We present a case with outspoken spontaneous vestibular schwannoma shrinkage and review the related literature. The patient was initially diagnosed with a left-sided, intrameatal vestibular schwannoma, which subsequently grew into the cerebello-pontine angle (CPA), followed by total shrinkage of the CPA component without any intervention over a 12-year observation period. The literature on spontaneous tumor shrinkage was retrieved by searching the subject terms “vestibular schwannoma, conservative management” in PubMed/MEDLINE database, without a time limit. Of the published data, the articles on “shrinkage” or “negative growth” or “regression” or “involution” of the tumor were selected, and the contents on the rate, extent and mechanism of spontaneous tumor shrinkage were extracted and reviewed. The reported rate of spontaneous shrinkage of vestibular schwannoma is 5-10% of patients managed conservatively. Extreme shrinkage of the tumor may occur spontaneously.
Vestibular schwannoma is the most frequent cerebellopontine angle tumor. The aim of our study is to reflect our experience in the surgical treatment of this tumor MATERIAL AND METHODS: Retrospective study of 420 vestibular schwannomas operated in our hospital between 1994-2014. We include tumor size, preoperative hearing, surgical approaches, definitive facial and hearing functional results, and complications due to surgery.
Background Rates of hearing preservation following surgery via middle fossa craniotomy in patients harboring tumors with unfavorable characteristics are significantly lower than for those patients with “favorable” tumors. Objectives We will present two cases both with unfavorable conditions, which underwent endoscopic-assisted middle fossa craniotomy (MFC) resection of intracanalicular vestibular schwannomas with preserved postoperative hearing. Methods Chart reviews were conducted on both patients. Their presentation, intraoperative details, and techniques, pre- and postoperative audiograms, and facial nerve outcomes are presented. Results Patient A had 5.6 × 6.8 × 13.2 mm intracanalicular tumor with unserviceable hearing (pure tone audiometry [PTA], 41; speech determination score [SDS], 47%; class D) but was blind so hearing preservation was attempted. Postoperative hearing was preserved (PTA, 47; SDS, 60%; class B). Patient B had a 5 mm round intracanalicular tumor immediately adjacent to the vestibule and cochlea without any fundal fluid present. Preoperative audiogram showed serviceable hearing (PTA, 48; SDS, 88%; class B). Postoperatively, aidable hearing was preserved (PTA, 51; SDS, 76%; class C). Conclusion Hearing preservation surgery via MFC can be enhanced with endoscopic-assisted dissection, especially in the lateral internal auditory canal. The superior optical view allows for preservation of cochlear nerve function and removal of residual tumor not otherwise seen on microscopy.
In this study, we investigated the pathophysiology and mechanism underlying sporadic forms of vestibular schwannoma (VS) by comparing VS tissue with normal nerve tissue using proteomics.
The purpose of this study is to compare the outcomes in patients who underwent microsurgical resection for recurrent vestibular schwannoma after microsurgical resection and previous radiation therapy.
The earliest examples of neurofibromatosis (in this case type 1, NF1) can be traced in the Ebers Papyrus (Ancient Egypt, 1.500 B.C.), in a Hellenistic statuette (Smyrna, 323 B.C.), in the coinage of the Parthians kings (247 B.C.) and in some 13th century monks' drawings. These earlier examples are somewhat less well defined as compared to the most recent better defined reports credited as having NF1 including an Inca child mummy (1480-1650 AD), Ulisse Aldrovandi’s homuncio (“Monstrorum Historia”, 1592 A.D.) with mosaic NF1 or the illustrations seen in the 18th century “Buffon’s Histoire Naturelle” and “Cruveilhier’s Anatomie Pathologique du Corps Human”. The first English language report on NF1 was made by Akenside in 1768 and the first systematic review by Robert William Smith in 1849, while Virchow’s pupil, Friedrich Daniel von Recklinghausen, in 1882, was the first to understand the origin of skin tumors and to name them neurofibromas. The touching story of Joseph C. Merrick (the “Elephant man,” (who had Proteus syndrome and not NF1), in 1884, played an important role in the later misconception of NF1, as did the novel by Vicotr Hugo on the hunchback Quasimodo. The studies by van der Hoeve (1921), Yakovlev and Guthrie (1931), and Van Bogaert (1935), categorized “von Recklinghausen’s” neurofibromatosis among the phakomatoses and the neurocutaneous syndromes. The first known mention of an acoustic neuroma (at autopsy) is attributed to Eduard Sandifort (1777 AD) while John H. Wishart made the earliest autoptic description of neurofibromatosis type 2 (NF2), in 1822, in a 21-year-old man with bilateral acoustic neuromas, who manifested signs since his infancy (Wishart subtype NF2). Smith likely described the first case of schwannomatosis in 1849. Older, Virchow, von Recklinghausen, and Verocay first classified “neuromas” and Masson and Penfield first used the word “schwannoma” taking it from Theodore Schwann’s works. In 1903 Henneberg and Koch described NF2 in detail. Young, Eldridge, and Gardner, in the late ‘70, established NF2 as a distinct familial entity (Gardner subtype NF2). Schwannomatosis, the late entry of the different forms of neurofibromatosis, was credited in the middle '90.
Object Vestibular schwannomas (VS) are common benign tumors of the vestibular nerve that cause significant morbidity. The current treatment strategies for VS include surgery or radiation, with each treatment option having associated complications and side effects. The transcriptional landscape of schwannoma remains largely unknown. Methods In this study the authors performed gene-expression profiling of 49 schwannomas and 7 normal control vestibular nerves to identify tumor-specific gene-expression patterns. They also interrogated whether schwannomas comprise several molecular subtypes using several transcription-based clustering strategies. The authors also performed in vitro experiments testing therapeutic inhibitors of over-activated pathways in a schwannoma cell line, namely the PI3K/AKT/mTOR pathway. Results The authors identified over 4000 differentially expressed genes between controls and schwannomas with network analysis, uncovering proliferation and anti-apoptotic pathways previously not implicated in VS. Furthermore, using several distinct clustering technologies, they could not reproducibly identify distinct VS subtypes or significant differences between sporadic and germline NF2-associated schwannomas, suggesting that they are highly similar entities. The authors identified overexpression of PI3K/AKT/mTOR signaling networks in their geneexpression study and evaluated this pathway for therapeutic targeting. Testing the compounds BEZ235 and PKI-587, both novel dual inhibitors of PI3K and mTOR, attenuated tumor growth in a preclinical cell line model of schwannoma (HEI-293). In vitro findings demonstrated that pharmacological inhibition of the PI3K/AKT/mTOR pathway with next-generation compounds led to decreased cell viability and increased cell death. Conclusions These findings implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy.
Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 2 years ago
Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing. Here, we developed a cerebellopontine angle (CPA) schwannoma model that faithfully recapitulates the tumor-induced hearing loss. Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor hepatocyte growth factor (HGF) levels. This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared with normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in patients with NF2.
Preserving facial nerve function is a primary goal and a key decision factor in the comprehensive management of vestibular schwannoma and other cerebellopontine angle (CPA) tumors.
Low CT Attenuation Values of Sinonasal Benign Tumours Relative to the Brainstem Identify Schwannomas
- ORL; journal for oto-rhino-laryngology and its related specialties
- Published over 2 years ago
On computed tomography (CT), sinonasal schwannoma displays as a soft-tissue mass without any distinctive features. Our aim was to define the radiological criteria for distinguishing schwannoma from other sinonasal benign tumours.