The study by Zhang et al., published in BMC Medical Imaging (2025), examines the prognostic and diagnostic role of baseline Fluorine-18-Fluorodeoxyglucose positron emission tomography/computerised tomography (18F-FDG PET/CT) in paediatric patients with congenital neuroblastoma. As congenital neuroblastoma constitutes a relatively rare subset of neuroblastoma with unique biological behaviour, the work addresses a significant knowledge gap in paediatric oncology imaging. This critical analysis considers the strengths, limitations, and broader implications of the paper, with attention to methodology, findings, and clinical significance.
Keywords: Congenital neuroblastoma, paediatric oncology, FDG PET/CT, prognostic imaging, tumour metabolism, recurrence risk.
Context and Rationale
Neuroblastoma is the most common extracranial solid tumour in children, but congenital cases comprise only about five per cent of the total incidence. Congenital neuroblastoma can range from indolent tumours that regress spontaneously to aggressive metastatic disease. This variability makes accurate prognostic assessment particularly challenging. Traditional markers such as MYCN amplification, chromosomal aberrations, and serum biomarkers (LDH and NSE) are well established in older patients, but their prognostic relevance in congenital cases remains less specific.
Against this background, the use of 18F-FDG PET/CT has gained prominence as a tool that combines anatomical and metabolic data. In neuroblastoma, it has been generally applied in staging, response assessment, and prognostic evaluation. Yet, relatively little has been written about its role specifically in congenital neuroblastoma. Zhang et al., therefore, set out to characterise the imaging features of this subset and explore potential prognostic associations.
Methodology
The study adopts a retrospective single-centre design, drawing on data from 28 paediatric patients who underwent PET/CT between June 2020 and June 2023. Inclusion and exclusion criteria were clearly defined, focusing on congenital onset (fetal or neonatal identification) with pathologically confirmed neuroblastoma and complete clinical and imaging data.
The methodology for PET/CT imaging acquisition and analysis was rigorous and consistent with international standards. Parameters such as SUVmax, SUVmean, MTV, and TLG were extracted for both primary and metastatic lesions, while whole-body measures (tMTV and tTLG) were also calculated. Dual review by senior nuclear medicine physicians, with adjudication by a third reviewer when necessary, increased reliability and reduced inter-observer variability.
Clinical data—including biomarker levels, genetic aberrations, and INRG staging—were systematically recorded, allowing integration of imaging with established risk factors. Patient outcomes were tracked through a median follow-up of 711 days, with recurrence-free survival used as the main endpoint.
The strengths of this methodology lie in its comprehensive imaging analysis and careful patient selection. However, being retrospective and limited to a small sample, the study is inherently constrained in its capacity to draw statistically robust prognostic conclusions. The lack of multivariate analysis, acknowledged by the authors, is a direct consequence of this limitation.
Findings
All primary tumours exhibited high FDG uptake, consistent with the metabolic aggressiveness typical of neuroblastoma. Metastatic involvement was observed in the liver and bone marrow, with most lesions demonstrating high uptake, though one hepatic metastasis showed normal FDG uptake, highlighting heterogeneity in tracer avidity.
Serum biomarkers were abnormal in most patients, with 26 of 28 showing raised NSE and 25 showing elevated LDH. MYCN amplification was relatively rare (3 patients), aligning with the lower frequency reported in congenital cases. Chromosomal aberrations were present in a minority, and all patients underwent surgery, supplemented by chemotherapy or radiotherapy in selected cases.
During follow-up, recurrence was observed in five patients (17.9%), though importantly, no deaths were reported, reflecting the generally favourable prognosis in this cohort. Recurrent cases tended to show higher metabolic parameters (SUVmax, SUVmean, MTV, TLG) compared to non-recurrent cases, suggesting that elevated baseline PET metrics may associate with increased risk of relapse.
These findings support the value of PET/CT in staging and potentially in prognostic stratification, although the authors refrain from asserting statistical significance due to sample size constraints.
