second diagnostic phase - special investigations

Last edited 04/2023 and last reviewed 05/2023

Second diagnostic phase - special investigations

• tumour markers
  • do not measure tumour markers during diagnosis except for:
    • AFP and hCG in patients with presentations compatible with germ-cell tumours (particularly those with mediastinal and/or retroperitoneal masses and in young men)
    • AFP in patients with presentations compatible with hepatocellular cancer
    • PSA in men with presentations compatible with prostate cancer
    • CA125 in women with presentations compatible with ovarian cancer (including those with inguinal node, chest, pleural, peritoneal or retroperitoneal presentations)
  • carefully interpret the results because of limited test specificity
    
    
• upper and lower gastrointestinal endoscopy
  • do not carry out upper or lower gastrointestinal (GI) endoscopy in patients with metastatic disease of unknown origin (MUO) unless the symptoms, histology or radiology suggest a GI primary tumour
    
    
• mammography
  • do not offer mammography routinely to women presenting with MUO, unless clinical or pathological features are compatible with breast cancer
    
• breast magnetic resonance imaging
  efer patients with adenocarcinoma involving the axillary nodes to a breast cancer MDT for evaluation and treatment. If no breast primary tumour is identified after standard breast investigations, consider dynamic contrast-enhanced breast magnetic resonance imaging (MRI) to identify lesions suitable for targeted biopsy
  
  
• positron emission tomography-computed tomography
  • offer positron emission tomography-computed tomography (18F-FDG PET-CT) to patients with provisional CUP presenting with cervical lymphadenopathy with no primary tumour identified on ear, nose and throat panendoscopy if radical treatment is considered to be an option.
  • consider 18F-FDG PET-CT in patients with provisional cancer with unknonw primary with extra-cervical presentations
    
    
• immunohistochemistry
  • use a panel of antibodies comprising cytokeratin 7 (CK7), CK20, thyroid transcription factor-1 (TTF-1), placental alkaline phosphatase (PLAP), oestrogen receptor (ER; women only) and PSA (men only) in all patients with adenocarcinoma of unknown origin
  • use additional immunohistochemistry to refine the differential diagnosis, guided by the results of the panel of antibodies

Reference:

• 1) NICE (April 2023). Metastatic malignant disease of unknown primary origin - Diagnosis and management of metastatic malignant disease of unknown primary origin