Cancer of Unknown Primary

Sophie Schellhammer

Background 

  • Cancer of unknown primary (CUP) accounts for 2% of all cancer diagnoses.
  • Often, CUP is discovered incidentally on imaging tests or due to symptomatic metastasis.

Presentation 

  • Variable presentation, can include generalized fatigue and weight loss, symptoms related to metastases, lymphadenopathy, or asymptomatic.

Initial Evaluation 

  • Physical exam: including pelvic / breast exam for females and prostate/testicular exam for males.
  • CMP, CBC w/ diff, UA, PSA in males.
  • CT C/A/P with contrast (reveals the origin in up to 35% of pts).
  • Once lesions are identified, should undergo biopsy of the most accessible lesion.
  • If imaging is suggestive of GI origin, or pt has liver metastasis without other obvious dominant lesion, colonoscopy and/or upper EGD should be performed.
  • If physical exam with breast abnormalities, or pt has axillary lymphadenopathy, bilateral mammography should be performed.
  • Breast MRI may be considered even in the setting of negative mammography if clinical suspicion is high.

Evaluation following biopsy 

Adenocarcinoma (70% of CUP)

  • Most common primary: pancreas, lung, HPB tree, and kidney.
  • Most common metastasis: liver, lungs, lymph nodes and bones.
  • If clinical suspicion is high for certain primary site, notify pathology to inform stain
    selection.
  • Serum studies such as CEA, CA19-9, AFP, CA 125, CA15-3 are often not sensitive or specific and will be elevated in the setting of many types of adenocarcinoma.

Neuroendocrine tumors (1% of CUP)

  • Low grade: Metastatic carcinoid or islet cell tumors sometimes present without obvious primary site, usually with liver metastases. In some pts, primary sites are later identified in the intestine or pancreas.
  • High grade: Usually aggressive malignancy, often with metastases in multiple sites. Lymph nodes in the retroperitoneum and mediastinum are frequently involved.

Squamous cell carcinoma (5% of CUP)

  • Work up depends on the location of adenopathy:
  • Upper and mid-cervical lymphadenopathy.
  • Most common primary: head and neck cancer
  • Evaluation: CT head and neck, direct laryngoscopy, nasopharyngoscopy.

Lower cervical/supraclavicular lymphadenopathy

  • Most common primary: lung or head and neck.
  • Evaluation: CT chest, CT head and neck, direct laryngoscopy as indicated.

Inguinal lymphadenopathy

  • Most common primary: anogenital.
  • Evaluation: Genital examination, anoscopy and DRE in all pts.
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