Regional Recurrences, Hyams Grade, and Methylation Immune Score Analysis in Esthesioneuroblastoma

Background: Esthesioneuroblastomas are rare tumors with a propensity for delayed regional recurrence. Although regional disease at presentation is relatively rare, delayed regional recurrences are not uncommon. As such, many institutions recommend prophylactic neck irradiation to avoid subsequent regional failure. The Hyams grading system is a pathologic grading system that has prognostic value. DNA methylation profiles have similarly helped stratify esthesioneuroblastomas into unique clusters. We aim to identify a priori biomarker of regional failure to help in identifying patient groups that may require elective nodal management.

Methods: We performed a retrospective review based on patients with esthesioneuroblastoma treated at the University Health Network between 1972 and 2016. Patients were stratified by Hyams low-grade (I–II) or high-grade (III–IV). Methylation profiling was performed on cases with available tissue for analysis. The magnitude of local immune activity, termed “immune score,” was obtained in the tumor samples using DNA methylation data described in the literature. Relevant prognostic features related to demographics, treatment, tumor extent and histopathology were collected. Rates of regional recurrences were reported as were rates of local, dural and distant recurrence. Survival analyses were completed using Kaplan–Meier methods comparing those with Hyams low-grade to those with high-grade tumor, and subsequently comparing those with low-immune scores to those with high-immune scores.

Results: Forty-four patients (mean age: 51.8 years; SD ±15; 52% male) met our inclusion criteria. Of our patient cohort, 26 patients had no treatment to the neck (irradiation and/or dissection) at presentation. Sixteen (62%) had Hyams low-grade tumor, and 10 patients (38%) had Hyams high-grade tumor. Fifteen patients had tissue available for immune score analysis. Follow-up periods ranged from 9 to 315 months (median: 84 months). Six (23%) patients had regional recurrences (median time to failure: 61 months). Of the neck recurrences, four were Hyams low-grade and two were Hyams high-grade. There were no statistically significant differences in 5-year regional control rates between the Hyams low-grade and high-grade tumors (81 vs. 90%; p = 0.30). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 93 versus 68% (p = 0.12). Patients with low-immune score trended toward higher five-year regional control (100 vs. 66% p = 0.19). There was no difference in 5-year overall survival in patients with low-immune scores compared with high-immune scores (75 vs. 80%, p = 0.76).

Conclusion: Esthesioneuroblastomas may recur in the neck either in an early or delayed fashion. Patients who recur early either locoregionally or regionally have a poorer prognosis. The current preliminary analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences. Immune profiling may help predict which patients are likely to develop regional recurrences and who may benefit from prophylactic neck treatment, although the small sample size limits our conclusions.

No conflict of interest has been declared by the author(s).