As we have already learned, hyperplasia is a normal cellular response to increased stress which results in an increased number of cells. Metaplasia is a normal cellular response to an abnormal circumstance where the cell is presented with a type of stress it is not equipped to handle which causes the tissue to change the type of cells present. Severe or prolonged hyperplasia or metaplasia can become dysplasia. Dysplasia is an abnormal change in the cells characteristics often resulting in the presence of immature cells. It is usually accompanied by loss of normal cell orientation, shape & size.

Dysplasia is rated by the grading system, which gives a numerical value based on the tissue’s level of differentiation. Low grade dysplasias are well differentiated pre-cancers that present low risk and rarely form cancer. High grade dysplasia is a type of early cancer that has a high risk of becoming malignant.   High grade dysplasia has not yet spread and is isolated within the basement membrane. The key different between cancer and hyperplasia/metaplasia/low grade dysplasia is that cancer is irreversible. Cancerous cells cannot return to normal.

Cancer is when cells grow, divide, and differentiate in an unregulated fashion as a result of genetic and epigenetic defects. Causes of cancer are complex and only partially understood. This cancerous tissue grows faster than the surrounding normal tissue usually resulting in a mass.

Cancers initially start as a single mutated cell. This cell then proliferates and result is an early mass of identical cells (clonal population). However, over time additional mutations occur due to genomic instability. This leads to a heterogeneous group of cells within the mass that have different abilities (such as invasion and metastasis). This is why most cancers take decades to form. A single mutation is usually not enough to cause metastatic cancer. Generally, many genetic and epigenetic changes must take place to convert a normal cell into a metastatic cancer.

There are two types of cancers, benign and malignant. Generally speaking, malignant cancers are “really bad” and benign cancers are “not so bad.” The key difference between the two classifications is metastatic potential. Malignant cells have the ability to invade tissue and metastasize (spread to other sites) while benign tumors do not. However, malignant cancers don’t always invade and metastasize.

Benign and malignant cancers look very different when viewed using a microscope. Benign tumors look very much like the normal tissue it was derived from. Malignant cancers on the other hand look very different than normal tissue and are easily identifiable from the surrounding tissue. This is because there are more genetic and epigenetic abnormalities in malignant cells (higher rate of mitosis & less regulatory control à genomic instability). These malignant cells no longer look like the mature cells in the surrounding tissue. The abnormalities have changed the cells into a more primitive cell type with a greater variety of characteristics. This is referred to as being Poorly Differentiated (AKA Anaplastic). DON’T confuse this with how easy it is to “differentiate” the cancer from the surrounding tissue, because poorly differentiated cancers are easy to find on a microscope. Benign cancers may only have a few defects present which mean they are still pretty similar to the normal cell the cancer originated from. These cells are similar to normal mature cells and therefore are Well Differentiated.

Benign Cancer & Normal Tissue:

• Regular, organized pattern of cell shape and arrangement
• Neighboring cells look very similar
• Normal sized nuclei
• Little mitosis

Malignant Cancer:

• Irregular, unorganized cell shape and arrangement
• Neighboring cells can look very different
• Big nuclei
• Lots of mitosis
• Hyper chromatic (darker color)

Pictures Used (In order of appearance)

• “Cancer Progression” by NIH available at http://en.wikipedia.org/wiki/File:Cancer_progression_from_NIH.png by Public Domain
• “Poorly Differentiated Adenocarcinoma”  by the Armed Forced Institute of Pathology available at http://commons.wikimedia.org/wiki/File:Poorly_differentiated_(solid)_adenocarcinoma_of_the_lung.jpg by Public Domain
• “Metastatic Hepatocellular Carcinoma” by Yale Rosen available at https://www.flickr.com/photos/pulmonary_pathology/5433130015/  by Creative Commons 2.0 Attribution-Share Alike
• “Colon Cancer 2” by  Emmanuelm available at http://en.wikipedia.org/wiki/File:Colon_cancer_2.jpg by Creative Commons 3.0 Attribution-Share Alike
• “Mixed Tumor of Salivary Gland” by Ed Uthman, MD available at http://en.wikipedia.org/wiki/File:Mixed_Tumor_of_the_Salivary_Gland.jpg  by Public Domain

Now that you have finished this video you should check out the next video in the Cell Injury, Cell Death & Cancer sections which covers Metastasis & Tumor Nomenclature.