Glioblastoma multiforme as a secondary malignancy following stereotactic radiosurgery of a meningioma: case report.

The documentation and exact incidence of stereotactic radiosurgery (SRS)-induced neoplasia is not well understood, with most literature restricted to single case reports and single-center retrospective reviews. The authors present a rare case of radiosurgery-induced glioblastoma multiforme (GBM) following radiosurgical treatment of a meningioma. A 74-year-old patient with a sporadic meningioma underwent radiosurgery following surgical removal of a WHO grade II meningioma. Eighteen months later she presented with seizures, and MRI revealed an intraaxial tumor, which was resected and proven to be a glioblastoma. As far as the authors are aware, this case represents the third case of GBM following SRS for a meningioma. This report serves to increase the awareness of this possible complication following SRS. The possibility of this rare complication should be explained to patients when obtaining their consent for radiosurgery.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Spinal meningiomas: clinicoradiological factors predicting recurrence and functional outcome.

OBJECTIVE Spinal meningiomas are benign tumors with a wide spectrum of clinical and radiological features at presentation. The authors analyzed multiple clinicoradiological factors to predict recurrence and functional outcome in a cohort with a mean follow-up of more than 4 years. The authors also discuss the results of clinical studies regarding spinal meningiomas in the last 15 years. METHODS The authors retrospectively reviewed the clinical and radiological details of patients who underwent surgery for spinal tumors between 2001 and 2015 that were histopathologically confirmed as meningiomas. Demographic parameters, such as age, sex, race, and association with neurofibromatosis Type 2, were considered. Radiological parameters, such as tumor size, signal changes of spinal cord, spinal level, number of levels, location of tumor attachment, shape of tumor, and presence of dural tail/calcification, were noted. These factors were analyzed to predict recurrence and functional outcome. Furthermore, a pooled analysis was performed from 13 reports of spinal meningiomas in the last 15 years. RESULTS A total of 38 patients were included in this study. Male sex and tumors with radiological evidence of a dural tail were associated with an increased risk of recurrence at a mean follow-up of 51.2 months. Ventral or ventrolateral location, large tumors, T2 cord signal changes, and poor preoperative functional status were associated with poor functional outcome at 1-year follow-up. CONCLUSIONS Spine surgeons must be aware of the natural history and risk factors of spinal meningiomas to establish a prognosis for their patients.

Spinal ependymomas. Part 1: Intramedullary ependymomas.

OBJECT Ependymomas represent the most common intramedullary tumor in adults. Despite their usually well-defined dissection plane, surgical morbidity has been documented to be considerably higher compared with other intramedullary entities. This study presents an analysis of risk factors for surgical morbidity and data on long-term results for intramedullary ependymomas. METHODS Among 1447 patients with tumors of the spinal canal treated between 1980 and 2014, 309 patients presented with intramedullary tumors. One hundred patients with intramedullary ependymomas underwent 102 operations. Mean age was 44 ± 15 years (range 8-74 years). Patients were followed by outpatient visits and questionnaires, with a mean follow-up of 77 ± 91 months. Short-term results were determined for individual symptoms and the McCormick Scale, whereas tumor recurrence rates were calculated with Kaplan-Meier statistics. RESULTS Compared with cervical ependymomas, those of the thoracic spine were associated with more severe motor deficits and gait problems at presentation. A total of 86.3% of patients with intramedullary ependymomas underwent gross-total resection (GTR). A low preoperative McCormick grade and first surgery were the strongest predictors for a GTR. Postoperatively, 67.6% of patients demonstrated a worse neurological state at discharge from the hospital. This deterioration was transient for 40.1% of the patients and permanent for 27.5%. In the long term, the McCormick grade remained unchanged from the preoperative grade in 74.5% of patients, while it was improved in 5.9% of patients and increased after surgery in 19.6% of patients. According to a multivariate analysis, the risk of permanent morbidity increased with a thoracic level of the ependymoma, advanced age, a long clinical history, presence of a tumor hemorrhage, and surgery on a recurrent tumor. In the long term, tumor recurrence rates correlated significantly with the amount of resection (4.2% and 18.5% in 20 years after GTR and partial resections, respectively). Postoperative neuropathic pain syndromes affected 37.0% of patients, whereas 4% demonstrated a postoperative myelopathy related to cord tethering at the level of surgery. CONCLUSIONS Intramedullary ependymomas are tumors best treated surgically. A complete resection indicates cure for the overwhelming majority of these patients. Surgery should be performed early by neurosurgeons who deal with these lesions on a regular basis to achieve high GTR rates. Permanent surgical morbidity varies most according to tumor location and patient age.

