Multimodal techniques failed to detect cytomegalovirus in human glioblastoma samples.

The role of the human cytomegalovirus (HCMV) in gliomagenesis is largely debated. Contradictory data exist regarding the sensitivity and specificity of HCMV detection techniques, including immunohistochemistry (IHC), in situ hybridization (ISH), and RNA and DNA sequencing. The aim of this study is to detect HCMV in glioblastoma (GBM) tumor samples using IHC, ISH, and real-time PCR (qPCR), as well as to correlate the findings with serological status and HCMV DNA load in blood. Forty-seven patients with histopathological diagnosis of GBM and HCMV serological status were retrospectively reviewed. HCMV DNA quantification in whole blood was performed in 31 patients. The detection of HCMV in tumor samples was performed using IHC in 42 cases, ISH in 10 cases, and qPCR in 29 cases. All but two patients were taking high steroid doses at the time of biological testing. HCMV seroprevalence was 68%. Active infection with HCMV DNA detected in blood was diagnosed in 6 out of 21 (28%) seropositive patients. HCMV was not detected in GBM samples using IHC or ISH, while qPCR was positive in one case (also positive for blood HCMV DNA). These data do not support a crucial role of HCMV in GBM tumorigenesis. HCMV might be reactivated in GBM patients, due to steroid treatment.

Management of pituicytomas: a multicenter series of eight cases.

PURPOSE: Pituicytomas and spindle cell oncocytomas (SCOs) are two rare neoplasms of the sellar and suprasellar region, known to be challenging as they are extremely vascular and almost always misdiagnosed, altering our surgical planning and the patients' outcomes. Also we argue that recent update concerning the pathology findings of these tumors should be more widely generalized to our practice. METHODS: This is a retrospective multicenter study, reporting the clinical manifestations, radiological characteristics, histopathological features, treatment strategies and long-term outcomes of patients who have been treated for a Pituicytoma at various institutions in Paris, France over the past 10 years. In addition, we compared our results to the world literature in order to identify similarities concerning the radiographic diagnosis and the treatment strategies of these tumors. RESULTS: Eight patients were operated on in four different hospitals. Misdiagnosis was constant before surgery, pituitary adenoma or craniopharyngioma being suspected. During surgery (transsphenoidal approach: six cases, transcranial approach: two cases) unusual tumors were noted, with important bleeding in most cases. Complete resection could be obtained in five patients. Pathological diagnosis was confirmed in all cases. During the follow up two recurrences occurred. One was subsequently treated with radiotherapy, the other underwent a second surgery. CONCLUSION: Recent updates concerning the histological diagnosis of pituicytomas should be generalized to our practice in order to provide a better understanding of this rare pathology and its natural course.

The prevalence of IgG4-positive plasma cells in hypophysitis: a possible relationship to IgG4-related disease.

AIMS: Hypophysitis is a rare chronic inflammation of the pituitary gland corresponding currently to six histopathological subtypes. Among them, immunoglobulin- G4-related hypophysitis was recently added in this classification. The aim of this study was to perform a retrospective histopathological and immunohistochemical analysis to evaluate the prevalence of IgG4-related hypophysitis and review reported cases. METHODS: All samples of hypophysitis from Lariboisiere hospital were reviewed by two pathologists to assess their subtypes. An immunohistochemistry against IgG4 and IgG was performed. Slides were numerized, and IgG4-positive plasma cells and IgG plasma cells were counted in three high-power fields to evaluate the ratio. RESULTS: Eight cases were included: 5 lymphocytic hypophysitis, 1 granulomatous subtype, and 2 IgG4-related hypophysitis, affecting two young women without other coaffected organ. CONCLUSION: Our results show that IgG4-related hypophysitis is not an exceptional entity. Storiform fibrosis and obliterative phlebitis, histopathological characteristics of IgG4-related disease in other organs, are lacking in pituitary lesions. This study proves the interest of immunohistochemistry for diagnosis of IgG4-related hypophysitis. Due to the sensibility of IgG4-disease to steroids in other organs, this finding could be of clinical relevance.

Combined Nasoseptal and Inferior Turbinate Flap for Reconstruction of Large Skull Base Defect After Expanded Endonasal Approach: Operative Technique.

