Neoplasm 2 Flashcards
Understand how invasion and metastasis are the most lethal features of malignant neoplasm
The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden
Untreated, this results in a vast number of ‘parasitic’ malignant cells
When primary tumour is excised, tiny group of cells may fall off
Secondary metastases can form and further cascade and spread
What processes must occur for a malignant cell to travel from primary to secondary site
Grow and invade at the primary site
Enter a transport system and lodge at a secondary site
Grow at the secondary site to form a new tumour (colonisation)
What can stop a malignant cell traveling to a secondary site
At all points, the cells must evade destruction by immune cells
Whole process is very inefficient
Many cancer cells are destroyed by mechanical trauma - cannot move within blood vessels
Embolic trauma
Many other cancer cells do not grow at secondary site
Many malignant cells lodge at secondary sites but these tiny cell clusters either die or fail to grow into clinically detectable tumours
Surviving microscopic deposits that fails to grow are called micrometastases
Tumour dormancy
Can be activated if immunosuppressed
When a malignant neoplasm relapses years after an apparent cure
What alterations are required for invasion into surrounding tissue
Altered adhesion - reduction in E-cadherin expression between malignant cells
Change in integrin expression causes altered adhesion between malignant cells and stromal protein
Stromal proteolysis - cells must degrade basement membrane and stroma to invade
Involves altered expression of proteases - notably matrix metalloproteinases (MMPs)
Altered motility - changes in actin cytoskeleton
Signalling through integrins is important - occurs via small G proteins such as members of Rho family
Motility - ability to move spontaneously and actively
What is epithelial-to-mesenchymal transition (EMT)
Three changes create a carcinoma cell phenotype that appears more like a mesenchymal cell than an epithelial cell
What does a cancer niche include
Malignant cells take advantage of nearby non-neoplasitc cells, which together form a cancer niche
Provide some growth factors and proteases
Includes stroma, fibroblasts, endothelial cells, inflammatory cells
Describe the routes of metastasis transport
Enter blood vessels via capillaries and venules
Enter lymphatic vessels
Enter fluid in body cavities (pleural, peritoneal, pericardial, brain ventricles)
Transcoelomic spread
Understand what determines the location of secondary metastasis site
Site could depend on regional drainage of blood, lymph or coelomic fluid
Lymphatic metastasis drains to lymph nodes
Transcoelomic spread to other areas in the coelomic space or to adjacent organs
Blood-born metastasis, normally spreads to next capillary bed that the cells encounter
Eg. Lung and liver
Seed and soil phenomenon - due to interactions between malignant cells and the local tumour environment (niche) at the secondary site
Explains the unpredictable distribution of blood-born metastases
Carcinomas typically spread via lymphatic first
Sarcomas tend to spread via blood stream
List the common sites of blood-borne metastases
Common sites of blood borne metastasis are lung, bone, liver and brain
List the neoplasms which commonly spread to bone
Breast, bronchus, kidney, thyroid and prostate
Prostate makes new bone and do not appear loosened compared to other bone cancer
Which neoplasms cause lytic and sclerotic lesions
Lytic lesions commonly caused by cancer to breast, lung, thyroid, kidney
Lytic lesions are light areas found in otherwise dense bone on an x-ray, which suggest that something has destroyed or replaced that part of bone
Sclerotic lesions commonly caused by prostate
Pathological thickening of bone
Describe the local effects of benign and malignant neoplasms
Direct invasion and destruction of normal tissue - osteosarcoma
Ulceration at a surface leading to bleeding
Could lead to inflammation of pleural or peritoneum
Compression of adjacent structures
Blocking tubes and orifices (opening)
Describe the systemic effects of neoplasms
Increasing tumour burden leads to a parasitic effect on the host
Together with secreted factors such as cytokines, can lead to loss of appetite, weight loss (cachexia), malaise (general discomfort), immunosuppression, thrombosis
Benign neoplasms of endocrine glands are well differentiated so typically produce hormones
Eg. Thyroid adenoma produces thyroxine
Malignant tumours sometimes produce hormones
Eg. Bronchial small cell carcinoma can produce ACTH or ADH while bronchial squamous cell carcinoma can produce PTH-like hormone
Miscellaneous systemic effects include neuropathies affecting the brain and peripheral nerves, skin problems such as pruritis and abnormal pigmentation, fever and myositis
Pruritis - excessive itching
Cytokines generate fever
Myositis - muscle inflammation leading to weakness