TRAF7 somatic mosaicism in a patient with bilateral optic nerve sheath meningiomas: illustrative case.

BACKGROUND: In the past decade, next-generation sequencing has spurred significant progress in the understanding of cytogenetic alterations that occur in meningiomas. Eighty percent of adult meningiomas harbor pathogenic somatic variants involving NF2, TRAF7, SMARCB1, KLF4, PI3K, or POLR2A. Somatic variants in TRAF7 associated with meningiomas usually localize to the gene's WD40 domains but are mutually exclusive to germline mutations, which cause a distinctive autosomal dominant syndrome. OBSERVATIONS: This case involved a 15-year-old girl with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis, and syndromic features, including craniosynostosis, brain anomalies, syndactyly, brachydactyly, epicanthus, and patent ductus arteriosus. Genetic testing of the meningioma specimen 7 years after biopsy showed a pathogenic p.R641C variant within the WD40 domain of the TRAF7 gene. Additional testing of unaffected tissues identified the same variant at lower allele frequencies, consistent with postzygotic somatic mosaicism. LESSONS: The authors report postzygotic somatic mosaicism for a p.R641C variant in the TRAF7 gene in a patient with bilateral optic nerve sheath meningiomas, diffuse meningiomatosis and a constellation of systemic findings previously recognized in patients with germline mutations of this gene. This is the first report of optic nerve sheath meningioma in a patient with mutation in the TRAF7 gene.

Management of NF2-associated vestibular schwannomas in children and young adults: influence of surgery and clinical factors on tumor volume and growth rate.

OBJECTIVE: The authors' aim was to evaluate the tumor volume and growth rate of neurofibromatosis type 2 (NF2)-associated vestibular schwannomas (VSs) and the clinical factors or type of mutations before and after surgery in children and adults younger than 25 years at the time of diagnosis. METHODS: A total of 579 volumetric measurements were performed in 46 operated tumors in 28 NF2 patients, using thin-slice (< 3 mm) T1-weighted contrast-enhanced MRI. The follow-up period ranged from 21 to 167 months (mean 75 months). Growth rate was calculated using a multilinear regression model. Mutation analysis of the NF2 gene was performed in 25 patients. RESULTS: Surgery significantly (p = 0.013) slowed the VS growth rate from 0.69 ± 1.30 cm3/yr to 0.23 ± 0.42 cm3/yr. Factors significantly associated with a higher growth rate of VSs were increasing patient age (p < 0.0005), tumor volume (p = 0.006), tumor size (p = 0.001), and constitutional truncating mutations in the NF2 gene (p = 0.018). VS growth rates tended to be higher in patients with spinal ependymomas and in right-sided tumors and lower in the presence of peripheral schwannomas; however, no statistical significance was achieved. CONCLUSIONS: Decompression of the internal auditory canal with various degrees of tumor resection decreases the postoperative tumor growth rate in children and young adults with NF2-associated VS. Patients with potential risk factors for accelerated growth (e.g., large volume, truncating mutations) and with increasing age should be monitored more closely before and after surgery.

Predicting hearing outcomes before primary radiosurgery for vestibular schwannomas.

