Cancer of unknown primary (CUP)

Cancer of unknown primary (CUP)

What is cancer of unknown primary?

Cancer of unknown primary (CUP) is a secondary cancer that has spread to a new location from somewhere else in the body. However, it’s not clear where in the body it started, so the primary cancer is unknown.

– Jane

For most people diagnosed with cancer, the primary cancer is easy to identify. Doctors conduct tests to find out where the cancer started to grow and to see if the cancer has spread.

When cancer is found in one or more secondary sites but it is not clear from the test results where the cancer began, the cancer is usually known as cancer of unknown primary, or CUP. Health professionals may also call it tumour of unknown origin (TUO), metastatic malignancy of unknown primary, or occult primary cancer.

Because it is a secondary cancer, CUP is considered advanced cancer. This means that in some cases, treatment focuses on controlling symptoms. In other cases, doctors actively treat the cancer while still making sure that symptoms are well managed. Your doctor will discuss the best approach for you.

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How can doctors tell it is a secondary cancer?

To diagnose secondary cancer, a specialist doctor called a pathologist examines the cancer cells under a microscope. The pathologist can see that the cancer cells do not belong to or originate in the surrounding tissue, and this can be confirmed by further laboratory tests. With CUP, the cells could possibly have come from a number of places but no primary cancer can be found.

Why can't the primary cancer be found?

There could be several reasons why the primary cancer cannot be found. It may be that:

  • the secondary cancers have grown and spread quickly, but the primary cancer is still too small to be seen on scans
  • your immune system has destroyed the primary cancer, but not the secondary cancer
  • the primary cancer cannot be seen on x-rays, scans or endoscopies because it is hidden by a secondary cancer that has grown close to it
  • the primary cancer has been removed during surgery for another condition without doctors realising the cancer was there, so some cancer cells remained behind and have since spread
  • there may never have been a primary cancer mass – a single cell may have changed into cancerous cells and then spread through the body.

Does it matter that the primary cancer can't be found?

Finding the primary cancer helps doctors decide what treatment to recommend. If it can’t be found, the treatment path can be less clear but treatment can still be given.

To plan the treatment, your doctor will try to learn as much as possible about the spread of the cancer, the cells involved, and your symptoms and medical history.

Who gets CUP?

CUP is diagnosed more often than many people realise – it is the 11th most common cancer in Australian women and the 12th most common cancer in Australian men.

There are nearly 3000 new cases of CUP diagnosed each year in Australia. For both men and women, CUP is more likely to occur over the age of 60.

What causes CUP?

Different cases of CUP will have different causes, but without knowing where the cancer started, it’s difficult to be specific. 

Cancer is a group of more than 200 different diseases. Each type has different risk factors, such as getting older, poor diet, smoking, excessive alcohol consumption, being overweight and certain infections. These risk factors may play a role in some cases of CUP.

What are the different types of CUP?

Even if tests can’t find where the cancer started, your doctor will try to work out what type of cell the cancer developed from. Knowing the type of cell helps doctors work out what sort of treatment is most likely to be helpful.

In about 95% of people with CUP, doctors can tell that they have some sort of carcinoma. Carcinoma means any cancer that begins in the cells lining the skin and internal organs (epithelial cells). There are different types of carcinoma depending on which type of epithelial cells are affected.

There are other forms of cancer that are not carcinomas. For example, lymphomas begin in the cells of the immune system, melanomas begin in the cells that give skin its pigment, and sarcomas begin in the cells of muscles, fat and other connective tissue.

Types of CUP

  • Adenocarcinomas develop from glandular cells, which form part of the lining of many organs.
  • Common primary sites include the breast, colon, prostate, stomach, pancreas, liver and lungs.
  • Most people with CUP have an adenocarcinoma.
Squamous cell carcinomas (SCC)
  • These carcinomas develop from squamous cells, which are thin, flat cells normally found on the surface of the skin or the lining of certain organs.
  • Common primary sites include the head and neck area, skin, oesophagus, lungs, vagina and cervix.
  • About 5% of people with CUP have squamous cell carcinomas.
Neuroendocrine carcinomas
  • These carcinomas develop from specialised nerve cells that sometimes produce hormones.
  • Common primary sites include the pancreas and gastrointestinal tract.
  • About 3% of people with CUP have neuroendocrine carcinomas.
Poorly differentiated carcinomas
  • There is enough detail to tell that the cells are carcinomas, but they look too abnormal to classify further.
  • About 30% of people with CUP have poorly differentiated carcinomas.
Undifferentiated neoplasms
  • Neoplasm is another word for tumour. In an undifferentiated neoplasm, the cells can be identified as cancerous, but it is not possible to work out whether they are a carcinoma, sarcoma, melanoma or another form of cancer.
  • About 5% of people with CUP have undifferentiated neoplasms.

This information was last reviewed in May 2016
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