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Primary tumors of the spinal cord are rare, accounting for 3-6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed to difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicating a tentative diagnosis of astrocytoma. The patient underwent resection of the lesion in the spinal canal from the cervical 6 level to the thoracic 2 level. Histopathology confirmed diagnosis of astrocytoma, WHO grade 2. Genetic analysis showed both IDH1 R132H mutation and KIAA1549-BRAF fusion. Therefore, our integrated diagnosis was astrocytoma, IDH mutation, WHO grade 2. Its molecular analyses include IDH1 R132H mutation and KIAA1549-BRAF fusion. After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.

Background: Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lowergrade gliomas that carry IDH2 mutations. Methods: Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test. Results: Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively). Conclusions: IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation. Key words: Isocitrate dehydrogenase 1; Isocitrate dehydrogenase 2; Telomerase reverse transcriptase; Glioma; Oligodendroglioma

The characteristics of H3.3 G34-mutant gliomas in adults have yet to be specifically described. Thirty adults with H3.3 G34-mutant diffuse gliomas were retrospectively reviewed for clinical and pathologic information. Molecular profiling using next-generation sequencing was performed in 29 of the 30 H3.3 G34-mutant patients with 1 patient lacking available tumor samples, as well as 82 IDH/H3 wild-type adult diffuse glioma patients. The age at diagnosis of H3.3 G34-mutant diffuse gliomas was significantly younger than IDH/H3 wild-type gliomas (24 vs. 57 y, P

Aims To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. Materials and methods 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). Results Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. Conclusion Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.

MGMT promoter methylation is considered as a prognostic and predictive biomarker indicating response to chemotherapy and radiotherapy in glioblastoma. A number of different methods and platforms including pyrosequencing (PSQ), quantitative methylation-specific PCR (qMSP) and immunohistochemistry (IHC), methylation-sensitive high resolution melting (MS-HRM) and NGS (Next Generation Sequencing) have been used to detect MGMT promoter methylation in gliomas. However, controversy remains about the most appropriate method to use for analyzing MGMT status. The MGMT promoter methylation status of a total of 350 gliomas and gangliogliomas was examined using PSQ, qMSP and IHC in parallel. Using PSQ as a recommended standard method, the sensitivity, specificity, positive/negative predictive value and correlation with the other assays were calculated. Among 350 glioma and ganglioglioma cases, the MGMT promoter tested positive for methylation in 53.1%, 55.4%, and 70.3% of the cases by PSQ, qMSP and IHC, respectively. The sensitivity and specificity of qMSP were 97.8% and 92.7%, respectively. Twelve cases that tested positive for methylation using qMSP were negative according to PSQ, and four cases that were negative according to qMSP tested positive according to PSQ. The concordance rate between PSQ and qMSP was 90.8%. The sensitivity and specificity of IHC for the detection of MGMT at the protein level were 84.4% and 45.7%, respectively. The concordance rate between PSQ and IHC was 30.8%. This study demonstrated that qMSP is an effective and rapid detection method for routine use in pathology laboratories for the identification of MGMT promoter methylation. A combination of IHC and qMSP assays can provide high sensitivity and specificity for the prediction of MGMT status. A few cases that tested negative with PSQ did harbor MGMT promoter methylation, as confirmed by qMSP and sequencing, and this subgroup of patients may benefit from temozolomide.

OBJECTIVE In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD. METHODS We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files. RESULTS Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years. SIGNIFICANCE Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId.

ETS-related gene (ERG) is an oncogene that is commonly found in prostate cancer (PCa). Several miRNAs have been reported to be associated with PCa. This study was undertaken to identify miRNAs that act as a tumor suppressor by targeting ERG. We collected 70 PCa and paired adjacent non-tumor (Adjacent-N) tissues and analyzed ERG expression by immunohistochemistry(IHC). Expression of 6 miRNAs (miR-21,-34a,-96,-125b,-150 and miR-1271) was analyzed by qRT-PCR. Luciferase reporter assay was performed to examine miRNA binding to the 3′-UTR of target genes. The effects of ectopic expression of miRNA on cell growth and MAPK signaling pathway were investigated in in PC-3 and LNCaP cell lines. Among 70 PCa cases, 13 (18.6%) were ERG positive. No significant difference of miR-34a, 96, 125b, and 150 expression was found between PCa and Adjacent-N tissues. Significantly higher level of miR-21 and lower level of miR-1271 expression were found in cancer tissues. Furthermore, miR-1271 was down-regulated in ERG-positive PCa cases (p

