安倍 雅人

Distinguishing primary central nervous system lymphoma (PCNSL) from glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is sometimes hard. Because the role of operation on them varies, accurate preoperative diagnosis is crucial. In this study, we evaluated whether a specific kind of chemical exchange saturation transfer imaging, i.e., amide proton transfer-weighted (APTw) imaging, was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. A total of 14 PCNSL and 27 glioblastoma, IDH-wildtype cases were evaluated. There was no significant difference in the mean APTw signal values between the two groups. However, the percentile values from the 1st percentile to the 20th percentile APTw signals and the width1–100 APTw signals significantly differed. The highest area under the curve was 0.796, which was obtained from the width1–100 APTw signal values. The sensitivity and specificity values were 64.3% and 88.9%, respectively. APTw imaging was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. To avoid unnecessary aggressive surgical resection, APTw imaging is recommended for cases in which PCNSL is one of the differential diagnoses.

Most osteomalacia-inducing tumors (OITs) are phosphaturic mesenchymal tumors (PMTs) that secrete fibroblast growth factor 23 (FGF23). These tumors usually occur in the bone and soft tissues, and intracranial OITs are rare. Therefore, intracranial OIT is difficult to diagnose and treat. This paper presents a case of intracranial OIT and shows a review of previous cases. A 45-year-old man underwent nasal cavity biopsy and treatment with active vitamin D3 and neutral phosphate for hypophosphatemia. Amplification of FGF23 mRNA level within the tumor was detected. Subsequently, the surgical specimen was diagnosed with a PMT and was considered the cause of the patient's osteomalacia. The patient was referred to a neurosurgery department for the excision of the intracranial tumor extending to the nasal cavity. After tumor removal, the serum levels of FGF23 and phosphorus were normalized as compared to preoperative those. The patient remains disease-free, without additional treatment, approximately 10 years after surgery, with no tumor recurrence. As per the literature, intracranial OITs usually occur in patients aged 8-69 years. Bone and muscle pain are major complaints. Approximately 60% of the patients reported previously had symptoms because of intracranial tumors. In some cases, it took several years to diagnose OIT after the onset of the osteomalacia symptoms. Laboratory data in such cases show hypophosphatemia and elevated FGF23 levels. Because FGF23 levels are associated with the severity of osteomalacia symptoms, total tumor resection is recommended. PMT and hemangiopericytoma (HPC) are histologically similar, but on immunochemistry, PMT is negative for signal transducer and activator of transcription 6 (STAT6), whereas HPC is positive. FGF23 amplification is seen in PMTs but not in HPCs. Therefore, the analysis of FGF23 and STAT6 was helpful in distinguishing PMTs from HPCs. In cases of hypophosphatemia and osteomalacia without a history of metabolic, renal, or malabsorptive diseases, the possibility of oncogenic osteomalacia should be considered.

Cyst formation in the third ventricle and the histopathological findings were rarely reported. We report a similar case of late-onset aqueductal membranous occlusion (LAMO) caused by a thin gliotic cyst and a review of related literature. A 28-year-old woman with enlarged lateral ventricles was referred to our hospital with complaints of headache and dizziness. In our hospital, the obvious cause of the hydrocephalus was unknown on any examination and we decided performing endoscopic third ventriculostomy for hydrocephalus. A thin cyst covering the entrance of the aqueduct was identified and we perforated it. Histopathological finding of the cyst wall was gliosis and our case was similar to LAMO, although not typical. The postoperative symptoms and ventricle size improved for 4 years. When suspecting cases similar to definition of LAMO, neuroendoscopic surgery would be the first-choice treatment and might detect causes undetectable on preoperative imaging such as our thin membrane.

BACKGROUND: We investigated the ability of magnetic resonance imaging (MRI) to distinguish primary central nervous system vasculitis (PCNSV) from glioblastoma to facilitate the development of an appropriate treatment for PCNSV. METHODS: We enrolled patients who were treated for PCNSV or glioblastoma at our center between January 2007 and August 2018. We compared the diagnoses of the 2 conditions by retrospectively reviewing patients' data for contrast-enhanced MRI, perfusion MRI, flow-sensitive black-blood (FSBB) imaging, and 1H-magnetic resonance spectroscopy (MRS). RESULTS: We evaluated 108 patients (6 PCNSV; 102 glioblastoma). We found a statistically significant correlation between diagnosis and the contrast pattern on MRI. Perivascular enhancement was observed in all cases of PCNSV as follows: ring-like, homogeneous, and irregular patterns were observed in 53 (60%), 18 (20%), and 17 (19%) cases of glioblastoma, respectively. We identified a statistically significant correlation between diagnosis and cerebral blood volume (CBV) in 3 patients with PCNSV who underwent perfusion MRI; and all had low CBVs. Among the 55 patients with glioblastoma who underwent perfusion MRI, low and high CBVs were detected in 3 and 52 patients, respectively. There was no significant correlation between diagnosis and FSBB findings. Evaluation of 1H-MRS data showed statistically significant differences between PCNSV and glioblastoma as functions of neuronal amino acid levels on long echo time MRS, with a slightly different amino acid profile, including glutamine + glutamate on short echo time MRS. CONCLUSIONS: Contrast-enhanced MRI, perfusion MRI, and quantitative analysis of 1H-MRS are valuable techniques for distinguishing PCNSV from glioblastoma before surgery.

