What is cancer of unknown primary?

The place where a cancer starts is called the primary site. From there, it can spread (metastasize) to other parts of the body. Cancers are named based on where they start, no matter where they spread. So a lung cancer that spreads to the liver is still lung cancer, not liver cancer.

Sometimes it’s not clear where a cancer may have started. In a small number of cases, the cancer is found when it has spread to one or more sites, but doctors aren’t sure where it started. This type of cancer is called cancer of unknown primary, or CUP. If the place where this cancer started is found later, the name is changed to that of where it started. For example, cancer might be found in a lymph node on the side of the neck and be called CUP. If tests later show that the cancer began in the lung, it would be called lung cancer (and treated as lung cancer) from then on.

When cancer is found, it makes sense to want to know where it came from. But the main reason to look for the primary site for a CUP is to guide treatment. Since a cancer that starts in one place needs the same treatments when it spreads, knowing where a cancer started tells the doctor what types of treatments to use. This is especially important for certain cancers that respond well to specific chemotherapy or hormone drugs. Knowing where the cancer started may tell the doctor which drugs to use to give the patient the best chance.

In many cases of CUP, the source of the cancer is never found, even with a careful search. But even when the primary site is not known, treatment can be helpful. Doctors can try to predict what kinds of treatment might be helpful by looking at certain things like:

• How the cancer cells look under a microscope
• The results of lab tests
• Which organs the cancer has already affected

Cancer types

Cancers are grouped based on the place where they started (their primary site). They can also be grouped by the types of cells they are made up of. This grouping is based on how the cancer cells look under the microscope and on certain lab tests of the cells. Knowing the type of cell could give doctors a clue as to where the cancer started.

Carcinomas

A carcinoma is a cancer that begins in the cells that line the inside or outside of a body organ. These cells are called epithelial cells. There are different types of carcinomas, based on how the cancer cells look under the microscope. The 2 most common types are squamous cell carcinoma and adenocarcinoma.

Squamous cell cancers

Cancers with flat cells that look like the cells found on the surface of the skin or lining of certain organs are called squamous cell cancers. These cancers can start in the mouth, throat, lungs, anus, cervix, vagina, and some other organs.

Adenocarcinomas

Cancers that grow from gland cells are called adenocarcinomas. Gland cells are found in many organs of the body, including some organs we don't think of as glands. For instance, most cancers of the stomach and colon are adenocarcinomas.

Other cancer types

Less common types of cancer can start from other cell types.

• Lymphomas start from cells of the immune system found in lymph nodes and other organs.
• Melanomas start from cells that make the skin’s tan or brown color.
• Sarcomas come from connective tissue cells that are usually found in tendons, muscle, fat, and related tissues.
• Germ cell tumors can begin in the testicles in men and the ovaries in women.

This list does not include all types of cancers, just the most common ones. (Note: Lymphoma often does not have a clear primary site, but is not thought of as a CUP. Although the primary site of a melanoma may not be clear, once a cancer is classified as a melanoma, it is no longer called a CUP.)

When the cancer cells look much like normal cells, they are said to be well differentiated. When they look very different from normal cells, they are called poorly differentiated. Often cancers of unknown primary are poorly differentiated.

Even though they don’t know where a cancer of unknown primary (CUP) started, doctors will do their best to learn as much as they can about it. This can help them select the best treatment. This is done by looking at the cancer cells under a microscope and doing some special tests.

When first looking at the cancer cells under a microscope, doctors usually place a CUP into 1 of 5 broad categories. (We talk about these in “Putting it all together” in the “How is cancer of unknown primary found?” section.) Many of these cancers can be better classified later on, after more testing is done. You should talk to your doctor about which tests it makes sense for you to have. If the results are not likely to improve your chances of survival or your quality of life, then maybe they shouldn’t be done.