Metastatic disease with no identified primary

ACR AC head and neck occult primary variants; CUP PET literature

Two questions are being asked at once: where is the primary, and what is the most accessible site to biopsy. The second is usually the more useful, because histology and immunohistochemistry identify the origin more often than imaging does.

Biopsy-proven or radiologically evident metastatic disease — nodal, hepatic, skeletal or pleural — with no primary identified on the imaging done so far.

Referenced decision support — confirm against your local protocol.

Decision support, not a directive. Protocols and timings shown are typical published ones — your local protocol takes precedence, and the vetting radiologist decides.

The request in front of you

Everything is optional. Leave a field alone and the answer assumes nothing — the verdict updates as you go.

Study requested

What the referrer actually asked for. It is evidence of intent, not a constraint on the right answer.

Contrast as written

What the request form says, not what it should say.

Age

Pick a band, or type an exact age if it matters.

years

Pregnancy status

Renal risk factors

The question a vetter can actually answer from the request. An explicit “none known” is a real answer, and it removes checks rather than deferring them.

Previous contrast reaction

The pathway — tap anything already done

Marking a study complete moves the answer on. A patient arrives partway through a pathway far more often than at the start of one.

Accept as requested

CT Abdomen and Pelvis — Portal Venous Phase

CT Abdomen and Pelvis

What we'd amend, and why

Contrast-enhanced CT of chest, abdomen and pelvis remains the first sweep because the commonest occult primaries — lung, pancreas, kidney, colon, ovary — are within its coverage and are found by it in a substantial share of cases. It simultaneously maps disease burden and, critically, identifies which deposit is the safest and most productive biopsy target.

Nothing needs resolving before this goes ahead. Routine checks below are owned downstream.

How was this decided?

pathwaystandard — Adults — occult primary search
rulerule-contrast-reaction-premed — Prior contrast reaction and elective premedication; checked by Nurse before the scan
rulerule-metformin — Metformin and iodinated contrast; checked by Radiographer at the scanner
rulerule-paeds-dose — Child-sized technique and contrast dose; checked by Radiographer at the scanner
rulerule-pregnancy-ionising — Pregnancy status before an ionising exposure; checked by Radiographer at the scanner
rulerule-renal-iodinated — Kidney function and intravenous iodinated contrast; checked by Radiographer at the scanner
rulerule-iv-access — Intravenous access adequate for the planned injection; checked by Radiographer at the scanner

Decision support only. Local protocol takes precedence.

Handled at the scanner(4)nothing for you to do

Settled and owned downstream. Each returns to a radiologist only on the stated trigger.

Metformin and iodinated contrast
Confirm whether the patient takes metformin or a metformin-containing combination, and if so whether ACR Category II applies (eGFR below 30, known or suspected AKI, or an arterial catheter study likely to cause renal embolisation). If Category I — that is, no AKI and eGFR at or above 30 — no action of any kind is needed.
Radiographer at the scannerAt the scanner
Flags back if: The patient takes metformin AND meets ACR Category II — eGFR below 30 mL/min/1.73 m2, known or suspected acute kidney injury, or an arterial catheter procedure with likely renal arterial embolisation. Metformin plus a normal or mildly reduced eGFR is explicitly NOT a flag-back: there is no need to stop metformin before or after intravenous iodinated contrast in Category I patients, and no need to re-check creatinine afterwards.
Child-sized technique and contrast dose
Confirm that a size- or weight-based protocol is selected — child-sized kV and mAs against size-based diagnostic reference ranges — and that contrast volume is calculated by weight rather than taken from an adult default. Weight-based iodinated contrast volumes of roughly 1.5–2.0 mL/kg are widely used in paediatric CT.
Radiographer at the scannerAt the scanner
Flags back if: No paediatric or size-based protocol exists on the scanner for the requested examination, or the requested coverage or number of phases exceeds what the clinical question needs — for example a multiphase study where a single phase answers it, or whole-body coverage for a focal question.
Pregnancy status before an ionising exposure
Make the pregnancy enquiry immediately before the exposure and record the answer. In the UK this is a statutory operator duty discharged at the time of exposure under the employer’s written procedures required by IR(ME)R 2017 — it is not something the vetting radiologist can perform or pre-empt, and a request is complete without it.
Radiographer at the scannerAt the scanner
Flags back if: The patient states that she is, or may be, pregnant AND the uterus is in or near the primary beam. The exposure is then paused for re-justification by the IR(ME)R practitioner before it proceeds.
Intravenous access adequate for the planned injection
Site and test a cannula that supports the protocol flow rate, preferring an antecubital or large forearm vein, and observe the injection for extravasation. A 20-gauge or larger cannula is preferred for flow rates of 3 mL/s or more.
Radiographer at the scannerAt the scanner
Flags back if: No cannula can be sited that supports the protocol flow rate — for example only a 22-gauge hand or foot cannula for a CT angiogram needing 4–5 mL/s; or the only available access is a central line or port that is not labelled power-injectable; or an extravasation occurs.

