Comprehensive molecular analyses for diagnosis and treatment guidance in an adult neuroblastoma patient

Abstract Metastatic cancers of unknown primary (CUP) pose significant diagnostic and therapeutic challenges. We present the case of a 63-year old male patient with a CUP showing neuroendocrine differentiation, metastasized to the iliac bone, bone marrow, supraclavicular and retroperitoneal lymph nodes. Immunohistochemical and molecular profiling revealed strong pan-neurotrophic tyrosine kinase (Trk) expression without NTRK-gene fusion, corroborating the neural cell origin. Following molecular tumor board (MTB) discussion, genome-wide methylation profiling suggested the diagnosis of a neuroblastoma but results were below diagnostic thresholds. Subsequent imaging and laboratory findings confirmed an INRGSS stage M neuroblastoma, a rare finding in older adults. Despite multimodal therapy, including polychemotherapy and immunotherapy according to pediatric GPOH neuroblastoma guidelines, disease progression necessitated an experimental approach. Comprehensive molecular analysis and MTB discussion revealed several potential treatment targets, leading to subsequent treatment including dinutuximab beta, nivolumab, cabozantinib, I-131-mIBG radionuclide therapy and alpelisib, unfortunately, all followed by disease progression. This case demonstrates the potential of comprehensive molecular analysis including methylation profiling for diagnosis and treatment guidance in rare tumors. Additional research is urgently required to improve outcomes in elderly patients with neuroblastoma.