Symptoms and diagnosis of cancers of unknown primary origin

There are no symptoms specific to cancers of unknown primary origin. In general, the disease may present with unexplained and persistent fatigue, weight loss, or pain.

Other symptoms may occur depending on the type and location of the metastases, such as a lump in the neck or armpit in the case of lymph node metastases, abdominal or bone pain, or unexplained shortness of breath in the case of lung metastases. In some instances, there are no symptoms, and metastases are discovered incidentally during imaging studies. In the presence of unexplained and persistent symptoms, it is important to seek medical advice.

The diagnosis of CUP is established after several imaging tests—most commonly whole-body CT scans, PET scans, and sometimes MRI—used to assess the extent of metastatic disease and to rule out the presence of a detectable primary tumor. In some cases, endoscopic examinations are performed to look for a primary tumor in the digestive tract, bronchi, or bladder.

In all cases, a sample of a metastasis is obtained, most often by biopsy or surgery. This sample is analyzed by a pathologist to confirm the diagnosis, identify the characteristics of the cancer cells, and attempt to determine their tissue of origin. The sample is also essential for molecular analyses, which may help identify the origin of the cancer or reveal potential therapeutic targets.