BACKROUND: Increasing indications for endoscopic endonasal approaches have led neurosurgeons to develop new reconstruction techniques for larger skull base defects. Vascularized grafts have been a great adjunction to reduce the rate of cerebrospinal fluid leak and can also be used to cover exposed critical structures such as the internal carotid artery. The nasoseptal flap and the inferior or middle turbinate flap are thus widely used in endoscopic skull base surgery, but may be insufficient for very large defects. OBJECTIVE: To present a new mucosal flap used to cover large skull base defects in which the mucosa of the inferior turbinate, inferior meatus, nasal floor, and nasal septum is harvested in 1 piece keeping both vascular pedicles intact (inferior turbinate and septal arteries). METHODS: We describe a surgical technique to harvest a combined inferior turbinate-nasoseptal flap. RESULTS: Technical pearls and surgical pitfalls are described through 2 clinical cases in which the nasoseptal mucosa was partially damaged during a previous surgery, rendering the nasoseptal flap insufficient by itself. The flap is harvested thanks to 2 mucosal cuts: a first circular cut around the choanal arch and the junction between the hard and the soft palate, and a second one combining classical cuts of the nasoseptal flap and the inferior turbinate flap. CONCLUSION: The inferior turbinate-nasoseptal flap can be a useful alternative in patients whose septal mucosa was partially damaged and/or with very large postoperative skull base defects.

The Chopsticks Technique for Endoscopic Endonasal Surgery-Improving Surgical Efficiency and Reducing the Surgical Footprint.

BACKGROUND: Variations and additions to the endoscopic endonasal exposure have been proposed around a modular strategy. These extensions are often necessary to provide additional working space and reduce conflict between the instruments and the endoscope. Resection of endonasal structures, which affects negatively the sinonasal quality of life, is thus undertaken not only to obtain tumor exposure but also to improve the maneuverability of the instruments. OBJECTIVE: Our objective was to achieve the same skull base exposures and tumor resections and limit the surgical footprint on sinonasal structures and patients' quality of life. METHODS: Our team developed a surgical technique in which the endoscope and a malleable rotative aspirator are held by the nondominant hand and the other main instrument in the dominant hand. This modification, which we call the chopsticks technique, allows the surgeon to use minimalistic exposures with an improved dynamic perception of the surgical field and reduced conflicts between the instruments. The endonasal structures that are left intact help support the instruments. The same surgical objectives, in terms of exposure and resection, are achieved. We describe our technique and a series of patients operated with this uninarial 3-instruments technique to discuss relevant operative nuances. CONCLUSIONS: We propose a technical modification that allows the surgeons to benefit from the advantages of a bimanual technique while still holding the endoscope. In our opinion, this technique may improve dynamic understanding of the anatomy and surgical efficiency and reduce the footprint of the surgery.

Regression of Giant Olfactory Groove Meningioma and Complete Visual Acuity Recovery after Discontinuation of Cyproterone Acetate.

PURPOSE: To report on the medical management of meningioma with compression of the optic chiasm associated with the use of cyproterone acetate (CA). CASE REPORT: A 65-year-old woman who was being treated with CA presented with a recent decrease in visual function, leading to discovery of a giant olfactory groove meningioma with compression of the optic chiasm. CA was discontinued immediately, and her visual function improved dramatically. At 13 months, in addition to a significant improvement in visual and neurocognitive symptoms, the tumor volume was reduced by 50%. CONCLUSION: In meningiomas associated with CA, treatment cessation may result in prompt improvement in symptoms and a reduction in tumor volume, even if the tumor is large and causing neurologic impairments.

Pediatric Chordomas: Results of a Multicentric Study of 40 Children and Proposal for a Histopathological Prognostic Grading System and New Therapeutic Strategies.

Pediatric chordomas are rare malignant neoplasms, and few data are available for optimizing therapeutic strategies and outcome. This study aimed at evaluating how best to manage them and to identify prognostic factors. This multicentric retrospective study included 40 children diagnosed with chordomas between 1966 and 2012. Clinical, radiological, and histopathological data, treatment modalities, and outcomes were reviewed. The median age was 12 years old. Most chordomas were histologically classical forms (45.5%) and were mostly located at the skull base (72.5%). The overall survival (OS) was 66.6% and 58.6%, and progression-free survival (PFS) was 55.7% and 52% at 5 and 10 years, respectively. Total resection was correlated with a better outcome (p = 0.04 for OS and PFS, log-rank). A histopathological/immunohistochemical grading system recently crafted for adults was applied. In a multivariate analysis, it significantly correlated with outcome (PFS and OS, p = 0.004), and the loss of BAF47 immunoexpression appeared to be a significant independent prognostic factor (PFS, p = 0.033). We also identified clinical and histopathological parameters that correlated with prognosis. A new grading system combined with the quality of surgical resection could help classify patients to postpone radiotherapy in case of low risk. Targeted therapy and reirradiation at recurrence may be considered as potential therapeutic strategies.

Neuronavigated Fiber Dissection with Pial Preservation: Laboratory Model to Simulate Opercular Approaches to Insular Tumors.

