Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions.

Meningiomas are the most common intracranial tumor, making up more than a third of all primary central nervous system (CNS) tumors. They are mostly benign tumors that can be observed or preferentially treated with gross total resection that provides good outcomes. Meningiomas with complicated histology or in compromising locations has proved to be a challenge in treating and predicting prognostic outcomes. Advances in genomics and molecular characteristics of meningiomas have uncovered potential use for more accurate grading and prediction of prognosis and recurrence. With the study and detection of genomic aberrancies, specific biologic targets are now being trialed for possible management of meningiomas that are not responsive to standard surgery and radiotherapy treatment. This review summarizes current epidemiology, etiology, molecular characteristics, diagnosis, treatments, and current treatment trials.

Early clinical trials of Toca 511 and Toca FC show a promising novel treatment for recurrent malignant glioma.

INTRODUCTION: Glioblastoma and anaplastic astrocytoma are two of the most aggressive and common glioma malignancies in adults. These high-grade gliomas (HGG) universally recur despite aggressive treatment modalities and have a median overall survival (mOS) of approximately 14 months from initial diagnosis. Upon recurrence, there is no standard of care and these patients have a dismal prognosis of around 9 months at time of recurrence. Areas covered: In this article, we assess the newly published phase I data of Toca 511 and Toca FC, a two-drug combination therapy for recurrent HGG (rHGG) tumors, for effectiveness and safety. Expert opinion: These early studies provide very encouraging results for Toca 511 and Toca FC in rHGG. This therapy had a response rate of 11.3% and a mOS of 11.9 months in 56 patients, an improvement compared to historical controls. Furthermore, all responders were complete responses after extended follow-up. The drug is well tolerated for most patients. Responders tended to be young and have high-performance scores prior to beginning therapy, but more studies are necessary to understand the patient profile that receives the most benefit. Randomized-controlled trials are warranted for Toca 511 and Toca FC to confirm drug efficacy.

Management of Glioblastoma Multiforme in Elderly Patients: A Review of the Literature.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, occurs most commonly in individuals older than 65 years of age, and is universally fatal. Increasing age compounds the poor prognosis of GBM, as elderly patients have markedly worse outcomes than younger patients. However, many of the studies previously investigating optimal treatment regimens exclude patients older than the age of 65 years and thus may not represent the best approaches to ensuring prolonged survival with preserved quality of life. This review aims to highlight the current literature on surgical and medical management, including our own experience, for GBM in the elderly patients, and to provide rational treatment approaches for a vulnerable, often-overlooked, patient population.

Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas.

Surgical resection is typically the first line of treatment for gliomas. However, the neurosurgeon faces a major challenge in achieving maximal resection in high-grade gliomas as these infiltrative tumors make it difficult to discern tumor margins from normal brain with conventional white-light microscopy alone. To aid in resection of these infiltrative tumors, fluorescence-guided surgery has gained much popularity in intraoperative visualization of malignant gliomas, with 5-aminolevulinic acid (5-ALA) leading the way. First introduced in an article in Neurosurgery, 5-ALA has since become a safe, effective, and inexpensive method to visualize and improve resection of gliomas. This has undoubtedly led to improvements in the clinical course of patients as demonstrated by the increased overall and progression-free survival in patients with such devastating disease. This literature review aims to discuss the major studies and trials demonstrating the clinical utility of 5-ALA and its ability to aid in complete resection of malignant gliomas.

Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and is universally fatal. Despite surgical resection, radiotherapy, and systemic chemotherapy, the median overall survival is less than 15 months. As current therapies are not tumor-specific, treatment commonly results in toxicity. The epidermal growth factor receptor variant III (EGFRvIII) is a naturally occurring mutant of EGFR and is expressed on approximately 20% to 30% of GBMs. As it is not expressed on normal cells, it is an ideal therapeutic target. Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. Phase I and II clinical trials have demonstrated significantly higher progression-free and overall survival times in vaccinated patients with EGFRvIII-expressing GBM tumors. Side effects are minimal and mainly consist of hypersensitivity reactions. Due to the efficacy and safety of rindopepimut, it is a promising therapy for patients with GBM. Currently, rindopepimut is undergoing clinical testing in an international Phase III trial for newly diagnosed GBM and a Phase II trial for relapsed GBM.

