Carcinoma of Unknown Primary

Carcinoma of unknown primary is a rare cancer diagnosis given when cancer has spread and the original site of the cancer is unknown. Treatment is based on what can be discovered and what’s the most likely type of cancer. Options include standard treatments and investigational drugs.


What is carcinoma of unknown primary (CUP)?

Carcinoma of unknown primary (CUP) is a diagnosis given when cancer is found in your body but it’s not known where the original cancer started.

Cancer can start in any tissue in your body. Where it first starts — the primary location — defines the cancer. In other words, if cancer begins in your liver and spreads (metastasizes) to your lung, it’s still called liver cancer and not lung cancer.

Cells of your tissues and organs have features that are unique to that tissue and other features that are shared by several tissue types. Features are things like the size and shape of the cells, their DNA and cell arrangement. Knowing various cell types helps doctors recognize healthy cells and cancer cells. Cancer changes the usual appearance of a cell type. Doctors can determine that cancer has spread when they find abnormal cell types in another part of your body where they don’t belong (for example, finding abnormal liver cells in your lung tissue).

Sometimes when cancer spreads to another area of your body and the abnormal cell features don’t lead to finding where cancer first started, the cancer is called carcinoma of unknown primary (CUP). It’s also known as occult primary tumor.


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Why can’t the primary cancer be found?

The primary cancer (cancer that first formed) may not be found because:

  • It was too small to be found by imaging tests.
  • Your body’s immune system destroyed it.
  • It was removed during an operation for another reason (not knowing any cancer was present).

How common is carcinoma of unknown primary?

Carcinoma of unknown primary is the diagnosis in about 2% of all cancers each year in the U.S.


Symptoms and Causes

What are the signs and symptoms of carcinoma of unknown primary (CUP)?

There are no unique symptoms to carcinoma of unknown primary (CUP). If you notice any of these general signs and symptoms of cancer, see your healthcare provider:

  • Lump or thickening in any part of your body.
  • Pain in your chest or abdomen.
  • Swollen, firm, non-tender lymph nodes — particularly noticeable on the sides of your neck, collarbone, under your arms or groin area.
  • A cough that doesn’t go away or hoarseness in your voice.
  • Change in bowel or bladder habits, such as constipation, diarrhea, or frequent urination.
  • Feeling of fullness or bloating in your abdomen.
  • Unusual bleeding or discharge.
  • Fever for no known reason.
  • Feeling tired.
  • Night sweats.
  • Unexpected weight loss or loss of appetite.

What causes cancer of unknown primary?

Cancer can have many different causes. Pinpointing a particular cause of carcinoma of unknown primary is especially difficult because the original site of the cancer is not known.

In general, cancer is the result of changes in the DNA of cells. These abnormal cells then divide, multiply and possibly spread to areas in your body beyond where they started.


Diagnosis and Tests

How is carcinoma of unknown primary diagnosed?

Your healthcare provider may first perform or order one or more of these standard tests:

  • Physical exam and history: Your healthcare providerwill first ask about your signs and symptoms then perform a physical exam, looking for lumps, swollen lymph nodes or anything unusual. Your provider will ask about your health history, your family’s medical history, your current health issues and current medications, vitamins and supplements or other treatments.
  • Urine test: This test checks the color and contents of your urine.
  • Blood studies: This blood test reports higher- or lower-than-normal levels of substances that are released into your blood by your body’s organs and tissues.
  • Complete blood count: This blood test checks the numbers and proportion of the red and white blood cells, platelets and hemoglobin.
  • Fecal occult blood test: A test uses a microscope to look for even the tiniest amount of blood in your poop (stool).

Is a biopsy always performed if there’s a suspicion of cancer?

If your healthcare provider finds a lump or your symptoms and initial round of tests indicate that you may have cancer, they will take a biopsy. During a biopsy, some cells or tissue are removed from your body (gathered in a needle through your skin or during an operation) so they can be looked at under a microscope.

A pathologist (a doctor who examines cells) uses different kinds of high-powered microscopes and dyes, stains or chemicals to make cell details easier to see and to look for changes in the DNA of cells. Certain cell changes or details are linked to certain types of cancers.

What types of imaging tests and other tests may be done to find where the cancer first began?

Several types of scans and other tests or procedures may be used, including:

  • Imaging: CT scan (computerized axial tomography), MRI (magnetic resonance imaging) and PET scan(positron emission tomography). These scans all show detailed pictures of the inside of your body. They can show details of abnormal areas, show how far cancer has spread and try to find where the cancer may have started.
  • Mammogram: This is an X-ray of breast tissue.
  • Endoscopy: An endoscope is a thin, tube-like instrument with a light and a lens for viewing and a tool to remove tissue samples. It is inserted through a cut (incision) or an opening in your body (mouth or rectum) to look at organs and tissues.
  • Tumor marker test: Tumor markers are substances released by certain cancers into the bloodstream. Examples of tumor markers include prostate-specific antigen (PSA) for prostate cancer, alpha-fetoprotein (AFP) for cancers of the liver and CA-125 for cancer of the ovary or fallopian tube.

