Prospective Randomized Controlled Trial Comparing Anesthetic Management With Remimazolam Besylate and Flumazenil Versus Propofol During Awake Craniotomy Following an Asleep-awake-asleep Method.

BACKGROUND: Awake craniotomy is performed to resect brain tumors in eloquent brain areas to maximize tumor reduction and minimize neurological damage. Evidence suggests that intraoperative anesthetic management of awake craniotomy with remimazolam is safe. We compared the time to arousal and efficacy of anesthetic management with remimazolam and propofol during awake craniotomy. METHODS: In a single-institution randomized, prospective study, patients who underwent elective awake craniotomy were randomized to receive remimazolam and reversal with flumazenil (group R) or propofol (group P). The primary end point was time to awaken. Secondary end points were time to loss of consciousness during induction of anesthesia, the frequency of intraoperative complications (pain, hypertension, seizures, nausea, vomiting, and delayed arousal), and postoperative nausea and vomiting. Intraoperative task performance was assessed using a numerical rating scale (NRS) score. RESULTS: Fifty-eight patients were recruited, of which 52 (26 in each group) were available for the efficacy analysis. Patients in group R had faster mean (±SD) arousal times than those in the P group (890.8±239.8 vs. 1075.4±317.5 s; P=0.013)and higher and more reliable intraoperative task performance (NRS score 8.81±1.50 vs. 7.69±2.36; P=0.043). There were no significant intraoperative complications. CONCLUSIONS: Compared with propofol, remimazolam was associated with more rapid loss of consciousness and, after administration of flumazenil, with faster arousal times and improved intraoperative task performance.

Epilepsy in Patients with Gliomas.

Brain tumor-related epilepsy (BTRE) is a complication that significantly impairs the quality of life and course of treatment of patients with brain tumors. Several recent studies have shed further light on the mechanisms and pathways by which genes and biological molecules in the tumor microenvironment can cause epilepsy. Moreover, epileptic seizures have been found to promote the growth of brain tumors, making the control of epilepsy a critical factor in treating brain tumors. In this study, we summarize the previous research and recent findings concerning BTRE. Expectedly, a deeper understanding of the underlying genetic and molecular mechanisms leads to safer and more effective treatments for suppressing epileptic symptoms and tumor growth.

Obstructive Hydrocephalus Due to Aggressive Posterior Fossa Tumor Exhibiting Histological Characteristics of Pilocytic Astrocytoma in Two Adult Neurofibromatosis Type 1 (NF1) Cases.

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome caused by germline alteration of the NF1gene. Among various NF1-related manifestations, obstructive hydrocephalus especially in adult NF1 cases is less frequently found. We report two adult NF1 cases exhibiting obstructive hydrocephalus due to an aggressive posterior fossa tumor exhibiting pathological characteristics of pilocytic astrocytoma as NF1-related manifestations. In these two cases, we performed endoscopic third ventriculostomy (ETV) and tumor biopsy as an initial treatment. The initial pathological diagnosis of the tumor is conventional pilocytic astrocytoma. After biopsy both cases revealed rapid tumor growth, therefore, we performed tumor removal, chemotherapy, and radiation therapy during an aggressive clinical course. However, both cases revealed dismal prognosis due to the progression of the tumor in spite of successful management of hydrocephalus by an initial ETV. DNA methylation analysis revealed that the tumor of one case matched high-grade astrocytoma with piloid features (HGAP). Most central nervous system tumors developed in NF1 are less aggressive such as pilocytic astrocytoma; however, recently a few studies revealed that HGAP, which has been a newly introduced malignant tumor in the World Health Organization Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS 5), rarely develops in NF1 cases. These findings suggested that HGAP might be one of the important causes of obstructive hydrocephalus in adult NF1 cases.

