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ABSTRACT: The purpose of this study was to distinguish pseudoprogression (PP) from early true progression in patients with glioblastoma (GBM) based on the presence of a mutation in isocitrate dehydrogenase 1 (IDH1). We retrospectively surveyed 32 patients with GBM or GBM with oligodendroglioma component (GBMO) who underwent biopsy or maximal tumor resection followed by concurrent radiotherapy and temozolomide (TMZ). We then selected patients with early radiological progression in magnetic resonance imaging within 6 months after concurrent radiotherapy and TMZ treatment. DNA was extracted from their tumor blocks. The IDH1 mutation was analyzed in the genomic region by direct sequencing as a biomarker for PP. Twenty-eight patients were diagnosed with GBM and four with GBMO. Eleven patients were discovered to have early radiological progression. PP was detected in two patients (6.3 %) diagnosed with GBMO and one patient with GBM. Both of the GBMO patients with PP had the IDH1 mutation, the one GBM patient with PP and the other eight patients with early true progression with wild type. The sensitivity and specificity of the IDH1 mutation for detecting PP were 66.7 and 100 %, respectively. This study suggests the IDH1 mutation may become a novel molecular biomarker for PP. Analyzing the IDH1 mutation, in the case of recognizing early radiological progression, may enable distinction of PP from early true progression, and we could determine the need for second-look surgery.
Brain Tumor Pathology 07/2012; · 1.19 Impact Factor
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ABSTRACT: Gliomas are regionally heterogeneous tumors. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) evaluates the heterogeneity of histological malignancy within the tumor. We present two patients with oligodendrocytic
tumors that showed discrepancies in the highest uptake areas with these two tracers. PET studies with MET and FDG were performed
on the same day, 2weeks before surgery. In both cases, biopsy specimens were separately obtained from the highest MET and
FDG uptake areas guided by intraoperative neuronavigation. Histological examinations demonstrated that the specimens from
the highest MET uptake area revealed low-grade oligoastrocytoma or oligodendroglioma, whereas histological anaplasias were
contained in the specimens from the highest FDG uptake area. With gliomas with oligodendroglial components, the MET uptake
ratio does not always correspond to histological anaplasia, which can be detected only by FDG PET. Sole application of MET
PET for preoperative evaluation may lead to misunderstanding of histological heterogeneity in gliomas, especially those with
oligodendroglial components. FDG and MET tracers play complementary roles in preoperative evaluation of gliomas.
KeywordsFluorodeoxyglucose-Glioma-Histological anaplasia-Methionine-Oligodendrocytic tumor-Positron emission tomography
Journal of Neuro-Oncology 04/2012; 101(2):335-341. · 3.21 Impact Factor
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Hiromi Kanno,
Hiroshi Nishihara,
Mitsuteru Oikawa,
Yoshimaru Ozaki, Junichi Murata,
Yutaka Sawamura,
Masahito Kato,
Kanako Kubota,
Mishie Tanino,
Taichi Kimura,
Kazuo Nagashima,
Tamio Itoh,
Shinya Tanaka
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ABSTRACT: Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical analysis of 12 PPT specimens, especially for expression of O(6) -methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB-1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade.
Neuropathology 03/2012; · 2.02 Impact Factor
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ABSTRACT: Hemangioblastoma in the medulla oblongata is a relatively rare tumor. We present the case of a giant hemangioblastoma occurring in the dorsal medulla oblongata. A 33-year-old man with no neurological symptoms was diagnosed with a hemangioblastoma in the dorsal medulla oblongata, and opted for observation in the outpatient department. After 22 months of observation time, MRI scans showed rapid local tumor progression and obstructive hydrocephalus. At this point, he presented with mild dysphagia as a preoperative neurological deficit. Total surgical removal of the tumor was performed after temporary ventricle drainage and preoperative embolization of the feeding artery. Postoperatively, he became fully conscious but developed bulbar palsy followed by tracheostomy. During the 12 months of postoperative follow-up, severe dysphagia was still present.
