Histopathological investigation of the 1p/19q-codeleted gliomas resected following alkylating agent chemotherapy.

PURPOSE: Lower grade gliomas with 1p/19q codeletion are often responsive to chemotherapy, and several of these have been treated using upfront chemotherapy and subsequent resection following tumor volume decrease. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in 1p/19-codeleted gliomas. METHODS: Fourteen 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry for Ki-67/MIB-1, CD68 as a pan-macrophage/monocyte marker, CD163 as a presumed marker of M2 polarity, and nestin and CD133 as markers of GSCs. RESULTS: The most frequent histological findings following chemotherapy included a sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 index decreased and the number of CD68 + cells increased after chemotherapy. The increasing rate of CD68 + cells in the post-/pre-chemotherapy specimens was inversely correlated with patient prognosis but not tumor response. The number of CD163 + cells, M2/M1 + M2 ratio, and the ratio of GSCs to total tumor cells increased after chemotherapy, and those in the post-chemotherapy specimens were negatively correlated with patient prognosis. There was a correlation between the M2/M1 + M2 ratio and the ratio of GSCs in both pre- and post-chemotherapy specimens. CONCLUSION: GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in 1p/19q-codeleted gliomas.

Magnetic resonance imaging texture analyses in lower-grade gliomas with a commercially available software: correlation of apparent diffusion coefficient and T2 skewness with 1p/19q codeletion.

Preoperative prediction of molecular information of lower-grade gliomas (LrGGs) helps to determine the overall treatment strategy as well as the initial surgical strategy. This study aimed to detect magnetic resonance imaging (MRI) texture parameters to predict the molecular signature of LrGGs using a commercially available software and routine MR images. Forty-three patients treated at Keio University Hospital who had World Health Organization grade II or III gliomas were included. All patients having preoperative T1- and T2-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted (DW) images were also included. Texture analyses of T2, FLAIR, and apparent diffusion coefficient (ADC) histograms were performed using a commercially available software. Texture parameters including kurtosis, skewness, and entropy were investigated to determine any correlation with the presence or absence of isocitrate dehydrogenase (IDH) mutations, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. ADC skewness and T2 skewness were significantly associated with 1p/19q codeletion status. ADC skewness of ≥ 0.25 predicted 1p/19q codeletion with a sensitivity and specificity of 80% and 65.2%, respectively (AUC = 0.728). T2 skewness of ≥ - 0.11 predicted 1p/19q codeletion with a sensitivity and specificity of 80% and 91.3%, respectively, (AUC = 0.866). None of the texture parameters were associated with IDH mutation and MGMT promoter methylation. MRI texture analysis using a commercially available software demonstrated that T2 skewness could predict 1p/19q codeletion with high sensitivity and specificity, suggesting a clinical utility.

Predictive markers for MGMT promoter methylation in glioblastomas.

The promoter methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene has been described as the most important predictor of chemotherapeutic response and patients' survival in glioblastomas (GBs). Therefore, prediction of the MGMT promoter methylation status by imaging would help to preoperatively decide the overall treatment strategy as well as surgical strategy. This study aimed to detect imaging parameters to predict MGMT promoter methylation in GBs by using a commercially available software. We investigated three imaging features (ring enhancement, tumor location, and laterality) and apparent diffusion coefficient (ADC) parameters in 48 newly diagnosed GBs treated at Keio University Hospital in 2006 or later. For ADC, texture analyses were performed. Regions of interest (ROIs) were drawn manually with reference to contrast-enhanced areas, excluding necrotic and cystic regions. Mean ADC value and ADC histogram parameters, including kurtosis, skewness, and entropy, were compared with MGMT promoter methylation. Each parameter was evaluated to determine correlation with MGMT promoter methylation, and the parameters with significant associations with the methylation status were correlated with the MGMT-positive cell ratio determined by immunohistochemistry (IHC) analysis. The mean ADC value and ADC entropy were significantly associated with MGMT promoter methylation. The combination of mean ADC value and ADC entropy predicted MGMT promoter methylation, with a PPV of 81.2% and specificity of 88.9%. The mean ADC value and ADC entropy were negatively correlated with the MGMT-positive cell ratio in the IHC analysis. This study demonstrated that texture analyses of ADC histograms in GBs were predictive of MGMT promoter methylation.