Effects of a Stimulus Response Task Using Virtual Reality on Unilateral Spatial Neglect: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of a stimulus response task using virtual reality (VR) for unilateral spatial neglect (USN). DESIGN: Double-blind randomized controlled trial. SETTING: Acute phase hospital where stroke patients are hospitalized. PARTICIPANTS: The participants were 42 patients (N=42) with right-hemisphere cerebral damage who had been experiencing USN in their daily lives. They were randomly assigned to 3 groups: a stimulus response task with a background shift (SR+BS group), a stimulus response task without a background shift (SR group), and an object gazing task (control group). INTERVENTIONS: The stimulus response task was to search for balloons that suddenly appeared on the VR screen. A background shift was added to highlight the search in the neglected space. The control task was to maintain a controlled gaze on a balloon that appeared on the VR screen. The intervention period was 5 days. MAIN OUTCOME MEASURES: The primary outcome was the participants' scores on a stimulus-driven attention test (SAT) using the reaction time. The stimuli of the SAT were divided into 6 blocks of 3 lines on each side (-3 to +3). The secondary outcomes were their scores on the Behavioral Intention Test conventional, Catherine Bergego Scale, and straight ahead pointing tests. RESULTS: In the SAT, there were significant interaction effects of reaction time between time and group factors in left-2, right+2, and right+3. The SR+BS and SR groups showed significant improvements in the reaction time of left-2 and right+3 compared with the control group. Moreover, the SR+BS group showed a significant improvement in the reaction time of left-2, which was the neglected space, compared with the SR group. However, there were no significant interaction effects of Behavioral Intention Test conventional, Catherine Bergego Scale, and straight ahead pointing. CONCLUSIONS: Our results suggest that the use of stimulus response tasks using VR combined with background shifts may improve left-sided USN.

Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases.

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Awake Craniotomy for Gliomas in the Non-Dominant Right Hemisphere: A Comprehensive Review.

Awake surgery has become a standard practice for managing diffuse low-grade gliomas (LGGs), particularly in eloquent brain areas, and is established as a gold standard technique for left-dominant-hemisphere tumors. However, the intraoperative monitoring of functions in the right non-dominant hemisphere (RndH) is often neglected, highlighting the need for a better understanding of neurocognitive testing for complex functions in the right hemisphere. This article aims to comprehensively review the current literature on the benefits of awake craniotomy in gliomas of the non-dominant right hemisphere. A systematic review was conducted using the PubMed and ScienceDirect databases with keywords such as "right hemisphere", "awake surgery", "direct electrical brain stimulation and mapping", and "glioma". The search focused on anatomical and surgical aspects, including indications, tools, and techniques of awake surgery in right cerebral hemisphere gliomas. The literature search identified 74 sources, including original articles, books, monographs, and review articles. Two papers reported large series of language assessment cases in 246 patients undergoing awake surgery with detailed neurological semiology and mapping techniques, while the remaining studies were predominantly neuroradiological and neuroimaging in nature. Awake craniotomy for non-dominant-hemisphere gliomas is an essential tool. The term "non-dominant" should be revised, as this hemisphere contributes significantly to essential cognitive functions in the human brain.

Molecular insights and the role of 18F-FDG-PET/CT in the diagnosis of spinal gliomas.

BACKGROUND: In recent years, molecular findings on spinal gliomas have become increasingly important. This study aimed to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis of spinal glioma. METHODS: This study included patients diagnosed with spinal cord glioma who underwent 18F-FDG-PET examination at the Department of Neurosurgery, Nagoya University Hospital between January 2016 and November 2023. The gliomas were divided into two groups, high-grade and low-grade, based on pathological and molecular studies. The maximum standardized uptake values (SUVmax) of the tumors were quantified and subsequently represented using receiver operating characteristic (ROC) curves. RESULTS: Eighteen participants were included in this study. Of the participants, seven had high-grade glioma with an SUVmax of 6.76 ± 0.72, and eleven had low-grade glioma with an SUVmax of 4.02 ± 1.78, and a statistically significant difference between the two groups. The ROC curve delineated an SUVmax cutoff value of 5.650, with an area under the curve (AUC) of approximately 0.909. Based on the cutoff value, the results of the diagnostic performance rendered a sensitivity and negative predictive value of 1.0, whereas the specificity and positive predictive value were 0.909 and 0.875, respectively. CONCLUSIONS: The present study shows that 18F-FDG-PET exhibits a markedly sensitive and negative predictive value in the assessment of spinal gliomas. Additionally, these findings have potential implications for the qualitative assessment of spinal gliomas using 18F-FDG-PET/CT. This imaging modality may be useful for making timely treatment decisions in situations where a detailed diagnosis by molecular analysis is not possible.

