Spinal Schwannomas Research Articles

Neurofibromatosis type 2 patient presenting with medulloblastoma

Background:Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a frequency of 1 in 25,000 live births and a penetrance of almost 100% by the sixth decade of life. The main tumors occurring in NF2 patients are bilateral vestibular schwannomas, other peripheral, cranial and spinal nerve schwannomas, intracranial and intraspinal meningiomas, ependymomas, and gliomas.Case Description:We report the case of a 6-year-old boy who presented with a 1-month history of nausea and recurrent vomiting. Physical examination was positive for ataxic gait and left-sided facial nerve palsy. Family history was positive for NF2 in the patient's father and paternal uncle. Magnetic resonance imaging brain revealed a solid enhancing lesion arising from the right cerebellar cortex, which was effacing the fourth ventricles and causing hydrocephalus. Craniotomy and excision of the lesion were performed. Histopathology report confirmed the diagnosis to be desmoplastic medulloblastoma. Based on the patients’ subsequent history and family history, he was diagnosed to be a case of NF2.Conclusion:This is the first case of medulloblastoma occurring in a patient with NF2 and raises the possibility of an association between medulloblastoma and NF2.

Acute worsing myelopathy due to intratumoral heamorrhage of spinal schwannoma (case report)

Acute worsing myelopathy due to intratumoral heamorrhage of spinal schwannoma (case report)

MS-02 * TRANSCRIPTOME ANALYSIS IDENTIFIES THE PI3K/AKT/mTOR PATHWAY AS A TARGETABLE PATHWAY IN SCHWANNOMA

Schwannomas are common benign tumors of the vestibular nerve, or arise from nerves within the spinal canal. Although benign, both Spinal schwannoma (SS) and vestibular schwannoma (VS) cause significant morbidities. The current treatment strategies for VS and SS include surgery or radiation with each treatment option having associated complications and side effects. The transcriptional landscape of schwannoma remains largely unknown. We interrogated the transcriptome by gene-expression array analysis of 49 schwannomas and seven normal control vestibular nerves to identify tumor-specific gene expression patterns. We identified over 4000 differentially expressed genes between control and schwannoma with network analysis uncovering proliferation and anti-apoptotic pathways previously not implicated in VS. Using several distinct clustering technologies, we could not reproducibly identify VS subtypes or significant differences between sporadic and germline NF2 associated schwannomas suggesting that VS comprises of a highly similar entity. We next performed a transcript analysis comparing VS to SS. Surprisingly; we identified few differential transcripts demonstrating that schwannoma maybe a homogenous entity. Current studies are focused on DNA methylation profiling and genome wide sequencing analysis. To date our group and others have identified that inactivating mutations in NF2 is the most recurrent aberration in schwannoma. The most recurrent activated pathway in schwannoma was over-expression of PI3K/AKT/mTOR signaling pathway, which is directly druggable and we evaluated this pathway for therapeutic targeting. Testing compounds BEZ235 and PKI-587, both novel dual inhibitors of PI3K and mTOR, attenuated tumor growth in a cell line model of schwannoma. Our In vitro findings demonstrated that pharmacological inhibition of the PI3K/AKT/mTOR pathway with next generation compounds lead to decreased cell viability, and increased cell death. Future work is testing these compounds in vivo using relevant cell lines and primary cultures of schwannoma. Our findings implicate that targeting the PI3K/AKT/mTOR pathway may serve as a potential treatment strategy.

Restless Legs Syndrome and lateralized periodic movements due to a spinal schwannoma

We describe a case of Restless Legs Syndrome (RLS) associated to periodic limb movements (PLMs) in a woman with a cervical schwannoma. Neurological examination, laboratory tests, neurography and electromyography were unremarkable. Neuroimaging evidenced a schwannoma at C3 level that compressed the right ventral surface of the medulla. Somatosensory-evoked potentials showed absence of the N13 after right median nerve stimulation and reduction of amplitude of the same component after left nerve stimulation. A video-polysomnography documented PLMs with a marked prevalence of the right-sided movements. We believe that the cervical schwannoma played a role in the pathogenesis of RLS and of lateralized PLMs.

