How cancer of unknown primary (CUP) is diagnosed
If you have any symptoms you will usually begin by seeing your GP, who will examine you. They will refer you to hospital for tests and for specialist advice and treatment. Some people are admitted directly to hospital if they have a symptom that’s making them very unwell.
The type of specialist doctor you’re referred to will depend on your symptoms. For example, if you have bowel or stomach symptoms, you’ll be referred to a gastroenterologist who treats problems of the digestive system. Or if you have kidney or bladder symptoms, you’ll see a urologist.
When it’s unclear where the primary cancer is, people may be referred to a specialist CUP team.
The specialist will ask about your general health, and your own and your family’s medical history. They will examine you and you may also have blood tests, x-rays and scans.
Your specialist will usually arrange for you to have some of the tests. For some people, these tests will diagnose the primary cancer.
When tests show a suspected cancer, you will usually have some tissue or cells removed to be examined under a microscope for cancer cells. This is called a biopsy. Some people with suspected CUP may be too unwell to have many of these tests. This may be because the cancer is very advanced or they may have other health problems.
If you decide to have treatment to relieve your symptoms rather than to treat the cancer, you may not need many tests. Treatment to control symptoms is known as supportive or palliative care.
Making decisions about tests
Back to top
Your doctors will want to find out as much as they can to help them plan the best treatment.
They will usually look for the most obvious primary cancers first. They will be guided by your symptoms and where the secondary cancer(s) are.
Your doctor may look at whether you have a strong family history of a certain cancer or a condition that increases your risk. They will also take your lifestyle into account, for example if you smoke or if a past occupation could have exposed you to asbestos or chemicals that increase the risk of certain cancers.
If the primary isn’t obvious, your doctors will need to do a series of tests. These will often be done in a particular order. Your specialist will use national guidelines to decide which tests are appropriate for you. The results of one test may suggest that another one would be useful. If the first tests don’t show what type of cancer you have, your doctors may try different tests for less obvious cancers.
Having tests can take up a lot of your energy and time. You shouldn’t have them if they aren’t likely to make a difference to your overall treatment or care.
Sometimes your specialist might advise you to begin treatment rather than have more tests.
One of the most important tests is a biopsy. This tells the doctors more about the type of cell the cancer developed from. Different tests are then done on the cells from the biopsy.
It’s not always possible to do a biopsy. Sometimes the cancer is too difficult to reach or a person is too unwell. Your specialist will discuss this with you and arrange other tests if you need them.
During a biopsy, a small piece of tissue or a sample of cells is removed so that it can be examined under a microscope. Sometimes a scan or ultrasound is used to help the doctor guide a biopsy needle to the exact area.
There are different types of biopsy. Your specialist will explain which of the following is best for you.
Fine needle aspiration (FNA) biopsy
This is a quick, simple procedure that can be done in the outpatient clinic. The doctor puts a fine needle into the lump and removes a few drops of fluid that will contain a sample of cells. You may have a local anaesthetic to numb the area where the needle goes in.
This test is similar to an FNA but uses a slightly larger needle. It can usually be done in the outpatient clinic. Your doctor will inject some local anaesthetic into the skin to numb the area first.
A core biopsy removes a larger amount of tissue than an FNA and can be often be more helpful with diagnosis.
If a lump or suspicious area is small enough, it can sometimes be completely cut out (excised) by a surgeon. For example, if you have a swollen lymph node, the whole node is removed.
Removing the whole lump means the doctors have as much tissue as possible. This will help them to make the diagnosis.
If the lump is near the surface, it’s normally a simple operation to remove it using a local anaesthetic. If the lump is deeper in the body, you’ll usually have a general anaesthetic and may need to stay in hospital overnight.
If the lump is very deep in the body and would need major surgery to remove it, your specialist may try a core or FNA biopsy first.
Sometimes the lump can be removed using an endoscope.
This procedure is similar to an excisional biopsy, but only part of the lump or tumour is removed. This is used when the lump is large and it would be too complicated to remove it all.
Removing fluid for testing
Back to top
Some people have a build-up of fluid next to the lung called a pleural effusion. Or they may have a collection of fluid in the tummy (abdomen) known as ascites. A sample of the fluid can be taken to check for cancer cells.
Your doctor will inject some local anaesthetic to numb the area before passing a small needle through the skin. Some of the fluid is drawn into a syringe and then examined under a microscope.
Removing fluid from the chest is called thoracentesis. Removing fluid from the abdomen is called paracentesis.
Your specialist may check whether the cancer is affecting the bone marrow. This is a spongy material that fills some of our bones and produces blood cells.
A small sample of bone marrow is taken from the back of the hip bone (pelvis) or occasionally the breast bone (sternum). The doctor puts a thin needle through the skin into the bone and takes a sample of the bone marrow. You’ll have a local anaesthetic to numb the area.
You may feel bruised and have an ache for a few days after having the sample taken. Mild painkillers can help.
Not everyone will need to have a bone marrow sample taken. Your doctor or specialist nurse can explain the procedure in more detail if they think it would be useful in your situation.
Examining the cells under a microscope
Back to top
A doctor called a pathologist will examine the sample to try to identify what kind of cell is involved and where in the body it first developed.
If the diagnosis isn’t clear, more tests can be done on the cells.
The biopsy tissue is treated with special proteins (antibodies). These attach to specific substances within some cancer cells. If the antibody attaches to the cell, it will give an idea of what type of cancer it is.
Many different antibodies may be needed to try to find out what type of cancer it is. The pathologist can also do tests to find out more about the type of cancer cells found.
These look at the changes in the chromosomes in a cell. This can be helpful as some chromosome changes are linked to certain cancers.
Hormone and protein receptors
Some cancer cells have receptors, which allow particular types of hormones or proteins to attach to the cancer cell. Tissue from the biopsy sample can be tested to see whether these receptors are present. This may help doctors find out where these cells came from.
Gene expression-based profiling (GeBP)
Back to top
Every cell type in our body has a unique genetic pattern. Research is looking at new ways of identifying genetic patterns in cancer tissue. This is called gene expression-based profiling. A number of tests are available in private hospitals. These look at the patterns of genes in the secondary tumour to try to find out the primary cancer.
At the moment, it’s not clear how helpful these techniques are or how best to use them. The results may help to narrow down which type of cancer it is. But they won’t necessarily be able to tell doctors the exact type of primary cancer. It may help doctors decide the best tests and treatments to try.
More research is needed to confirm the benefits of GeBP and you may be asked to take part in a clinical trial.