Isocitrate dehydrogenase (IDH) wild-type diffuse astrocytic tumors tend to be pathologically diagnosed as glioblastomas (GBMs). We previously reported that myoinositol to total choline (Ins/Cho) ratio in GBMs on magnetic resonance (MR) spectroscopy was significantly lower than that in IDH-mutant gliomas. We then hypothesized that a low Ins/Cho ratio is a poor prognosis factor in patients with GBMs, IDH-wild-type. In the present study, we calculated the Ins/Cho ratios of patients with GBMs and investigated their progression-free survival (PFS) and overall survival (OS) to determine their utility as prognostic marker. We classified patients with GBMs harboring wild-type IDH (n = 27) into two groups based on the Ins/Cho ratio, and compared patient backgrounds, pathological findings, PFS, OS, and copy number aberrations between the high and low Ins/Cho groups. Patients with GBMs in the low Ins/Cho ratio group indicated shorter PFS (P = 0.021) and OS (P = 0.048) than those in the high Ins/Cho group. Multivariate analysis demonstrated that the Ins/Cho ratio was significantly correlated with PFS (hazard ratio 0.24, P = 0.028). In conclusion, the preoperative Ins/Cho ratio can be used as a novel potential prognostic factor for GBM, IDH-wild-type.

Primary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell-like (non-GCB) phenotype; marked histiocytic infiltrates and abundant non-neoplastic T-cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD-L1), while immune cells in the microenvironment were positive for PD-L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.

Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-L-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.

Abstract Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.

BACKGROUND: The extent of resection has been reported to be associated with overall survival in gliomas. The use of 5-aminolevulinic acid (5-ALA) has been recognized to increase the extent of tumor resection. OBJECTIVE: To evaluate what factors affect the intraoperative fluorescence after administration of 5-ALA in gliomas. METHODS: Correlation of intraoperative fluorescence and several clinical, radiographic, molecular biologic, and histopathologic characters was retrospectively evaluated in 104 patients (53 males and 51 females; mean age 54.2 yr) with gliomas at our institution. To clarify the mechanisms that mutant isocitrate dehydrogenase (IDH) affect the intraoperative fluorescence, in Vitro experiments using genetically engineered glioma cells harboring mutant IDH1 were performed. RESULTS: Intraoperative fluorescence was observed in 82 patients (78.8%). In addition to age, magnetic resonance imaging enhancement, World Health Organization grades, and MIB-1 index, the status of IDH was revealed to be correlated with intraoperative fluorescence. In Vitro assay revealed that mutant IDH indirectly reduced the amount of exogenous 5-ALA-derived protoporphyrinogen IX in glioma cells by increasing activity of ferrochelatase and heme oxygenase 1. CONCLUSION: Mutant IDH1/2-induced metabolite changes of exogenous 5-ALA were suggested to contribute to the lesser intraoperative fluorescence in gliomas with mutant IDH1/2 than in those without.

The CIC-DUX4 translocation is the most common genetic alteration of small round cell sarcomas without EWSR1 rearrangement. These "Ewing-like sarcomas" usually occur in peripheral soft tissues, and rare primary central nervous system (CNS) tumors have been described. We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3-C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 10 months. Target RNA sequencing analysis revealed the CIC-DUX4 fusion gene. Methylation array analysis resulted in a diagnosis of "methylation class CNS Ewing sarcoma family tumor with CIC alteration". Although this tumor lacked characteristic histological features such as lobular structures in association with desmoplastic stroma, relatively uniform nuclei with prominent nucleoli and eosinophilic cytoplasm, which are often found in CIC-rearranged sarcomas of soft tissue, were identified. Recently, many CNS and soft tissue tumors require genetic analysis for precise diagnosis. To consider certain molecular testing, careful histological examination is essential.

According to the 2016 World Health Organization (WHO) classification of central nervous system tumors, diffuse astrocytic and oligodendroglial tumors are differentiated by the presence of isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q co-deletion). IDH-mutant astrocytoma often has p53 and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation, showing the alternative lengthening of telomeres (ALT) phenotype, while IDH-mutant and 1p/19q-co-deleted oligodendroglioma often have wild-type p53 and telomerase reverse transcriptase (TERT) promoter mutation, showing telomerase activation. This study analyzed IDH, ATRX, and TERT promoter mutations, and the correlation between them. Immortalized cells overcome the telomere-related crisis by activating telomerase or ALT. In glioma, telomerase is mainly activated by TERT promoter mutation, while ALT is usually associated with ATRX mutation. Although the mechanism of how ATRX mutation induces ALT remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising.