Cellular Transformation

  • Some factor, as discussed above, causes a cell to be transformed to a neoplastic cell that is not controlled by normal body processes. Probably most transformed cells die because they are too abnormal to function or are abnormal enough for the body's immune system to destroy them. However, if the factors promoting neoplasia persist, a transformed cell may some day give rise to a clone that does continue to grow.

  • Malignant neoplasms do not tend to arise from benign neoplasms (e.g., malignant melanomas do not come from benign nevi). However, in some cases such as adenomas of the colon, the appearance of the benign neoplasm is a step toward possible malignancy, because oncogenic forces are at work producing additonal abnormalities in DNA in existing lesions.

  • There are "pre-cancerous" conditions in which malignant neoplasia is more likely to occur (but not in every case): liver cirrhosis, chronic ulcerative colitis, atrophic gastritis, epidermal actinic keratosis, and oral leukoplakia. In these cases, there is ongoing cellular proliferation for repair of damaged tissue, often from ongoing inflammation. Abnormal cell proliferation leads to a greater likelihood for mutation to occur.

Clonality

  • Neoplastic cells tend to be monoclonal, or similar in genetic makeup, indicating origin from a transformed cell. Non-neoplastic proliferations (such as reactions to inflammation) have cells that are polyclonal in origin.

  • The concept of "tumor progression" holds that subclones may arise over time from the original malignant clone. These subclones may differ from the original clone in characteristics such as invasiveness, metastatic potential, and response to therapy. The subclones may arise from acquisition of additional mutations.

Tumor Genetics

Neoplasms have a greater tendency to demonstrate karyotypic abnormalities such as translocations, deletions, and gene amplifications (which are also activators of proto-oncogenes). Leukemias and lymphomas are famous with chronic myelogenous leukemia, and the t(8:14) translocation in Burkitt lymphoma.

Tumor growth

  • In general, the less differentiated a neoplasm, the faster it grows. The cell cycle of neoplastic cells is not shortened, rather the growth fraction of cells proliferating is increased. This is offset by neoplastic cell death. Tumor growth is expressed as a "doubling time" or the time to increase twice in volume (e.g., from 1 to 1.3 cm diameter). An aggressive malignant neoplasm doubles in 1 to 3 months, while benign neoplasms double in years.

  • Some neoplastic growth is influenced by host factors. Estrogenic hormones aid growth of breast fibroadenomas or carcinomas and uterine leiomyomas because the tumor cells have hormone receptors.

  • Growth is also dependent upon the ability of the tumor to develop a blood supply. Factors secreted by neoplastic cells promote angiogenesis and fibroblast proliferation.

Characteristics of Transformed (Neoplastic) Cells

  • Neoplastic cell growth is not inhibited by contact with surrounding cells and is not dependent on anchorage to a solid surface.

  • They are discohesive and transplantable--favoring invasion and metastasis.

  • Tumor cells can bind to laminin and fibronectin in connective tissues, then secrete collagenases or proteases, and then invade.

  • Neoplastic cells may attain "immortality" or the ability to keep dividing indefinitely.