Carcinoma of unknown primary Definition and clinical features Carcinoma which metastasises before primary site large enough to identify. 3% of cancer cases. 50% present with multiple sites of involvement, and 50% a single site, commonly liver, bones, lung, or lymph nodes.

1. Carcinoma of unknown primary
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2. Definition and clinical features
Carcinoma which metastasises before primary site large
enough to identify.
3% of cancer cases.
50% present with multiple sites of involvement, and 50%
a single site, commonly liver, bones, lung, or lymph nodes.

3. Subtypes
4 subtypes on microscopy:
Well/moderate differentiated adenocarcinoma (50%).
Poor/undifferentiated adenocarcinoma (30%).
 Squamous cell carcinoma (15%).
Undifferentiated carcinoma (5%).

4. Final diagnosis
20% identified when alive, 10% identified on autopsy,
70% never identified.
When identified: lung, pancreas, GI, breast,
gynaecological.

5. Investigations
General approach:
Full examination including rectal and pelvic, and breast if
female.
Bloods: FBC, U+E, LFT, Ca2+ (especially if confusion), LDH,
urinalysis (haematuria may point to GU cancer).
Imaging: CXR, CT chest-abdo-pelvis.
Biopsy and histology of affected sites.

6. Further investigations if specific cancer suspected:
Tumour markers: AFP (hepatocellular, germ cell), β-hCG (germ cell), PSA
(prostate), CA-125 (ovarian), CA 19-9 (pancreas, bile duct).
Endoscopy
Mammography in all women with adenocarcinoma, especially if there is
axillary lymphadenopathy. MRI if results unclear.
PET-CT if there is cervical lymphadenopathy.
Immunohistochemistry: cytokeratin 7 and 20 (adenocarcinoma), TTF1 (non-
small cell lung cancer), PLAP, estrogen receptor, PSA.
Ascites cytology: can specify adenocarcinoma – thus rule out lymphoma – but
not much else.

7. Management
Key goal: identify those with treatable cancer.
Complications and prognosis
Median survival: 6 months.
Worse prognosis if:
Poorly-differentiated histology.
↑Serum markers: alk phos, LDH, CEA.
Lymphadenopathy, multiple sites.
Poor performance status, weight loss.

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