Management of persistent soft tissue residuals exhibiting an imaging paradox (^123I-MIBG-negative/^68Ga-DOTA-NOC-positive) in high-risk neuroblastoma following immunotherapy: a case report

Managing persistent soft tissue residual disease in high-risk neuroblastoma (HR-NB) remains a clinical challenge, particularly when conventional response assessments suggest remission but residual lesions persist. Determining whether such lesions represent inactive treatment-related changes or viable tumor has important implications for subsequent management. We report a 4-year-and-11-month-old girl with HR-NB who received multimodal therapy, including induction chemotherapy, surgery, radiotherapy, autologous stem cell transplantation, and seven cycles of dinutuximab beta-based immunotherapy. Following treatment, standard evaluations demonstrated complete bone marrow clearance and a ^123I-MIBG Curie score of 0, suggesting an excellent systemic response. However, a persistent paravertebral residual lesion remained detectable on imaging. Notably, ^68Ga-DOTA-NOC PET/CT demonstrated persistent tracer uptake despite negative ^123I-MIBG findings, creating an imaging discordance that raised concern for residual viable disease. Subsequent "third-look" surgical resection confirmed viable neuroblastoma within the lesion. Pathological examination revealed a markedly increased Ki-67 labeling index compared with the post-induction specimen (50% versus 8%), indicating persistent proliferative activity and suggesting biological heterogeneity within the residual lesion. This case highlights the diagnostic and therapeutic challenges posed by persistent soft tissue residual lesions after immunotherapy. The discordance between ^123I-MIBG and ^68Ga-DOTA-NOC imaging suggests that conventional imaging alone may not fully characterize selected residual lesions. In patients with persistent masses and discordant imaging findings, multimodal functional imaging may provide complementary information to guide clinical decision-making. The favorable outcome observed in this patient, who remains in sustained remission following surgical resection without additional antitumor therapy, supports consideration of an integrated management strategy combining multimodal imaging assessment and appropriately timed surgical intervention for selected cases of persistent residual disease.