Flashcards in Neoplasia 2 Deck (25)
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?
- Stromal Proteolysis
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?
- 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
List the 5 common neoplasms that most frequently spread to bone
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)
- Hormone production (by endocrine tumour)
- Skin problems (Pruritus, abnormal pigmentation)
- 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