Cancer

A group of disease involving abnormal cell growth with the potential to invade or spread to other parts of the body.

Definitions:

• Neoplasia - 'new growth'. The collection of cells and stroma composing new growths are referred to as neoplasms.
• Tumour - now equated with neoplasm, although originally described swelling caused by inflammation.
• Oncology - the study of tumours or neoplasms.
• Benign tumours remain localised at their site of origin
• Malignancy/cancer: a tumour that can invade and destroy adjacent structures and spread to distant sites.
  • Sarcoma - malignancy arising in solid mesenchymal tissues
  • Carcinoma - malignancy arising from epithelial cells
  • Lymphoma - malignancy originating from lymphocytes
  • Leukaemia - malignancy arising from blood-forming cells
• Carcinoma in situ: severe dysplasia involving the full thickness of the epithelium, but without penetrating the basement membrane
• Dysplasia - disordered growth. May be a precursor to malignant transformation, but does not always progress to cancer.
• Metaplasia - the replacement of one type of cell with another type, usually in response to tissue damage, repair and regeneration
• Metastasis - the spread of a tumour to sites are physically discontinuous with the primary tumour, an event that unequivocally marks a tumour as malignant
• Differentiation - the extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologically and functionally
• Anaplasia - lack of differentiation
• Sentinel lymph node - the first node in a regional lymph node basin that receives lymph flow from the primary tumour

Characteristics of malignant neoplasms

• Differentiation and anaplasia
  • Benign tumours are generally well-differentiated
  • Malignant neoplasms usually have characteristic morphological changes
    • Pleomorphism - variation in cell size and shape
    • Abnormal nuclear morphology
    • Proportion of cells in mitosis, reflecting rate of proliferation
    • Loss of polarity - orientation of cells with respect to each other or to other external supporting structures
    • Presence of ischaemic necrosis due to outgrowing their blood supply
• Local invasion
  • Progressive invasion and destruction of surrounding tissue - poorly-demarcated, without well-defined cleavage planes.
  • Benign tumours usually grow and expand slowly, and hence usually develop a rim of compressed fibrous tissue called a capsule. The capsule consists of ECM deposited by fibroblasts in response to hypoxic damage. This makes the benign tumour discrete, non-fixed, and easily enucleated.
• Metastasis
  • Unequivocally marks a tumour as malignant
  • Invasiveness permits malignant tumours to penetrate blood vessels, lymphatics and body cavities, providing the opportunity for spread
  • All malignant tumours can metastasise
  • 'Liquid' tumours (leukaemias and lymphomas) are metastatic at diagnosis
  • The metastatic cellular cascade
    • Invasion of the extracellular matrix
      • Must breach the basement membrane, traverse the interstitial connective tissue, and penetrate the vascular BM
      • Dissociation of cancer cells from one another (E-cadherin function lost)
      • Degradation of BM/connective tissue - secretion of proteolytic enzymes - matrix metalloproteinases (MMP), cathepsin D, and urokinase plasminogen activator
      • Tumour cells change the way they attach to ECM proteins, making them less 'fixed' in place
      • Locomotion through degraded basement membranes and zones of matrix proteolysis
    • Vascular dissemination, tissue homing, and colonisation
      • Could relate to anatomical vascular drainage, tropism of particular types of tumour cells (?complementary homes to originating tissue), and escape from tumour dormancy in target tissue
      • Extravasation required at target tissue - little is known
  • Pathways of spread
    • Direct seeding
      • When a cancer penetrates into an open field lacking physical barriers (peritoneal, pleural, pericardial, subarachnoid, joints)
    • Lymphatic
      • Most common pathway for carcinomas
    • Haematogenous
      • Typical of sarcomas, but also sometimes carcinomas
      • LVI is a concerning feature in the primary tumour
      • Metastatic cells often come to rest in the first capillary bed they encounter (liver, lungs)

Staging:

• Local
• Locally advanced: Cancer that has spread from where it started, to nearby tissues or nodes.
• Metastatic