Cancer of unknown primary (CUP)

Question 1

Define Malignancy of undefined primary origin (MUO):

Answer 1

metastatic malignancy identified on the basis of a limited number of tests, without an obvious primary site, before comprehensive investigation.

Question 2

Define Provisional carcinoma of unknown primary origin (provisional CUP):

Answer 2

metastatic epithelial or neuro-endocrine malignancy identified on the basis of histology or cytology, with no primary site detected despite a selected initial screen of investigations, before specialist review and possible further specialised investigations.

Question 3

Define Confirmed carcinoma of unknown primary origin (confirmed CUP):

Answer 3

metastatic epithelial or neuro-endocrine malignancy identified on the basis of final histology, with no primary site detected despite a selected initial screen of investigations, specialist review and further specialised investigations as appropriate.

Question 4

Initial diagnostic phase in CUP

Answer 4

• comprehensive history and physical examination
• full blood count; urea, electrolytes and creatinine; liver function tests;
calcium; urinalysis; lactate dehydrogenase
• chest X-ray
• myeloma screen (when there are isolated or multiple lytic bone lesions)
• symptom-directed endoscopy
• CT scan of the chest, abdomen and pelvis
• tumour markers: PSA in men, CA125 in women with peritoneal malignancy or ascites, AFP and hCG
• testicular ultrasound in men with presentations compatible with germ-cell tumours
• biopsy and standard histological examination with immunohistochemistry where necessary

Question 5

Which tumour markers should be used during the secondary diagnostic phase of CUP?

Answer 5

Tumour markers
•Do not measure during diagnosis except:
• AFP and hCG in presentations compatible with germ-cell tumours (particularly mediastinal and/or retroperitoneal masses and in young men)
• AFP in presentations compatible with hepatocellular cancer.

• Do not measure during diagnosis except:
• PSA in presentations compatible with prostate cancer
• CA125 in presentations compatible with ovarian cancer (including inguinal node, chest, pleural, peritoneal or retroperitoneal presentations). Carefully interpret the results because of limited test specificity.

Do not use gene-expression-based profiling to identify primary tumours in patients with provisional CUP.