Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

Recurrence of Biphenotypic Sinonasal Sarcoma With Cerebral Hemorrhaging.

Biphenotypic sinonasal sarcoma (BSNS) is a newly classified tumor that is characterized by neural and myogenic differentiation. The authors herein report a rare patient of the recurrence of BSNS with intracranial hemorrhaging and a review of the literature. A 70-year-old man presented with disturbance of consciousness and vomiting blood. He had undergone resection of a sinonasal tumor 11 years earlier and shown no recurrence at his last follow-up 4 years ago. Computed tomography showed cerebral hemorrhaging around a low-density mass that occupied the left frontal base and left ethmoid sinus. Total resection was performed. A histological examination of tumor specimens obtained from the first and the second resections revealed almost the same characteristic morphological features and the patient was diagnosed with BSNS. The lesion was negative for any fusion genes, as previously reported. The long-term progression of BSNS is not clear. This case appears to be the first reported recurrence of BSNS with cerebral hemorrhaging. Biphenotypic sinonasal sarcoma should be considered to need long-term follow-up.

A Single Oral Dose of Geranylgeranylacetone Upregulates Vascular Endothelial Growth Factor and Protects against Kainic Acid-Induced Neuronal Cell Death: Involvement of the Phosphatidylinositol-3 Kinase/Akt Pathway.

BACKGROUND: Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein inducer, against ischemic insult or kainic acid (KA)-induced neuronal cell death. Phosphatidylinositol-3 kinase (PI3K)/Akt is thought to be an important factor that mediates neuroprotection. However, the signaling pathways in the brain in vivo after oral GGA administration remain unclear. METHODS: We measured and compared hippocampal neuron density to investigate the effect of GGA on KA-induced cell death in rats. We evaluated the effects of pretreatment with wortmannin (Wort), a specific PI3K inhibitor, on GGA-induced neuroprotection against KA-induced cell death. To clarify the relationship between PI3K/Akt activation and neuroprotection, we used immunoblot analysis to determine the amounts of p-Akt and vascular endothelial growth factor (VEGF) proteins present after GGA administration with or without Wort treatment. RESULTS: Neuroprotective effects of GGA (pretreatment with a single oral dose of GGA, 800 mg/kg, 48 h before KA injection) were prevented by Wort pretreatment, which indicates that the selective PI3K/Akt pathway may mediate the GGA-dependent protection. Oral GGA-induced p-Akt and VEGF, and GGA pretreatment enhanced KA-induced VEGF, both of which were prevented by Wort pretreatment. CONCLUSION: These results suggest that a single oral dose of GGA induces p-Akt and that GGA plays an important role in neuroprotection against KA-induced neuronal cell death through VEGF induction.

Dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation on the middle cranial fossa.

A 46-year-old woman presented with headache and right hemiparesis. MRI demonstrated a mass in the left middle fossa. Total resection was performed. A histological examination of the tumor specimen showed several characteristic morphological features. A chordoid meningioma showing an epithelial-like palisade arrangement was observed. An anaplastic short spindle cell tumor exhibiting a fascicular pattern was considered to be a rhabdomyosarcoma. After conventional radiotherapy, the tumor was well controlled without any neurological deficit for 20 months. When subsequent recurrences were observed, the patient was treated by surgery, stereotactic radiosurgery and chemotherapy. Thirty-two months after the initial treatment, the patient died due to intracranial dissemination and an autopsy was performed. The histological examination of the recurrent and autopsy specimens showed a prominent sarcoma component. This case appears to be the first reported intracranial tumor diagnosed as a dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation.

Venous air embolism (VAE) associated with stereotactic biopsies.

BACKGROUND: Venous air embolism (VAE) is a serious potential complication of neurosurgical procedures. Stereotactic biopsies can also cause VAE; therefore, we evaluated VAE patients to call attention to the risk of VAE associated with stereotactic biopsies. METHODS: In this report, symptomatic VAE was defined as paroxysmal coughing with associated symptoms. Air in the dural sinus, cortical vein and/or pterygoid plexus on postoperative computed tomography (CT) scans was considered to be a radiographic VAE. RESULTS: Three patients developed symptomatic VAE following 36 stereotactic biopsies, and the incidence of symptomatic VAE was 8.3 % (3/36). There were five patients with evidence of radiographic VAE on postoperative CT scans, with an incidence of 13.8 % (5/36). A high angle of the head seemed to be associated with VAE, allowing air to flow into the central venous system. CONCLUSIONS: The present report emphasizes that VAE should be recognized as an important adverse effect of stereotactic biopsies because VAE occasionally requires additional treatment and/or termination of surgery. Surgeons must be aware of the possibility of VAE, especially when it is necessary to position the patient's head at a high angle.

