What tumor marker is most appropriate for a 12-week-old child with Beckwith-Wiedemann syndrome (BWS) who has an increased risk for liver lesions, such as hepatoblastoma?

Tumor Marker for Beckwith-Wiedemann Syndrome with Liver Lesion Risk

The answer is D - AFP (alpha-fetoprotein). For a 12-week-old child with Beckwith-Wiedemann syndrome at increased risk for hepatoblastoma, serum AFP measured every 3 months through age 4 years is the recommended tumor marker, combined with abdominal ultrasound surveillance. 1, 2

Rationale for AFP Monitoring in BWS

AFP is specifically recommended for hepatoblastoma screening in Beckwith-Wiedemann syndrome because:

• BWS confers a 2,280-fold increased relative risk for hepatoblastoma, making surveillance essential 1
• AFP screening is highly sensitive for hepatoblastoma detection and can distinguish hepatoblastoma from benign hemangiomas 1
• AFP elevation often precedes ultrasound detection, as hepatoblastomas can grow rapidly, and screening results in detection at lower, more treatable stages 1
• Most hepatoblastomas in BWS occur within the first year of life, with the oldest reported at 30 months 1

Recommended Surveillance Protocol

For this 12-week-old infant with BWS, implement the following standardized protocol:

• Full abdominal ultrasound AND serum AFP measurements every 3 months from birth through the 4th birthday 1, 2
• After age 4, continue renal ultrasound only every 3 months through age 7 for Wilms tumor surveillance 1
• Physical examination by a geneticist or pediatric oncologist twice yearly 1

Critical Interpretation Considerations

AFP values in BWS patients require specialized interpretation:

• AFP levels in BWS infants tend to be elevated above normal pediatric values through the first years of life 1
• Individual AFP values must be interpreted in the context of the trend over time, with expectation of declining values through infancy 1, 3
• Interpretation should be done by or in consultation with physicians familiar with AFP monitoring in these syndromes, particularly geneticists and oncologists 1, 3
• Very high AFP values (>50,000 ng/ml after 2 months of age) correlate with identifiable liver lesions 4

Common Pitfalls to Avoid

Be aware of these important caveats:

• AFP can be elevated in benign conditions including hemangiomas and hemangioendotheliomas, not just hepatoblastoma 4, 5
• In severe BWS phenotypes with high tumor risk (such as paternal UPD11), more frequent monitoring than every 3 months may be warranted in the neonatal period 6
• Elevated AFP should prompt correlation with imaging findings; atypical ultrasound features (lobulated margins, calcifications, heterogeneity, diminished vascularity) raise concern for hepatoblastoma 1, 3
• If two successive AFP increases occur, proceed to MRI with hepatobiliary contrast agent for superior lesion characterization 3

Why Other Options Are Incorrect

The other answer choices are not appropriate for hepatoblastoma screening:

• Urine HVA and VMA (Option B): These catecholamine metabolites are used for neuroblastoma screening, which is only recommended in BWS patients with specific CDKN1C mutations 7, 2
• PSA (Option C): Prostate-specific antigen is irrelevant in pediatric patients and has no role in BWS surveillance
• Urine oxalic acid (Option A): This has no role in cancer surveillance for BWS