Ectopic olfactory neuroblastoma is associated with increased frequency of syndrome of inappropriate antidiuretic hormone secretion and reduced disease control: Case series with systematic review and pooled analysis

Introduction: Olfactory neuroblastoma (ONB) is a rare malignant tumor originating from the olfactory neuroepithelium, typically within the sinonasal cavity. Cases of ONB originating outside of the olfactory cleft area are extremely rare and are referred to as “ectopic” (eONB), in contrast to “orthotopic” tumors (oONB). ONB has been associated with paraneoplastic syndromes (PNSs), including the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study investigate the association between eONB and SIADH and compared the prognosis of eONB to oONB. Methods: A systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, focusing on studies reporting eONB and oONB associated with SIADH. Data from four newly identified eONB cases were reported and a pooled analysis was performed. Statistical analyses were conducted to evaluate the prevalence of SIADH in eONB and oONB and to compare clinical outcomes in the two groups. Results: eONB had a significantly higher prevalence of SIADH (18.3%) compared to oONB (2.0%; p < 0.0001). Patients with eONB were younger, with a slight predominance of females. Recurrence-free survival and time-to-recurrence of eONB were worse than oONB, independently of other prognosticators. Conclusions: eONB is associated with a significantly higher incidence of SIADH than oONB, suggesting distinct biological characteristics. Moreover, patients with eONB had worse prognostic outcomes. Further research is needed to understand the underlying mechanisms and improve management strategies for eONB.