No shinkei geka. Neurological surgery 03/2012; 40(3):229-34. · 0.13 Impact Factor
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ABSTRACT: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with an extremely poor prognosis in spite of multimodal treatment approaches. The median survival time of patients with GBM is 15 months, and only 3-5% of patients survive longer than 36 months. Those patients who survive over 36 months after the initial diagnosis are defined as long-term survivors. In this study, we retrospectively performed clinical and molecular analyses of five long-term survivors of GBM (>36 months) and twenty four GBM patients with poor survival time as control group (<36 months) to identify any prognostic factors that potentially contribute to survival. The O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) gene methylation status was evaluated by performing methylation specific polymerase chain reaction assays. The mutation of isocitrate dehydrogenase 1 and 2 were evaluated by the direct sequencing method. All five cases were primary GBMs and the coexistence of the oligodendroglioma component was checked for each case as GBM with oligodendroglioma component. All five cases showed MGMT promoter methylation (5/5). IDH1 mutation was detected in two of the long-term survivors with oligodendroglioma component (2/5) while no IDH1 mutation was detected in the control group. All patients were treated by gross total removal followed by radiotherapy and various chemotherapies including temozolomide. MGMT promoter methylation and IDH1 mutation might be favorable factors for long-term survival in GBM patients.
No shinkei geka. Neurological surgery 02/2012; 40(2):129-35. · 0.13 Impact Factor
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ABSTRACT: Two glioblastoma multiforme patients underwent (18)F-FMISO (fluoromisonidazole) positron emission tomography study to access the tumor oxygenation status before and immediately after fractionated radiotherapy concomitant with temozolomide chemotherapy. In both cases, a prominent (18)F-FMISO tumor accumulation observed in the first study was notably decreased in the second study, which was supposed to be a reoxygenation of the tumor. As far as we investigated, this is the first report of the changes of oxygenation status in glioblastoma multiforme treated through radiation therapy with temozolomide.
Japanese Journal of Clinical Oncology 12/2011; 42(2):120-3. · 1.78 Impact Factor
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ABSTRACT: Isolated oculomotor nerve palsy occasionally occurs in patients with cavernous sinus invasion with or without pituitary apoplexy. We describe two cases of pituitary apoplexy without cavernous sinus invasion presenting with isolated oculomotor palsy. In both cases, computed tomography (CT) showed erosion of the right posterior clinoid process. Magnetic resonance imaging (MRI) depicted pituitary adenoma with apoplexy protruding latero-posteriorly to the right cavernous sinus. The medio-posterior wall of the cavernous sinus was markedly displaced latero-posteriorly by the tumor, and there was no evidence of cavernous sinus invasion. Oculomotor palsy may be caused first by unilateral erosion of the posterior clinoid process, resulting in latero-posterior protrusion of the adenoma. Hemorrhage may result in sudden kinking of the oculomotor nerve at the entrance of the oculomotor trigone.
Acta Neurochirurgica 09/2011; 153(12):2453-6; discussion 2456. · 1.52 Impact Factor
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ABSTRACT: We report an unusual case of neurohypophyseal germinoma with abundant fibrous tissue and clival invasion that was initially misdiagnosed as lymphocytic hypophysitis. A 40-year-old woman presented with diabetes insipidus and panhypopituitarism after delivering her second son and which lasted for 4 years. Magnetic resonance imaging showed the intrasellar mass extending to the suprasellar region with enlarged pituitary stalk. The mass was heterogeneously enhanced and invaded the clivus. Biopsy of the intrasellar mass was performed via the trans-sphenoidal route, and histological examination revealed marked fibrous tissue and infiltration of lymphocytes, with no evidence of tumor cells. Lymphocytic hypophysitis was the initial diagnosis, and corticosteroid therapy was begun. Despite intensive treatment, the lesion enlarged and clinical symptoms worsened 2 weeks after surgery. Subtotal removal of the mass was performed, and a second histological examination revealed typical findings of the germinoma. Subsequently, the patient underwent chemoradiotherapy, and complete remission was achieved. Histological diagnosis is sometimes incorrect in fibrous tumors at the sellar region, and biopsy from several points is strongly recommended for this entity.
Brain Tumor Pathology 09/2011; 29(1):58-62. · 1.19 Impact Factor
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ABSTRACT: Gliomas are regionally heterogeneous tumors. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-methionine (MET) evaluates the heterogeneity of histological malignancy within the tumor. We present two patients with oligodendrocytic tumors that showed discrepancies in the highest uptake areas with these two tracers. PET studies with MET and FDG were performed on the same day, 2 weeks before surgery. In both cases, biopsy specimens were separately obtained from the highest MET and FDG uptake areas guided by intraoperative neuronavigation. Histological examinations demonstrated that the specimens from the highest MET uptake area revealed low-grade oligoastrocytoma or oligodendroglioma, whereas histological anaplasias were contained in the specimens from the highest FDG uptake area. With gliomas with oligodendroglial components, the MET uptake ratio does not always correspond to histological anaplasia, which can be detected only by FDG PET. Sole application of MET PET for preoperative evaluation may lead to misunderstanding of histological heterogeneity in gliomas, especially those with oligodendroglial components. FDG and MET tracers play complementary roles in preoperative evaluation of gliomas.
Journal of Neuro-Oncology 01/2011; 101(2):335-41. · 3.21 Impact Factor
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ABSTRACT: A 43-year-old female presented with a giant skull base atypical meningioma manifesting as rapid progression of impaired consciousness. The meningioma was located in the ethmoid sinus, sphenoid sinus, nasal cavity, and left middle temporal fossa, and the intracranial portion of the tumor involved the left temporal region with massive surrounding brain edema in the left temporal lobe and basal ganglia. She underwent emergent fronto-temporo-parietal decompressive craniectomy, and the intracranial portion of the tumor was resected to control intracranial pressure. She recovered consciousness and neurological function dramatically, and subsequently underwent radical tumor resection via combined extended transbasal and left lateral transzygomatic infratemporal fossa approaches one month after the initial surgery. The extensive brain edema completely disappeared after tumor resection, and the patient fully recovered without neurological deficits except anosmia and small visual field defect. Rapid neurological deterioration and disturbance of consciousness caused by extensive peritumoral brain swelling are unusual in meningioma. In this case, the extemporaneous decompressive craniectomy was highly useful in the management of increased intracranial pressure.
Neurologia medico-chirurgica 01/2011; 51(11):789-92. · 0.61 Impact Factor
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Shigeru Yamaguchi,
Shunsuke Terasaka,
Hiroyuki Kobayashi,
Takuhito Narita,
Kenji Hirata,
Satoshi Shiga,
Reiko Usui,
Shinya Tanaka,
Kanako Kubota, Junichi Murata,
Katsuyuki Asaoka
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ABSTRACT: The aim of this study was to evaluate the usefulness of combined use of positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-methionine (MET) for the preoperative evaluation of gliomas and to investigate the feasibility of PET in glioma surgery.
Preoperative FDG (n=25) and/or MET (n=22) PET studies were performed in 26 patients with primary and recurrent adult gliomas. We qualitatively (visual analysis) and quantitatively evaluated the uptake of both tracers in the tumor location. For quantitative analysis, data were analyzed by a region of interest method using the standard uptake value (SUV) and a calculated uptake ratio. We investigated the correlation among the tracer uptake ratios, histological tumor grading and tumor proliferation activity.
On visual inspection, no patient (0/9) with high uptake of FDG had low grade gliomas and 94% (14/15) had high grade gliomas, while uptake of MET was present in all patients. On quantitative analysis, histological tumor grade was most reflected in FDG uptake ratio compared with contralateral white matter. The tumor/normal brain (T/N) uptake ratio of MET increased stepwise with increasing histological grade but was not significantly different from tumor grade. In comparison of FDG and MET uptake ratio with proliferation activity, a significant correlation was shown for FDG uptake ratio, but not for the T/N ratio of MET.
MET is useful in detecting and delineating the extent of the tumor, but not in evaluating tumor grade and proliferative activity. The FDG uptake ratio correlates well with tumor grade and proliferative activity. Preoperative PET studies with FDG and MET play complementary roles in the planning of glioma surgery, and integrated information from both tracers helps us to plan the extent of tumor resection.
No shinkei geka. Neurological surgery 07/2010; 38(7):621-8. · 0.13 Impact Factor
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ABSTRACT: A rare case of a brainstem variant of reversible posterior leukoencephalopathy syndrome (RPLS) is reported. A 34-year-old man with a past history of untreated chronic renal failure and hypertension was admitted to our hospital complaining of severe nuchal headache lasting for about four days. His neurological examination was normal, however physical examination revealed his blood pressure was 216/120 mmHg. Computed tomography imaging (CT) showed his brain stem with a low attenuation. Magnetic resonance imaging (MRI) revealed extensive hyperintensity and enlargement of the midbrain and pons on T2 weighted and fluid attenuated inversion-recovery (FLAIR) image. However, there was no abnormal lesion seen in either bilateral occipital lobe. Diffusion-weighted image (DWI) was normal at the brainstem, but apparent diffusion coefficient (ADC) values were slightly elevated at the left midbrain. There was no contrast enhancement. His symptom and radiological finding improved soon after his blood pressure was controlled. A repeated MRI taken two weeks later showed complete resolution of the lesion. RPLS associated with predominant involvement of the brainstem and sparing of the supratentorial region is rare, but it should be differentiated from brain stem infarction, pontine glioma, central pontine myelinolysis and infective encephalitis, since the neulological consequences are potentially fully reversible after adequate and prompt treatment.