OBJECTIVE: Optimizing outcomes in the management of patients with vestibular schwannomas (VSs) requires consideration of the patient's goals. Earlier recognition of VS by imaging has led to an evolution in management. Stereotactic radiosurgery (SRS) has emerged as a frequently used strategy designed to reduce management risks, obtain long-term tumor control, and preserve current neurological function. The authors analyzed features that impact hearing preservation rates in patients with serviceable hearing prior to SRS. METHODS: The study included 307 patients who had serviceable hearing (Gardner-Robertson hearing scale [GR] grade 1 or 2, speech discrimination score ≥ 50%, pure tone average ≤ 50 dB) at the time of SRS. The authors evaluated parameters that included age, tumor volume, hearing status, disequilibrium, tinnitus, Koos class, sex, and tumor margin dose. The Pittsburgh Hearing Prediction Score (PHPS) was evaluated as a method to predict long-term hearing outcomes in these cases. RESULTS: At a median of 7.6 years after SRS (range 1-23 years), tumor control was achieved in 95% of patients. The overall serviceable hearing preservation rate was 77.8% at 3 years, 68.8% at 5 years, and 51.8% at 10 years. The PHPS assigns a total of 5 points based on patient age (1 point if < 45 years, 2 points if 45-59 years, and 3 points if ≥ 60 years), tumor volume (0 points if < 1.2 cm3, 1 point if ≥ 1.2 cm3), and GR grade (0 points if grade 1 hearing, 1 point if grade 2 hearing) The serviceable hearing preservation rate was 92.3% at 10 years in patients whose score total was 1. In contrast, none of the patients whose PHPS was 5 maintained serviceable hearing at 10 years (p < 0.001). CONCLUSIONS: SRS resulted in a high rate of long-term tumor control and cranial nerve preservation. The PHPS helped to predict long-term hearing preservation rates in patients who underwent SRS when they still had serviceable hearing. The best long-term hearing preservation rates were found in younger patients with smaller tumor volumes.

Management of multiple meningiomas.

OBJECTIVE Multiple meningiomas account for 1%-10% of meningiomas. This study describes epidemiological aspects of the disease and its management, which is more challenging than for single tumors. METHODS A consecutive series of adult patients with ≥ 2 spatially separated meningiomas was reviewed. Patients with neurofibromatosis Type 2 were excluded. The authors collected clinical, imaging, histological, and treatment data to obtain information on epidemiology, management options, and outcomes of active treatment and surveillance. RESULTS A total of 133 consecutive patients were included over 25 years, with a total of 395 synchronous and 53 metachronous meningiomas, and a median of 2 tumors per patient. One hundred six patients had sporadic disease, 26 had radiation-induced disease, and 1 had familial meningiomatosis. At presentation, half of the patients were asymptomatic. In terms of their maximum cross-sectional diameter, the tumors were small (≤ 2 cm) in 67% and large (> 4 cm) in 11% of the meningiomas. Fifty-four patients had upfront treatment, and 31 had delayed treatment after an observation period (mean 4 years). One in 4 patients had ≥ 2 meningiomas treated. Overall, 64% of patients had treatment for 142 tumors-67 with surgery and 18 with radiotherapy alone. The mean follow-up was 7 years, with 13% of treated patients receiving salvage therapy. Approximately 1 in 4 patients who underwent surgery had ≥ 1 WHO Grade II or III meningioma. Meningiomas of different histological subtypes and grades in the same patient were not uncommon. CONCLUSIONS Multiple meningiomas are often asymptomatic, probably because the majority are small and a significant proportion are induced by radiation. Approximately two-thirds of patients with multiple meningiomas require therapy, but only one-third of all meningiomas need active treatment. The authors recommend surveillance for stable and asymptomatic meningiomas and therapy for those that are symptomatic or growing.

Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas.

OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients experienced worsening of trigeminal nerve function. Facial nerve function worsened in 1 patient (2.5%). No significant differences in tumor control, hearing preservation, or complications were found in comparing the results of GKRS for NF2-related VS versus GKRS for sporadic VS. CONCLUSIONS With modern GKRS, the use of low margin doses for treating growing VSs in patients with NF2 demonstrates good long-term tumor control rates. Feiling-Gardner phenotype and tumor volume smaller than 6 cm3 seem to be independently associated with prolonged progression-free survival, highlighting the clinical importance of phenotype assessment before GKRS treatment. In addition, no significant differences in tumor control rates or complications were found in the matched-control cohort analysis comparing GKRS for VS in patients with NF2 and GKRS for sporadic VS. These results show that GKRS is a valid treatment option for NF2-related VS, in addition to being a good option for sporadic VS, particularly in patients with the Feiling-Gardner phenotype and/or tumors that are small to medium in size. Larger tumors in patients with the Wishart phenotype appear to respond poorly to radiosurgery, and other treatment modalities should therefore be considered in such cases.

Long-term outcome after Gamma Knife radiosurgery for acoustic neuroma of all Koos grades: a single-center study.