The histone H3 K27M mutation has been frequently reported in most diffuse midline gliomas. However, the relationship between the H3 K27M mutation and clinical outcomes of gliomas from different anatomical locations is still not fully understood. A total of 120 patients with diffuse midline gliomas were selected for this retrospective observational study. The status of H3 K27M, ATRX, TP53, and IDH was evaluated using immunohistochemistry and Sanger sequencing. Of the 120 patients aged from 4 to 76 years (median, 27 years), 61 (50.8%) were harboring the H3 K27M mutation. Tumors were mainly located in the brainstem, ATRX thalamus, and spinal cord, but also in the cerebellum, corpus callosum, and the lateral ventricle. Patients with H3 K27M-mutant diffuse midline gliomas had a significantly shorter overall survival than H3 wild-type counterparts (P = .001). However, the H3 K27M mutation was mainly associated with a poorer prognosis in infratentorial gliomas compared with the corresponding H3 wild-type gliomas (P < .0001), but not in supratentorial gliomas (P = .603). Moreover, patients with H3 K27M-mutant gliomas in unusual anatomical locations had a better prognosis than did those with corresponding tumors in the brainstem. This study may provide guidance for better treatment stratification decisions for diffuse gliomas bearing the H3 K27M mutation, which arise in different locations of the brainstem, thalamus, spinal cord, or other sites.

Aims To study three atypical glioneuronal tumours (GNTs), in order to shed light on the clinical and pathological features of this diverse tumour group. Methods and results Clinical and neuropathological data for each case were retrospectively reviewed. Case 1 involved a 17-year-old boy with left leg movement difficulty. A mass lesion in the basal ganglia was detected radiologically; histopathological features included neurocytic/perivascular rosettes and a pilocytic astrocytoma component. Case 2 involved a 33-year-old man with intractable epilepsy. His left parietal lobe contained a cyst-like mass, resembling dysembryoplastic neuroepithelial tumour and rosette-forming glioneuronal tumour of the fourth ventricle microscopically. Case 3 involved a 21-year-old woman with a mass lesion in the mesencephalic tegmentum extending to the third and fourth ventricles and the suprasellar region. The lesion contained perivascular/neurocytic rosettes and an oligodendroglioma-like component. None of the tumours expressed an isocitrate dehydrogenase I mutation of the R132H type or contained a 1p/19q deletion, a BRAFV600E mutation, or KIAA1549–BRAF fusion. Conclusions We describe three GNTs with atypical histopathology and locations. Additional cases and molecular studies are needed to better understand the biological nature of GNTs and to refine their classification system.

Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor's possible confusion with other malignant tumors.

Sturge–Weber syndrome (SWS) is a rare syndrome characterized by capillary‐venous malformations involving skin and brain. Many patients with SWS also suffer from drug‐resistant epilepsy. We retrospectively studied a series of six SWS patients with epilepsy and extensive neurosurgical resections. At time of surgery, the patients' age ranged from 11 to 35 years (with a mean of 20.2 years). All surgical specimens were well preserved, which allowed a systematic microscopical inspection utilizing the 2011 ILAE classification for focal cortical dysplasia (FCD). Neuropathology revealed dysmorphic‐like neurons with hypertrophic cell bodies reminiscent to those described for FCD type IIa in all cases. However, gross architectural abnormalities of neocortical layering typical for FCD type IIa were missing, and we propose to classify this pattern as FCD ILAE type IIIc. In addition, our patients with earliest seizure onset also showed polymicrogyria (PMG; n = 4). The ictal onset zones were identified in all patients by subdural electrodes, and these areas always showed histopathological evidence for FCD type IIIc. Four out of five patients had favorable seizure control after surgery with a mean follow‐up period of 1.7 years. We concluded from our study that FCD type IIIc and PMG are frequently associated findings in SWS. FCD type IIIc may play a major epileptogenic role in SWS and complete resection of the associated FCD should be considered a prognostic key factor to achieve seizure control.