Imaging scoring systems for preoperative molecular diagnoses of lower-grade gliomas.

Recent advance in molecular characterization of gliomas showed that patient prognosis and/or tumor chemosensitivity correlate with certain molecular signatures; however, this information is available only after tumor resection. If molecular information is available by routine radiological examinations, surgical strategy as well as overall treatment strategy could be designed preoperatively.With the aim to establish an imaging scoring system for preoperative diagnosis of molecular status in lower-grade gliomas (WHO grade 2 or 3, LrGGs), we investigated 8 imaging features available on routine CT and MRI in 45 LGGs (discovery cohort) and compared them with the status of 1p/19q codeletion, IDH mutations, and MGMT promoter methylation. The scoring systems were established based on the imaging features significantly associated with each molecular signature, and were tested in the another 52 LrGGs (validation cohort).For prediction of 1p/19q codeletion, the scoring system is composed of calcification, indistinct tumor border on T1, paramagnetic susceptibility effect on T1, and cystic component on FLAIR. For prediction of MGMT promoter methylation, the scoring system is composed of indistinct tumor border, surface localization (FLAIR), and cystic component. The scoring system for prediction of IDH status was not established. The 1p/19q score ≥ 3 showed PPV of 96.2% and specificity of 98.1%, and the MGMT methylation score ≥ 2 showed PPV of 77.4% and specificity of 67.6% in the entire cohort.These scoring systems based on widely available imaging information may help to preoperatively design personalized treatment in patients with LrGG.

The oligodendroglial histological features are not independently predictive of patient prognosis in lower-grade gliomas.

The relevance of oligodendroglial histological features to patient prognoses is controversial. 93 LrGGs resected for about 2 decades were re-assessed based on WHO2007 with special interest to pure oligodendroglial diagnosis (oligodendroglioma or anaplastic oligodendroglioma) and presence of CFO features. Those histological features, patients OS, and tumor chromosomal/genetic characteristics were correlated each other in each of the 3 IDH-1p/19q-based molecular groups. There was significant association between 1p19q status with the oligodendroglial histological diagnosis as well as presence of CFO in the entire cohort. The oligodendroglial diagnosis was associated with longer OS in IDHmut/codel group; however, this association was not significant in the multivariate analyses. In IDHmut/noncodel and IDH-wildtype groups, the oligodendroglial diagnosis was not associated with patient OS. Presence of CFO was not associated with patient OS in any molecular groups. Gain of 8q was associated with the oligodendroglial diagnosis in IDHmut/noncodel group. Neither the oligodendroglial diagnosis nor CFO was predictive for the methylation status of the MGMT gene in any molecular groups. The oligodendroglial histological features are not independently predictive of either patient prognosis or chemotherapeutic response in LrGGs, leaving the possibility of marginal favorable association only in IDHmut/codel tumors.

Microscopic biopsy after unsuccessful endoscopic biopsy for primary central nervous system lymphoma of the corpus callosum: A case report.

INTRODUCTION AND IMPORTANCE: Primary central nervous system lymphoma (PCNSL) is a rare tumor with a poor prognosis. Early brain biopsy is essential to avoid a diagnostic delay. To date, reports of successful diagnosis for PCNSL of the corpus callosum by endoscopic biopsy are rare. CASE PRESENTATION: Herein, we report the case of an elderly woman with PCNSL of the corpus callosum who initially presented with rapidly progressive dementia. The condition was finally diagnosed by microscopic biopsy after unsuccessful endoscopic biopsy. Moreover, the postoperative course was uneventful. She is currently receiving systemic chemotherapy. CLINICAL DISCUSSION: Early diagnosis and subsequent systemic chemotherapy with or without whole brain radiotherapy are critical for PCNSL. Endoscopic biopsy may be a diagnostic option for suspected PCNSL, although stereotactic needle biopsy is most commonly used. CONCLUSION: Utilizing neuronavigation and 5-aminolevulinic acid (ALA) fluorescence guidance could be helpful in identifying lesions insufficiently exposed by endoscopic visualization. However, cerebrospinal fluid (CSF) loss due to the endoscopic approach through the ventricle might be a cause of neuronavigation misregistration.