Predictive factors of post-operative apathy in patients with diffuse frontal gliomas undergoing awake brain mapping.

Patients with diffuse frontal gliomas often present with post-operative apathy after tumour removal. However, the association between apathy and tumour removal of gliomas from the frontal lobe remains unknown. This study aimed to investigate the factors influencing post-operative apathy after tumour removal in patients with diffuse frontal gliomas. We compared the demographics and clinical characteristics of patients with and without post-operative apathy in a cohort of 54 patients who underwent awake brain mapping for frontal gliomas. The frequency of clinical parameters such as left-sided involvement, high-grade tumour types (WHO grades III, IV), main tumour location in the anterior cingulate gyrus (ACC) and/or dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) was significantly greater in the apathetic group compared to the non-apathetic group. The apathetic group scored significantly lower on neuropsychological assessments such as the Letter Fluency Test among the Word Fluency Tests than the non-pathetic group (p = .000). Moreover, the scores of Parts 3, and 3-1 of the Stroop test were significantly lower in the apathetic group than those in the non-apathetic group (p = .023, .027, respectively). Multivariate model analysis revealed that the appearance of post-operative apathy was significantly related to side of the of lesion [left vs. right, hazard ratio (HR) = 8.00, 95% confidence interval (CI) = 1.36-46.96, p = .021], location of the main tumour in the frontal lobe (ACC/DLPFC/OFC vs. others, HR = 7.99, 95% CI = 2.16-29.59, p = .002), and the Letter Fluency Test (HR = .37, 95% CI = .15-.90, p = .028). Post-operative apathy is significantly associated with ACC and/or DLPFC and OFC in the left hemisphere of diffuse frontal gliomas. Apathy in frontal gliomas is correlated with a decline in the Letter Fluency Test scores. Therefore, this instrument is a potential predictor of post-operative apathy in patients with diffuse frontal gliomas undergoing awake brain mapping.

Latest classification of ependymoma in the molecular era and advances in its treatment: a review.

Ependymoma is a rare central nervous system (CNS) tumour occurring in all age groups and is one of the most common paediatric malignant brain tumours. Unlike other malignant brain tumours, ependymomas have few identified point mutations and genetic and epigenetic features. With advances in molecular understanding, the latest 2021 World Health Organization (WHO) classification of CNS tumours divided ependymomas into 10 diagnostic categories based on the histology, molecular information and location; this accurately reflected the prognosis and biology of this tumour. Although maximal surgical resection followed by radiotherapy is considered the standard treatment method, and chemotherapy is considered ineffective, the validation of the role of these treatment modalities continues. Although the rarity and long-term clinical course of ependymoma make designing and conducting prospective clinical trials challenging, knowledge is steadily accumulating and progress is being made. Much of the clinical knowledge obtained from clinical trials to date was based on the previous histology-based WHO classifications, and the addition of new molecular information may lead to more complex treatment strategies. Therefore, this review presents the latest findings on the molecular classification of ependymomas and advances in its treatment.

[Intraoperative Functional Monitoring in Brain Tumor Surgery].

Invasive brain tumors, especially gliomas, often arise in the eloquent areas of the brain that are involved in language and motor function. The most important goal of brain tumor removal is to safely remove the maximum amount of tumor while preserving neurological function. Maximizing the amount of removed tumor is thought to improve prognosis by prolonging both the progression-free and overall survival periods of patients. In the present study, we review the intraoperative monitoring techniques for motor function-sparing surgery for gliomas arising near the eloquent areas of the brain and electrophysiological monitoring techniques for motor function-sparing surgery for brain tumors arising deep within the brain. In brain tumor surgery, monitoring of direct cortical motor evoked potentials(MEPs), transcranial MEPs, and subcortical MEPs is integral for preserving motor function.

Rapid detection of the MYD88 L265P mutation for pre- and intra-operative diagnosis of primary central nervous system lymphoma.