Angiocentric glioma (AG) is a rare, slow-growing tumour of the central nervous system. It is often associated with refractory epilepsy and occurs most commonly in children and young adults. We herein report nine cases of AG, including four with atypical histological findings.The clinical data and clinicopathological findings of nine cases with AG histological features were described.All nine patients had a history of refractory epilepsy with a mean history of 4.4 years and a median age of 17.6 years at surgery. The AG lesions were located in the superficial cerebrocortical region. Histological examination of these cases revealed characteristic structural features of AG, including bipolar spindle-shaped cells with an angiocentric growth pattern. However, four cases also exhibited atypical histological features: one had astroblastoma-like characteristics, two had a distinct cystic region with an onion-like structure and myxoid changes, and the other one had a region involving many abnormal neurones reminiscent to ganglioglioma. All were positive for glial fibrillary acidic protein and vimentin. Eight cases were positive for epithelial membrane antigen (EMA), with a dot-like staining pattern. A diffuse D2-40 staining was visible in these cases, with two having similar staining pattern to EMA. All cases were immunonegative for BRAF V600E and isocitrate dehydrogenase-1 R132H mutations.Our results demonstrate that atypical histological features can be present in AG. A collection of more cases and further molecular analyses are required to confirm our findings.

The beginning of Chinese neuropathology can be traced to the early years of the 20th century. In the 1920s to 1940s, a few neurologists from Beijing and Shanghai, such as Cheng Yu-lin, Hsu Yin-kuei, Huang Ke-wei, Zhang Yuan-chang, and Wang Wei-zeng, went to Europe and the United States for training in clinical neuropathology (1). When they returned to China, they became the pioneers of Chinese neuropathology. In 1938, Drs. Hsu Yin-kuei and Cheng Yu-lin published a landmark article on the neuropathology of carbon monoxide poisoning in the famous journal Brain (2). Clinical neuroscience was still under the umbrella of internal medicine in that period. In 1951, neurology and psychiatry were separated as independent subjects with the founding of the Chinese Neurology and Psychiatry Society. From then on, Chinese clinical neuroscience and neuropathology experienced a great development. The important forum, Clinicopath-ological Conferences (CPCs) in Neurology, was imported to China in the 1950s. The most famous CPC in China was the Beijing CPC, which was formally established by Prof. Huang Ke-wei in 1978 and has continued since then for more than 30 years. The current manager is Prof. Wang Lu-ning. The Beijing CPC is held monthly on the second to last Wednesday afternoon at the Chinese PLA General Hospital and is attended by members from all the teaching hospitals with departments of neurology in Beijing. Two puzzling cases provided by the hospitals on a rotating basis are presented and discussed at every session. Moreover, …

To investigate the expression of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 in refractory epilepsy associated malformation of cortical development (MCD) tissues.A total of 43 cases of refractory epilepsy were involved in the study, and all the patients were treated in Xuanwu Hospital during 2005 - 2008, including focal cortical dysplasia type IIa (11 cases) and type IIb (11 cases), tuberous sclerosis complex (10 cases) and ganalioglioma (11 cases), and other 12 cases were used as control. These cases were divided into 7 study groups and immunohistochemical EnVision method was used. To detect the location and intensity of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 expression in every group. Then the Image-Pro Plus 6.0 image processing and analysis software were used to measure the number, area, integrating absorbance (IA) of positive cells in every samples. The statistical software SPSS 16.0 was used to analyze the data.The immunolocalization of TSC1 and TSC2 was similar. It could be observed the expression of various levels in the cytoplasm of dysmorphic neurons, balloon cells, giant cells, ganglioglioma cells and normal neurons. TSC1 staining in normal neurons was more notably than others but TSC2 staining in giant cells was weaker than other samples. p-mTOR mainly presented in giant cells, which could also be observed in astrocyte. P-4E-BP1 presented in the cytoplasm and nuclear membrane of balloon cells, giant cells and ganglioglioma cells, the staining of giant cells was stronger than balloon cells, but their staining were weaker than ganglioglioma cells. P-p70S6K mainly expressed in giant cells and less commonly presented in balloon cells. P-S6 typically presented in all abnormal glioneuronal cells and it nearly did not present in the normal neurons of N-CTX group.PI3K pathway, at least in part, involves in the occurrence of MCD, and may play an important role in the pathogenesis.

To investigate the clinical and radiological characteristics of cortical vein thrombosis for early diagnosis and treatment.Retrospective analysis was carried out with the clinical cases of cortical vein thrombosis in 2010. The symptoms, sign, neuroimaging were analyzed and related literatures were reviewed.Four patients were collected, average age was forty years old. The main symptoms were headache and focal neurological signs in varying degrees, infarction or hemorrhage in one or two sides of parietal lobe could be found in CT or MRI. Hemorrhage was found in two patients, infarction was found in one patient, hemorrhage and infarction were both found in another patient.Headache and focal neurological signs are the common sings and symptoms of patients with cortical vein thrombosis. CT and MRI are effective methods for the diagnosis of cortical vein thrombosis.

