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Cancer: Metastasis

Cancer: Metastasis. By Joshua Bower and Asfand Baig Peer Support 2013/2014. Define metastasis. Ability of malignant cells to invade and spread to distant (non-contiguous) sites. Distinguish between a primary and secondary tumour. Primary - site where the malignant neoplasm arises

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Cancer: Metastasis

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  1. Cancer: Metastasis • By Joshua Bower and Asfand Baig • Peer Support 2013/2014

  2. Define metastasis • Ability of malignant cells to invade and spread to distant (non-contiguous) sites

  3. Distinguish between a primary and secondary tumour • Primary - site where the malignant neoplasm arises • Secondary - the site where the initial neoplasm has metastasised to

  4. By what routes do cancers spread? [4] • Locally • Haematogenously (in the blood) • Via lymphatics • Transcoelomically (across a cavity; peritoneum or pleura)

  5. Where do tumours of lymph node cells sit? • In the subcapsular sinus - a region with few lymphocytes, thus permitting free lymph flow

  6. List FOUR common sites for cancer metastasis [4] • Brain • Bone • Lung • Liver

  7. Give THREE examples of primary tumours which commonly metastasise • Prostate • Breast • Lung • Problem based learning! PBL

  8. A patient with known prostate cancer presents with paralysis of his legs. What is your diagnosis? • Spinal cord compression • Cancer cells have metastasised to the spinal cord and the tumour is compressing the nerves • The prostatic venous plexus connects with vertebral veins, which is why it commonly spreads to the spinal cord

  9. Describe the 8 steps of metastasis • BLACK - Basement membrane invasion • EXCLAIMED - Passage through Extra Cellular Matrix • “I’M - Intravasation • INSIDE - Immune interaction • POTTER” - Platelet adhesion • AFTER - Adhesion to endothelium • ESCAPING - Extravasation • AZKABAN - Angiogenesis

  10. The Shawshank 8 • (1 BM invasion) – he picks through the wall • (2 ECM passage) – the room gets filled with water • (3 intravasation) – he breaks into the sewer • (4 immune interaction) – the sewer is filled with poo • (5 platelet adhesion) – the poo is sticky • (6 adhesion to endothelium) – he adheres to the sewer using poo • (7 extravasation) – he breaks out of the sewer • (8 angiogenesis) – his new life!

  11. Slightly more detail… • + BLACK - Basement membrane invasion - MMP (matrix metalloproteinase) stimulation • + Exclaimed - Passage through Extra Cellular Matrix - MMP- • + 'im - Intravasation - MMP stimulation and altered integrins • + Inside - Immune interaction - decreased MHC class I expression • + Potter' - Platelet adhesion - GF release (helps it travel around) • + AFTER - Adhesion to endothelium - CD44 expression • + ESCAPING - Extravasation - intergin expression and MMP stimulation • + AZKABAN - Angiogenesis - VEGF, and other angiogenic GFs

  12. Give TWO factors which can help cells spread [2] • Increased motility(reduced integrin expression reduces the contact between cell and stroma; reduced cadherin expression allows cells to move apart) • Altered synthesis of enzymes that breakdown the basement membrane and stroma(matrix metalloproteinases, MMPs)

  13. What are the THREE classes of matrix metalloproteinases? • Collagenases (degrade collagen I-III) • Gelatinases (degrade collagen IV and gelatin) • Stromelysins (degrade collagen IV and proteoglycans)

  14. What acts to counterbalance MMPs? • Tissue inhibitors of metalloproteinases (TIMPs) • The balance of MMP:TIMP is important, and is a potential source of therapy

  15. Give THREE reasons why all malignant cells don’t metastasise [3] • Distant site environment may be inappropriate for growth of malignant cells • Incorrect receptors • Metabolic factors • Failure of angiogenesis

  16. Give THREE mechanisms by which angiogenesis can occur [3] • Tumour-induced stimulation of angiogenesis (malignant cells could release angiogenic factors e.g. VEGF) • Vasculogenic mimicry(tumour cells use their plasticity to express an endothelial phenotype to link up to the existing vascular system) • Vessel co-option(invade into surrounding vessels, with death of lining endothelial cells leading to tumour cells lining vascular spaces)

  17. Give an example of an anti-angiogenic factor • Angiostatin • Endostatin • Vasostatin • Thrombospondin

  18. List FOUR factors which determine the effect a tumour will have [4] • Site of tumour • Extent of local spread • Site of metastasis • Extent of metastatic spread • Functional effects • Paraneoplastic effects

  19. Give an example of a paraneoplastic effect • Dermatomyositis (autoimmune attack of skin and muscle as a reaction to a tumour) • Cachexia • Anaemia • Clubbing

  20. You have a patient with small cell carcinoma of the lung.What treatment option are you unlikely to carry out? • Surgery - because by the time of diagnosis, it has almost universally metastasised

  21. Name THREE common sites for metastatic spread in the thorax • Lung • Pleura • Mediastinal lymph nodes

  22. What is in situ malignancy? • An epithelial neoplasm with features of malignancy, but with no basement membrane invasion

  23. A patient with carcinoid tumour of the jejunum with liver and bony mets presents with flushing, diarrhoea and wheezing.What is your diagnosis? • Carcinoid syndrome - severe liver mets result in the failure of adequate serotonin metabolism

  24. Give FOUR local effects of malignant neoplasias [4] • Destruction of surrounding tissue • Obstruction or constriction of a hollow viscus • Ulceration • Infiltration into NAVL • Space-occupying lesions (eg in the brain)

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