Spinal Schwannoma Presenting With a Subdural Hemorrhage

Spinal Schwannoma Presenting With a Subdural Hemorrhage

TP53, MSH4, and LATS1 Germline Mutations in a Family with Clustering of Nervous System Tumors

Exome DNA sequencing of blood samples from a Li-Fraumeni family with a TP53 germline mutation (codon 236 deletion) and multiple nervous system tumors revealed additional germline mutations. Missense mutations in the MSH4 DNA repair gene (c.2480T>A; p.I827N) were detected in three patients with gliomas (two anaplastic astrocytomas, two glioblastomas). Two family members without a TP53 germline mutation who developed peripheral schwannomas also carried the MSH4 germline mutation, and in addition, a germline mutation of the LATS1 gene (c.286C>T; p.R96W). LATS1 is a downstream mediator of the NF2, but has not previously been found to be related to schwannomas. We therefore screened the entire coding sequence of the LATS1 gene in 65 sporadic schwannomas, 12 neurofibroma/schwannoma hybrid tumors, and 4 cases of schwannomatosis. We only found a single base deletion at codon 827 (exon 5) in a spinal schwannoma, leading to a stop at codon 835 (c.2480delG; p.*R827Kfs*8). Mutational loss of LATS1 function may thus play a role in some inherited schwannomas, but only exceptionally in sporadic schwannomas. This is thefirst study reporting a germline MSH4 mutation. Since it was present in all patients, it may have contributed tothe subsequent acquisition of TP53 and LATS1 germline mutations.

Surgical strategies for removal of intra- and extraforaminal dumbbell-shaped schwannomas in the subaxial cervical spine.

Spinal dumbbell-shaped schwannoma is common neoplasm, usually occurring in the cervical spine. Posterior or anterolateral approaches are frequently used to remove this benign tumor. We analyzed how much amount of tumor could be possible to be totally removed with posterior approach. Surgery was performed on 41 cases of cervical, dumbbell-shaped subaxial schwannomas with both intra- and extraforaminal involvement. The same surgeon performed all the procedures. Mean follow-up was 42.5months (24-108months). A combined anterolateral and posterior approach was used if the extraforaminal tumor was larger than 10mm. A posterior approach and unilateral facet removal were used if it was smaller than 10mm. We performed MRI and serial dynamic X-rays for postoperative 2years. We used the posterior approach with facetectomy in 35 cases and the combined approach in six. Complete removal was achieved with the combined approach in all six, and with the posterior approach in 28 of 35 cases. With the posterior approach, the extraforaminal dimension of totally resected tumors ranged from 3 to 5.4mm. Subtotal resection was limited to extraforaminal tumors larger than 5.7mm. On follow-up, instability on dynamic X-ray was not observed before 24months in any patient after unilateral facetectomy. Total removal of intra- and extraforaminal cervical subaxial schwannomas could be possible using a posterior approach with facet removal if the size of extraforaminal tumor was less than 5.4mm.

Malignant peripheral nerve sheath tumors presenting as spinal dumbbell tumors: clinical outcomes and characteristic imaging features.

To investigate the clinical outcomes and imaging features of malignant peripheral nerve sheath tumors (MPNSTs) presenting as spinal dumbbell tumors. We retrospectively reviewed the clinical outcomes and imaging features of consecutive cases of spinal dumbbell MPNSTs (n=8) and schwannomas (n=15). A maximal diameter>5 cm was more frequently seen in MPNSTs (88%) than in schwannomas (14%). Irregularly lobulated margins occurred frequently in MPNSTs (75%), but not in schwannomas (21%). Indistinguishable boundaries were observed in 63% of MPNSTs, but only 7% of schwannomas. Osteolytic bone destruction was found exclusively in MPNSTs (50% of MPNSTs vs. 0% of schwannomas). There is little clinical information relating to spinal dumbbell MPNSTs. We propose that the following imaging features are suggestive of spinal dumbbell MPNSTs: maximal diameter>5 cm, irregularly lobulated shape, boundary indistinguishable from surrounding tissues, and osteolytic bone destruction.