Chordoid glioma is a rare, slowly growing tumor of the CNS, which is always located in the third ventricle of adults. Chordoid glioma has classic histological features consisting of clusters and cords of epithelioid tumor cells embedded within a mucinous stroma with rich lymphoplasmacytic infiltrate. The important distinctive immunohistochemical feature of this neoplasm is strong and diffuse reactivity for GFAP. Here, we report four cases of chordoid glioma that occupied the anterior portion of the third ventricle or suprasellar region. These four cases were all adult females with almost typical clinical, radiological, histologic and immunohistochemical characteristics of chordoid glioma. However, in one case there was an unusual histologic finding with regard to the papillary region. In this region, elongated tumor cells were observed radiating toward a central vessel to form characteristic papillary structures. Immunohistochemically, three cases showed strong reactivity for GFAP, and one exhibited weak reactivity. All cases were focally positive for epithelial membrane antigen, CD34 and D2-40, but negative for neurofilament protein (NFP). Several ultrastructural investigations have supported the ependymal origin of chordoid glioma. In some cases of immunoreactivity for NFP, some authors have supposed that chordoid glioma originates from a multipotential stem cell with glial and neuronal cell differentiation. With regard to the present four cases with immunoreactivity for D2-40 (an ependymal marker) and CD34 (undifferentiated neural precursors) and based on previously published data, we considered that the majority of chordoid gliomas had an ependymal origin, and that a small minority might have originated from a multipotential stem cell having ependymal and neuronal cell differentiation.

To investigate the diagnostic significance of D2-40 and annexin-1 in the ependymal tumors.To analyses the expression of D2-40, annexin-1, EMA and Ki-67 by immunohistochemistry in 52 cases of ependymal tumors (48 cases of ependymomas, 4 cases of choroid plexus papilloma) from Xuanwu Hospital from 2005 to 2009. Ten cases of corresponding normal brain tissue were also obtained as control.Thirty-two of forty-eight (66.7%) cases of ependymomas were positive for D2-40. "Dot-like" and "ring-like" structures were commonly observed in ependymomas (55.3%, 21 of 38 cases) and anaplastic ependymomas (5 of 6 cases) with D2-40 staining. There was no difference in the expression between D2-40 and Ki-67 (r(s) = -0.013, P = 0.931). For annexin-1, 87.5% (42 of 48 cases) of the ependymomas were positive. The specific "granular structures" and cilium were observed in ependymomas (1 of 4 cases of myxopapillary ependymomas and 11 of 38 cases of ependymomas respectively) for annexin-1. The difference in expression between annexin-1 and Ki-67 was statistically significant (r(s) = -0.405, P = 0.005). D2-40 in combination of EMA and annexin-1 increased the positive rate to 100% in ependymomas. Choroid plexus papillomas were all positive for D2-40 and annexin-1. The control tissue was negative for D2-40 but positive for annexin-1 in the capillaries.The specific structures are valuable in diagnosing of ependymal-genetic tumors, and are highlighted by D2-40 and annexin-1. D2-40 in combination of EMA and annexin-1 is a useful diagnostic marker for ependymal tumors.

To study the clinicalpathologic features of intracranial multiple lesions.The clinical, radiologic and pathologic features of intracranial multiple lesions in 62 cases during the period from 2005 to 2009 in Xuanwu Hospital were retrospectively reviewed.There were 32 males and 30 females in 62 cases. The mean age of seize onset and duration of disease were 37.4-year-old and 11.6 months, respectively. The lesions could affect cerebral hemisphere, basal ganglia, brain stem, cerebellum and other parts, most lesions were located above the tentorium. Pathological diagnosis as follows: 13 patients with glioma; metastatic tumors in 13 cases; 12 cases of central nervous system infection; immune-mediated inflammatory demyelinating disease in 8 cases; 5 cases of primary lymphoma of central nervous system; primary angiitis of the central nervous system 3 cases; mitochondrial encephalopathy 2 cases; vein thrombosis in 2 cases; Rosai-Dorfman disease in 2 cases; 2 case of radiation encephalopathy. Among them, mitochondrial encephalopathy and vein thrombosis lesions located in the cortex; metastatic tumor and blood-borne infection mainly involving junction of grey and white matter; glioma, radiation encephalopathy and demyelinating disease include white matter lesions; vascular inflammation showed cortical and subcortical white matter lesions.A variety of tumor and non-neoplastic diseases can be expressed in intracranial multiple lesions, which gliomas, metastatic tumor and central nervous system infections are more common. In order to improve the diagnosis of intracranial multiple lesions, active work in the brian biopsy, study the clinical, imaging and pathological findings must be closely.

