Evolution of a Cancer

Morphologic Changes

As mutations accumulate in a given cell, there is a progressive loss of regulation of the cell cycle, differentiation, and cell-to-cell adhesion and interaction. These changes are accompanied by progressive abnormalities in morphology (appearance) of the cells. At times, changes in cellular appearance or number are normal responses to physiologic stresses. For example, failure to exercise a muscle will result in atrophy, while repeated exercise produces hypertrophy. Increases in the number of cells can also be temporary responses to stress of some type. For example, pressure on the later aspect of the foot can result in a callus. This would be characterized as hyperplasia, in which there is an increase in the number of cells, but the morphology of the cells and their relationship to one another remains normal. Hyperplasia is a normal response to a specific stimulus, and the cells of a hyperplastic growth remain subject to normal regulatory control mechanisms. On the other hand, dysplasia is a term used by pathologists to describe a spectrum of abnormalities that are indicative of a pre-cancerous state. When dysplasia is present, there is abnormal proliferation, and the cells have a distinctly abnormal and variable appearance; cells vary in shape and size, and there is evidence that cell to cell interaction has broken down resulting in a disorganized appearance of the tissue. The illustration below summarizes these changes in cell morphology.

Dysplasia is illustrated in the histologic section from a biopsy of the uterine cervix shown below. The area to the right encircled with red illustrates dyplasia; the cells have not yet progressed to cancer, but they are in danger of doing so, so they would be considered "pre-malignant." Dysplasia can revert back to hyperplasia, but it may also become malignant. Therefore, dysplasia should be carefully monitored or treated.      


Dysplasia on a Biopsy from the Uterine Cervix


Image source: http://library.med.utah.edu/WebPath/FEMHTML/FEM008.html


Dysplasia on a Pap Smear


Carcinoma in Situ and Invasive Carcinoma

Carcinoma "in situ" literally means cancer in place. These cells have transitioned to being cancerous, but they have not yet invaded the adjacent tissues. Note that, in the illustration below, the in situ cancer is still confined to the epithelial layer from which it arose. If left untreated, the in situ cancer may remain confined to the epithelial layer indefinitely, but it may acquire additional mutations that enable it to progress to an invasive cancer..


Source: http://www.ndhealthfacts.org/wiki/Oncology_%28Cancer%29

The progression begins with a mutation that makes the cell more likely to divide. The altered cell and its descendants grow and divide too often, a condition called hyperplasia. At some point, one of these cells experiences another mutation that further increases its tendency to divide; this cell's descendants divide excessively and look abnormal, a condition called dysplasia. As time passes, one of the cells experiences yet another mutation, causing very abnormal structure, loss of differentiation, and loss of contact between the cells; however, it is still confined to the epithelial layer from which it arose, so it is called a cancer in situ. The in situ cancer may remain contained indefinitely, but additional mutations may occur that enable it to invade neighboring tissues and shed cells into the blood or lymph, the tumor is said to be an invasive cancer (malignant). The escaped cells may establish new tumors (metastases) at other locations in the body. Source: http://science.education.nih.gov/supplements/nih1/cancer/guide/understanding1.htm


Metastasis is the movement or spreading of cancer cells from one organ or tissue to another and proliferate at the new site. Cancer cells usually spread through the bloodstream or the lymph system. The tumor mass can also spread locally, compress other structures, and damage surrounding tissues.


Source: http://www.nature.com/nrc/journal/v3/n1/fig_tab/nrc967_F1.html

The video below illustrates metastasis.

alternative accessible content