The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: refinements in diagnostic criteria and impact of multimodal treatments on survival

Objectives: To provide a comprehensive review of the clinical and histopathological features of olfactory neuroblastoma
(ONB) and other sinonasal neuroendocrine neoplasms (NENs), in order to refine diagnostic criteria,
analyze treatment outcomes, and identify prognostic factors.
Methods: Data from an Italian multi-institutional database were analyzed. Patients were treated surgically via a
minimally-invasive endoscopic approach followed by adjuvant radiotherapy or radiochemotherapy.
Neoadjuvant cisplatin/etoposide chemotherapy was administered in cases of poorly-differentiated tumors. A
centralized pathology review was performed in all cases. Patients were prospectively observed for survival.
Overall (OS) and Disease-free survival (DFS) estimates were determined from Kaplan-Meier analysis and compared
using the log-rank test. Statistically significant variables were entered in a multivariate Cox regression
model.
Results: 98 patients with a median follow-up of 53 months were included. Morphology review and the incorporation
of cytokeratin 8/18 in the immunohistochemical panel modified the final diagnosis in 8/98 (8.2%)
cases. The neoplasms were ultimately classified into four groups with different immunohistochemical profiles
and clinical behaviors: ONB in 67 cases (5-year-OS, 91.6%); NEC (poorly-differentiated neuroendocrine carcinoma)
in 22 cases (5-year-OS, 42.6%); MiNEN (mixed neuroendocrine/non-neuroendocrine neoplasm) in five
cases (5-year-OS, 0%,0/5 cases); and NET (well-differentiated neuroendocrine tumor) in four cases (5-year-OS,
50%, 2/4 cases). Hyams grade and Ki67 index were independent prognostic factors for ONB. Neoadjuvant
chemotherapy appeared to be associated with improved OS and DFS for NEC, independent of other clinicopathological
variables.
Conclusions: Induction chemotherapy improves survival outcomes in patients affected by poorly-differentiated
tumors. Recent advances in histopathological diagnosis, including CK8/18 staining, allow to plan the most
appropriate range of multimodal treatments.