Metastatic Cancer With Unknown Primary Site Differential Diagnoses

Updated: Apr 04, 2022
  • Author: Winston W Tan, MD, FACP; Chief Editor: Wafik S El-Deiry, MD, PhD  more...
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Diagnostic Considerations

The definition of cancer of unknown primary origin varies depending on the study, but most studies require that some minimum investigations be conducted before the term is applied. The patient should have a biopsy-proven malignancy. The evaluation should include a detailed history and physical examination, including head and neck, rectal, testicular, pelvic, and breast examinations.

Lab and radiological studies should include the following:

  • Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss)
  • Urinalysis (microscopic hematuria may be a sign of occult genitourinary malignancy)
  • Liver and renal function tests
  • Stool for occult blood
  • Chest radiograph
  • Computed tomography of abdomen and pelvis
  • Mammography in women
  • Measurement of prostate-specific antigen (PSA) in men

All chronic debilitating diseases are in the initial differential diagnosis. However, once a histological diagnosis of a malignancy is made, the list of differential diagnoses is narrowed to neoplastic conditions.