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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
Cancer: Metastasis

  • By Joshua Bower and Asfand Baig

  • Peer Support 2013/2014


Define metastasis
Define metastasis

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


Distinguish between a primary and secondary tumour
Distinguish between a primary and secondary tumour

  • Primary - site where the malignant neoplasm arises

  • Secondary - the site where the initial neoplasm has metastasised to


By what routes do cancers spread 4
By what routes do cancers spread? [4]

  • Locally

  • Haematogenously (in the blood)

  • Via lymphatics

  • Transcoelomically (across a cavity; peritoneum or pleura)


Where do tumours of lymph node cells sit
Where do tumours of lymph node cells sit?

  • In the subcapsular sinus - a region with few lymphocytes, thus permitting free lymph flow



Give three examples of primary tumours which commonly metastasise
Give THREE examples of primary tumours which commonly metastasise

  • Prostate

  • Breast

  • Lung

  • Problem based learning! PBL


A patient with known prostate cancer presents with paralysis of his legs what is your diagnosis
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


Describe the 8 steps of metastasis
Describe the 8 steps of metastasis of his legs.

  • 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


The shawshank 8
The of his legs. 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!


Slightly more detail
Slightly more detail… of his legs.

  • + 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


Give two factors which can help cells spread 2
Give TWO factors which can help cells spread [2] of his legs.

  • 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)


What are the three classes of matrix metalloproteinases
What are the THREE classes of matrix metalloproteinases? of his legs.

  • Collagenases (degrade collagen I-III)

  • Gelatinases (degrade collagen IV and gelatin)

  • Stromelysins (degrade collagen IV and proteoglycans)


What acts to counterbalance mmps
What acts to counterbalance MMPs? of his legs.

  • Tissue inhibitors of metalloproteinases (TIMPs)

  • The balance of MMP:TIMP is important, and is a potential source of therapy


Give three reasons why all malignant cells don t metastasise 3
Give THREE reasons why all malignant cells don of his legs. ’t metastasise [3]

  • Distant site environment may be inappropriate for growth of malignant cells

  • Incorrect receptors

  • Metabolic factors

  • Failure of angiogenesis


Give three mechanisms by which angiogenesis can occur 3
Give THREE mechanisms by which angiogenesis can occur [3] of his legs.

  • 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)


Give an example of an anti angiogenic factor
Give an example of an anti-angiogenic factor of his legs.

  • Angiostatin

  • Endostatin

  • Vasostatin

  • Thrombospondin


List four factors which determine the effect a tumour will have 4
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


Give an example of a paraneoplastic effect
Give an example of a paraneoplastic effect have [4]

  • Dermatomyositis (autoimmune attack of skin and muscle as a reaction to a tumour)

  • Cachexia

  • Anaemia

  • Clubbing


Cancer metastasis
You have a patient with small cell carcinoma of the lung. have [4]What treatment option are you unlikely to carry out?

  • Surgery - because by the time of diagnosis, it has almost universally metastasised


Name three common sites for metastatic spread in the thorax
Name THREE common sites for metastatic spread in the have [4]thorax

  • Lung

  • Pleura

  • Mediastinal lymph nodes


What is in situ malignancy
What is have [4]in situ malignancy?

  • An epithelial neoplasm with features of malignancy, but with no basement membrane invasion


Cancer metastasis

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


Give four local effects of malignant neoplasias 4
Give FOUR local effects of malignant neoplasias [4] and bony mets presents with flushing, diarrhoea and wheezing.

  • Destruction of surrounding tissue

  • Obstruction or constriction of a hollow viscus

  • Ulceration

  • Infiltration into NAVL

  • Space-occupying lesions (eg in the brain)