What is Tumour of unknown primary (TUP)?

Tumour of unknown primary is defined as the presence of a metastatic cancer without a known primary site of origin.
A malignant tumour (cancer) is made up of an abundance of cancer cells. Some of these cells may break away from the original tumour (the primary tumour) and spread to other parts of the body. The new tumours that these cells form in other sites are called metastases, or secondary tumours.
The type of cells in the secondary tumours is usually similar to that of the primary tumour. For example, bowel cancer that has spread to the liver will have the same cell type in both sites (i.e. the secondary tumour in the liver contains bowel cancer cells). This enables us to identify the origin (primary site) of metastases/secondary tumours.
However, not all cancers behave in the same manner. Some secondary tumours are made up of cells which cannot be identified under the microscope, making it impossible to tell what kind of a primary cancer they have come from. This kind of cancer forms a different clinical entity: tumour of unknown primary.


TUP is common. It accounts for 2-5% of all cancers.
The average age when patients are diagnosed is 59 years. It is slightly more common in males.

Risk Factors

The exact cause of tumour of unknown primary is unknown. Risk factors depend on the different underlying primary tumours.
Reasons causing failure of detection of the primary tumour include:

  • Early spread of dividing cells from the original tumour to distant sites and failure to grow at the primary/original site – the secondary sites are thus detectable while the primary sites are not.


  • The possibility that the primary tumour is hidden by larger secondary tumours close to it and is thus not seen on x-ray and scans.



Most patients with malignant tumours of unknown primary have fairly advanced-staged cancers.
Staging of tumours of unknown primary is completely different from other tumours. It is already known the tumour has spread/metastasised, so the goal is to locate the primary origin. Staging tests should be individualized based on the specific findings under the microscope and the general condition of the patient.

How is it Diagnosed

The usual basic tests will be done, including those to look at the blood and other blood components. Other general tests will determine the function of the liver and kidney. A chest x-ray may also be done. In some cases, tumour markers may be used.


The disease is generally associated with poor outcome, with an average survival of 5 to 6 months. Overall, the survival rate at 5 years after diagnosis is less than 10%.
There are, however, a few exceptions of TUPs where prolonged survival may be achieved with proper treatment, for example squamous cell carcinomas of cervical and inguinal lymph nodes, adenocarcinoma of the axilla in a female patient etc.


If a primary site is strongly suggested, treatment is based upon the usual treatment for advanced cancer arising from that site.
Certain groups of patients with no obvious primary origin can be treated with specific chemotherapy, for example:

  • Women with lymph node abnormalities in the underarm region (treated as stage II breast cancer)
  • Men with raised PSA level or distant spread to the bone (treated as advanced prostate cancer)
  • Lymph node abnormalities in the neck region (treated as advanced head and neck cancer)If the patient does not fall into any of the subgroups (which happens in most cases), general blind chemotherapy is used. Current chemotherapy have improved treatment outcome in these patients, with an average survival of about 12 months.


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