Are there stages to carcinoma of unknown primary like there are with other cancers?

Normally, cancers are staged based on the extent of how far they spread in your body. Carcinoma of unknown primary (CUP) has already spread to other areas of your body when it’s found. Because it’s not known where the cancer began or how long it’s been present, there’s no staging system for CUP.

Management and Treatment

How is carcinoma of unknown primary (CUP) treated?

Since there’s no staging for carcinoma of unknown primary (CUP) because it has already spread and the primary cancer site may not be known, your healthcare provider plans treatment based on what is known and what is thought to be the most likely type of cancer.

Your healthcare team will consider where the cancer was found in your body, what type of original cells the cancer cells look like, how abnormal the cells look and your test results.

Treatments usually considered include:

  • Surgery: Your surgeon will remove the cancer along with a little healthy tissue surrounding it. This approach is used if your cancer is thought to be limited to one area. Radiation or chemotherapy may follow to kill any remaining cancer cells.
  • Radiation therapy: Radiation may be external (beams of radiation targeted on the cancer) or internal (radioactive seeds, wires, needles or catheters placed in or near the cancer). Radiation therapy is used if cancer is thought to be limited to one area.
  • Chemotherapy: This is a drug treatment that either kills cancer cells or stops their growth. One or more drugs can be given by IV or taken by mouth or placed directly into an area of your body. Chemotherapy is recommended if cancer is thought to be in more than one area.
  • Hormone therapy: Some hormones can cause some cancers to grow. Hormone therapy means using drugs, surgery or radiation to block the action of hormones to prevent cancer from growing and spreading.
  • Targeted therapy: This approach uses drugs or substances to attack cancer cells while not harming nearby healthy cells. Some of these products are used to treat specific types of cancers but may help treat some cases of CUP if the type of cancer cell is known.

Your healthcare providers will also provide pain relief and other treatments to manage your symptoms.

How is carcinoma of unknown primary (CUP) treated if it returns?

Carcinoma of unknown primary (CUP) that recurs is usually treated within a clinical trial with an investigational drug. Your healthcare team will determine where in your body cancer has returned, the type of cancer it is and how it was treated before. You and your healthcare team will decide the treatment option that is best for you.

What’s involved in participating in a clinical trial and where can I find more information?

Clinical trials enroll people from all points in their plan of care — before, during or after starting standard treatment approaches. People involved in cancer clinical trials receive either a standard treatment or a new treatment. Neither you nor your healthcare professional knows which treatment you’re receiving.

Clinical trials are done to find out if the new drug is safe and effective or even better than the standard treatment. All drugs approved for use in the U.S. must have undergone clinical trials. Talk with your healthcare team to discuss if this is a good treatment choice for you.


Can carcinoma of unknown primary be prevented?

Like other cancers, certain risk factors can increase your risk of cancer. However, having or not having risk factors doesn’t guarantee that you will or won’t get cancer. Still, known cancer risks that you can act on to improve your general health and perhaps lower your risk of cancer include:

  • Stop smoking if you smoke. Smoking increases the risk of many cancers.
  • Eat a healthy diet full of vegetables, fruits, beans, legumes and lean proteins.
  • Lose weight if you are overweight.
  • Wear sunscreen, hats and other protective clothing to reduce the risk of skin cancer.
  • Stay physically active.
  • Limit your alcohol intake — women should not drink more than one alcoholic beverage per day and men, no more than two.

Outlook / Prognosis

What outcome is possible if I have carcinoma of unknown primary?

Because carcinoma of unknown primary (CUP) is not the primary cancer and has already spread when it was found, the potential to cure the cancer is less likely than finding a primary cancer early. Survival rates vary from person to person, ranging from months to several years. Life expectancy depends on factors that affect outcomes including:

  • Where the cancer is found.
  • How much it has spread to other organs and tissues.
  • The type of cancer cells and how abnormal they look under a microscope.
  • Your general health.
  • Your response to treatments you have already received.

A note from Cleveland Clinic

Hearing news that you have cancer is scary. Know that your healthcare team is with you. They will perform the needed tests and scans to develop and create the best possible treatment plan. Keep in mind that there’s always hope and that survival statistics are based on large numbers of people who had the disease. What might happen in your case is unique to you. Also know that many treatments for cancer are available and many investigational drugs can be tried through a clinical trial. Don’t hesitate to discuss your concerns, fears and prognosis with your team. Not only can they be a source of knowledge, comfort and support, they can also direct you to other healthcare professionals skilled in coping with stress and anxiety that often come with a diagnosis of cancer and can help you find local support groups.

Medically Reviewed

Last reviewed on 06/24/2021.

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