Metastatic disease

• Metastasis


  Primary tumour → locally invasive → in situ cells breach BM → downregulates E-cadherin expression → cells detach from tumour → secrete proteolytic enzymes → degrade & attach to ECM components → degrade BM → intravasation → transport to distant site → tumour cells may become trapped → platelets adhere to cancer cell → microthrombus → cancer cell push aside endothelium → direct contact w/ BM → days, microthrombus dissolved by proteases → cancer cell proliferates in lumen → cancer cell breaks through BM & invades tissue parenchyma → extravasation (dormant macrometastases) → metastasis
• What can cancer be classified based on?

  Primary site

  Histopathology

  Location of metastasis

  TNM
• Classification of cancer based on primary site

  Carcinomas

  • originate from epithelial cells
  • most common cancer that causes metastatic disease

  Sarcomas

  • originates from mesenchymal cells

  Lymphomas & leukaemias

  • Arise from haematopoietic cells in bone marrow & lymph nodes
  • Can cause widespread disease without forming discrete metastases
• Classification of cancer based on histopathology


  Adenocarcinoma

  • Often arises in organs with glandular or secretory tissue (breast, colon)

  Squamous cell carcinoma

  • Typically found in areas exposed to environmental damage (skin, lungs & cervix)

  Melanoma

  • Originates from melanocytes (often in skin, but can occur in eyes or intestines)
• Classification of cancer based on metastasis


  Lymph node

  • Cancer cells spread to nearby lymph nodes before other parts of the body

  Distant

  • Cancer cells travel through blood vessels to distant sites
  • Liver → common for GI cancers
  • Lung → common for many cancers
  • Bone → common for prostate & breast cancers
  • Brain → common for lung cancer
• TNM Staging 


  T = tumour (extent of invasion depth of tumour into bowel wall)

  • T1 - invasion into mucosa/submucosa
  • T2 - invasion into muscularis propria
  • T3 - mesocolic fat
  • T4 - perforation of the serosa

  N = nodal disease (number of lymph nodes involved)

  • N0 - no lymph nodes
  • N1 - 1-3 lymph nodes
  • N2 - 4 or more lymph nodes

  M = metastases (presence of distant metastasis)

  • M0 - no metastasis
  • M1 - metastasis present
• What are paraneoplastic syndromes?


  Group of disorders triggered by an abnormal immune response to a neoplasm

  Seen in around 10% of pts with advanced malignant disease