14. Neoplasia 2 Flashcards
What is tumour burden?
Refers to the total amount of cancer tissue in the body
What are the most lethal features of malignant neoplasms?
Invasion and metastasis
Compare invasion and metastasis
Invasion:
Breach of the 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. Unequivocally marks a tumour as malignant
What are the 3 stages of invasion and metastasis?
(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
What is neoplastic growth at a secondary site called?
Colonisation
How efficient in invasion and metastasis?
whole process is inefficient - THE CELLS MUST EVADE DESTRUCTION BY IMMUNE CELLS
What 3 alteration occur in cancer cells for invasion to occur, what is this change called and why?
INVASION INTO SURROUNDING TISSUE BY CARCINOMA CELLS REQUIRES:
altered adhesion, stromal proteolysis and motility
Epithelial-to-mesenchymal transition (EMT): three changes together create a carcinoma cell phenotype that sometimes appears more like a mesenchymal cell than an epithelial cell. the 3 changes allow the cancer cell to detach from other cells and invade
What does altered adhesion in malignant cells involve?
Between malignant cells: reduction on E-cadherin expression
Between malignant cells and stromal protein: changes in Integrin expression
What does altered stromal proteolysis in malignant cells involve?
Altered expression of proteases, notably matrix metalloproteinases (MMPs)
• Malignant cells take advantage of nearby non-neoplastic cells, which provide growth factors and proteases, , WHICH TOGETHER FORM A CANCER NICHE
Why is altered stromal proteolysis important?
Cells must degrade basement membrane and stroma to invade
What does altered motility of malignant cells involve?
Involves changes in the actin cytoskeleton
What is a cancer niche?
a supportive network for cancer cells to invade:
a combination of stroma, fibroblasts, endothelial cell, inflammatory cells
How does signalling through integrins occur in malignant cells?
Via small G proteins such as members of Rho family
What are the 3 different routes malignant cells can be transported?
(1) blood vessels via capillaries and venules;
(2) lymphatic vessels;
(3) fluid in body cavities
Give examples of fluid filled body cavities that malignant cells can metastasise through.
pleura, peritoneal, pericardial and brain ventricles
What is metastasise through fluid filled cavities called?
transcoelomic spread
What is the greatest barrier to successful metastasis of malignant cells?
Failed colonisation
What are micrometastases?
Surviving microscopic deposits of malignant cells that fail to grow at a secondary site
- tumour dormancy
What is tumour dormancy?
Cells cease dividing but survive in a quiescent state while waiting for appropriate environmental conditions to begin proliferation again
why do tumours need to build their own vasculature?
As the tumours grow, middle cells become hypoxic so need new blood vessels - this means there is more opportunity for metastasis via the vessels - angiogenesis
Where are the two most common sites of blood borne metastasis and why?
Lungs and liver as they have vast capillary beds that drain blood from various sites in the body
What is the common cause of malignant neoplasm relapse?
typically due to one or more micrometastases starting to grow
Why are organ donations not accepted from a cancer/previous cancer patient?
Could have micrometastases that may start to grow post transplant - particularly common with metastatic melanoma
- especially due to immunosuppression after surgery
What determines the site of a secondary tumour?
- Regional drainage of blood, lymph or coelomic fluid
2. “seed and soil” phenomenon
Where would you expect secondary site of a lymphatic metastasis to be?
to draining lymph nodes
Where would you expect secondary site of a transcoelomic metastasis to be?
Other areas in the coelomic space or to adjacent organs
Where would you expect secondary site of a blood-borne metastasis to be?
Sometimes (but not always) to the next capillary bed that the cells encounter (e.g. lungs, hepatic portal system)
What is the seed and soil phenomenon?
Is due to interactions between malignant cells and the local tumour environment (i.e. the niche) at the secondary site - the cancer cells need to be able to reach the site and have a hospitable environment to survive
- explains the seemingly unpredictable distribution of blood-borne metastases,
What is the common route of spread in carcinomas?
