13 - Neoplasia 2 Flashcards
What is a tumour burden?
- When malignant cells acquire the ability to invade and spread to distant sites, this leads to ‘parasitic’ malignant cells
- Once primary tumour removed, tumour can reappear in other sites due to metastases
How do malignant cells get from a primary site to a secondary site and what difficulties do the cells face?
- Grow and invade at primary site
- Enter a transport system and lodge at secondary site
- Grow at secondary site and form tumour (colonisation)
At all stages they can be destroyed by immune cells
How does invasion of malignant cells to surrounding tissue occur in general and what happens to the name of these cells when these cellular changes occur?
- Altered adhesion
- Stromal proteolysis
- Motility
Carcinoma cell appears more like a mesenchymal cell than epithelial so this is called epithelial-to-mesenchymal transition (EMT)
How does altered adhesion occur in malignant cells?
- Reduction in e-cadherin expression between the malignant cells
- Reduction in integrin expression between malignant cell and stroma
How does proteolysis of the basement membrane occur in malignant cells and what can these cells do once they have broken down the basement memrbane?
- Cells express matrix metalloproteinases (MMPs) to degrade basement membrane and stroma
- Malignant cells grow with nearby non-neoplastic cells to form a cancer niche. Non-neoplastic cells can provide growth factors and proteases
- Malignant cells secrete local mediators to recruit this cancer niche
How does altered motility of the malignant cells occur?
- Changes in actin cytoskeleton
- Actin interacting with integrins. Signalling occurs through integrins via small G proteins such as members of the Rho family (RAS)
How can malignant cells be transported to different sites, the transport systems)
Angiogenesis and lympogenesis can occur when the tumour is establishing which help it to spread
What is the greatest barrier to the formation of a metastasis?
- Colonisation
- Tiny malignant cell clusters lodge at secondary sites and either die or fail to grow. However, surviving microscopic deposits can remain and form micrometastases
Why can a person have a tumour removed and then have a malignant neoplasm relapse a few years later?
Person may have many micrometastases that cannot be detected clinically and they grow. This is tumour dormancy
How can you predict the site of a secondary tumour?
- Depends on the mode of transport of the malignant cells
- Blood-borne metastases are harder to predict (regional drainage or seed and soil theory)
Why do we get tumour dormancy?
Why do blood bourne metastases normally lodge in the lung and the liver?
They travel in the blood and the lung is the first area with a capillary bed, small vessels where it can lodge
What is the seed and soil hypothesis of metastasis?
- Cancer cells are seeds and the organ the seed interacts with is the soil
- Explains why metastases only occur in some areas, e.g more in the bone than the spleen, as they harbour a better environment for the cells
- Distant metastasis is not as unpredictable as we think
How do carcinomas and sarcomas typically spread in the body?
- Carcinomas by lymphatics
- Saarcomas by blood stream
What are common sites of blood-bourne metastases?
- Lung
- Bone
- Liver
- Brain
What neoplasms most frequently form secondary’s in the bone?
- Prostate
- Breast
- Bronchus
- Kidney
- Thyroid
What are the four stages of a cancer?
Depends on how far the spread is, local being lymph nodes locally, stage 4 being blood spread
What does it mean by malignant neoplasms have ‘personalities’?
- Different neoplasms have different characteristics
- E.g small cell bronchial carcinoma metastasise early in their cours but basal cell carcinoma almost never metastasises
- Likelihood of metastasis depends on the size of the primary tumour
What are the effects of neoplasms on the body in general?
Benign usually only due to local primary effects and hormones
What are paraneoplastic syndromes?
A set of signs and symptoms that is the consequence of cancer in the body, but unlike mass effect, is not due to the local presence of cancer cells.
What are some local effects of neoplasms?
- Direct invasion and destruction of normal tissue
- Ulceration of surface leading to blleding
- Compression of adjacent structures
- Blocking of tubes/openings
What are some systemic effects of malignant neoplasms?
Burden: Reduced appetite, weight loss, cachexia, malaise, immunosuppression (can also be due to direct bone marrow destruction), thrombosis
Hormone: Paraneoplastic syndromes due to well differentiation and secreting hormones (mainly benign)
Misc: Neuropathies of brain and peripheral nerves, skin problems such as pruritis and abnormal pigmentation, fever, finger clubbing and myositis
DUE TO CYTOKINES AND INCREASING TUMOUR BURDEN
What is a polyp?
A small benign growth typically found on a mucous membrane
What is a leiomyoma?
- Fibroids
- Benign growth of smooth muscle, mainly in the uterus, small bowel and oesophagus
What type of tumour of this, what is its cell of origin, where is it found and how does it behave?
- Teratoma (Dermoid cyst)
- Typically in skull, ovary, face, tailbone
- Arise from germ cells and contain mainly skin. They are benign in ovaries but often malignant in the testes so well differentiated in ovaries
What is a struma ovarii?
Goitre of the ovary
- Tumour in the ovary containing thyroid tissue
What is this?
- Pepper pot skull
- Lots of lytic lesions
- Typical of multiple myeloma
An autopsy of a woman with lung cancer is carried out and this MRI is obtained, what is the likely cause of her death?
- Metastases
- Malignancy is causing brain shift and coning which is pressing on respiratory centre at brainstem
Where can malignant melanomas arise?
- Skin
- Intestines
- Eye
