Neoplasia: etiology, pathogenesis, classification and nomenclature
A neoplasm is an abnormal mass of tissue, the growth of which is not physiologically normal and occurs as a result of cell division without control.
Given we have just studied hyperplasia, an increased cell number as an adaptive response, the question could be asked, how does a neoplasm differ from hyperplasia. Simply put, a neoplasm is the proliferation of a single cell, while hyperplasia is many cells undergoing cellular division, creating a heterogeneous cellular collection (polyclonal).
Etiology
In order for uncontrolled cell proliferation, we need a genetic mutation which will affect one of the following:
- Encoding of the cyclins or CDKs (responsible for controlling the cell cycle checkpoints)
- Encoding of the proteins that respond to these complexes
- Encoding of the regulation of these complexes
- Encoding of growth factors/mitogens (mitogens relieve negative controls)
- External growth factor receptors
- Tumour suppressor genes
We call genes that code for the above (i.e. genes with the potential to cause cancer) proto-oncogenes, except the tumour suppressor genes, which cause cancer when they are lost. As and when they mutate (if they do), causing variation of function, they become oncogenes. Damage to these genes can be as a result of exposure to external carcinogens, or simply internal DNA damage (such as ROS damage).
One such important gene is TP53, a monitor of stress in the cell and involved in DNA repair, cellular senescence and apoptosis. Damage to this gene is one of the leading causes of cancer.
Pathogenesis
Damage to proto-oncogenes predisposes the individual to the proliferation of cells without adequate controls, this may be as a result of not responding appropriately to growth factors, or alternatively cell cycle checkpoints not successfully holding the cycle. This causes uncontrollable cellular reproduction.
Classifications
Neoplasia can be benign or malignant, let us consider the key features of the two:
- Benign
- Well differentiated
- Slow growth
- Cohesive
- Expansile
- Capsule
- No invasion/infiltration
- Malignant
- Poorly differentiated
- Rapid growth
- Non-cohesive
- No capsule
- Invasion
- Metastasis
Benign (left): grows by expansion and stays at its site. Malignant (right): invades through the wall into surrounding tissue, blood vessels (red, blue) and lymphatics (green), the route to metastasis.
Image: “Types of tumor cells” by Manu5, CC BY-SA 4.0, via Wikimedia Commons.
Nomenclature
Cell of origin + oma (benign) or, where malignant sarcoma (if of mesenchymal origin), carcinoma (if of epithelial origin)
- Glandular Epithelium
- Adenoma or Adenocarcinoma
- Fibroblasts
- Fibroma or Fibrosarcoma
- Osteoblast
- Osteoma or Osteosarcoma
- Lipocyte
- Lipoma or Liposarcoma