Anticonvulsant and antioxidant effects of lamotrigine on pilocarpine-induced status epilepticus in mice.

OBJECTIVES: The anticonvulsant and antioxidant effects of lamotrigine on status epilepticus (SE) are incompletely understood. We assessed these effects of lamotrigine on pilocarpine (Pilo)-induced SE in mice. METHODS: Male C57BL/J6 mice were assigned to three groups: the control group, Pilo (400 mg/kg, s.c.)-induced SE (Pilo group) and lamotrigine (20 mg/kg, i.p.) treated (Pilo/lamotrigine group). The latency to SE of Racine's stage 3 or higher, the mortality rate within 2 h of Pilo administration, and the duration of SE until sacrifice were examined. Nitric oxide (NO), malondialdehyde and glutathione of oxidative stress biomarkers were detected in the hippocampus of the sacrificed animals in the above groups. NO was also detected in the cultured rat hippocampal neurons treated with 4 µM Pilo, Pilo+100 µM lamotrigine (Pilo/lamotrigine) and Pilo/lamotrigine+ N-methyl-D-aspartic acid (NMDA) receptor antagonist (10 µM MK-801, 3 µM ifenprodil) to examine the antioxidant effects of lamotrigine via non-NMDA-related pathways. RESULTS: lamotrigine prolonged the latency to SE, the SE duration until sacrifice, and decreased the mortality rate in mice with Pilo-induced SE. Lamotrigine also decreased hippocampal concentrations of NO and malondialdehyde and increased the concentrations of glutathione in the SE model. Furthermore, there were significant differences in NO concentrations between groups of cultured rat hippocampal neurons treated with Pilo and Pilo/lamotrigine, and with Pilo/lamotrigine and Pilo/lamotrigine+MK-801. CONCLUSION: Our findings suggest that lamotrigine exerts anticonvulsant and antioxidant effects on SE, but its antioxidant activity may not be fully exerted via NMDA-related pathways.

Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C.

BACKGROUND: The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. METHODS: An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ±â€…10 Gy boost (arm A) or WBRT ±â€…boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS). RESULTS: Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. CONCLUSIONS: This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

OBJECTIVE: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS: Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS: The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

Sialic acid-binding immunoglobulin-like lectin-15 expression on peritumoral macrophages is a favorable prognostic factor for primary central nervous system lymphoma patients.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) is a new immune checkpoint molecule and its role of primary central nervous system lymphoma (PCNSL) tumor microenvironment has been unclear. We explored the Siglec-15 and programed death-ligand 1 (PD-L1) expression in tumor tissues and analyzed the association between the expression of these molecules and overall survival in newly diagnosed PCNSL. A total of 60 patients diagnosed with diffuse large B-cell lymphoma in PCNSL were included in this study. The Siglec-15 and PD-L1 expression on tumor cells, intratumoral macrophages and peritumoral macrophages were immunohistochemically evaluated. The expression of Siglec-15 and PD-L1 was greater in macrophages than in tumor cells. Regarding peritumoral macrophages, the number of Siglec-15-positive samples (n = 24) was greater than the number of PD-L1-positive samples (n = 16). A multivariate Cox analysis showed that the Siglec-15 positivity of peritumoral macrophages and performance of high-dose methotrexate-based chemotherapy were independent predictors of overall survival (hazard ratio: 0.295 and 0.322, respectively). The Kaplan-Meier survival curves showed that patients with Siglec-15-positive peritumoral macrophages had longer overall survival than those with Siglec-15-negative peritumoral macrophages (median overall survival: 3018 days and 746 days, respectively; p = 0.0290). Our findings indicate that the expression of Siglec-15 on peritumoral macrophages induces a favorable outcome in PCNSL patients.

Perfusion Parameter Obtained on 3-Tesla Magnetic Resonance Imaging and the Ki-67 Labeling Index Predict the Overall Survival of Glioblastoma.

