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Objective  In the management of facial nerve schwannoma (FNS), surgical tumor resection is now often being replaced with more conservative approaches, such as observation with serial imaging or stereotactic radiosurgery (SRS). Given the scarcity of these lesions, determining the optimal management of FNS remains challenging and subject of debate with multiple treatment approaches supported in the literature. Methods  A retrospective chart review was performed in two academic centers for patients diagnosed with FNS between 1996 and 2017. The clinical presentation, treatment modalities employed, tumor control rates, and facial nerve function (FNF) outcomes (House-Brackmann system) were assessed and analyzed. Results  The study comprised 50 adult patients. Initial treatment modalities included observation with serial clinicoradiologic review in 27 patients (54%), surgery in 17 patients (34%), and SRS in 6 patients (12%). The FNF were decreased in more than half of the patients who had surgery. Nonetheless, more than 80% of the patients who were initially managed with observation or SRS had stable or improved FNF. Conclusion  A prevailing trend toward more conservative treatment modalities for FNS has evolved over time, providing relatively long-term preservation of FNF. As there are multiple management options available, it is of paramount importance that the treating physician be familiar with all treatment modalities and outcomes and counsel patients appropriately. The surgery should be reserved for large tumors and poor FNF at initial presentation or follow-up while watchful observation with imaging is the treatment of choice for rest of the patients.

In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions. Targeted analysis of glucose metabolism pathways demonstrated a tendency towards a shift from tricarboxylic acid cycle (Krebs cycle) to glycolysis and anabolic reactions in cells treated with Poly(A:U). Glycolysis assays confirmed that TLR3 stimulation enhanced the capacity of malignant cells to switch from oxidative phosphorylation to extra-mitochondrial glycolysis. We found evidence that HIF-1α is involved in this process: addition of the TLR3 agonist resulted in a higher cell concentration of the HIF-1α protein, even in normoxia, whereas knocking-down TLR3 resulted in a lower concentration, even in hypoxia. Finally, we assessed TLR3 expression by immunohistochemistry in a series of 7 HNSCC specimens and found that TLR3 was detected at higher levels in tumors displaying a hypoxic staining pattern. Overall, our results demonstrate that TLR3 stimulation induces the Warburg effect in HNC cells in vitro, and suggest that TLR3 may play a role in tumor adaptation to hypoxia.