Idiopathic unilateral oculomotor nerve palsy: A case report.

Cranial nerve III palsy, also known as oculomotor nerve palsy, may result from various causes; however, the etiology remains unknown in some instances. The aim of this case report is to present the authors' experience with two cases of idiopathic cranial nerve III palsy, together with a review of the literature. Case 1 is a 78-year-old woman and case 2 is a 75-year-old man, both having no history of trauma and no vascular risk factors. They presented to the authors' hospital with diplopia and palpebral ptosis and were diagnosed with idiopathic unilateral cranial nerve III palsy. They received oral steroids for treatment. One patient recovered completely within 3 months, while the other patient did not recover regardless of long-term follow-up. Idiopathic cranial nerve III palsy can occur in otherwise healthy individuals and often recover in several months. Careful examinations to rule out other causes and then steroid treatment should be considered after early diagnosis.

Early prediction of clinical outcomes in patients with aneurysmal subarachnoid hemorrhage using computed tomography texture analysis.

Radiological evaluation of subarachnoid hemorrhage (SAH) is often subject to interobserver variability. The aim of this study was to retrospectively detect computed tomography (CT) texture parameters in the early postictal state to predict cerebral vasospasm, delayed cerebral ischemia (DCI), and functional outcome in aneurysmal SAH using quantitative CT texture analysis (CTTA) via a commercially available software program and routine CT images. 40 patients with aneurysmal SAH surgically treated at the Keio University Hospital during a four-year period were analyzed. CT texture analyses were performed using a commercially available software program (Synapse Vincent). The following texture parameters of blood clots in the subarachnoid space and cerebral edema were assessed: mean CT value, entropy, skewness, and kurtosis. The mean CT value of blood clots in the subarachnoid space was significantly associated with cerebral vasospasm, DCI, and functional outcome. The mean CT value ≥ 49.64 Hounsfield units (HU) predicted cerebral vasospasm with a sensitivity and specificity of 85.7% and 61.5%, respectively (area under the curve [AUC] = 0.758). The mean CT value ≥ 49.95 HU predicted DCI with a sensitivity and specificity of 100% and 60.6%, respectively (AUC = 0.810). The mean CT value ≥ 53.00 HU predicted poor functional outcome with a sensitivity and specificity of 56.3% and 91.7%, respectively (AUC = 0.747). CTTA using a commercially available software program demonstrated that the mean CT value of clots in the subarachnoid space in the early postictal state could predict vasospasm, DCI, and clinical outcome with a high sensitivity and specificity.

Prediction of postoperative recurrence of chronic subdural hematoma using quantitative volumetric analysis in conjunction with computed tomography texture analysis.

Chronic subdural hematoma (CSDH) is a common disease in older individuals with a substantial rate of recurrence. The mechanism of CSDH recurrence remains unclear. This study aimed to detect imaging parameters that could indicate the risk for CSDH recurrence by using quantitative volumetric analysis and computed tomography (CT) texture analysis (CTTA). Clinical and imaging parameters were retrospectively investigated in 147 newly diagnosed CSDH lesions in 114 patients surgically treated at the Keio University Hospital during a 6-year period. For CT images, quantitative volumetric and texture analyses were performed. Hematoma volume, postoperative air volume, hematoma density, and texture parameters including kurtosis, skewness, and entropy were evaluated and compared with CSDH recurrence rate. Data were statistically evaluated, and a difference of p < 0.05 was considered significant. Reoperation for CSDH recurrence was required in 27 sides (18.4%) of 26 patients. Multivariate analysis showed that postoperative hematoma volume and postoperative hematoma density were independent risk factors for symptomatic CSDH recurrence that required reoperation. Postoperative hematoma volume, postoperative significant residual air, and postoperative hematoma density were also identified as independent risk factors for potential CSDH recurrence. Preoperative hematoma entropy was prone to be associated with both symptomatic and potential CSDH recurrence in univariate analysis, but not in multivariate analysis because of confounding factors. Quantitative volumetric analysis and CTTA could aid in distinguishing individuals at risk for CSDH recurrence.