OBJECTIVE The authors present long-term follow-up data on patients treated with Gamma Knife radiosurgery (GKRS) for acoustic neuroma. METHODS Six hundred eighteen patients were radiosurgically treated for acoustic neuroma between 1992 and 2016 at the Department of Neurosurgery, Medical University Vienna. Patients with neurofibromatosis and patients treated too recently to attain 1 year of follow-up were excluded from this retrospective study. Thus, data on 557 patients with spontaneous acoustic neuroma of any Koos grade are presented, as are long-term follow-up data on 426 patients with a minimum follow-up of 2 years. Patients were assessed according to the Gardner-Robertson (GR) hearing scale and the House-Brackmann facial nerve function scale, both prior to GKRS and at the times of follow-up. RESULTS Four hundred fifty-two patients (81%) were treated with radiosurgery alone and 105 patients (19%) with combined microsurgery-radiosurgery. While the combined treatment was especially favored before 2002, the percentage of cases treated with radiosurgery alone has significantly increased since then. The overall complication rate after GKRS was low and has declined significantly in the last decade. The risk of developing hydrocephalus after GKRS increased with tumor size. One case (0.2%) of malignant transformation after GKRS was diagnosed. Radiological tumor control rates of 92%, 91%, and 91% at 5, 10, and 15 years after GKRS, regardless of the Koos grade or pretreatment, were observed. The overall tumor control rate without the need for additional treatment was even higher at 98%. At the last follow-up, functional hearing was preserved in 55% of patients who had been classified with GR hearing class I or II prior to GKRS. Hearing preservation rates of 53%, 34%, and 34% at 5, 10, and 15 years after GKRS were observed. The multivariate regression model revealed that the GR hearing class prior to GKRS and the median dose to the cochlea were independent predictors of the GR class at follow-up. CONCLUSIONS In small to medium-sized spontaneous acoustic neuromas, radiosurgery should be recognized as the primary treatment at an early stage. Although minimizing the cochlear dose seems beneficial for hearing preservation, the authors, like others before, do not recommend undertreating intracanalicular tumors in favor of low cochlear doses. For larger acoustic neuromas, radiosurgery remains a reliable management option with tumor control rates similar to those for smaller acoustic neuromas; however, careful patient selection and counseling are recommended given the higher risk of side effects. Microsurgery must be considered in acoustic neuromas with significant brainstem compression or hydrocephalus.

Voxel-based lesion mapping of meningioma: a comprehensive lesion location mapping of 260 lesions.

OBJECTIVE In the present study the authors aimed to determine preferred locations of meningiomas by avoiding descriptive analysis and instead using voxel-based lesion mapping and 3D image-rendering techniques. METHODS Magnetic resonance images obtained in 248 treatment-naïve meningioma patients with 260 lesions were retrospectively and consecutively collected. All images were registered to a 1-mm isotropic, high-resolution, T1-weighted brain atlas provided by the Montreal Neurological Institute (the MNI152), and a lesion frequency map was created, followed by 3D volume rendering to visualize the preferred locations of meningiomas in 3D. RESULTS The 3D lesion frequency map clearly showed that skull base structures such as parasellar, sphenoid wing, and petroclival regions were commonly affected by the tumor. The middle one-third of the superior sagittal sinus was most commonly affected in parasagittal tumors. Substantial lesion accumulation was observed around the leptomeninges covering the central sulcus and the sylvian fissure, with very few lesions observed at the frontal, parietal, and occipital convexities. CONCLUSIONS Using an objective visualization method, meningiomas were shown to be located around the middle third of the superior sagittal sinus, the perisylvian convexity, and the skull base. These observations, which are in line with previous descriptive analyses, justify further use of voxel-based lesion mapping techniques to help understand the biological nature of this disease.

Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.

OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-ß (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative for SPS. Left untreated, however, these tumors can cause significant morbidity, and not all patients are candidates for resection. SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2-associated schwannomas, suggesting a shared etiology. This SPS pattern is distinct from that of other tumors of the peripheral nerve sheath.

The response of spinal cord ependymomas to bevacizumab in patients with neurofibromatosis Type 2.

