History and exam
Key diagnostic factors
common
pain (e.g., abdomen, chest, bone)
Abdominal pain due to peritoneal irritation. Chest pain due to pleural irritation. Bone pain due to pathologic fracture with bony involvement.
family history of cancer
A detailed family history should assess the possibility of an inherited cancer syndrome.
constitutional symptoms
Patients often report nonspecific constitutional symptoms (e.g., weakness, fatigue, malaise, anorexia, poor appetite, early satiety, nausea, malaise, and weight loss).
Such symptoms tend to be progressive, and lead to a decline in overall health and performance status, and decreased ability to tolerate recommended treatments.
Other diagnostic factors
common
jaundice
Obstructive jaundice may be present due to pancreaticobiliary lesions.
symptoms of postobstructive pneumonia
For example cough, wheeze, and dyspnea.
Occurs with parenchymal lung involvement.
hemoptysis
Occurs with parenchymal lung involvement
ascites
May indicate peritoneal adenocarcinoma.
cervical chain adenopathy
There may be localized swelling if superficial lymph nodes are involved.
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.[28] Smoking more cigarettes, and longer duration of smoking, was associated with higher CUP risk.
uncommon
palpable mass
May be noted on physical exam.
neuropathic 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.
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.[28]
hepatomegaly
May be noted on exam due to liver involvement.
Risk factors
weak
age >60 years
Cancer of unknown primary (CUP) most commonly occurs in older people (age >60 years).[2][9] [10]
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.[9]
In the UK, between 2016 and 2018, approximately 60% of new cases were diagnosed in people ages 75 years or more.[10]
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