Efficacy of a topical gelatin-thrombin hemostatic matrix, FLOSEAL®, in intracranial tumor resection.

BACKGROUND: Hemostasis plays an important role in safe brain tumor resection and also reduces the risk for surgical complications. This study aimed to evaluate the efficacy of FLOSEAL®, a topical hemostatic agent that contains thrombin and gelatin granules, in brain tumor resections. METHODS: We evaluated the hemostatic effect of FLOSEAL by scoring the intensity of bleeding from 1 (mild) to 4 (life threatening). We assessed the rate of success of hemostasis with 100 patients who underwent intracranial tumor resection. We also investigated the duration of the operation, the amount of intra- and postoperative bleeding, the number of hospital stays, and adverse events in patients who used FLOSEAL compared with those who did not use FLOSEAL. RESULTS: FLOSEAL was applied to a total of 109 bleeding areas in 100 patients. A total of 95 bleeding areas had a score of 1 and 91 (96%) showed successful hemostasis. Thirteen bleeding areas scored 2 and 8 (62%) showed hemostasis with the first application of FLOSEAL. The second application was attempted with five bleeding areas and four showed hemostasis. About 94% (103/109 areas) of bleeding points successfully achieved hemostasis by FLOSEAL. Moreover, FLOSEAL significantly decreased the amount of intraoperative bleeding and postoperative bleeding as assessed with computed tomography on 1 day postoperatively compared with no use of FLOSEAL. There were no adverse events related to FLOSEAL use. CONCLUSION: Our results indicate that FLOSEAL is a reliable, convenient, and safe topical hemostatic agent for intracranial tumor resection.

Immunohistochemistry for O6-methylguanin-DNA methyltransferase in glioblastomas defined by WHO2016: Correlation with promoter methylation status and patients' progression-free survival with the cut-off value determined by ROC analysis.

Although promoter methylation status is known to correlate with response to alkylating agents, immunohistochemistry (IHC) is the only available method for MGMT status in many institutions. However, the clinical utility of MGMT IHC is controversial. A hundred and twenty four cases of primary glioblastoma diagnosed by morphology-based criteria over 2 decades were re-appraised based on WHO 2016 classification. Tumor MGMT status was evaluated by IHC and methylation-specific PCR (MSP) to see if any correlation between the results of the 2 methods. The association with patients' prognoses was also investigated. Among 124 cases, 116 were confirmed to be glioblastoma by definition of WHO2016, and median overall survival (OS) of glioblastoma, IDH-wildtype and epithelioid glioblastoma were 18 and 27 months, respectively. MGMT promoter methylation status significantly correlated with progression-free survival (PFS) (p = 0.014) but not with OS (p = 0.364) in patients with glioblastoma by the integrated diagnosis. With the cut-off value of 24.5% of positive cell ratio as determined by receiver operating characteristic (ROC) analysis, there was a good correlation between the results of IHC and MSP (p = 0.08 × 10-24). Accordingly, there was a marginal association between the results of IHC and patients' PFS (p = 0.063), but not OS (p = 0.563). When the patients were divided into pre and post temozolomide era, the association of MGMT promoter methylation status with PFS was only noted in the patients of temozolomide era (pre, p = 0.432; post, p = 0.015).

A Case of Aggressive Recurrent Intracranial Subdural Hematoma Associated with Angiosarcoma Originating from the Skull.

BACKGROUND: Angiosarcoma often arises as a cutaneous disease in the scalp and the face; however, subdural hematoma (SDH) associated with angiosarcoma is extremely rare. CASE DESCRIPTION: A 72-year-old woman visited our hospital with gait disorder and progressive consciousness disturbance approximately 3 months after a minor head injury. Initially, on reviewing the results of imaging studies, she was diagnosed with traumatic chronic SDH. Despite repeated operations thereafter, including the embolization of the middle meningeal artery, her general condition progressively worsened, and computed tomography of head repeatedly showed the recurrence of SDH. Based on histopathologic and intraoperative findings, she was finally diagnosed with angiosarcoma originating from the skull. She died shortly thereafter because of aggressive recurrent intracranial SDH caused by leptomeningeal dissemination. CONCLUSIONS: In addition to cancers metastatic to the skull or dura mater, angiosarcoma should be included in the differential diagnosis for patients with repeated SDH and bone defect. An effective treatment for angiosarcoma with SDH that shows an unfavorable prognosis has not been established; however, an early diagnosis might be useful for a novel treatment.