The myeloid differentiation primary response gene 88 (MYD88) L265P mutation is a disease-specific mutation of primary central nervous system lymphoma (PCNSL) among the central nervous system tumors. Accordingly, this mutation is considered a reliable diagnostic molecular marker of PCNSL. As the intra-operative diagnosis of PCNSL is sometimes difficult to achieve using histological examinations alone, intra-operative detection of the MYD88 L265P mutation could be effective for the accurate diagnosis of PCNSL. Herein, we aimed to develop a novel rapid genotyping system (GeneSoC) using real-time polymerase chain reaction (PCR) based on microfluidic thermal cycling technology. This real-time PCR system shortened the analysis time, which enabled the detection of the MYD88 L265P mutation within 15 min. Rapid detection of the MYD88 L265P mutation was performed intra-operatively using GeneSoC in 24 consecutive cases with suspected malignant brain tumors, including 10 cases with suspected PCNSL before surgery. The MYD88 L265P mutation was detected in eight cases in which tumors were pathologically diagnosed as PCNSL after the operation, while wild-type MYD88 was detected in 16 cases. Although two of the 16 cases with wild-type MYD88 were pathologically diagnosed as PCNSL after the operation, MYD88 L265P could be detected in all eight PCNSL cases harboring MYD88 L265P. The MYD88 L265P mutation could also be detected using cell-free DNA derived from the cerebrospinal fluid of two PCNSL cases. Detection of the MYD88 L265P mutation using GeneSoC might not only improve the accuracy of intra-operative diagnosis of PCNSL but also help the future pre-operative diagnosis through liquid biopsy of cerebrospinal fluid.

Efficacy and safety of bevacizumab, irinotecan, and temozolomide combination for relapsed or refractory pediatric central nervous system embryonal tumor: a single-institution study.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of combination therapy with bevacizumab (Bev), irinotecan (CPT-11), and temozolomide (TMZ) in children with central nervous system (CNS) embryonal tumor relapse. METHODS: The authors retrospectively examined 13 consecutive pediatric patients with relapsed or refractory CNS embryonal tumors who received combination therapy comprising Bev, CPT-11, and TMZ. Specifically, 9 patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumor (AT/RT), and 1 had CNS embryonal tumor with rhabdoid features. Of the 9 medulloblastoma cases, 2 were categorized in the Sonic hedgehog subgroup and 6 in molecular subgroup 3 for medulloblastoma. RESULTS: The complete and partial objective response rates were 66.6% in patients with medulloblastoma and 75.0% in patients with AT/RT or CNS embryonal tumors with rhabdoid features. Furthermore, the 12- and 24-month progression-free survival rates were 69.2% and 51.9% for all patients with recurrent or refractory CNS embryonal tumors, respectively. In contrast, the 12- and 24-month overall survival rates were 67.1% and 58.7%, respectively, for all patients with relapsed or refractory CNS embryonal tumors. The authors observed grade 3 neutropenia, thrombocytopenia, proteinuria, hypertension, diarrhea, and constipation in 23.1%, 7.7%, 23.1%, 7.7%, 7.7%, and 7.7% of patients, respectively. Furthermore, grade 4 neutropenia was observed in 7.1% of patients. Nonhematological adverse effects, such as nausea and constipation, were mild and controlled with standard antiemetics. CONCLUSIONS: This study demonstrated favorable survival outcomes in patients with relapsed or refractory pediatric CNS embryonal tumors and thus helped to investigate the efficacy of combination therapy comprising Bev, CPT-11, and TMZ. Moreover, combination chemotherapy had high objective response rates, and all adverse events were tolerable. To date, data supporting the efficacy and safety of this regimen in the relapsed or refractory AT/RT population are limited. These findings suggest the potential efficacy and safety of combination chemotherapy in patients with relapsed or refractory pediatric CNS embryonal tumors.

Easy-to-use machine learning system for the prediction of IDH mutation and 1p/19q codeletion using MRI images of adult-type diffuse gliomas.