BACKGROUND: Pulsed arterial spin-labeling, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) are useful for predicting glioma survival. We performed a comparative review of multiple parameters obtained using these pulse sequences on 3-Tesla magnetic resonance imaging (MRI) including the molecular status and Ki-67 labeling index in newly diagnosed supratentorial glioblastomas. METHODS: A total of 35 patients with glioblastomas underwent pulsed arterial spin-labeling, DTI, and MRS studies using 3-Tesla MRI preoperatively. The isocitrate dehydrogenase (IDH) mutation status, methylguanine-DNA methyltransferase methylation status, and Ki-67 labeling index were calculated from the tumor specimen. Cutoff values were identified by analyzing a receiver operating characteristic curve, and the multivariate survival statistical technique was performed to determine the significant and independent parameters for predicting overall survival. RESULTS: The multivariate Cox analysis showed that the maximum/mean relative cerebral blood flow (rCBF) ratio and the Ki-67 labeling index were significant and independent predictive parameters with a cutoff value of 1.589 for the maximum rCBF ratio, 1.286 for the mean rCBF ratio, and 19% for the Ki-67 labeling index and hazard ratios of 6.132 and 5.119, respectively. The Kaplan-Meier survival curves showed that patients with higher rCBF ratios and Ki-67 labeling indices had a shorter overall survival than others, with median overall survival durations of 479 (95% CI, 370-559) and 1243 (95% CI, 666-NA) days, respectively (P = 0.000167). CONCLUSIONS: Our findings indicate that the preoperative rCBF ratio and Ki-67 labeling index are useful parameters for predicting the overall survival of cerebral glioblastomas.

Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas.

Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut-LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut-LGGs classified by chromosome 1p/19q codeletion (IDHmut/1p19qcodel and IDHmut/1p19qnoncodel) and performed genome-wide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data. These analyses showed that tumor mutational burden correlated positively with malignant transformation rate, and chemotherapy and radiotherapy significantly suppressed tumor growth but increased malignant transformation rate per cell by 1.8 to 2.8 times compared with before treatment. This model revealed that prompt adjuvant chemoradiotherapy prolonged malignant transformation-free survival in small IDHmut-LGGs (≤ 50 cm3). Furthermore, optimal treatment differed according to genetic alterations for large IDHmut-LGGs (> 50 cm3); adjuvant therapies delayed malignant transformation in IDHmut/1p19qnoncodel but often accelerated it in IDHmut/1p19qcodel. Notably, PI3K mutation was not associated with malignant transformation but increased net postoperative proliferation rate and decreased malignant transformation-free survival, prompting the need for adjuvant therapy in IDHmut/1p19qcodel. Overall, this model uncovered therapeutic strategies that could prevent malignant transformation and, consequently, improve overall survival in patients with IDHmut-LGGs. SIGNIFICANCE: A mathematical model successfully estimates malignant transformation-free survival and reveals a link between genetic alterations and progression, identifying precision medicine approaches for optimal treatment of IDH-mutant low-grade gliomas.

Well-differentiated Astroblastoma with Both Focal Anaplastic Features and a Meningioma 1 Gene Alteration.

A 6-year-old female was incidentally found to have a brain tumor. Magnetic resonance imaging (MRI) demonstrated a gadolinium-enhanced mass in the left parietal lobe. We performed gross total resection with the assistance of fluorescent guidance by 5-aminolevulinic acid (5-ALA). A histological examination of the tumor specimen showed well-differentiated astroblastic features with focal anaplasia. Fluorescence in situ hybridization (FISH) revealed meningioma 1 (MN1) gene alteration and supported our diagnosis. She received local radiotherapy and oral temozolomide followed by maintenance temozolomide chemotherapy, and the tumor was well controlled without any neurological deficit for 27 months. Our case is considered to be valuable since it describes a patient who is diagnosed to have a well-differentiated astroblastoma with both focal anaplastic features and MN1 gene rearrangement. A larger study is warranted to establish evidence supporting the diagnosis and treatment of astroblastoma with molecular characteristic features. MN1 alteration will be a diagnostic marker for astroblastoma in the future.

Prognostic relevance of genetic alterations in diffuse lower-grade gliomas.