To investigate the immunohistochemical expression of isocitrate dehydrogenase 1 gene (IDH1) R132H in glioma and its diagnostic utility.Immunohistochemical study of IDH1R132H expression was performed on formalin-fixed paraffin-embedded tissue samples of 75 gliomas, including 33 cases of grade II, 20 cases of grade III and 22 cases of grade IV tumors. Six cases of pilocytic astrocytoma and 12 cases of gliosis were used as controls.Nineteen in 33 cases of grade II (57.6%), 8 in 20 cases of grade III (40.0%), 6 in 22 cases of grade IV (27.3%) showed positive cytoplasmic staining of IDH1R132H. Scattered invasive glioma cells at the tumor periphery also expressed IDH1R132H. Gliomas involving the frontal lobe showed more strong IDH1R132H staining. In contrast, none of the pilocytic astrocytomas and gliosis showed IDH1R132H staining. Moreover, the rate of p53 immunopositivities were 42.4% (14/33) in grade II, 65.0% (13/20) in grade III and 77.3% (17/22) in grade IV gliomas. There were no statistic correlations between expression of IDH1R132H and p53.IDH1R132H tends to express preferentially in low-grade gliomas, and it thus may serve as a valuable marker in distinguishing low grade gliomas from gliosis.

Although the increased prevalence of Parkinson’s disease (PD) with aging suggests that aging processes predispose dopamine neurons to degeneration, the mechanism involved remains unknown. Dopamine neurons contain significant amounts of neuromelanin, and the amount of neuromelanin increases with aging. In the present study, age-related changes in the number of nigral neurons expressing neuromelanin (NM), α-synuclein, and tyrosine hydroxylase (TH) were stereologically analyzed in the postmortem brains of 28 healthy humans with an age range of 17–84 years. Stereological counting of NM content, α-synuclein content, and TH immunoreactivity revealed significant accumulation of NM and α-synuclein in neurons during the aging process. In cells containing a large amount of NM, α-synuclein-immunoreactive cells in aged individuals outnumbered those of younger individuals. In non-NM cells, the α-synuclein expression profile was similar across age groups. Furthermore, TH-immunoreactive neurons decreased significantly with aging, which was associated with accumulation of NM and α-synuclein. Our results suggest that age related accumulation of NM might induce α-synuclein over-expression and thereby make dopamine neurons more vulnerable to injuries.

To study the immunohistochemical expression and diagnostic significance of CD34 in brain tumors of patients with refractory epilepsy.Immunohistochemical study for CD34 was performed on formalin-fixed paraffin-embedded tissue blocks of 54 cases of brain tumors occurring in patients with refractory epilepsy. The tumor types included ganglioglioma (GG, number = 21), dysembryoplastic neuroepithelial tumor (DNT, number = 8), tumors/lesions which had the transitional features that between glioneuronal hamartia and mixed neuronal-glial tumor (number = 21) and pleomorphic xanthoastrocytoma (PXA, number = 4). Cases of glioblastoma (number = 4) and oligoastrocytoma (number = 5) were used as controls.Twenty of the 21 cases of GG, 1 of the 8 cases of DNT, 16 of the 21 cases of tumors/lesions which had the transitional features and 3 of the 4 cases of PXA showed cytoplasmic and membranous positivity for CD34. The adjoining brain tissues in 9 of the 18 cases of GG, 6 of the 16 cases of tumors/lesions which had the transitional features and 1 of the 3 cases of PXA also expressed CD34. In contrast, only 1 case of glioblastoma showed membranous positivity for CD34.CD34 preferred to staining for GG and PXA. Which represent a valuable tool for distinguishing GG, PXA and DNT, oligoastrocytoma, glioblastoma.