XI cranial nerve cervical schwannoma – Case report

Cisternal spinal accessory schwannoma are still a rare condition without neurofibromatosis with only 32 cases reported so far. We describe a cisternal accessory schwannoma presented in a 36-year-old woman with posterior cervical pain and cervical mieolopaty, defined by grade IV tetraparesia. A suboccipital craniectomy with C1 posterior arch resection was performed. During microsurgical dissection together with electrophysiological monitoring and nerve stimulation tumor was identified as having the spinal accessory root as its origins. Carefully intraneural dissection was then performed with complete lesion removal, histopatological examination confirmed the hypothesis of schwannoma. The patient was free from pain and improved her neurological status with no accessory nerve palsy. Complete surgical resection is indicated for such lesions and can be achieved with good outcome.

Differentiation of Spinal Schwannomas and Myxopapillary Ependymomas

Retrospective clinical study. The objective of this study is to evaluate magnetic resonance imaging and pathologic features of spinal schwannomas (SCHs) and myxopapillary ependymomas (MPEs) with focus on differentiating 2 disease entities. Few studies have reported on the differentiation of SCHs and MPEs. Fifty-three patients were retrospectively reviewed with histologically confirmed spinal SCHs (41 patients) or MPEs (12 patients) of the cauda equina and/or conus medullaris. We evaluated neurological deterioration after surgery in association with the intraoperative findings of the tumor, as well as with the preoperative magnetic resonance images and postoperative histologic findings. Patients in the SCH group had a greater mean age at surgery and a greater mean disease duration. In the SCH group, all 24 tumors that were homogeneously hyperintense on the T2-weighted (T2W) images showed rim enhancement on the postcontrast T1-weighted (T1W) images. Moreover, all 14 of the SCHs with homogeneous enhancement on the postcontrast T1W images were isointense on the T2W images. However, in the MPE group, all 8 of the tumors that were homogeneously hyperintense on T2W images showed homogeneous enhancement on their postcontrast T1W images. It is very important to differentiate SCHs and MPEs before surgery, because there are reported cases of dissemination of MPEs through cerebrospinal fluid throughout the neuraxis; the tumor must be removed en block to prevent this. Although MPEs and SCHs may have similar imaging characteristics, detailed examination of the magnetic resonance T2W image and postcontrast T1W image facilitates their differentiation.

Chemoprevention for neurofibromatosis 2: just over the horizon?

Chemoprevention for neurofibromatosis 2: just over the horizon?

Exploring Therapeutic Targets in Schwannoma Through Integrative Analysis

Vestibular schwannomas (VS) are common benign tumors of the vestibular nerve and spinal schwannomas (SS) arise form nerves within the spinal canal. SS are the most common intradural extramedullary spinal tumors, representing 30% of such lesions and both VS and SS both cause significant morbidity. The current treatment strategies for VS and SS include surgery or radiation with each treatment option having associated complications and side effects. The transcriptional landscape of schwannoma remains largely unknown. We first performed gene expression profiling of 49 VS schwannomas and seven normal control vestibular nerves to identify tumor-specific gene expression patterns. We identified over 2000 differentially expressed genes between control and schwannoma with network analysis uncovering proliferation and anti-apoptotic pathways previously not implicated in VS. Furthermore, using several distinct clustering technologies, we could not reproducibly identify distinct VS subtypes or significant differences between sporadic and germline NF2 associated schwannomas suggesting that VS comprises of a highly similar entity. We next performed a transcript analysis comparing VS to SS. Surprisingly; we identified few differential transcripts demonstrating that schwannoma in general is a homogenous entity. Current studies are focused on copy number, DNA methylation profiling and genome wide sequencing analysis. Preliminary data suggests that NF2 is the major driver of schwannoma as previously implicated. Interestingly, we identified several novel and recurrent point mutations of NF2 in exon 1 of both VS and SS, which may lead to loss of function. Our most recurrent activated pathway in schwannoma was overexpression of PI3K/AKT/mTOR signaling pathway, which is directly druggable and evaluated this pathway for therapeutic targeting. Testing compounds BEZ235 and PKI-587, both novel dual inhibitors of PI3K and mTOR, attenuated tumor growth in a pre-clinical cell line model of schwannoma (HEI-293). Our In vitro findings demonstrated that pharmacological inhibition of the PI3K/AKT/mTOR pathway with next generation compounds lead to decreased cell viability, and increased cell death in VS, SS but not normal schwann cells. Future work is testing these compounds in vivo using relevant cell lines and primary cultures of VS/SS. Our 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.

