Now you've been introduced to the concept and definition of metastasis, I'm going to go over a common method of staging for cancer, the TNM system, in which metastasis plays a major role. The TNM staging system in cancer is by far the most commonly used staging system in cancer diagnosis and is used to determine a patient's prognosis and the course of treatment to be used for a certain patient. Most cancers use this system, except blood cancers and some nervous system cancers. So the T in TNM stands for Tumor. The N for the N in node in Lymph node. And the M is for Metastasis. As you'll see, metastasis plays a big role in determining how serious a person's cancer is, and how to treat it. So let's talk about each of these individually. The T in TNM stands for tumor, and the stage of a primary tumor depends on its size. The larger the tumor, the worse the stage. Usually, tumors are not immediately obvious. Tumors are found through various imaging techniques, which you'll hear more about in lecture five, physical and examination and surgery. You can see here at CAT scan or CT scan of a liver tumor and ultrasound of a breast tumor and a picture of a colon tumor found during surgery. Physical exams can lead to these types of imaging studies. For instance, the digital rectal exam or DRE is use to screen for prostate cancer and if then are abnormality is felt upon examination, further examination and imaging studies are performed. For some cancers such as stomach cancer, there is no way to access the primary tumor site by physical examination, so sometimes, lymph nodes are palpated or touched to determine whether a tumor may be present. But imaging is always necessary to confirm. Speaking of lymph nodes, the N in TNM refers to the involvement of lymph nodes in the cancer. First, lets review the lymphatic system. The lymphatic system is comprised of lymphatic vessels, similar to blood vessels, that carry fluid called lymph from tissues throughout the body to lymph nodes and then deposits the lymph into the blood stream. The lymphatic system is important because it carries away excess fluid from in between cell so as to maintain a constant volume and composition of tissue. It also acts as an immunological defense mechanism by taking away waste and bacteria and exposing it to immune cells. Lymph is mostly comprised of water, white blood cells, and various molecules like proteins, fats, and sugars. The lymph nodes of the lymphatic system are important in cancer diagnosis and treatment because cancer cells can get into the lymph and drain into lymph nodes. Cancer typically spreads to regional lymph nodes, which means the closest lymph node to the primary tumor. For instance, prostate cancer cells drain into inguinal lymph nodes, which you can see on the diagram. And breast cancer cells drain into lymph nodes nearby the mammary glands, as well as axillary lymph nodes. This is why lymph node palpation is a common part of physical examination. So the TNM system is typically binary when it comes to the end of TNM. Basically, N0 means cancer has not been found in the lymph node, whereas N1 means cancer has been found in a regional or nearby lymph nodes. When cancer is found in lymph nodes beyond the local region, it represents the worst diagnosis and prognosis. And this is actually often reflected in the next part of TNM metastasis. What you see here is histology of a normal lymph node on the left where all the purple dots represented nuclei of millions of immune cells that usually comprise most of the lymph node. On the right, you see large tumor mass that is taking up almost the entire lymph node, and only a small portion of normal lymph node tissue is remaining on the upper right portion there. So the final letter M of TNM represents our topic today, metastasis. Once a cancer has reached metastatic capability, it has become quite aggressive and most likely fatal. Metastasis can be difficult to find via physical examination. But once cancer has been found, a primary goal of the physician is to determine whether or not that cancer has spread, so imaging studies are typically ordered. Here you can see four representative images of metastatic tumors found in some of the more common sites of metastasis. On the left is an x ray of a bone metastasis, meaning a tumor from another organ that became cancerous and metastasized to the bone. Then you see an x ray of a lung metastasis, a CT image of a liver metastasis and an MRI of a brain metastasis. I'd like to go over an example of a specific TNM staging system for an individual cancer type, prostate cancer. Each cancer follows similar rules and numbers, but can vary slightly depending on how the cancer typically behaves. For prostate cancer, the primary tumor can be classified as T1, T2, or T3, depending on how large the tumor is, and whether or not it has become invasive which, if you look in the diagram, the blue tumor labeled T3 has done that and become invasive in the picture. For the N, for prostate cancer, it's a binary numbering system, either N0 for no lymph node involvement or N1 for lymph node involvement. For our prostate cancer, N1 only refers to nearby lymph nodes, which you can see in the picture. If lymph nodes further away are involved, they are classified in the M portion of TNM, metastases are classified as either M0 for no metastasis, M1a for far away lymph node involvement, M1b for metastasis to bone tissue, which is the most common cyto metastasis in prostate cancer, or M1C for metastasis to other tissues. So an example of a serious tumor stage in prostate cancer would be T3, N1, M1B, which is a large tumor that is invasive which has gone to nearby lymph nodes and also metastasized to the bone. And that would be a more serious tumor than a T1, N0, M0, which is a smaller tumor that has not gone to either lymph nodes or metastasized. At this point, we have finished section B, which was T and M staging tumors and then we're going to move on to section C which is the actual metastatic cascade.
