R2.1: Features Of Malignant Cells

Microscopic Features

There are several features that can be used to differentiate normal cells from malignant cells.

  • Invasion: Malignant cells do not respect tissue boundaries, and can be seen infiltrating or invading into surrounding structures
  • Increased mitotic rate: Mitoses are rarely seen in normal tissues. Malignant cells will often have increased numbers of mitoses. Mitoses are typically counted 'per high power field'. More aggressive tumours typically have a higher mitotic rate; however these tumours are typically more sensitive to radiation.
  • Differentiation and Anaplasia: Normal cells are usually structured in a particular way that corresponds with their function. This is known as differentiation. Malignant cells may become less differentiated as part of their path to malignancy. This is known as anaplasia.
    • Well differentiated maligant cells show features similar to the parent tissue. For example, well differentiated adenocarcinoma cells will tend to form gland-like structures; well differentiated squamous cell carcinomas may show intercellular bridging or keratin formation.
    • Poorly differentiated cells have lost most of their resemblance to the parent tissue, which may be difficult to identify without special staining techniques.
    • Anaplastic cells have no resemblence to their parent tissue, and usually indicate a very aggresive malignancy.

Anaplastic Features

  • Loss of normal tissue architecture: Normal cells are usually arranged in an orderly fashion. Epithelial cells often have polarity, with their nuclei at a specific location. Malignant cells lose this architecture and are arranged haphazardly.
  • Pleomorphism: Malignant cells may show a range of shapes and sizes, in contrast to regularly sized normal cells. The nuclei of malignant cells are often very large (often larger than the entirety of a normal cell) and may contain prominent nucleioli.
  • Hyperchromatic nuclei: The nuclei of malignant cells typically stain a much darker colour than their normal counterparts.
  • High nuclear-cytoplasmic ratio: The nuclei of malignant cells often take up a large part of the cell compared with normal cell nuclei
  • Giant cells: Some malignant cells may coalesce into so-called giant cells, which might contain the genetic material of several smaller cells.

Hallmarks of Cancer

There are six classical hallmarks of malignancy:

  • Self sufficiency in growth signals - malignant cells are able to grow without an external stimulus to do so
  • Lack of response to growth inhibition - this is often due to loss of tumour suppressor genes, which would normally put the growth of the cell on hold
  • Unlimited replicative capacity - normal cells may only multiply a set number of times before they become senescent (unable to divide further). Malignant cells circumvent this limit through activation of telomerase.
  • Avoidance of apoptosis - normal cells trigger apoptotic pathways in response to uncontrolled growth signalling. Apoptosis is often suppressed by malignant cells to avoid this fate
  • Angiogenesis - malignant tumours must form new blood vessels in order to expand locally. Angiogenesis is also important for allowing malignant cells to metastasise
  • Invasion and Metastasis - malignant tumours invade surrounding normal tissues and may also spread throughout the body.