Adult-type diffuse gliomas are divided into Astrocytoma, IDH-mutant, Oligodendroglioma, IDH-mutant and 1p/19q-codeleted and Glioblastoma, IDH-wildtype based on the IDH mutation, and 1p/19q codeletion status. To determine the treatment strategy for these tumors, pre-operative prediction of IDH mutation and 1p/19q codeletion status might be effective. Computer-aided diagnosis (CADx) systems using machine learning have been noted as innovative diagnostic methods. However, it is difficult to promote the clinical application of machine learning systems at each institute because the support of various specialists is essential. In this study, we established an easy-to-use computer-aided diagnosis system using Microsoft Azure Machine Learning Studio (MAMLS) to predict these statuses. We constructed an analysis model using 258 adult-type diffuse glioma cases from The Cancer Genome Atlas (TCGA) cohort. Using MRI T2-weighted images, the overall accuracy, sensitivity, and specificity for the prediction of IDH mutation and 1p/19q codeletion were 86.9%, 80.9%, and 92.0%, and 94.7%, 94.1%, and 95.1%, respectively. We also constructed an reliable analysis model for the prediction of IDH mutation and 1p/19q codeletion using an independent Nagoya cohort including 202 cases. These analysis models were established within 30 min. This easy-to-use CADx system might be useful for the clinical application of CADx in various institutes.

Clinical characteristics and radiological features of glioblastoma, IDH-wildtype, grade 4 with histologically lower-grade gliomas.

The 2021 World Health Organization (WHO) classification of central nervous system tumors applied molecular criteria and further integrated histological and molecular diagnosis of gliomas. This classification allows for the diagnosis of isocitrate dehydrogenase wild-type (IDHwt) glioblastoma (GBM), and WHO grade 4 with histologically lower-grade gliomas (LrGGs), even in the absence of high-grade histopathologic features, such as necrosis and/or microvascular proliferation. They contain at least one of the following molecular features: epidermal growth factor receptor amplification, chromosome 7 gain/10 loss, or telomerase reverse transcriptase promoter mutation. In the imaging features at the time of histological diagnosis, a gliomatosis cerebri growth pattern was frequently observed in these tumors. Furthermore, this growth pattern was significantly higher in IDHwt GBM, WHO grade 4, with histological grade II gliomas. Although the exact prognosis of IDHwt GBM, WHO grade 4, with histologically LGGs remains unknown, its OS was approximately 1-2 years similar to that of histologically IDHwt GBM, WHO grade 4, despite histopathological features similar to IDHmut LrGGs. These findings reinforce the need for the analysis of molecular features, regardless of presenting similar clinical characteristics and imaging features to IDHmut LrGGs.

Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series.

Isocitrate dehydrogenase wild-type (IDHwt) diffuse astrocytomas feature highly infiltrative patterns, such as a gliomatosis cerebri growth pattern with widespread involvement. Among these tumors, localized IDHwt histologically diffuse astrocytomas are rarer than the infiltrative type. The aim of this study was to assess and describe the clinical, radiographic, histopathological, and molecular characteristics of this rare type of IDHwt histologically diffuse astrocytomas and thereby provide more information on how its features affect clinical prognoses and outcomes. We retrospectively analyzed the records of five patients with localized IDHwt histologically diffuse astrocytomas between July 2017 and January 2020. All patients were female, and their mean age at the time of the initial treatment was 55.0 years. All patients had focal disease that did not include gliomatosis cerebri or multifocal disease. All patients received a histopathological diagnosis of diffuse astrocytomas at the time of the initial treatment. For recurrent tumors, second surgeries were performed at a mean of 12.4 months after the initial surgery. A histopathological diagnosis of glioblastoma was made in four patients and one of gliosarcoma in one patient. The initial status of IDH1, IDH2, H3F3A, HIST1H3B, and BRAF was "wild-type" in all patients. TERT promoter mutations (C250T or C228T) were detected in four patients. No tumors harbored a 1p/19q codeletion, EGFR amplification, or chromosome 7 gain/10 loss (+ 7/ - 10). We assessed clinical cases of localized IDHwt histologically diffuse astrocytomas that resulted in malignant recurrence and a poor clinical prognosis similar to that of glioblastomas. Our case series suggests that even in patients with histologically diffuse astrocytomas and those who present with radiographic imaging findings suggestive of a localized tumor mass, physicians should consider the possibility of IDHwt histologically diffuse astrocytomas.

The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas.

