Neoplasia 2 Flashcards
Invasion define
breach of basement membrane
progressive infiltration and destruction of surrounding tissues
3 step journey for metastasis
Grow and invade at primary site
Enter transport system (lodge at secondary)
Grow at secondary site and form new tumour
Invasion needs (3 things)
Altered adhesion
Stromal proteolysis
Motility
(epithelial to mesenchymal transition) - change of phenotype
How is altered adhesion achieved?
Reduced E-cadherin expression (looser attachments to eachother)
Changes to integrin expression (looser attachments to basement membrane)
How is stromal proteolysis achieved?
Altered expression of proteases - MATRIX METALLOPROTEINASES
= degrading stroma and basement membrane allows invasion
What is the ‘niche’?
Stroma, fibroblasts, endothelial cells and inflammatory cells present - non neoplastic cells
Malignant cells take advantage and use GF and proteases
How is motility achieved?
Changes in cytoskeleton
How does neoplasm spread to second site?
Blood vessels (haematogenous spread)
Lymphatic vessels
Fluid in body cavities (transcoelomic spread)
Barrier to successful metastasis
Failed colonisation
Instead lodge at secondary sites as tiny clinically undetectable cell clusters
What are micrometastases?
Microscopic deposits of tumours that fail to grow
What determines site of secondary tumours?
Regional drainage (blood, lymph or coelomic fluid)
eg breast cancer can cause enlarged axillary lymph nodes
Transcoelemic spread determined by
Other areas in coelemic space (eg within pleural sac) or adjacent organs
Blood borne metastasis spread
next capillary bed (lungs and liver common)
What is seed and soil phenomenon
Explains unpredictable distribution of blood borne metastases
Interaction of malignant cell and tumour environment (seed is tumour, niche is soil)
Which cancers spread via which routes?
Carcinoma = lymphatics first Sarcomas = blood stream first
(common sites - lung, bone, liver and brain)
What should you think if there is malignant tumour found in bone?
Usually as a result of metastasis (from breast, prostate, bronchus, kidney or thyroid)
Metastases to bone features
Haematogenous spread usually
Axial skeleton (skull, spine, pelvis)
Asymptomatic or pain is only symptom
Pathological fractures seen
What do most cancers cause in bone?
Osteolytic lesions - destruction of bone tissue
What cancer has opposite effects and causes osteosclerotic metastases due to increase production of bone?
Prostate cancer
very white blobby x ray
Personalities of malignant neoplasms
Small cell carcinoma of bronchus - very aggressive
Basal cell carcinoma of skin - often does not metastasise
Benign neoplasms often slow growing, chilled
How does body protect against tumour cells?
Recognised by immune system as non-self (cell mediated mechanism)
Tumour antigens presented by MHC to CD8+ cytotoxic T cells
Problems with immunity protection against tumours
Immunosuppressed more at risk (transplant patients)
Tumours can avoid immune system
How can tumours avoid immune system?
Loss/reduced expression of histocompatibility antigens
Expression of factors that suppress immune system
Failure to produce tumour antigen
Effects of neoplasms
direct local Systemic effects: Increase tumour burden (metabolism increased) Secretion of hormones Unexplained effects
Local effects neoplasm
Direct invasion and destruction of tissue
Ulceration –> bleeding
Compression of adjacent structures
Blocking tubes/orifices
Raised pressure due to tumour growth/swelling (brain)
Systemic effects neoplasia
Parasitic effect on host
Secreted cytokines and tumour: Reduce appetite and weight loss Malaise Immunosuppression Thrombosis (hypercoagulative state)
Production of hormones (usually benign)
What are paraneoplastic syndromes?
Development of signs/symptoms that cannot be explained by distribution of tumour or by production of hormones from tissue that tumour arose from
(bodies response to tumour)
Why is paraneoplastic syndrome important?
Earliest sign
Significant clinical problems/fatal
Affect treatment
Paraneoplastic examples
Hypercalcaemia
Syndrome of inappropriate ADH secretion
Hypercalcaemia (why?)
Osteolysis (cancer induces via primary bone lesions or secondary)
Production of calcaemic humoral substances (PTHrP)
SIADH
Small cell lung cancer Causes hyponatraemia (sodium diluted with lots of water)
Micellanoeus neoplastic symptoms
Neuropathies (CNS and PNS)
Skin problems (pruritus, abnormal pigmentation)
Fever
Clubbing
Myositis (muscle inflammation = weak tired and painful)
Hypoglycaemia (some secrete insulin?)