Preoperative Prediction of Solitary Fibrous Tumor/Hemangiopericytoma and Angiomatous Meningioma Using Magnetic Resonance Imaging Texture Analysis.

BACKGROUND: Solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is radiologically difficult to distinguish from meningioma, especially angiomatous meningioma. This study aimed to detect texture parameters to distinguish SFT/HPC from angiomatous meningioma using magnetic resonance imaging texture analysis with commercially available software. METHODS: We retrospectively investigated textural parameters in 43 newly diagnosed SFTs/HPCs, angiomatous meningiomas, and other World Health Organization (WHO) grade I meningiomas treated at Keio University Hospital. For T1 contrast-enhanced, T2, and apparent diffusion coefficient (ADC) images, texture analyses were performed. Regions of interest were drawn manually with reference to the greater signal on contrast-enhanced T1-weighted images. ADC values and texture parameters, including kurtosis, skewness, and entropy, were evaluated and compared between these 3 groups. RESULTS: The mean ADC value was significantly high in angiomatous meningioma, compared with SFT/HPC and other WHO grade I meningioma. ADC entropy was highest in SFT/HPC, followed by angiomatous and other WHO grade I meningioma. T2 skewness was significantly high in SFT/HPC, compared with angiomatous and other WHO grade I meningioma. T1 contrast-enhanced skewness was significantly low in angiomatous meningioma, compared with other WHO grade I meningioma. Mean ADC value distinguished SFT/HPC from angiomatous meningioma with a positive predictive value (PPV) of 62.5% and specificity of 62.5%. ADC entropy distinguished SFT/HPC from angiomatous meningioma with a PPV of 100% and specificity of 100%. ADC skewness distinguished SFT/HPC from angiomatous meningioma with a PPV of 66.7% and specificity of 71.4%. CONCLUSIONS: This study demonstrated that magnetic resonance imaging texture analysis was useful for distinguishing SFT/HPC from meningioma, especially angiomatous meningioma.

Transvenous Embolization of the Basilar Plexus Before Endoscopic Transsphenoidal Transclival Surgery.

BACKGROUND: The endoscopic transclival approach is a method for reaching the anterior side of the brainstem. In making this approach, bleeding from the basilar plexus is often observed when cutting the dura overlying the clivus. Controlling such bleeding is essential. CASE DESCRIPTION: We performed a transvenous embolization of the basilar plexus before making the transclival approach. After embolization, bleeding from the basilar plexus during the operation decreased considerably. CONCLUSIONS: To our knowledge, this is the first report of transvenous embolization of the basilar plexus. If the basilar plexus is well developed on preoperative computed tomographic venography or digital subtraction angiography, this procedure is useful for controlling bleeding during endoscopic transclival surgery.

Postnatal delayed exacerbation of dural sinus malformation associated with brainstem cavernous malformations: A case report.

Dural sinus malformation (DSM) is a rare paediatric vascular malformation characterised by abnormal dilation of the posterior dural sinus. Owing to its rarity, the pathophysiology of DSM has not been fully elucidated. We report a case of prenatally diagnosed DSM with an unusual clinical course. We detected DSM in a male foetus in the 26th week of gestation by using foetal ultrasonography. Although the DSM regressed during the foetal stage and the arteriovenous shunt was insignificant in the neonate, the shunt rapidly developed four months after birth. The neonate also had postnatal de novo brainstem cavernous malformation (CM), which also developed rapidly, supposedly due to the aggravated venous hypertension resulting from the DSM. We successfully treated the aggravated shunts by endovascular transarterial and transvenous embolisation six times over two years and, subsequently, the clinical condition and the size of the brainstem CM became stable. The DSM and CM seemed to have a metameric origin. Such aberrant cases could help to further the understanding of DSM.