No shinkei geka. Neurological surgery 11/2009; 37(11):1105-9. · 0.13 Impact Factor
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ABSTRACT: Intrinsic tumors arising in the dorsal midbrain cause obstructive hydrocephalus and have an indolent clinical course. Positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) and l- [methyl-(11)C]methionine (MET) was used to evaluate the biological behaviors of dorsal midbrain tumors.
The authors report on 4 patients (3 males and 1 female) with dorsal midbrain tumors who presented with obstructive hydrocephalus. A diagnosis was made with MR imaging in each patient. To manage the hydrocephalus, endoscopic third ventriculostomy was performed in all cases. The patients did not undergo any other surgical procedures except endoscopic biopsy procedure, chemotherapy, or radiation therapy. The patients in 3 cases underwent FDG- and MET-PET within 6 months of CSF-diverting procedures, and the patient in 1 case underwent PET 10 years after the procedure.
After the CSF-diverting procedure, clinical symptoms resolved or improved in all patients. Gliosis or glial proliferation was diagnosed in 1 patient, and possible low-grade glioma in 2 patients. Although all tumors appeared hyperintense on T2-weighted MR images, their appearance on T1-weighted images was variable (iso- and/or hypointense), and partial lesion enhancement was observed on images from 2 patients. On the other hand, the PET features of these lesions were almost identical, and the scans did not show a high uptake of FDG and MET compared with the cortical uptake in a normal brain. The mean tumor tissue/normal tissue ratio of FDG uptake was 0.65, and that of MET was 0.99.
Positron emission tomography findings suggested that the indolent dorsal midbrain lesion had nontumorous characteristics, thus supporting a good prognosis. Positron emission tomography studies may be more informative and predictive of the biological behavior of dorsal midbrain tumors than a biopsy procedure.
Journal of Neurosurgery Pediatrics 05/2009; 3(4):270-5. · 1.53 Impact Factor
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Ken Sasai,
Miho Nodagashira,
Hiroshi Nishihara,
Eiko Aoyanagi,
Lei Wang,
Masahito Katoh, Junichi Murata,
Yoshimaru Ozaki,
Tamio Ito,
Shin Fujimoto,
Sadao Kaneko,
Kazuo Nagashima,
Shinya Tanaka
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ABSTRACT: Evaluation of O6-methylguanine-DNA methyltransferase (MGMT) expression is important for antiglioma therapy as many clinical trials have demonstrated that promoter hypermethylation and low level expression of MGMT are associated with an enhanced response to alkylating agents. However, here we report that the current strategies used to evaluate MGMT status in gliomas are unreliable. We observed discordance in the MGMT expression status when immunohistochemical evaluation and polymerase chain reaction-based methylation assessments were used: 73% of gliomas with methylated MGMT promoter had substantial numbers of MGMT-immunopositive tumor cells. Furthermore, when MGMT expression was tested in tumor homogenates using reverse transcription-polymerase chain reaction, 43% of tumors were found positive, in comparison to only 24%, when histologic samples were assayed immunohistochemically. To explain these inconsistencies we undertook a detailed immunohistochemical evaluation of tumor samples and found that some gliomas demonstrated remarkably high expression of MGMT in the entire tumor whereas others contained only a small immunopositive area. Additionally, we found that gliomas contained various types of non-neoplastic cells expressing MGMT, including lymphocytes, vascular endothelial cells, and macrophages/microglias, which contribute to overall MGMT expression detected in tumor homogenates, and thus result in overestimation of tumor MGMT expression. Therefore, to correctly establish MGMT expression in the tumor, which could be informative of glioma sensitivity to alkylating agents, exclusion of non-neoplastic brain components from analysis is required.
The American journal of surgical pathology 07/2008; 32(8):1220-7. · 4.06 Impact Factor
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ABSTRACT: Two cases of clear cell ependymoma (CCE) of the fourth ventricle are reported in a 49-year-old woman with dysphagia and a 59-year-old woman with dizziness and gait disturbance. CCE is a relatively new variant of ependymoma added to the WHO classification of tumors in 1993. Tumor cells display an oligodendroglioma-like appearance with a clear perinuclear halo. Most infratentorial CCE tumors are located in the cerebellum. There are only three cases, including the present two cases, that have been reported to affect the fourth ventricle.
Neuropathology 01/2005; 24(4):330-5. · 2.02 Impact Factor
