Vestibular Schwannoma: What We Know and Where We are Heading

Abstract

Vestibular schwannoma (VS) is a Schwann cell-derived tumour arising from the vestibulocochlear nerve. Although benign, it represents a threat to intracranial structures due to mass effect and carries a small risk of malignant transformation. VS therefore represents an important healthcare burden. We review the literature regarding pathogenesis, risk factors, and diagnosis of VS. The current and future potential management strategies are also discussed. A narrative review of all relevant papers known to the authors was conducted. The majority of VS remain clinically stable and do not require interventional procedures. Nevertheless, various surgical techniques exist for removing VS, the most common of which are translabyrinthine and retrosigmoid approaches. Due to surgical risks such as hearing loss, facial nerve dysfunction, post-operative headache, and cerebrospinal fluid leakage, a "watch and rescan" approach is adopted for most patients. Radiotherapy is a useful alternative and has been shown to have a similar response for growth restriction. Due to the heterogeneous nature of VS, there is a lack of consensus regarding management of tumours that are too large for conservative management but too small to indicate surgery. Emerging biologic therapies, such as Bevacizumab, Everolimus, and Lapatinib, as well as anti-inflammatories like aspirin are promising potential treatments; however, long-term evidence of their efficacy is required. The knowledge base regarding VS continues to improve. With increased understanding of the pathogenesis of these tumors, we believe future work should focus on pharmacologic intervention. Biologic therapies aimed toward improved patient outcomes are particularly promising.

Keywords: Diagnosis; Management; Pathology; Review; Schwannoma; Vestibular.

Fig. 1

Illustration of a histologic sample of vestibular schwannoma. a Antoni A tissue. Areas of tumor containing abundant spindle cells, with twisted nuclei and indistinctive cytoplasmic borders, arranged in short, well-composed bundles. Acellular pathognomonic features of a schwannoma, called Verocay bodies, are also seen. b Antoni B tissue. Areas of tumor composed of loosely arranged Schwann cells laden with foamy macrophages and surrounding foci of necrosis, cystic changes, and haemorrhage. In some tumor cells, degenerative nuclear changes can be seen (200 × , hematoxylin and eosin). Reproduced with permission from ‘’Frequency of loss of heterozygosity of the NF2 gene in schwannomas from Croatian patients’’. Reproduced with permission from Pećina-Slaus et al. [10]

Fig. 2

Mechanisms of NF2 gene-related VS development. (A) In a steady-state, unphosphorylated merlin restricts cell proliferation by inhibiting Rac and p21-activated kinase (Pak) [14]. (B) NF2 gene mutations lead to merlin deficient cells, causing Rac activation leading to intercellular adhesion and cell proliferation [15]. (C) Merlin deficient cells also deregulate various intracellular pathways causing cell proliferation [12]. (D) Mutations to NF2 also affect other pathways, seen in schwannomatosis, leading to eventual cell proliferation—although this is poorly understood [16]