Marked response of gliomatosis cerebri to temozolomide and whole brain radiotherapy.

Gliomatosis cerebri (GC) represents an unfortunate, rare variant of glioma with a very poor prognosis. Given this lesion's rarity, little information exists on appropriate treatment options. The diffuse, infiltrative nature of GC precludes any surgical resection and limits therapy. Because of the improved survival seen with the use of temozolomide (TMZ) in malignant glioma, a rigorous systematic review of the published literature was performed to ascertain the benefit of TMZ in GC. We identified all GC cases in the literature where there was enough information to ascertain a clear response to a specific chemoradiotherapeutic treatment. In addition to our experience with a recent case, we have identified 61 patients with GC in the published literature who demonstrated a positive radiographic or clinic response after treatment. Statistical analysis of survival was performed by Kaplan-Meier analysis. A positive radiographic and clinical response was seen in patients ranging in age from 4 to 84 years. Overall median survival in patients diagnosed with GC who demonstrated a response after treatment was 25 months, with 1- and 2-year survival rates of 89% and 55%, respectively. The most common treatment regimens for responders included TMZ alone (26.2%), external whole-brain radiotherapy (WBRT) (26.2%), and concomitant TMZ and WBRT (20%). Our patient was treated with concomitant TMZ (150 mg/m(2)/day over 5 days) and WBRT (50 Gy) and has remained with a complete radiographic response after 36 months. In conclusion, patients with GC confirmed by surgical biopsy should be aggressively treated with concomitant TMZ and WBRT, as marked responses have been seen, and this appears to offer overall survival benefit.

Conquering mount fuji: resolution of tension pneumocephalus with a foley urinary catheter.

Tension pneumocephalus is the presence of air or gas in the cranium that is under pressure. It occurs due to disruption of the skull, including trauma to the head or face, after neurosurgical procedures and occasionally, spontaneously (Schirmer et al., 2010). Patients typically present with headache but can also have neurological deficits such as decreased mental status, numbness, and weakness (Schirmer et al., 2010). It is diagnosed by computerized tomography (CT) scan (Michel, 2010). The characteristic finding is that the two frontal poles of the brain are separated by air. After diagnosis, treatment is imperative for both symptomatic relief and preventing further compression. We present a case of a patient who presented with tension pneumocephalus and unconventional treatment that resulted in clinical improvement of his symptoms and radiographic resolution of his condition.

Guidelines for the management of obstructive hydrocephalus from suprasellar-prepontine arachnoid cysts using endoscopic third ventriculocystocisternostomy.

Intracranial endoscopy has emerged as an innovative surgical tool for various intracranial procedures, but its use remains limited to neurosurgeons trained in this minimally invasive technique. Complex, skull base arachnoid cysts represent one entity that is challenging to treat because of adjacent critical neurovascular structures; however, the advent of intracranial endoscopic techniques has revolutionized treatment. Arachnoid cysts located in the suprasellar-prepontine skull base region can cause obstructive hydrocephalus or symptomatic mass effect and require urgent decompression. These patients may present with nonfocal symptoms that can quickly lead to a life-threatening condition if not accurately diagnosed and treated. The authors present a summary of the world literature of suprasellar-prepontine arachnoid cysts (SPACs) to ascertain clinical presentations and provide class III evidentiary treatment guidelines for this uniquely challenging type of arachnoid cyst. Urgent endoscopic third ventriculostomy results in normalization of intracranial pressure, return of normal CSF flow, and relief of symptoms.

Central nervous system.

Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In adults, about half of all CNS tumors are malignant, whereas in pediatric patients, more than 75% are malignant. For most benign CNS tumors that require treatment, neurosurgeons can offer curative resections or at least provide significant relief from mass effect. Unfortunately, we still lack effective treatments for most primary and secondary malignant CNS tumors. However, the past decade has witnessed an explosion in the understanding of the early molecular events in malignant primary CNS tumors, and for the first time in history, oncologists are seeing that a plethora of new therapies targeting these molecular events are being tested in clinical trials. There is hope on the horizon for the fight against these deadly tumors. The distribution of CNS tumors by location has remained constant for numerous years. The majority of primary CNS tumors arise in the major cortical lobes. Twenty nine percent of primary CNS tumors arise from the dural meninges that encase the CNS structures. The vast majority of these are meningiomas, of which over 90% are benign. About 10% of primary CNS tumors are found in the sella turcica region, where the pituitary gland resides. Other much less common sites of primary CNS tumors include the pineal region, ventricular system, cerebellum, brain stem, cranial nerves, and spinal cord. The distribution of CNS tumors by histology has seen a slight increase in more malignant tumors over the past decade, possibly due to increased neuroimaging practices or environmental exposures. Arising from glial cells, gliomas represent over 36% of all primary CNS tumors and consist of astrocytomas, oligodendrogliomas, ependymomas, mixed gliomas, and neuroepithelial tumors. The benign meningiomas make up 32% of primary CNS tumors, followed by nerve sheath tumors and pituitary tumors. Primary CNS lymphomas, embryonal tumors, and craniopharyngiomas are uncommon. The most common gliomas are astrocytomas, and these tumors are typically classified by the World Health Organization (WHO) as Grades I through IV. Grade IV, the most malignant grade of astrocytoma, includes glioblastoma multiforme (GBM), the most common malignant primary CNS glioma in adults, which represents 51% of all CNS gliomas. GBM is unfortunately the most challenging to effectively treat and has the worst patient survival. This chapter is therefore primarily devoted to the current understanding of this topic. Here we describe the molecular and cellular events associated with malignant glioma initiation and progression. We also review the importance of glioma stem cell biology and tumor immunology in early gliomagenesis. In addition, we present a brief description of the most common malignant primary CNS glioma in pediatric patients - medulloblastoma, as well as familial cancer syndromes that include gliomas as part of the syndrome.

The future role of personalized medicine in the treatment of glioblastoma multiforme.

Glioblastoma multiforme (GBM) remains one of the most malignant primary central nervous system tumors. Personalized therapeutic approaches have not become standard of care for GBM, but science is fast approaching this goal. GBM's heterogeneous genomic landscape and resistance to radiotherapy and chemotherapy make this tumor one of the most challenging to treat. Recent advances in genome-wide studies and genetic profiling show that there is unlikely to be a single genetic or cellular event that can be effectively targeted in all patients. Instead, future therapies will likely require personalization for each patient's tumor genotype or proteomic profile. Over the past year, many investigations specifically focused simultaneously on strategies to target oncogenic pathways, angiogenesis, tumor immunology, epigenomic events, glioma stem cells (GSCs), and the highly migratory glioma cell population. Combination therapy targeting multiple pathways is becoming a fast growing area of research, and many studies put special attention on small molecule inhibitors. Because GBM is a highly vascular tumor, therapy that directs monoclonal antibodies or small molecule tyrosine kinase inhibitors toward angiogenic factors is also an area of focus for the development of new therapies. Passive, active, and adoptive immunotherapies have been explored by many studies recently, and epigenetic regulation of gene expression with microRNAs is also becoming an important area of study. GSCs can be useful targets to stop tumor recurrence and proliferation, and recent research has found key molecules that regulate GBM cell migration that can be targeted by therapy. Current standard of care for GBM remains nonspecific; however, pharmacogenomic studies are underway to pave the way for patient-specific therapies that are based on the unique aberrant pathways in individual patients. In conclusion, recent studies in GBM have found many diverse molecular targets possible for therapy. The next obstacle in treating this fatal tumor is ascertaining which molecules in each patient should be targeted and how best to target them, so that we can move our current nonspecific therapies toward the realm of personalized medicine.