Background: Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown. Methods: Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308). The results were validated using a dataset from 414 LGG cases available from The Cancer Genome Atlas (TCGA). Results: In Oligodendroglioma, IDH-mutant and 1p/19q codeleted, NOTCH1 mutations (P = 0.0041) and incomplete resection (P = 0.0019) were significantly associated with shorter survival. In Astrocytoma, IDH-mutant, PIK3R1 mutations (P = 0.0014) and altered retinoblastoma pathway genes (RB1, CDKN2A, and CDK4) (P = 0.013) were independent predictors of poor survival. In IDH-wildtype LGGs, co-occurrence of 7p gain, 10q loss, mutation in the TERT promoter (P = 0.024), and grade III histology (P < 0.0001) independently predicted poor survival. IDH-wildtype LGGs without any of these factors were diagnosed at a younger age (P = 0.042), and were less likely to have genetic lesions characteristic of glioblastoma, in comparison with other IDH-wildtype LGGs, suggesting that they likely represented biologically different subtypes. These results were largely confirmed in the cohort of TCGA. Conclusions: Subtype-specific genetic lesions can be used to stratify patients within each LGG subtype. enabling better prognostication and management.

p73gamma transactivates the p21 promoter through preferential interaction with the p300/CBP-associated factor in human prostate cancer cells.

Several p73 variants have been reported with different carboxy-terminal structures and transcriptional activities. We showed that p73gamma had stronger transactivation activity than the other splicing variants such as alpha, beta and delta by analysing p21 promoter activity in human prostate cancer PC3 cells. The transactivation activity of p73gamma was similar to that of p53 and was enhanced by co-transfection with p300/CBP-associated factor (PCAF). In vitro pull-down assay, p73 variants were able to bind to PCAF with a similar extent. However, in vivo co-immunoprecipitation assays showed that p73gamma interacted preferentially with PCAF. Neither in vitro-translated nor in vivo-immunoprecipitated p73gamma were able to bind to oligonucleotides containing the p53 consensus binding site. However, p73gamma acetylated by PCAF restored DNA binding activity. Differential functions of p73 variants are supposed to be regulated by the structural differences of carboxy-terminal region. Our results revealed that p21 promoter activity was affected by differential interactions of p73 variants with PCAF and its acetylation.

Gamma Knife surgery for primary central nervous system lymphoma: usefulness as palliative local tumor control.

OBJECT: Although there is no established treatment for primary central nervous system lymphoma (PCNSL), therapeutic protocols involving high-dose methotrexate therapy followed, in some cases, by whole-brain radiotherapy (WBRT) have generally been adopted, and they have yielded relatively favorable results. Gamma Knife surgery (GKS) is a stopgap measure to treat patients with PCNSL. The authors summarize the results of their cases and evaluate the efficacy and usefulness of GKS. METHODS: Between June 1999, and June 2005, 22 patients suffering from PCNSL were treated with GKS at the authors' institution and were followed up for more than 6 months. Some combination of chemotherapy and/or WBRT and/or microsurgery had been performed in 18 of the 22 patients before GKS. The remaining four patients had not undergone any previous treatment. In these patients, the mean tumor volume was 4.14 cm3, and the tumors were treated with a mean margin dose of 16.5 Gy to the 52.8% isodose line. Magnetic resonance imaging demonstrated the disappearance of the GKS-treated lesions; however, new lesions were observed in other regions of the brain in 10 patients and repeated GKS was performed in some cases. No local recurrences were observed an average of 19.4 months after GKS, and good level of quality of life (QOL) was maintained during this period. CONCLUSIONS: Gamma Knife surgery should be performed only for local tumor control as a stopgap measure in the treatment of PCNSL. It is noninvasive and safe, and its effects occur rapidly. Its use improves prognosis and enhances the patient's quality of life. Gamma Knife surgery should be considered one of the treatment strategies for patients with PCNSLs.

Cisplatin resistance and transcription factors.

