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Carcinoma of Unknown Primary Treatment (PDQ®)

  • Last Modified: 05/02/2014

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General Information About Carcinoma of Unknown Primary



Carcinoma of unknown primary (CUP) is a rare disease in which malignant (cancer) cells are found in the body but the place the cancer began is not known.

Cancer can form in any tissue of the body. The primary cancer (the cancer that first formed) can spread to other parts of the body. This process is called metastasis. Cancer cells usually look like the cells in the type of tissue in which the cancer began. For example, breast cancer cells may spread to the lung. Because the cancer began in the breast, the cancer cells in the lung look like breast cancer cells.

Sometimes doctors find where the cancer has spread but cannot find where in the body the cancer first began to grow. This type of cancer is called a cancer of unknown primary (CUP) or occult primary tumor.

Tests are done to find where the primary cancer began and to get information about where the cancer has spread. When tests are able to find the primary cancer, the cancer is no longer a CUP and treatment is based on the type of primary cancer.

Sometimes the primary cancer is never found.

The primary cancer (the cancer that first formed) may not be found for one of the following reasons:

  • The primary cancer is very small and grows slowly.
  • The body’s immune system killed the primary cancer.
  • The primary cancer was removed during surgery for another condition and doctors didn’t know cancer had formed. For example, a uterus with cancer may be removed during a hysterectomy to treat a serious infection.

The signs and symptoms of CUP are different, depending on where the cancer has spread in the body.

Sometimes CUP does not cause any signs or symptoms. Signs and symptoms may be caused by CUP or by other conditions. Check with your doctor if you have any of the following:

  • Lump or thickening in any part of the body.
  • Pain that is in one part of the body and does not go away.
  • A cough that does not go away or hoarseness in the voice.
  • Change in bowel or bladder habits, such as constipation, diarrhea, or frequent urination.
  • Unusual bleeding or discharge.
  • Fever for no known reason that does not go away.
  • Night sweats.
  • Weight loss for no known reason or loss of appetite.

Different tests are used to detect (find) cancer.

The following tests and procedures may be used:

  • Physical exam and history : An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

  • Urinalysis : A test to check the color of urine and its contents, such as sugar, protein, blood, and bacteria.

  • Blood chemistry studies : A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

  • Complete blood count : A procedure in which a sample of blood is drawn and checked for the following:

  • Fecal occult blood test : A test to check stool (solid waste) for blood that can only be seen with a microscope. Small samples of stool are placed on special cards and returned to the doctor or laboratory for testing. Because some cancers bleed, blood in the stool may be a sign of cancer in the colon or rectum.

If tests show there may be cancer, a biopsy is done.

A biopsy is the removal of cells or tissues so they can be viewed under a microscope by a pathologist. The pathologist views the tissue under a microscope to look for cancer cells and to find out the type of cancer. The type of biopsy that is done depends on the part of the body being tested for cancer. One of the following types of biopsies may be used:

If cancer is found, one or more of the following laboratory tests may be used to study the tissue samples and find out the type of cancer:

  • Histologic study: A laboratory test in which stains are added to a sample of cancer cells or tissue and viewed under a microscope to look for certain changes in the cells. Certain changes in the cells are linked to certain types of cancer.

  • Immunohistochemistry : A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer.

  • Reverse transcriptionpolymerase chain reaction (RT-PCR) test: A laboratory test in which cells in a sample of tissue are studied using chemicals to look for certain changes in the genes.

  • Cytogenetic analysis : A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes. Changes in certain chromosomes are linked to certain types of cancer.

  • Light and electron microscopy : A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.

When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found, a diagnosis of CUP may be made.

The cells in the body have a certain look that depends on the type of tissue they come from. For example, a sample of cancer tissue taken from the breast is expected to be made up of breast cells. However, if the sample of tissue is a different type of cell (not made up of breast cells), it is likely that the cells have spread to the breast from another part of the body. In order to plan treatment, doctors first try to find the primary cancer (the cancer that first formed).

Tests and procedures used to find the primary cancer depend on where the cancer has spread.

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.

  • When cancer is found above the diaphragm (the thin muscle under the lungs that helps with breathing), the primary cancer site is likely to be in the upper part of the body, such as in the lung or breast.
  • When cancer is found below the diaphragm, the primary cancer site is likely to be in the lower part of the body, such as the pancreas, liver, or other organ in the abdomen.
  • Some cancers commonly spread to certain areas of the body. For cancer found in the lymph nodes in the neck, the primary cancer site is likely to be in the head or neck, because head and neck cancers often spread to the lymph nodes in the neck.

The following tests and procedures may be done to find where the cancer first began:

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the chest or abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

  • Mammogram : An x-ray of the breast.

  • Endoscopy : A procedure to look at organs and tissues inside the body to check for abnormal areas. An endoscope is inserted through an incision (cut) in the skin or opening in the body, such as the mouth. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of disease. For example, a colonoscopy may be done.

  • Tumor marker test : A procedure in which a sample of blood, urine, or tissue is checked to measure the amounts of certain substances made by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the body. These are called tumor markers. The blood may be checked for the levels of CA-125, CgA, alpha-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), or prostate-specific antigen (PSA).

Sometimes, none of the tests can find the primary cancer site. In these cases, treatment may be based on what the doctor thinks is the most likely type of cancer.

Certain factors affect prognosis (chance of recovery).

The prognosis (chance of recovery) depends on the following:

  • Where the cancer began in the body and where it has spread.
  • The number of organs with cancer in them.
  • The way the tumor cells look when viewed under a microscope.
  • Whether the patient is male or female.
  • Whether the cancer has just been diagnosed or has recurred (come back).

For most patients with CUP, current treatments do not cure the cancer. Patients may want to take part in one of the many clinical trials being done to improve treatment. Clinical trials for CUP are taking place in many parts of the country. Information about clinical trials is available from the NCI Web site.