Typically spread first to draining lymph nodes and then to blood-borne distant sites
Where are the common sites of blood borne metastasis?
lung, bone, liver and brain
What is the common route of spread in sarcomas?
via blood stream
Which neoplasms most frequently spread to bone?
Breast, bronchus, kidney, thyroid and prostate
Majority are osteolytic lesions due to destruction of
the bone tissue.
Prostate cancer actually causes osteosclerotic
metastases as it causes increased production of
disorganised abnormal bone
Which neoplasms most frequently spread to adrenal glands?
lung
What is the difference between grade and stages in consideration to tumours?
Grade: marker of differentiation and suggests that a tumour is more likely to behave aggressively
Stage: looking at how far the tumour has spread:
Tumour - marker of how far it has spread locally
Nodal metastasis - marker of how many lymph node metastasis there are and which lymph node groups are involved
Metastasis distant - solid organs not lymph nodes
What are malignant neoplasm personalities?
Some malignant neoplasms are more aggressive and metastasise very early in their course (e.g. small cell bronchail carcinoma)
Others almost never metastasise, e.g. basal cell carcinoma of the skin
How are effects of neoplasms classified?
Direct local effects: by primary neoplasm and/or the secondary neoplasm
Indirect systemic effects:
• Increasing tumour burden
• Secreted hormones
• Miscellaneous effects
What does indirect systemic effects of neoplasms include and what are these referred to as?
Include effects of increasing tumour burden, secreted hormones and/or miscellaneous effects
Referred to as paraneoplastic syndromes
What are the most relevant effects of benign neoplasms?
Local effects from the primary and indirect hormonal effects
What are local effects of primary and secondary neoplasms due to?
(1) direct invasion and destruction of normal tissue;
(2) ulceration at a surface leading to bleeding;
(3) compression of adjacent structures and
(4) blocking tubes and orifices
5. Raised pressure due to tumour growth or swelling
(brain)
What are the systemic effects of neoplasia?
• Increased tumour burden results in a parasitic effect on the host
• Together with secreted factor such as cytokines
– Reduced appetite and weight loss (cachexia)
– Malaise
– Immunosuppression
– Thrombosis
• Production of hormones
– Usually benign tumours
• Hypercalcaemia
– Probably the most common
Give an example of benign neoplasm of endocrine gland.
Thyroid adenoma
- benign neoplasms usually well differentiated so produce hormones
Give an examples of malignant neoplasm of endocrine gland.
- bronchial small cell carcinoma can produce ACTH or ADH
- bronchial squamous cell carcinoma can produce a
PTH-like hormone
Explain how tumours can cause hypercalcaemia as a systemic effect
- Osteolysis – induced by cancer due to either primary bone lesions such as myeloma or secondary metastases
- Production of calcaemic humoral substances by extraosseous neoplasms
What are Paraneoplastic Syndromes?
Some cancer bearing individuals develop signs and symptoms that cannot readily be explained by the
anatomic distribution of the tumour or by then production of hormones from the tissue in which the tumour arose.
Important because:
• May be the earliest manifestation of an occult neoplasm
• Can cause significant clinical problems and be fatal
• Can mimic metastatic disease and confound treatment
What are some miscellaneous systemic effects of neoplasms?
- neuropathies affecting the brain and peripheral nerves
- skin problems such as pruritis and abnormal pigmentation
- fever
- finger clubbing - commonly in lung cancer
- myositis
How does our body fight tumours?
- Tumour cells can be recognised by the immune system as non-self and destroyed.
- This is mediated by predominantly cell mediated mechanisms
- Tumour antigens are presented on the cell surface of major histocompatibility complex molecules and are recognised by CD8 + cytotoxic T cells
in immunocompetent patient’s how can tumours avoid the immune system?
– The loss or reduced expression of histocompatibility antigens
– Expression of certain factors that suppresses the immune system
– Failure to produced tumour antigen
