History and exam

Key diagnostic factors

common

bone pain

May be associated with pathologic fracture.

family history of cancer

A detailed family history should assess the possibility of an inherited cancer syndrome.

Other diagnostic factors

common

jaundice

Obstructive jaundice may be present due to pancreaticobiliary lesions.

ascites

May indicate peritoneal adenocarcinoma.

personal history of previous cancer

May indicate the possibility of an inherited cancer syndrome.

history of smoking

Cohort data indicate that current smokers are at an increased risk for cancer of unknown primary site (CUP) compared with never-smokers.[37]​ Smoking more cigarettes, and longer duration of smoking, was associated with higher CUP risk.

uncommon

pain

May be from peritoneal or pleural irritation.

palpable mass

May be noted on physical exam.

symptoms of postobstructive pneumonia

For example cough, wheeze, and dyspnea.

Occurs with parenchymal lung involvement.

neurologic pain or weakness

Suggests possible brain or peripheral nervous system metastases.

headaches

Suggests possible central nervous system involvement, which can be present in several tumor subtypes. It may provide some clues but is not specific for a particular tumor type.

seizures

Suggests possible central nervous system involvement, which can be present in several tumor subtypes. It may provide some clues but is not specific for a particular tumor type.

cervical chain adenopathy

There may be localized swelling if superficial lymph nodes are involved.

constitutional symptoms

Patients often report a nonspecific deterioration in their overall health: for example, weakness, fatigue, malaise, anorexia, poor appetite, early satiety, nausea, malaise, and weight loss. Such symptoms tend to be progressive.

depression

Can be a symptom of central nervous system (CNS) involvement, but can also suggest infection or electrolyte derangement or other influences.

CNS involvement can be present in several tumor subtypes. It may provide some clues, but is not specific for a particular tumor type.

delirium

Can be a symptom of central nervous system (CNS) involvement, but can also suggest infection or electrolyte derangement or other influences.

CNS involvement can be present in several tumor subtypes. It may provide some clues, but is not specific for a particular tumor type.

history of heavy alcohol consumption

One cohort study found that cancer of unknown primary site risk increased with higher levels of alcohol intake.[37]

hepatomegaly

May be noted on exam due to liver involvement.

hemoptysis

Occurs with parenchymal lung involvement.

Risk factors

weak

age >60 years

In a US population-based cohort of patients with cancer of unknown primary site diagnosed between 2010 and 2014, median age at diagnosis was 71 years.​[8]

In the UK, between 2016 and 2018, approximately 60% of new cases were diagnosed in people ages 75 years or more.[9]

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