BACKGROUND: Approximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated the safety, pharmacokinetics, pharmacodynamics, and efficacy of DS-1001. METHODS: This was a multicenter, open-label, dose-escalation, phase I study of DS-1001 for recurrent/progressive IDH1-mutant (R132) glioma (N = 47) (NCT03030066). DS-1001 was administered orally at 125-1400 mg twice daily. Dose-escalation used a modified continual reassessment method. RESULTS: The maximum tolerated dose was not reached. Eight patients were continuing treatment at the data cutoff. Most adverse events (AEs) were grade 1-2. Twenty patients (42.6%) experienced at least 1 grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, and dry skin. The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Median progression-free survival was 10.4 months (95% confidence interval [CI], 6.1 to 17.7 months) and not reached (95% CI, 24.1 to not reached) for the enhancing and non-enhancing glioma cohorts, respectively. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples. CONCLUSIONS: DS-1001 was well tolerated with a favorable brain distribution. Recurrent/progressive IDH1-mutant glioma patients responded to treatment. A study of DS-1001 in patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 glioma is ongoing (NCT04458272).

CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma.

BACKGROUND: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. METHODS: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. RESULTS: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. CONCLUSIONS: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.

Dural Arteriovenous Fistula Mimicking a Brain Tumor on Methionine-positron Emission Tomography: A Case Report.

In this article, we report a case wherein a brain tumor was suspected based on computed tomography and magnetic resonance imaging findings. We made an initial diagnosis of malignant brain tumor based on methionine-positron emission tomography (PET) findings, but the correct diagnosis was dural arteriovenous fistula (DAVF). The patient was a 45-year-old man with DAVF who developed headache. Methionine-PET imaging showed high methionine uptake in the lesion. Although the tumor was strongly suspected from the findings of methionine-PET, the diagnosis of DAVF could be made correctly only by interpreting digital subtraction angiography and computed tomographic angiography. The findings of methionine-PET, which is considered useful in the diagnosis and denial of brain tumors, made the diagnosis of DAVF more difficult. The increased uptake of methionine-PET in DAVF is an important finding because, to our knowledge, this study is the first to report such finding. The results of this study might be useful for differential diagnoses when the diagnosis is uncertain.

Surgical management of brain metastasis as a part of systematic metastases from adenoid cystic carcinoma of the external auditory canal: illustrative case.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) is a rare tumor that accounts for approximately 5% of all EAC tumors. ACC is generally known as a slow-growing tumor, but patients often experience recurrence or distant metastasis in the long clinical course. While the major pattern of recurrence is pulmonary metastasis, brain metastasis of ACC of the EAC is rare. OBSERVATIONS: The authors describe the case of a 72-year-old male who was diagnosed with ACC of the EAC. Approximately 7 years later, brain magnetic resonance imaging revealed an intra-axial homogenously enhancing mass lesion that had no direct connection with the skull base in the left frontal lobe. The patient underwent tumor resection and histopathological examination revealed a mixture of cribriform and tubular patterns. The image and pathological characteristics of the tumor were similar to those of primary ACC or ACC from other sites of origin. LESSONS: While patients with ACC of the EAC often experience recurrence or distant metastasis in the long clinical course, they survive for a relatively long period of time, even though an optimal treatment has not been established. The authors therefore recommend surgical resection for brain metastasis of ACC of the EAC to improve neurological symptoms.

11C-methionine- and 18F-FDG-PET double-negative metastatic brain tumor from lung adenocarcinoma with paradoxical high 18F-FDG uptake: A case report.

Background: Imaging with 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and 11C-methionine (MET)-PET can delineate primary and metastatic brain tumors. Lesion size affects the sensitivity of both scans and histopathological features can also influence FDG-PET, but the effects on MET-PET have not been elucidated. Case Description: We report an unusual case of metastatic brain tumors without accumulation of FDG or MET, contrasting with high FDG uptake in the primary lung lesion. The brain lesions were identified as adenocarcinoma with a more mucus-rich background, contributing to the indistinct accumulation of both FDG and MET. Conclusion: Histopathological characteristics can affect both MET and FDG accumulation, leading to findings contradicting those of the primary lesion.