Biopsy for cancer of unknown primary (CUP)

If you have cancer of unknown primary (CUP) you may have a biopsy. This tells your doctor more about the cancer. There are different types of biopsy.

About biopsy for cancer of unknown primary (CUP)

Cancer of unknown primary (CUP) means that your doctor is not sure where the cancer started.

You may have a biopsy to help your doctor find out more about the cancer. A biopsy means taking a sample of cells or tissue from an abnormal area. This might be:

  • an obvious lump or swelling
  • something the doctor can feel when they examine you, such as an enlarged liver
  • something that can be seen on a scan.

The sample is examined under a microscope for cancer cells and tested to find out more.

There are different types of biopsy. Your doctor will explain which is best for you.

Having a biopsy for cancer of unknown primary (CUP)

Most types of biopsy can be done as an outpatient at a clinic or in the x-ray department. You will usually be given a local anaesthetic to numb the area first. The doctor then uses a needle to remove a small piece of tissue or a sample of cells.

The doctor may use a scan or ultrasound to help guide a biopsy needle to the exact area. If the suspected cancer is small and near the surface of the body, the doctor may remove the whole thing. This may mean removing a swollen lymph node rather than a tumour.

If the suspected cancer is deeper in the body, you may have a general anaesthetic and need to stay overnight. The doctor may remove the whole tumour. Or if the lump is large and difficult to remove, they may only take a small part of it.

It is not always possible to do a biopsy. Sometimes the cancer is too difficult to reach, or a person is too unwell. Your specialist doctor will discuss this with you and arrange other tests if you need them.

Removing fluid for testing

Some people have a build-up of fluid around the lung. This is called a pleural effusion. Or they may have a collection of fluid around the tummy (abdomen). This is called ascites. If there is a build-up of fluid, a sample of it can be taken and checked for cancer cells.

You have an injection of local anaesthetic to numb the area. The doctor uses a needle to remove some fluid. Sometimes the doctor uses an ultrasound to help find the best area to get a sample from.

Removing bone marrow for testing

You might have a bone marrow test to check whether the cancer is affecting the bone marrow. Bone marrow is a spongy material in the middle of our bones. It is where blood cells are made.

Not everyone needs to have a bone marrow test. If this test is likely to be useful in your situation, your cancer doctor or specialist nurse will explain the test in more detail.

Testing biopsy samples

When a biopsy has been taken, it is sent to a pathologist at a laboratory. A pathologist is a doctor who specialises in studying cells. They look at the sample under a microscope to check for cancer cells.

The results from the biopsy help you and your cancer doctor find out more about the type of cancer you have.

Identifying cancer types

For most secondary cancer diagnoses, doctors can find out where the cancer cells have spread from by looking at them under a microscope. For example, cells from a primary breast cancer that have spread to the liver usually still look like breast cancer cells. With CUP, doctors cannot always tell which part of the body the cancer cells are from.

But cancers are made up of different types of cells. These can be grouped based on the type of cells they are made up of. Knowing the type of cell can give the doctors a better idea about where the cancer may have started. This helps them to plan the best treatment.

Carcinomas are the most common type of cancer cell. About 85% of all cancers in the UK are carcinomas. They are cancer cells that start in the epithelial tissues. The epithelial tissues cover or line all the organs in the body. Our skin and the linings of cavities inside the body, such as the chest cavity, are also made of epithelial cells.

There are a few different types of carcinomas (see below).


These cancers grow from gland cells that line or cover some organs in the body. Gland cells make substances that the body needs, such as hormones. Adenocarcinomas are the most common type of cancer cell found in people with CUP.

Adenocarcinomas usually start in one of the following areas:

  • breasts
  • lungs
  • bowel
  • pancreas
  • kidneys
  • liver
  • stomach
  • ovaries
  • womb.

Squamous cell carcinomas

These cancers develop from flat cells that are usually found on the surface of the skin or in the inner lining of organs. They can develop in organs such as the lungs, gullet (oesophagus), cervix and the head and neck area.

Neuroendocrine carcinomas

These are a rarer type of cancer. They are made up of nerve cells that produce hormones.

Poorly or undifferentiated cancer cells

  • Poorly differentiated cancer cells look very different from normal cells.
  • Undifferentiated cancer cells look extremely different to normal cells.

Both poorly and undifferentiated cancer cells make it difficult to tell the type of primary cancer. Further tests may sometimes tell the doctors more.

Other tests on the biopsy

Some other tests can be done on a biopsy sample. They may give doctors more information about the type of cancer you have.

You may have one of the following tests:

  • Immunohistochemistry test

    this test finds out whether there are particular proteins (antibodies) on the surface of the cell. These may be linked to some cancer types.

  • Cytogenetic test

    this test looks at the changes in the chromosomes in a cell. Changes in the structure of some chromosomes can be linked to some cancer types.

  • Hormone and protein receptor test

    this test looks at cancer cells with receptors. Some cancer cells have receptors which certain types of hormones or proteins to attach to. Identifying these may help doctors find out where the cancer cells came from.

Gene expression-based profiling (GEBP)

GEBP looks for patterns of genes in the secondary cancer tissue taken at biopsy. These patterns can help doctors find out what the primary cancer might be. This can help them decide which treatments are most suitable for you.

These types of tests are still being developed. It is not clear how helpful they are. Doctors are still trying to find out how best to use them. The results may help narrow down which type of cancer it is, but cannot tell doctors the exact type of primary cancer. GEBP may still help doctors make decisions about which other tests you should to have, and which treatments to use.

At the moment, gene profiling tests for people with CUP are not available on the NHS. But you may be able to have them as part of a clinical trial. Or GEBP may be available privately or covered by private health insurance companies.