the 4 common sites of blood-borne metastases

- Lung
- Bone
- Liver
- Brain


List the 5 common neoplasms that most frequently spread to bone

- Breast
- Bronchus
- Kidney
- Thyroid
- Prostate


Describe the majority of bone metastases

Describe the bone metastases caused by prostate cancer

Osteolytic lesions due to destruction of bone tissue

Osterosclerotic, as production of disorganised abnormal bone is increased


What do we mean by “ Malignant tumours have personalities”

Some malignant neoplasms are more aggressive and metastasise very early

(Small cell carcinoma of bronchus presents early with widespread systemic metasteses, Basal cell carcinoma of skin almost never metastasises)


What is the likelihood of metastasis related to

Related to size of primary neoplasm


What are 3 ways tumours can avoid the immune system?

- Loss of/ reduced expression of histocompatabilty antigens
- Expression of factors that suppress the immune system
- Failure to produce tumour antigen


Identify 5 local effects of Neoplasms

- Raised pressure (tumour growth or swelling)
- Compression of adjacent structures
- Obstruction of tubes and orifices
- Ulceration at surface leading to bleeding
- Direct invasion and destruction of normal tissue


List 12 systemic effects of Neoplasms

- Cachexia (Weakness and wasting of body)
- Malaise
- Immunosuppression
- Thrombosis
- Hormone production (by endocrine tumour)
- Neuropathies
- Skin problems (Pruritus, abnormal pigmentation)
- Fever
- Clubbing
- Myositis (Any condition causing muscle inflammation)
- Hypercalcaemia (most common)
- Paraneoplastic Syndromes


What is a Paraneoplastic Syndrome? (Affect 10% of people with cancer)

A set of signs and symptoms in a cancer patient, that can’t readily be explained by the anatomical distribution of the tumour OR by the production of hormones from the tissue in which the tumour arise


What are 3 significant things about Paraneoplastic syndromes

- May be the earliest manifestation of an occult neoplasm
- Can mimic metastatic disease
- Can confound treatment


What is an occult neoplasm?

A metastatic tumour whose primary site can’t be identified