Critical Evaluation
Strengths
- Novelty and relevance – The study contributes to an under-researched area by focusing specifically on congenital neuroblastoma, rather than neuroblastoma in general.
- Comprehensive imaging assessment – Use of both lesion-based and whole-body PET parameters provides a thorough evaluation of metabolic activity and tumour burden.
- Integration with clinical and biological markers – By correlating imaging with biomarkers and genetic data, the study highlights the potential of PET/CT as part of a multimodal risk stratification approach.
- Favourable clinical outcomes – The absence of mortality across the cohort underscores both the distinctive biology of congenital neuroblastoma and the importance of identifying which patients might benefit from less aggressive management.
Limitations
- Small sample size – With only 28 patients, of whom five experienced recurrence, statistical analyses were necessarily limited. Prognostic claims remain tentative.
- Single-centre, retrospective design – Findings may not be generalisable, and the possibility of selection bias cannot be excluded.
- Lack of comparator imaging modalities – 123I-MIBG remains the standard in neuroblastoma imaging. While some reference is made, the study does not directly compare FDG PET/CT with MIBG, limiting assessment of its relative value.
- Limited exploration of spontaneous regression – Although the discussion acknowledges the phenomenon, only a single illustrative case is provided. A deeper examination of imaging predictors of regression versus progression would have been valuable.
- Incomplete biomarker evaluation – Important factors such as TERT mutation status and serum ferritin were not assessed, which weakens the study’s integration of imaging with molecular prognostics.
Clinical and Research Implications
This paper reinforces the notion that congenital neuroblastoma generally has a good prognosis, but also that recurrence occurs in a notable minority. For clinicians, the results suggest that elevated baseline PET parameters could flag higher-risk cases, supporting closer surveillance or more active treatment. Conversely, for patients with low metabolic tumour burden, PET/CT might eventually help to justify a more conservative management strategy, sparing infants unnecessary exposure to chemotherapy or radiotherapy.
From a research perspective, the study underlines the need for larger multicentre prospective cohorts to validate these observations and to define reliable PET thresholds for risk stratification. Harmonisation of methodologies, particularly regarding MTV and TLG measurement thresholds, is essential if PET metrics are to become standardised prognostic tools.
The work also invites future comparison between FDG PET/CT and MIBG imaging in congenital neuroblastoma. Given that MIBG is less sensitive in some tumour subtypes, FDG PET/CT may have a complementary role, particularly in patients with MIBG-negative disease. Integrating PET/CT parameters with molecular profiling could ultimately provide a more precise stratification framework.
Conclusion
Zhang et al. present an important contribution to the understanding of congenital neuroblastoma, offering a detailed characterisation of baseline PET/CT features in a rare and heterogeneous disease. Their findings suggest that high metabolic activity on PET correlates with recurrence risk, although the study’s limitations preclude definitive prognostic conclusions.
The paper is methodologically sound and clinically relevant, but its impact lies more in raising questions than providing final answers. It highlights the promise of FDG PET/CT in congenital neuroblastoma but also demonstrates the pressing need for larger, standardised, prospective studies to clarify its prognostic value and integrate it into clinical protocols.
In summary, the study stands as a useful exploratory step towards refining prognostic assessment in congenital neuroblastoma, emphasising the value of metabolic imaging while acknowledging the challenges of rare disease research.
Reference
Zhang, K., Wang, G., Wang, X. et al. The baseline 18F-FDG PET/CT imaging features in pediatric patients with congenital neuroblastoma. BMC Med Imaging 25, 330 (2025). https://doi.org/10.1186/s12880-025-01863-2
Disclaimer
This editorial review is an independent critical analysis of the study by Zhang et al., published in BMC Medical Imaging (2025). It is provided for informational and educational purposes only and does not constitute medical advice. The views expressed are those of the author of this review and do not necessarily reflect the views of the original study authors, the journal, or any affiliated institutions. Clinicians and researchers should consult the original publication and relevant clinical guidelines before making diagnostic or therapeutic decisions.