Evaluating Bone Marrow Involvement in Pediatric Neuroblastoma: Traditional Methods and Emerging Technologies-A Systematic Review.

Neuroblastoma (NB) is the most common extracranial solid neoplasm affecting the pediatric population. It shows a high prevalence of bone marrow infiltration (BMI), which substantially impacts the disease's staging and prognostic assessment. Conventional methodologies, including bone marrow biopsy (BMB) and aspirate (BMA), have been extensively employed; nevertheless, the advent of novel technologies presents a promising avenue for diagnostic accuracy. This systematic review is designed to critically analyze and compare the established techniques (BMB and BMA) versus novel diagnostic approaches-such as immunocytology, RT-qPCR, and multiparametric flow cytometry (FCM), along with functional imaging like MIBG scintigraphy and FDG-PET/CT-in assessing BMI in pediatric NB. An exhaustive search was performed across the PubMed and Embase databases, identifying 2694 scholarly articles. Following a meticulous screening process and the application of inclusion criteria centered on diagnostic accuracy, sensitivity, and specificity about BMI, a total of 140 articles were selected for qualitative analysis. While BMB remains the gold standard for diagnosing and staging BMI in NB, recent advances in molecular techniques and functional imaging have shown superior sensitivity and specificity. Immunocytology and RT-qPCR can detect minimal residual disease (MRD) with higher sensitivity compared to traditional methods. Functional imaging modalities, particularly FDG-PET/CT and MIBG scintigraphy, have demonstrated improved accuracy in assessing bone marrow involvement with the added advantage of evaluating the entire bone marrow, overcoming the limitations of focal sampling in BMB. The integration of advanced molecular diagnostics and functional imaging with traditional biopsy methods enhances the accuracy of BMI in NB.