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

Sometimes it's not clear where a cancer may have started. When cancer is found in one or more metastatic sites but the primary site is not known, it is called a cancer of unknown primary (CUP) or an occult primary cancer. This happens in a small portion of cancers.

Further tests may eventually find the primary site of some of these cancers. When this happens, they are no longer considered a cancer of unknown primary and are renamed and treated according to where they started.

As an example, a person may have an enlarged lymph node on the side of the neck. When it is removed, it is found to contain cancer. But under the microscope it does not look like a cancer that normally starts in lymph nodes. At this point it might be called a cancer of unknown primary. The way it looks under the microscope 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 larynx might be found. From then on, the patient is said to have laryngeal cancer rather than a cancer of unknown primary and will get treated for that type of cancer.

In many cases of CUP, the source of the cancer is never determined. Even the most thorough search may not find the source of the cancer. Even when doctors do autopsies on people who have died of cancer of unknown primary, they are often still unable to find the site where the cancer started.

But even if the primary site is not known, treatment can still be successful. How the cancer looks under the microscope, the results of lab tests, and information about which organs it has already affected can help doctors predict what kinds of treatment might be helpful.

General cancer types

Cancers are classified based on their primary site, and 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 may give doctors a clue as to where the cancer started.

Squamous cell cancers

Cancers formed by flat cells that resemble cells normally found on the surface of the skin or the linings of certain organs are called squamous cell cancers or squamous cell carcinomas. (A carcinoma is a cancer that starts in cells that line the inside or outside of a body organ.) Squamous cell cancers can start in the mouth, throat, esophagus, lungs, anus, cervix, vagina, and some other organs.

Adenocarcinomas

Cancers that develop from gland cells (cells that secrete a substance) 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, most cancers in the stomach and intestines are adenocarcinomas. About 4 of 10 lung cancers are adenocarcinomas. Adenocarcinomas can also develop in many other organs.

Other cancer types

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

• Lymphomas develop 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, bones, cartilage, and related tissues.

• Germ cell tumors can develop in the testes (testicles) in men or the ovaries in women, or in the parts of the body where these organs 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 the cells do not look much like normal cells, the cancers are called poorly differentiated. Cancers of unknown primary are often poorly differentiated.

Broad categories of cancers of unknown primary

When first looking at the cancer cells under a microscope, doctors usually place a cancer of unknown primary (CUP) into 1 of 5 broad categories. Many of these cancers can be better classified later on, after more extensive testing is done.

Adenocarcinoma

As noted before, these cancers develop from gland cells. They make up about 6 of 10 cases of CUP.

Poorly differentiated carcinoma

When looking at these cancers under a microscope, there is enough detail to tell that they are carcinomas, but the cells are too irregular to classify them further. These cancers make up about 3 of 10 cases of CUP. On further testing, about 10% of these turn out to be lymphoma, melanoma, or sarcoma.

Squamous cell cancer

These cancers look like the flat cells on the surface of the skin or the linings of certain organs.

Poorly differentiated malignant neoplasm

These are clearly cancers, but the cells are so abnormal that the doctor can't tell what type of cell they may have started from. Most of these turn out to be lymphomas, sarcomas, or melanomas. Some turn out to be carcinomas upon further testing.

Neuroendocrine carcinoma

These rare cancers start from cells of the diffuse neuroendocrine system. This system consists of cells that are like nerve cells in certain ways and like hormone-making endocrine cells in other ways. These cells do not form an actual organ like the adrenal or thyroid glands. Instead, they are scattered throughout other organs like the esophagus, stomach, pancreas, intestines, and lungs. These cancers account for a small number of CUP cases. (Some poorly differentiated cancers are found to be neuroendocrine carcinomas upon further testing.)

Even when doctors don't know where the cancer started, they do their best to classify the type of cancer. This can help them select the best treatment. Some cancers respond very well to specific treatments, so it is very important to classify the cancer as much as possible. This is best done by looking at the cancer under a microscope and doing special tests in the lab (see the section, "How is a cancer of unknown primary diagnosed?").

Imaging tests and even surgery may also help find 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 types of cancer with the best hope for responding to treatment have been ruled out by certain tests, it usually becomes less important to find the exact origin or cancer type. In some cases, tests to find a primary site might be uncomfortable and may not be helpful. If the results are not likely to improve your survival or quality of life, the tests should not be done.

Last Medical Review: 10/15/2009
Last Revised: 10/15/2009