BACKGROUND: Advances in the oncologic and functional results of insular surgery have been reported recently. Such successes have been made possible by the advent of the transopercular approach under awake monitoring and by improved anatomic and functional knowledge of white matter pathways surrounding the insula. Nonetheless, given the rarity of insular tumors, it is difficult to get familiar with the complex 3-dimensional anatomy of the different neuronal and vascular structures encountered during a transopercular insular resection. We thus propose to develop a laboratory model allowing to train transopercular approaches of the insula. METHODS: Two hemispheres prepared with Klinger's technique were dissected under light microscope, preserving all pial membranes. The different steps of the dissection were video recorded. RESULTS: Preservation of pial membranes enabled us to simulate subpial resection, both during operculum removal and during insular cortex resection. The medial wall of the resection was defined by the inferior-fronto-occipital fasciculus, protecting from the lenticulostriate arteries. CONCLUSION: In this paper, we show that Klinger dissection with preservation of pial membranes provides a realistic model of insular surgery, allowing surgeons to learn and train on this highly specialized surgery.

Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors.

Chordomas are slow-growing malignant neoplasms. Determination of histopathologic prognostic factors using a large cohort study has been limited by their low incidence. In this retrospective study, we investigated the clinical, histopathologic, and immunohistochemical prognostic factors in 287 chordomas from 111 patients assessed by central pathologic review. Expression patterns of a variety of markers, including vascular endothelial growth factor (VEGF), mTOR pathway, c-kit, HER2, epidermal growth factor receptor (EGFR) and STAT3, and KRAS, BRAF, EGFR, and PIK3CA mutations were analyzed. On univariate analysis, the results confirm surgery as the best treatment, as judged by patient progression-free survival (PFS) and overall survival (OS). Proton therapy, the presence of a dedifferentiated component, mitotic figures, and Ki67 and p53 labeling indices correlated with PFS . Necrosis and apoptosis correlated with OS. Based on these findings, we propose a histopathologic grading system that correlates with PFS and OS. On multivariate analysis, extent of resection, tumor grade, and proton therapy were independent prognostic factors of PFS; extent of resection, tumor location, and grade were independent prognostic factors of OS. Based on the expression of EGFR, pSTAT3, VEGF, and mTOR pathway proteins, (in 85.9%, 79.1%, 85.7%, and 46% of chordomas, respectively), and 2 new mutations in the PIK3CA gene, we also provide evidence for potential therapeutic targets.

Anterior extrusion of fusion cage in posttraumatic cervical disk disease.

Anterior interbody fusion of the cervical spine (ACDF) with bone grafts or cages has become the gold standard for treating cervical disk disease. Several technical modifications have been developed, but currently no consensus exists regarding the optimal technique. In addition, there is also evidence that complications are frequently associated with this procedure. A frequent cause for implant failure in monosegmental ACDF is cage migration into the vertebral end plates or the spinal canal. We report a patient admitted for sudden quadriparesis with complete motor deficit caused by posttraumatic cervical disk protrusion at C4-C5, resulting in spinal compression. ACDF using a titanium stand-alone cage was performed and cured the patient. At the 1-year follow-up visit, imaging showed asymptomatic anterior complete extrusion of the cage out of the disk space. To our knowledge, such an anterior cage migration without trauma has not been reported in the literature to date, and we tried to find technical reasons to explain this complication.

Initial experience using awake surgery for glioma: oncological, functional, and employment outcomes in a consecutive series of 25 cases.

BACKGROUND: Awake glioma surgery aims to maximize resection to optimize prognosis while minimizing the risk of postoperative deficits. OBJECTIVE: To evaluate oncological, functional, and employment outcomes in the first cohort of patients having this type of surgery at our institution and to determine the effects of any learning curve. METHODS: All cases of awake adult (>18 years of age) glioma surgery were recorded between the introduction of this technique in 2011 until the end of 2013. Extent of tumor resection was quantified on magnetic resonance imaging and compared with the objective prediction from a resection probability map. Cognitive status was assessed preoperatively and at 3 months postoperatively. Patients were questioned about their job and capability of working before and after surgery. RESULTS: Twenty-five patients were included in the analysis. No new motor or language deficits were noted at 6 weeks after surgery. Postoperative magnetic resonance imaging showed complete resection in 11 of 13 patients with glioblastoma and >98% resection in the other 2 patients. For patients with World Health Organization grade II glioma, 3 had total, 4 had subtotal, and 3 had partial resections. Comparison between cognitive levels before and after surgery showed no change in 4 patients, improvement in some tests in 2 patients, and deterioration in some tests in 3 patients. Of 20 patients working at the time of diagnosis, 16 returned to work. CONCLUSION: These oncological and functional results of awake glioma surgery during the learning curve are comparable to results from established centers. The use and utility of resection probability maps are well demonstrated. The return to work level is high.