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Cancer of unknown primary
In metastatic cancer without a clear primary, work-up rests on pathology — CK7 and CK20 stains and then specific markers — and on focused imaging; the goal is to find a "favourable" subset treated like a known primary, or a molecular target for treatment.
Why it matters in the exam
The exam asks about immunohistochemical stains that support a given origin — for example a colorectal origin in a liver metastasis, or a lung origin in a brain metastasis — and about the approach to subsets in which treatment is targeted and may be curative. The typical scenario is a patient with liver or bone metastases, a biopsy showing adenocarcinoma and a negative initial work-up.
Remember the favourable subsets: a woman with an axillary node (treated as breast cancer), a woman with serous peritoneal carcinomatosis (as ovarian cancer), a man with blastic bone metastases and a high PSA (as prostate), squamous carcinoma in neck nodes (as head and neck), and a young man with a midline tumour (as a germ cell tumour). In the rest, platinum-based chemotherapy is given and NGS-guided therapy is considered.
Key points
- Work-up of cancer of unknown primary rests on pathology, led by CK7 and CK20, and on imaging and a full physical examination.
- CK7-negative with CK20, CDX2 and SATB2 positive supports a colorectal origin; TTF-1 and napsin A support a lung origin.
- Favourable subsets are treated like the presumed primary, and some have a chance of cure.
- A woman with an axillary node is treated as breast cancer, and a young man with a midline tumour as a germ cell tumour.
- In the unfavourable subset platinum-based chemotherapy is given and NGS is sent to look for a molecular target.
Summary table
| Stain profile | Possible origin | Directing markers |
|---|---|---|
| CK7-negative, CK20-positive | Colon | CDX2 and SATB2 positive |
| CK7-positive, CK20-negative | Lung, breast, thyroid, ovary, endometrium | Lung — TTF-1 and napsin A; breast — GATA3 and ER; thyroid — TTF-1 and thyroglobulin; ovary — PAX8 and WT1 |
| CK7-positive, CK20-positive | Urinary tract, pancreas and bile ducts, stomach | Urinary tract — GATA3 and p63 |
| CK7-negative, CK20-negative | Liver, kidney, prostate, squamous | Liver — HepPar-1 and arginase; kidney — PAX8; prostate — PSA and NKX3.1; squamous — p40 |
| Not carcinoma | Melanoma, lymphoma, germ cell, neuroendocrine, sarcoma | Melanoma — SOX10 and S100; lymphoma — CD45; germ cell — SALL4 and OCT4; neuroendocrine — chromogranin and synaptophysin |
| Favourable subsets | Axilla in a woman; serous peritoneum in a woman; blastic bone with PSA in a man; squamous in the neck; midline in a young man | Treated like the presumed primary, sometimes with curative intent |
| Unfavourable subset | Platinum-based chemotherapy (carboplatin with paclitaxel) | NGS to find a molecular target — targeted treatment improved outcomes in a trial |
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
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Sources
- ESMO Clinical Practice Guideline: Cancers of unknown primary site, 2023 — Diagnosis, treatment and follow-up
- NCCN Clinical Practice Guidelines in Oncology: Occult Primary, 2026 — Immunohistochemistry and favourable subsets
- Dabbs, Diagnostic Immunohistochemistry, 6th ed. (2022) — Immunohistochemistry of metastatic carcinomas of unknown primary
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.