OBJECTIVE People with neurofibromatosis Type 2 (NF2) have a genetic predisposition to nervous system tumors. NF2-associated schwannomas stabilize or decrease in size in over half of the patients while they are receiving bevacizumab. NF2 patients treated with bevacizumab for rapidly growing schwannoma were retrospectively reviewed with regard to ependymoma prevalence and response to treatment. METHODS The records of 95 NF2 patients receiving bevacizumab were retrospectively reviewed with regard to spinal ependymoma prevalence and behavior. The maximum longitudinal extent (MLE) of the ependymoma and associated intratumoral or juxtatumoral cysts were measured on serial images. Neurological changes and patient function were reviewed and correlated with radiological changes. RESULTS Forty-one of 95 patients were found to have ependymomas (median age 26 years; range 11-53 years). Thirty-two patients with a total of 71 ependymomas had scans appropriate for serial assessment with a mean follow-up of 24 months (range 3-57 months). Ependymomas without cystic components showed minimal change in MLE. Twelve patients had ependymomas with cystic components or syringes. In these patients, reductions in MLE were observed, particularly due to decreases in the cystic components of the ependymoma. Clinical improvement was seen in 7 patients, who all had cystic ependymomas. CONCLUSIONS Bevacizumab treatment in NF2 patients with spinal cord ependymomas results in a decrease in the size of intratumoral and juxtatumoral cysts as well as adjacent-cord syringes and a decrease in cord edema. This may provide clinical benefit in some patients, although the changes do not meet the current criteria for radiological tumor response.

Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation.

The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I-V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene.

Multifocal granulocytic sarcoma of the spine mimicking neurofibromatosis Type 2: case report.

In this report the authors report on a patient with a very indolent course of granulocytic sarcoma, characterized by steroid-induced remission of spinal and cranial tumors and recurrence over a period of several years. This 24-year-old man with history of leukemia presented with rapid-onset quadriparesis secondary to multiple extraaxial masses of the cervicothoracic spine, from C-5 to T-3, and lumbosacral spine, from L-5 to the coccyx. Although the imaging features were highly suggestive of neurofibromatosis Type 2, the patient's history and clinical course were consistent with granulocytic sarcoma; repeat imaging and, later, needle biopsy definitively established the diagnosis of granulocytic sarcoma. Laminectomy and surgical decompression of the spine were not required and, arguably, could have posed unnecessary risk to the patient. This case illustrates that the successful management of a patient presenting with profound neurological deficits due to intradural spinal cord tumors may sometimes be nonsurgical.

Late malignant transformation of vestibular schwannoma in the absence of irradiation: case report.

Late malignant transformation of vestibular schwannoma (VS) following irradiation has previously been reported 29 times in the literature. Here, the authors report the first late malignant transformation of VS unrelated to neurofibromatosis or radiation exposure. After undergoing a near-total excision of a histologically benign VS, the patient developed malignant regrowth of the tumor remnant 42 months after the primary excision. This case challenges the dogmatic belief of absolute causality between radiation exposure and late malignant transformation of VS, and has important implications regarding future counseling and consent for the treatment of patients with VS.

Genomic landscape of intracranial meningiomas.

Meningiomas are the most common primary intracranial neoplasms in adults. Current histopathological grading schemes do not consistently predict their natural history. Classic cytogenetic studies have disclosed a progressive course of chromosomal aberrations, especially in high-grade meningiomas. Furthermore, the recent application of unbiased next-generation sequencing approaches has implicated several novel genes whose mutations underlie a substantial percentage of meningiomas. These insights may serve to craft a molecular taxonomy for meningiomas and highlight putative therapeutic targets in a new era of rational biology-informed precision medicine.

Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non-skull base meningiomas.

