How cancer of unknown primary is diagnosed
Usually you 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’re a woman with gynaecological symptoms, you’ll see a gynaecologist.
At the hospital 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 a blood test and a chest x-ray to check your general health.
One of the most important tests is a biopsy, because it provides doctors with information 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 to have the procedure. Your specialist will discuss this with you and, if necessary, arrange other tests instead.
During a biopsy, a small piece of tissue or a sample of cells is removed so that it can be examined under a microscope. If you’re having a biopsy of an area or organ inside the body, you’ll have a general anaesthetic and may need a short stay in hospital. 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 inserts a fine needle into the lump and removes a sample of cells.
If the secondary cancer is near the skin’s surface, a needle can be inserted into the area to remove a sample of tissue. Your doctor will inject some local anaesthetic into the skin to numb the area first.
Sometimes, if a lump or suspicious area is small enough, it can be completely cut out (excised). For example, if you have a swollen lymph node, the whole node is removed. You’ll usually have this biopsy under a general anaesthetic.
Removing fluid for testing
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Some people have a build-up of fluid next to the lung (pleural effusion) or fluid collecting in the tummy area (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.
Examining the cells under a microscope
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A doctor called a pathologist examines the cells to try to identify what kind of cell is involved and where in the body it developed (the primary). Techniques to examine cells are developing and there are specialised tests that can be done.
Immunohistochemistry tests treat the biopsy tissue with antibodies and dyes to see if it shows a specific substance found in some types of cancer. Tests can also be done to find out more about the type of cancer cells found. Cytogenetic tests look at the changes in the chromosomes in a cell. This can be helpful as some chromosome changes are linked to certain cancers.
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 or not, which may help doctors find out where these cells came from.
Gene expression profiling tests
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Every cell type in our body has a unique genetic pattern. Research is looking at new ways of identifying genetic patterns in cancer tissue (gene profiling). A number of tests available privately look at the patterns of genes in CUP to try to identify the primary cancer. But at present it’s not clear how helpful these techniques are or how best to use them. The results may help narrow down which type of cancer it is, but won’t necessarily be able to tell doctors the exact type of primary cancer. There is no evidence that having these tests changes the way people with CUP are treated or that they improve their outlook.
The National Institute for Health and Clinical Excellence (NICE) currently gives advice on how cancers should be treated in the NHS in England and Wales. NICE advises that gene profiling tests shouldn’t be used to try to find the primary cancer in people with suspected CUP except as part of a clinical trial.
Making decisions about tests
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Your specialist will decide which tests are appropriate for you. Having tests can take up a lot of your energy and time. You shouldn’t be put through these if they aren’t likely to make a difference to your overall treatment or care.
If tests rule out the primary cancers that have a better outlook, your specialist might advise you to begin treatment rather than have more tests. This means they can get on with controlling the cancer and its symptoms.