Resident Physician University of California San Francisco San Francisco, CA, US
Introduction: Vestibular schwannomas (VS) are benign nerve sheath tumors which arise from the vestibulocochlear nerve and are often treated with radiosurgery, resection, or a combinatorial approach. Epigenetic profiling has recently defined subgroups for these tumors. However, little is known about differences in clinical phenotype associated with these molecular profiles.
Methods: A retrospective study was conducted of 65 patients with either newly diagnosed or recurrent VS. Banked tumor specimens collected at the time of resection underwent DNA methylation profiling, bulk RNA sequencing, and single-nucleus RNA sequencing and results were used to categorize patients into two molecular subgroups: immune enriched or neural crest enriched. Clinical data collected from the electronic medical record including presenting symptoms, preoperative hearing score by AAO-HNS, linear tumor growth rate, and prior treatments were analyzed to evaluate differences between groups.
Results: Of 65 total patients 37 patients were categorized as Immune-enriched (IE) and 29 as Neural Crest-enriched (NC). The majority of patients had extracanalicular extension on imaging (95% in the IE group and 97% in the NC group). Approximately 40% patients underwent radiosurgery prior to surgical resection. Clinically patients with the IE VS were more likely to present with tinnitus (51 vs 21%, p=.001) and loss of facial sensation (35 vs 21%, p=.012) but equally likely to have vertigo, ventriculomegaly, or sudden onset hearing loss. Preoperative audiogram data was available for approximately one third of patients and demonstrated an AAO-HNS hearing class of D for most patients (69% of IE patients, 72% of NC patients). Tumor size was not significantly different between groups on initial presentation.
Conclusion : Epigenetic profiling can categorize VS into molecular subgroups, and these molecular profiles may correlate with distinct clinical presentation phenotypes.
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