Pathways

Big forks are separate pathways; the first whose conditions match is the one used.

Adults — occult primary search

Matches your inputsDefault

Role	Study & protocol	Why this answers the question
First line	CT Abdomen and Pelvis CT Abdomen and Pelvis — Portal Venous Phase usually appropriate	Contrast-enhanced CT of chest, abdomen and pelvis remains the first sweep because the commonest occult primaries — lung, pancreas, kidney, colon, ovary — are within its coverage and are found by it in a substantial share of cases. It simultaneously maps disease burden and, critically, identifies which deposit is the safest and most productive biopsy target.
First line	CT Chest CT Chest — Contrast-Enhanced (Venous Phase)	Lung is the commonest occult primary and the thorax is covered in the same acquisition. A small peripheral primary is easily overlooked when attention is on bulky nodal or hepatic disease, so it should be searched for deliberately on lung windows.
Second line	FDG PET-CT FDG PET-CT — skull base to mid-thigh	Where CT has not found the primary, whole-body FDG imaging identifies a candidate site in a meaningful proportion of patients and covers regions — tongue base, tonsil, bowel — where a small primary is invisible on unenhanced or venous CT. It also redirects the biopsy to the most metabolically active and therefore most diagnostically productive lesion.
Problem solving	MRI Head and Neck (Soft Tissue Neck) MRI Neck — head and neck cancer staging	For squamous carcinoma in a cervical node, the primary is usually in the tongue base or tonsil, and high-resolution MRI of those subsites is what finds submucosal disease that endoscopy and CT both miss.

Pitfalls

Escalating through every modality before the histology comes back. Immunohistochemistry frequently settles the origin and makes further imaging unnecessary.
Requesting PET-CT before contrast-enhanced CT, then having to repeat cross-sectional imaging anyway because the PET CT component cannot characterise the liver.
Ignoring the biopsy question. Naming the most accessible deposit in the report changes the patient pathway more than another scan will.
Over-calling physiological bowel or muscle uptake on FDG as a primary, and sending the patient for an unnecessary endoscopy.
Forgetting that some primaries are characteristically FDG-poor, so a negative PET does not close the search.
Continuing the primary search in a patient who has developed neurological signs. Back pain with weakness, a sensory level or sphincter disturbance is cord compression and needs whole-spine MRI within 24 hours; the occult primary is the less urgent question by a wide margin.

Priors — what to pull first

Review all prior imaging, including studies done for unrelated reasons. The primary is often visible in retrospect on a scan performed months earlier.
Where a mammogram, endoscopy or skin examination has already been done, record it — the imaging search should not duplicate a negative clinical work-up.

What makes a good request

A good request states what tissue has already been obtained and what the immunohistochemistry showed. That result narrows the imaging search more than any additional modality does.
Cervical nodal presentation with squamous histology is a distinct pathway aimed at the tongue base, tonsils and nasopharynx, and belongs with head and neck imaging rather than with body CT.
The value of finding the primary is treatment selection, not completeness. Where a treatable pattern is already established by histology, further imaging searching for a primary should be justified rather than reflexive.
One presentation suspends the search entirely. Back pain with any neurological symptom or sign in a patient with metastatic disease is spinal cord compression until whole-spine MRI says otherwise, and that scan is done within 24 hours of the suspicion — sooner if the deficit is progressing — with dexamethasone and the acute oncology or spinal surgical referral started alongside it. Finding the primary can wait a day; walking cannot. The suspected-bone-metastases card owns that pathway in full.

How these studies are acquired

Contrast, phases and timing for every study on the pathways above.

CT Abdomen and Pelvis — Portal Venous Phase CT Chest — Contrast-Enhanced (Venous Phase)FDG PET-CT — skull base to mid-thigh MRI Neck — head and neck cancer staging

Confirm locally

CT Abdomen and Pelvis — Portal Venous Phase: timings are typical — confirm against local protocol.
Timings, contrast volumes and rates above are typical published values. Your department's protocol, scanner and patient population decide the actual numbers.
Safety thresholds and premedication policy follow local policy where it differs from the cited guidance.

References

Implemented from the cited published sources. Educational and workflow support only; confirm against current guidelines and local policy before clinical use.