Spinal cystic schwannoma: an MRI evaluation.

Spinal cystic schwannomas are a very rare entity and have been reported in only a few case reports in literature; its diagnosis and management has remained a challenge. This study reviewed the results of magnetic resonance imaging (MRI) of 12 patients (7 men and 5 women; aged 37 - 67 years; mean age: 52.75 years) with pathologically proven cystic schwannoma of the spine and discussed their differential diagnosis. All patients underwent surgery at our institutions between June 2000 and April 2012. MRI showed well-delineated intradural and extramedullary lesion of iso- to low signal intensity on T1 weighted images, high signal intensity on T2 weighted images, and rim enhancement on contrast-enhanced images. A precise understanding of the MRI features of spinal schwannomas, especially the typical characteristic of enhancement, may help clinicians in their pre-operative diagnoses and surgical planning.

A Purely Paraspinally Located Schwannoma from a Dorsal Root of a Spinal Nerve

Background: Spinal Schwannomas are benign nerve sheet tumors and the most common intradural extramedullary tumors of the spine, mainly occurring in the cervical and lumbar region. Case Description: Here we illustrate the case of a 34-year-old woman with a paraspinal lesion presenting with severe lumbar pain. There were no focal sensory or motor deficits. Magnetic resonance imaging (MRI) disclosed a nodular lesion embedded in the paraspinal lumbar musculature, suspicious of tumorous growth. Complete surgical excision of the lesion was performed with clear margins and neuropathological analysis revealed a Schwannoma. Postoperative imaging confirmed a gross total resection with no recurrence after 6 months. Conclusion: Although Schwannomas are frequently encountered in the lumbar spine, a location distinct from the spinal canal is very rare. To be adequately treated, it needs to be considered in the differential diagnosis of any spinal or paraspinal mass. As with other accessible and symptomatic lesions, the treatment of choice is complete excision with clean margins to avoid local recurrence.

Cystic spinal schwannomas: A short series of six cases. Can we predict them preoperatively?

Background:Spinal schwannomas are benign tumors arising from the spinal nerve root sheaths and are the commonest intradural extramedullary spinal tumors. Though cystic changes in schwannomas are well described, predominantly cystic schwannomas are uncommon lesions and form a different spectrum of conditions as compared with the commonly seen intradural extramedullary solid lesions.Case Description:We present a case series of six patients with spinal intradural extramedullary cystic schwannomas. Two patients had uniloculated cystic schwannomas, two patients had multi-loculated cystic lesions with thick walls and intralesional septations, and two patients had giant cystic schwannomas, one of which had an extradural extension. We report two cases in which preoperative radiological dilemma was encountered and discuss the differential diagnoses of this uncommon entity.Conclusion:Cystic spinal schwannomas may be confused with other cystic lesions in the spine, differentiating them preoperatively is important and in this regard, contrast-enhanced magnetic resonance imaging plays a vital role. Frozen section histopathology should be used to identify them at surgery. It is important to detect these lesions at surgery, as total excision is possible and almost always results in good long-term neurological outcome.