OBJECTIVE The objective of this study was to identify the natural history and clinical predictors of postoperative recurrence of skull base and non-skull base meningiomas. METHODS The authors performed a retrospective hospital-based study of all patients with meningioma referred to their institution from September 1993 to January 2014. The cohort constituted both patients with a first-time presentation and those with evidence of recurrence. Kaplan-Meier curves were constructed for analysis of recurrence and differences were assessed using the log-rank test. Cox proportional hazard regression was used to identify potential predictors of recurrence. RESULTS Overall, 398 intracranial meningiomas were reviewed, including 269 (68%) non-skull base and 129 (32%) skull base meningiomas (median follow-up 30.2 months, interquartile range [IQR] 8.5-76 months). The 10-year recurrence-free survival rates for patients with gross-total resection (GTR) and subtotal resection (STR) were 90% and 43%, respectively. Skull base tumors were associated with a lower proliferation index (0.041 vs 0.062, p = 0.001), higher likelihood of WHO Grade I (85.3% vs 69.1%, p = 0.003), and younger patient age (55.2 vs 58.3 years, p = 0.01). Meningiomas in all locations demonstrated an average recurrence rate of 30% at 100 months of follow-up. Subsequently, the recurrence of skull base meningiomas plateaued whereas non-skull base lesions had an 80% recurrence rate at 230 months follow-up (p = 0.02). On univariate analysis, a prior history of recurrence (p < 0.001), initial WHO grade following resection (p < 0.001), and the inability to obtain GTR (p < 0.001) were predictors of future recurrence. On multivariate analysis a prior history of recurrence (p = 0.02) and an STR (p < 0.01) were independent predictors of a recurrence. Assessing only patients with primary presentations, STR and WHO Grades II and III were independent predictors of recurrence (p < 0.001 for both). CONCLUSIONS Patients with skull base meningiomas present at a younger age and have less aggressive lesions overall. Extent of resection is a key predictor of recurrence and long-term follow-up of meningiomas is necessary, especially for non-skull base tumors. In skull base meningiomas, recurrence risk plateaus approximately 100 months after surgery, suggesting that for this specific cohort, follow-up after 100 months can be less frequent.

Benign meningiomas (WHO Grade I) with atypical histological features: correlation of histopathological features with clinical outcomes.

OBJECT World Health Organization (WHO) Grade I (benign) meningiomas with atypical features may behave more aggressively than similarly graded tumors without atypical features. Here, the prognostic significance of atypical features in benign meningiomas was determined. METHODS Data from patients diagnosed with WHO Grade I benign meningiomas per the 2007 WHO criteria and who underwent surgery between 2002 and 2012 were retrospectively reviewed. Patients were stratified by the absence or presence of 1 to 2 atypical features with review of the clinical and histological factors. RESULTS A total of 148 patients met the inclusion criteria (n = 77 with atypia; n = 71 without atypia). The median follow-up duration after pathological diagnosis was 37.5 months. Thirty patients had progression/recurrence (P/R) after initial treatment, and 22 (73%) of 30 patients with P/R had 1-2 atypical features. The presence of atypical features was significantly associated with P/R (p = 0.03) and independent of the MIB-1 labeling index. The 1-year and 5-year actuarial rates of P/R were 9.6% versus 1.4% and 30.8% versus 13.8% fortumors with and without atypical features, respectively. Higher Simpson grade resection (II-IV vs I) was associated with the increased risk of P/R (p < 0.001). Stratification of patients into low-risk (Simpson Grade I), intermediate-risk (Simpson Grade II-IV with no atypical features), and high-risk groups (Simpson Grade II-IV with atypical features) was significantly correlated with increased risk of P/R (p < 0.001). CONCLUSIONS Patients with benign meningiomas with atypical features and those undergoing Simpson Grade II-IV resection are at significantly increased risk of P/R. Patients with these features may benefit from the consideration of additional surgery and/or radiation therapy.

Questioning the need for ICU level of care in pediatric patients following elective uncomplicated craniotomy for brain tumors.

OBJECTIVE The object of this study is to address what factors may necessitate the need for intensive care monitoring after elective uncomplicated craniotomy in pediatric patients who are initially managed in a non-intensive care unit setting postoperatively. METHODS A retrospective chart review was undertaken for all patients who underwent elective craniotomy for brain tumor between April of 2007 and April of 2012 and who were directly admitted to the floor postoperatively. Factors such as age, tumor type, craniotomy location, neurological comorbidities, reason for transfer to intensive care unit (ICU) level of care (if applicable), time between admittance to floor and transfer to ICU level of care, and reason for transfer to ICU level of care were assessed. RESULTS Adjusted logistic regression found 2 significant positive predictors of postoperative transfer to the ICU after initial admission to the floor: primitive neuroectodermal tumor pathology (OR 44.10, 95% CI 1.24-1572.16, p = 0.04), and repeat craniotomy during the same hospitalization (OR 13.97, 95% CI 1.21-160.66, p = 0.03). Conversely, 1 negative factor was found: low-grade glioma pathology (OR 0.05, 95% CI 0.00-0.87, p = 0.04). CONCLUSIONS Select pediatric patients may not require ICU level of care after elective uncomplicated pediatric craniotomy. Additional studies are needed to adequately address which patients would benefit from initial ICU admittance following elective craniotomies for brain tumors.