Response of malignant scalp dermatofibrosarcoma to presurgical targeted growth factor inhibition.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive, malignant cutaneous tumor that sparingly presents on the scalp. Dermatofibrosarcomas often result from the formation of a fusion oncogene on translocated or supernumerary ring chromosomes 17 and 22, causing the overexpression of PDGFRbeta driven by the COL1A1 promoter. Because of uncertainty surrounding appropriate treatment of aggressive scalp DFSP, the authors performed an extensive review of the available data from a MEDLINE (Ovid) search to describe the clinical presentation and treatment options for this rare tumor. Their search identified 39 different cases, including the illustrative case presented in this study. Adjuvant therapy for this malignant lesion is not universally established in the literature. In the present case, the authors successfully treated a locally invasive scalp DFSP with presurgical therapy that specifically inhibited the PDGFbeta receptor. Imatinib significantly shrank the DFSP tumor mass, reduced hypervascularity, reduced metabolic activity on PET scanning, and permitted a safe gross-total resection. Although wide excision and Mohs micrographic surgery remain the standard surgical treatments for DFSP, the authors illustrate that presurgical chemotherapeutic treatment by imatinib provides a critical adjunct to traditional therapy.

Cerebellar cryptococcoma in a patient with undiagnosed sarcoidosis: case report.

OBJECTIVE: We describe a patient with undiagnosed sarcoidosis who presented with a rare isolated cerebellar cryptococcoma masquerading as a metastatic brain tumor. CLINICAL PRESENTATION: A 58-year-old man with a history of resected squamous cell carcinoma of the larynx and pulmonary nodules was found to have a left cerebellar lesion on neuroimaging after presenting with a 4-month history of occipital headaches. Neuroimaging revealed a large, lobulated, intra-axial, left cerebellar hemispheric mass with peripheral nodular enhancement, mild adjacent edema, and dense focal areas of calcification. INTERVENTION: The patient underwent a left suboccipital craniotomy for gross total resection of the left cerebellar mass. Pathological examination of the resected specimen demonstrated a cryptococcoma, which was confirmed with a positive cerebrospinal fluid cryptococcal antigen. Postoperative evaluation revealed pulmonary sarcoidosis. CONCLUSION: Central nervous system cryptococcoma is a rare infection that may present in a patient with no known history of immunosuppression and no clinical signs of infection. Diagnostically, this can be difficult to distinguish from a brain tumor. Central nervous system cryptococcoma is an opportunistic infection that typically occurs in the presence of an immunosuppressed state. Sarcoidosis should be considered a predisposing factor because patients with this underlying disease have an increased susceptibility to this central nervous system fungal infection.

Myxopapillary ependymoma and fatty filum in an adult with tethered cord syndrome: a shared embryological lesion? Case report.

OBJECTIVE AND IMPORTANCE: Myxopapillary ependymoma and fatty fila are traditionally thought to arise via completely different pathophysiologies. Recognition of these distinct pathologies in the same patient is important for appropriate treatment and prognosis. CLINICAL PRESENTATION: A 28-year-old woman presented with low back pain, bilateral leg radiculopathies, and mild leg weakness suggestive of tethered cord syndrome. Magnetic resonance imaging revealed lesions in the area of the conus medullaris consistent with a myxopapillary ependymoma and fatty filum. INTERVENTION: Under the surveillance of intraoperative electromyographic monitoring, the patient underwent an L4-S2 laminectomy for transection of the fatty filum and gross total resection of the mass. Histopathological examination confirmed the presence of these two distinct pathologies. CONCLUSION: We report an unusual case of a myxopapillary ependymoma coexisting with a fatty filum in an adult patient. To the best of our knowledge, this association has not yet been reported. This raises the interesting question of a possible associative or causative relationship between these distinct pathologies, which have traditionally been thought to arise from different mechanisms.