Lesson 1 Classification, Diagnosis, Imaging

• Tumour


  An abnormal growth
• Benign


  Localised, non-invasive, not usually life-threatening. Can sometimes develop into malignant tumours

  
• Malignant


  Capable of invading normal tissue

  
• Metastasis


  Growing in other parts of the body
• Cancer


  Unregulated growth, invasive and capable of spreading

  
• Cancer - breaking the multicellularity "deal"


  • cell-to-cell adhesion
  • cell-to-cell communication, cooperation
  • specialisation of cells
  • "fitness" and evolution operate on the multicellular organism, not each cell

  
• Tumours composed of rogue cells that act "selfishly", prioritising their own survival and proliferation over that of the organism
• Cancers are particularly common in vertebrates, especially humans
• Features of cancers used to classify them

  • Cell type or organ of origin
  • Size
  • Spread
  • Growth rate
  • Microscopic appearance, proportion of mitoses
  • Molecular features (eg HER2 positive)

  
• Stage

  Chronic –slow, or acute - fast
• Grade

  Chronic –slow, or acute - fast
• Cancers are classified according to the cell type from which they were derived

  
• Carcinomas


  Common, most develop in organs or glands. Include hepatocellular carcinoma (liver), renal cell carcinoma (kidney). Some derive from epithelium (eg skin, oesophagus). Can metastasise via blood or lymph
• Sarcomas


  Rare: ~1% of cancers, more common in children. From supportive/connective tissues such as bones, tendons, cartilage, muscle, fat. Examples: osteosarcoma (bone), rhabdomyosarcoma (smooth muscle). Usually metastasise via blood
• Carcinomas


  • Renal cell carcinoma
  • Squamous cell carcinoma of the skin
• Sarcomas


  • Osteosarcoma
• Leukaemia


  Commence in bone marrow or blood. Derive from immature myeloid or lymphoid cells
• Leukaemia


  • Acute lymphocytic leukaemia (ALL): Very immature cells with larger nuclei
  • Acute myeloid leukaemia (AML): Very large, immature myeloid cells
• Lymphoma


  Commence in lymph nodes, spleen, tonsils, or thymus

  
• Grading


  Piece of tumour, from biopsy or resected lump analysed by pathologist. Numerical grade assigned on basis of histology: microscopic appearance. Low grade cancers look similar to "normal" tissue. High grade cancers look less differentiated and contain more mitotic cells

  
• Advantages of grading: low-tech, cheap and quick
• Disadvantages of grading: heterogeneity of samples, subjective(ish)
• Breast cancer grading

  • Grade 1
  • Grade 2
  • Grade 3

  
• Rakha et al. Breast Cancer Research 2010 12:207

  
• Staging


  Size and spread of cancer (observation during surgery, imaging)

  
• Staging classifications


  • T0: Impalpable ("unfeelable")
  • T1: Small, minimal invasion
  • T2: Bigger and/or more invasion
  • T3: Very big and/or even further invasion
  • N0: No lymph node involvement
  • N1: Regional lymph node involvement
  • N2,3: More & distant nodal groups
  • M0: No distant metastases
  • M1: Distant metastases present
• Precise definitions vary between tumour types
• The T, N, M classifications are grouped to give a "Stage" diagnosis
• Colorectal cancer staging system (by American Joint Committee on Cancer)


  • T0: No evidence of primary tumour
  • Tis: Tumour "in situ": intramucosal
  • T1: Tumour invades submucosa
  • T2: Tumour invades into muscle
  • T3: Tumour invades through muscle into serosa
  • T4: Tumour penetrates into visceral peritoneum
  • N0: No lymph node metastasis
  • N1: Metastasis in 1-3 regional lymph nodes
  • N2: Metastasis in 4+ regional lymph nodes
  • N3: Metastasis to distant lymph node(s)
  • M0: No distant metastases
  • M1: Distant metastases present (eg liver, lungs, brain)

  
• 5 year survival rates for colorectal cancer stages

  • 100%: Tis N0M0 (Stage 0)
  • 93%: T1-2N0M0 (Stage I)
  • 78%: T3-4N0M0 (Stage II)
  • 74%: Any T, N1M0 (Stage III A, B)
  • 44%: Any T, N2M0 (Stage IIIC)
  • 8%: Any T, Any N, M1 (Stage IV)