Cisplatin is one of the most potent and widely used anti-cancer agents in the treatment of various solid tumors. However, the development of resistance to cisplatin is a major obstacle in clinical treatment. Several mechanisms are thought to be involved in cisplatin resistance, including decreased intracellular drug accumulation, increased levels of cellular thiols, increased nucleotide excision-repair activity and decreased mismatch-repair activity. In general, the molecules responsible for each mechanism are upregulated in cisplatin-resistant cells; this indicates that the transcription factors activated in response to cisplatin might play crucial roles in drug resistance. It is known that the tumor-suppressor proteins p53 and p73, and the oncoprotein c-Myc, which function as transcription factors, influence cellular sensitivity to cisplatin. So far, we have identified several transcription factors involved in cisplatin resistance, including Y-box binding protein-1 (YB-1), CCAAT-binding transcription factor 2 (CTF2), activating transcription factor 4 (ATF4), zinc-finger factor 143 (ZNF143) and mitochondrial transcription factor A (mtTFA). Two of these-YB-1 and ZNF143-lack the high-mobility group (HMG) domain and can bind preferentially to cisplatin-modified DNA in addition to HMG domain proteins or DNA repair proteins, indicating that these transcription factors may also participate in DNA repair. In this review, we summarize the mechanisms of cisplatin resistance and focus on transcription factors involved in the genomic response to cisplatin.

Transcription factors and drug resistance.

Intrinsic or acquired resistance to anticancer agents is a major obstacle to the success of chemotherapy. Anticancer agents are known to modulate signal transduction pathways and alter expression of genes that play an important role in drug resistance. Emerging evidence suggests that the complexity of genomic response against anticancer agents arise from elaborate gene expression by multiple transcription factors. Here, we briefly describe the development of solid tumours and the appearance of drug-resistant cells. We also review what is known of the transcription factors that are involved in resistance to drugs, particularly cisplatin.

Stereotactic biopsy with electrical monitoring for deep-seated brain tumors.

OBJECTIVE: The stereotactic biopsy is widely integrated into clinical practice as an efficient and safe procedure for histologic diagnoses. However, the surgical risk increases when the lesions are close to the eloquence of the adjacent brain. The present report describes two patients with deep-seated brain tumors who underwent a stereotactic biopsy with electrical monitoring and demonstrates the importance of this technique. METHODS: The tentative target and trajectory were determined on a stereotactic map from the Schaltenbrand and Wahren atlas. A Cosman-Roberts-Wells stereotactic frame was applied to the patient. Electrical recording along a single trajectory was used to identify the circumscribed neuronal structures, and electrical simulation was administered to the target. The biopsy point was decided when no adverse events were observed with a low electric current level. RESULTS: A 34-year-old male patient with anaplastic astrocytoma in the putamen and thalamus and an 81-year-old female patient with malignant lymphoma in the midbrain underwent stereotactic biopsies with electrical monitoring. The biopsies were successfully performed without any resulting neurologic deficits. CONCLUSIONS: This report describes two patients with deep-seated brain tumors who underwent stereotactic biopsies with electrical recording and stimulation. The electrical monitoring appears to be a useful technique to complement the ordinary image-guided biopsy.

Functional motor recovery of an infant after a huge ependymoma resection.

Huge supratentorial ependymomas are rarely encountered tumors, even in the infant population. A recovery from complete hemiplegia following a tumor resection including the primary motor cortex was observed. A 5-month-old girl presented with a conjugate deviation to the right and a head circumference that had gradually expanded since birth. Magnetic resonance imaging (MRI) demonstrated a well-enhanced huge mass extending into the right hemisphere. A subtotal removal with the primary motor cortex was performed. However, a regrowth of the residual tumor was observed and, thereafter, the patient underwent a subsequent surgical intervention 5 months later. The histological findings demonstrated an ependymoma. Her motor function was dramatically improved after rehabilitation and no tumor recurrence was detected for 10 years. A diffusion tensor imaging study showed that the motor fibers arose from the residual frontal lobe. The successful surgical management of ependymoma may depend on a total microscopic resection. In a case demonstrating a huge ependymoma, we had to remove a very thin motor cortex with the tumor. However, the motor function recovered completely. The motor damage inflicted at an early developmental age may be fully compensated due to the neuroplasticity of the residual brain.

Malignant fibrous histiocytosis after high-dose proton radiation therapy for anaplastic astrocytoma.

This report presents a 70-year-old male who presented with a rare malignant fibrous histiocytosis after high-dose proton radiation therapy for anaplastic astrocytoma. To our knowledge, malignant fibrous histiocytosis caused by proton therapy has not been reported, therefore the clinical features of this complication are described and previous cases are reviewed.