Minimally Invasive Resection of an Extradural Far Lateral Lumbar Schwannoma with Zygapophyseal Joint Sparing: Surgical Nuances and Literature Review

Introduction. Spinal schwannomas are benign nerve sheath tumors. Completely extradural schwannomas of the lumbar spine are extremely rare lesions, accounting for only 0,7–4,2% of all spinal NSTs. Standard open approaches have been used to treat these tumors, requiring extensive muscle dissection, laminectomy, radical foraminotomy, and facetectomy. In this paper the authors present the case of a minimally invasive resection of a completely extradural schwannoma. Operative technique literature review is presented. Material & Methods. A 50-year-old woman presented with progressive complains of chronic right leg pain and paresthesia. The magnetic resonance imaging revealed a giant well-encapsulated dumbbell-shaped extradural lesion at the L3-L4 level. The patient underwent a minimally invasive gross total resection of the tumor using a tubular expandable retractor system. Results. The patient had complete resolution of radiculopathy in the immediate postoperative period and she was discharged home, neurologically intact, on the second postoperative day. Postoperative MRI demonstrated no evidence of residual tumor. At latest follow-up (18 months) the patient remains asymptomatic. Conclusion. Although challenging, this minimally invasive procedure is safe and effective, being an appropriate alternative, with many potential advantages, to the open approach.

A case report of multiple spinal schwannomas causing acute hemiparesis by intratumoral hemorrhage

A case report of multiple spinal schwannomas causing acute hemiparesis by intratumoral hemorrhage

Giant Hemorrhagic Cervical Schwannoma in a Young Woman with Acute Quadriparesis: Case Report

Giant Hemorrhagic Cervical Schwannoma in a Young Woman with Acute Quadriparesis: Case Report Schwannomas are the most common extramedullary spinal tumors. The acute hemorrhagic onset of a spinal schwannoma is a rare occurrence.We report the case of a 32-year-old woman who presents with acute onset of quadriparesis due to a hemorrhagic intradural schwannoma. The tumor arose from left C1-C2 roots and extended downward from C1 to C5 vertebral levels. An emergency posterior osteoplastic laminotomy extending from C2 to C4 was performed anden bloc resection of the tumor was achieved. Histological diagnosis was schwannoma with hemorrhagic components.

A Purely Cystic Giant Sacral Schwannoma Mimicking a Bone Cyst: A Case Report

Approximately 1--5% of the spinal schwannomas arise in the sacrum and frequently grow to a considerable size before becoming symptomatic; hence, the term “giant sacral schwannoma” refers to tumors extending into the vertebral body and the extraspinal space (1). Most schwannomas are solid or heterogeneous solid tumors, but they can rarely undergo cystic degeneration, xanthomatous change, or hemorrhage (2). A completely cystic appearance with only thin peripheral wall enhancement is extremely rare. A few cases of solitary cystic schwannomas arising from the spine have been previously reported (3-8). To the best of our knowledge, there is only one previous reported case of a giant solitary cystic schwannoma of the sacrum. Here, we describe a rare case of a totally cystic giant sacral schwannoma presenting as lumbar back pain. Institutional review board approval was obtained.

Lumbar Cystic Intradural Schwannoma: A Case Report

Background Data: Intradural lumbar cystic schwannomas are very rare entity and only about 10 case reports have been reported in the literature. The diagnosis and management remains a challenge for clinical physicians.Purpose: Our objective in presenting this particular case is to highlight the atypical radiological features of intradural spinal schwannoma and how to deal with it surgically and follow up. Study Design: case report. Material and Methods: A case of cystic intradural lesion in a previously healthy 29 years old male is reported. Low back pain and lately right sciatica were the only symptoms. After pre-operative evaluation and preparation, this patient was operatedon prone position under general anesthesia. Results: Although the lesion originates from nerve tissue, only 50% of cases have a direct relation with the nerve. Hence complete excision without sacrificing nerve roots is usually feasible and is curative in most cases as in our case. The patient recovered totally intact without any motor, sensory or sphincteric disturbance. The postoperative histological picture of cystic schwannoma, which was not in the preoperative list of differential diagnoses, is discussed. Conclusion: A successful surgical outcome depends on early diagnosis [beforeneurological damage has occurred], meticulous investigation [on any intractable nonspecific low back pain], and complete excision. (2014ESJ066)