Cancers often spread from their primary site (the part of the body in which the cancer started) to one or more metastatic sites (other parts of the body). Cancers are named according to their primary site, regardless of where in the body they spread. For example, a lung cancer that spreads to the lymph nodes, adrenal glands, and the liver is still classified as lung cancer and not as a lymphoma (cancer of the lymph nodes), adrenal cancer, or liver cancer.

A small number of cancers first appear in one or more metastatic sites, and the primary site is not known. These cancers are called cancer of unknown primary (CUP). The primary site of some of these cancers may eventually be found by additional tests. When this happens, they are no longer considered a cancer of unknown primary and are renamed according to the newly discovered site of origin.

One example would be a person with an enlarged lymph node on the side of the neck. When it is removed, it is found to contain cancer. But the appearance of the cancer under the microscope does not look like a cancer that starts in lymph nodes. At that point it might be called cancer of unknown primary. Often, though, its appearance might suggest that the cancer started in the mouth, throat, or voice box (larynx). During a thorough exam of this area, a small cancer of the pharynx might be found. From then on, the patient is said to have pharyngeal cancer rather than cancer of unknown primary and will receive treatment that is appropriate for that cancer. Similarly, if a cancer is found to have started in the lung, breast, or other organ, it is no longer considered a cancer of unknown primary.

In many cases of CUP, the source of the cancer is never discovered. Even the most thorough search may not find the source of the cancer. When doctors perform autopsies on people who have died of cancer of unknown primary, they are often unable to find the site where the cancer started. In one study from the Mayo Clinic, doctors could only find the site of origin in 55% of cases that they autopsied. When the primary site of the cancer is found, it is usually the lung, pancreas, or intestinal tract.

Cancer Types

In addition to being classified according to their primary site, all cancers are also named according to their appearance under the microscope. This may or may not give doctors a clue as to where they started.

• Cancers formed by flat cells that resemble cells normally found on the surface of the skin or the linings of the mouth, throat, or vagina are called squamous cell cancers.

• Cancers that develop from gland cells are called adenocarcinomas. Gland cells are found in many organs of the body, including some that are not usually thought of as glands. For example, almost all cancers from the intestinal tract are adenocarcinomas. About 40% of lung cancers are adenocarcinomas. Adenocarcinomas can also develop in many other organs.

• Lymphoma develops from cells of the immune system found in lymph nodes and several other organs.

• Melanomas develop from cells that produce the skin's tan or brown color.

• Sarcomas develop from connective tissue cells that usually are present in tendons, ligaments, muscle, fat, and related tissues.

• Germ cell tumors mostly seen in men begin in testes (testicles) or parts of the body where the testes developed in the fetus.

This list is not intended to include all types of cancers but merely to name the most common ones.

When the cancer cells closely resemble normal cells of the organ where they start, the cancer is called well differentiated. When they have very little similarity to normal cells, the cancers are called poorly differentiated. In general, cancers of unknown primary tend to be poorly differentiated.

Even though they don’t know where the cancer started, doctors will do their best to classify the type of cancer. This can help doctors select the best treatment. Some cancers respond very well to specific treatments, usually drugs. Therefore, it is very important to classify the cancer. This is best done by looking at the cancer under a microscope and performing special tests, particularly immunohistochemistry, in the laboratory (see the section (See the section "How Is Cancer of Unknown Primary Diagnosed?").

There are also imaging tests and even surgery that might help find the answer to where the cancer started. But it is important for you and your doctor to discuss how much good it will do you to go through all this. When the cancers with the best hope for responding to treatment have been excluded by certain tests however, it usually becomes less important to find the exact origin or type of a cancer. In some cases, tests to find a primary site might be uncomfortable and are usually fruitless. If the results are not likely to improve your survival or quality of life, the tests should not be done.