Cancer of unknown primary origin

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Cancer of unknown primary origin (CUP) is the diagnosis when metastatic cancer is found but the place where the cancer began (the primary site) cannot be determined. About two to four percent of all cancer patients have a cancer whose primary site is never identified. Treatment for CUP depends on many factors, including where the metastatic cancer is found, what the cancer cells look like under a microscope, and the patient’s age and general health. Recent advances in diagnostic techniques have improved doctors' abilities to find the primary sites, even when the original diagnoses are "CUP."


Cancer can begin in any organ or tissue of the body. The primary, or original, tumor is usually named for the part of the body or the type of tissue in which the cancer begins. The disease may spread (metastasize) from the primary tumor and form metastatic tumors in other parts of the body. For example, breast cancer cells can metastasize to the lungs and cause the growth of a new tumor. When this happens, the tumor in the lung is called metastatic breast cancer because it is composed of breast cancer cells, not lung cancer cells.

Each year in the United States, several thousand people are diagnosed with metastatic cancer whose primary cancer site is not known. When the primary site cannot be identified, this disease may be called cancer of unknown primary (CUP). Most often, the metastatic cancer is first found in the lymph nodes, liver, lung, or bone.

Identification of the primary tumor[edit]

In recent years, microscopic and other diagnostic techniques have improved dramatically. For this reason, doctors can now determine the primary site in about four out of five cases first diagnosed as CUP. In some cases, the part of the body where cancer cells are first found helps the doctor decide which diagnostic tests will be most helpful. Doctors also have other clues that help them find the primary site:

When the cancer cells are poorly differentiated (that is, they look less evolved than normal cells when viewed under a microscope), the cancer may be either a lymphoma or a germ cell tumor. Lymphomas begin in the lymphatic system. Germ cell tumors usually begin in the ovaries and testes.

In patients in whom the primary cancer is eventually found, the lung and pancreas are the most common primary cancer sites. CUP also may be traced to the breast, prostate, colon, or rectum as the primary site.

Sometimes, however, even when doctors use very sophisticated methods to try to identify the primary site, the part of the body the cancer cells came from cannot be determined. About 2 to 4 percent of all cancer patients have a cancer whose primary site is never found.

Identifying the primary tumor site is important because knowing its location and type often helps doctors plan the best treatment. Treatment that is specific to the suspected type of cancer is likely to be more effective. Still, when diagnostic tests have not identified the primary site, doctors must decide whether the potential benefits of more extensive testing outweigh a patient’s discomfort and the financial costs.


CUP is a term that refers to many different cancers. For that reason, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells and the patient’s age and overall physical condition. No method is standard, but chemotherapy, radiation therapy, hormone therapy, and surgery may be used alone or in combination to treat patients who have CUP. Even when the cancer is unlikely to be cured, treatment may help the patient live longer or improve the patient’s quality of life. However, the potential side effects of the treatment must be considered along with the potential benefits.


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