Background: Neuroblastoma (NB) is the most common extracranial solid tumor in young children, with bone marrow (BM) involvement critically impacting prognosis. The International Neuroblastoma Response Criteria Bone Marrow Working Group (INRC-BMWG) has proposed standardized guidelines for BM response assessment. However, the practical utility, limitations, and role of immunohistochemistry (IHC) and maturation changes within these criteria remain underexplored. Methods: This study retrospectively analyzed 36 consecutive cases of NB with BM metastasis at presentation or post-induction. BM response categories were assigned using INRC-BMWG criteria. Quantitative assessment included tumor area, differentiation, and stroma composition. A minimum of two IHC markers (synaptophysin/chromogranin and PHOX2B) were routinely used, with S100 applied selectively to identify Schwannian stroma. Functional imaging (MIBG/FDG PET) was performed at diagnosis, midway, and therapy completion, with concordance to histopathological response calculated. Results: Of 257 BM biopsies, 110 (42.8%) showed tumor infiltration; 36 cases were evaluable pre- and post-therapy. According to INRC-BMWG, 4 were categorized as complete response, 8 as minimal disease, 6 as progressive disease, and 17 as stable disease. IHC improved minimal disease detection and prevented misclassification. Maturation features were observed in over a third of minimal/stable disease cases, though not currently included in response criteria. Imaging-pathology concordance was highest in complete and progressive response categories, but lower in minimal disease (33.3%). Conclusion: INRC-BMWG guidelines provide a robust framework for BM response assessment in NB, but may benefit from inclusion of maturation features and refined necrosis interpretation. Integration of IHC and imaging with histology offers more accurate, clinically relevant response evaluation.