The number of patients with intractable epilepsy undergoing surgical management in China is increasing rapidly. We retrospectively reviewed 435 consecutive cases of intractable epilepsy receiving surgical resection from 2005 to 2008 in our hospital, looking specifically at the neuropathological findings. The three most common causes of intractable epilepsy were focal cortical dysplasia (FCD; 52.9%), scar lesions (22.8%) and brain tumors (11.7%). Hippocampal sclerosis was identified in 74 cases (17.0%), although most of these were accompanied by dual pathology with FCD (especially Palmini type IB), scar lesions or tumors. Among FCD cases, Palmini type I lesions are the most frequently observed abnormality, with a preferred location in the temporal lobe (60.1%) and often accompanied by dual pathology. In contrast, Palmini type II FCD lesions occurred predominantly in the frontal regions and with a lower age of onset. Most tumors were mixed neuronal-glial tumors, mainly ganglioglioma (19 cases) and dysembryoplastic neuroepithelial tumor (10 cases), with a trend toward a temporal location and usually accompanied by cortical dysplasia in the peritumor area. Our data on the neuropathology of intractable epilepsy in China show that glioneuronal lesions are the most prominent cause of intractable epilepsy, and this is consistent with reports from other countries.

To investigate the pathological changes and pathogenesis of the MELAS syndrome (mitochondrial encephalopathy lactic acidosis stroke-like episodes) by using the method of immunohistochemical staining in the brain biopsy specimens with anti-mitochondrial antibody (AMA).We performed immunohistochemical staining in 3 confirmed MELAS patients' paraffin-imbued brain biopsy specimens.Small vessel proliferation and the uneven thickness of the wall were found in the 3 MELAS patients. A lot of brown deposits was shown in the wall of small vessels and also noted in neurons.The main pathological change in the MELAS brain biopsy immunohistochemical staining with AMA was the small vessel proliferation, indicating that abnormal mitochondria accumulated in the vascular smooth muscle, endothelial cell and neurons of the lesion sites. This finding was consistent with the electron microscopic discovery and valuable for the diagnosis of MELAS.

To study the clinicopathologic features of brain tumors occurring in patients with medically intractable epilepsy.The clinical, radiologic and pathologic features of brain tumors occurring in 35 patients with intractable epilepsy encountered during the period from January, 2005 to April, 2008 in Xuanwu Hospital were retrospectively reviewed.The mean age of seizure onset and duration of disease were 14.3-year-old and 8.6 years, respectively. Abnormal signals were observed in 94.3% of cases (33/35) by magnetic resonance imaging. The histologic types of brain tumors included ganglioglioma (13/35, WHO grade I and 6/35, WHO grade II), dysembryoplastic neuroepithelial tumor (3/35, WHO grade I), pleomorphic xanthoastrocytoma (3/35, WHO grade II), diffuse astrocytoma (1/35, WHO grade II), oligoastrocytoma (1/35, WHO grade II), angiocentric glioma (1/35, WHO grade I) and meningioangiomatosis (1/35). The 6 remaining cases showed features seen in between glioneuronal hamartoma and mixed neuronal-glial tumor. Most of these tumors were located in the temporal lobe (27/35) and associated with focal cortical dysplasia. Immunohistochemical study showed a remarkable expression of CD34 in gangliogliomas.Brain tumors in patients with medically intractable epilepsy are almost always benign and located in the temporal lobe. Most of them represent mixed neuronal-glial tumors and some show transitional features in-between glioneuronal hamartoma and mixed neuronal-glial neoplasm. The similar morphologic pattern and biological behavior of glioneuronal hamartoma and mixed neuronal-glial tumor may suggest a common pathogenetic mechanism.

To discuss the correlation between characteristics of interictal epileptiform discharge (IED) and histopathological changes in epilepsy patients with focal cortical dysplasia (FCD) in order to explore the epileptogenicity of various IED.Twenty-two consecutive patients suspected as with FCD who were to undergo epilepsy surgery received intracranial electrode implantation and long-term video-EEG monitoring before the resective surgery and the postoperative pathology proved the diagnosis of FCD. According the long-term EEG monitoring results, the IEDs were divided into four catalogs: isolated spike, slow repetitive spike, repetitive spike, and paroxysmal fast. The possible epileptogenic cortex with intense IED was resected in the operation to undergo histopathologic study and hemi-quantificational scoring of parvalbumin (PV) by immunocytochemistry.The resected specimens of 20 cases were studied. There were not significant differences in the PV quantificational score between any 2 IED subtypes (F = 1.198, P = 0.342). However, the spike type had the highest PV score: 8.00, while the repetitive spike type had the lowest PV score: 5.60. On the other hand, FCD of different severity in terms of pathological changes tended to have different kind of IED.Despite the insignificant differences between various kinds of IED, isolated spike has the highest PV scores meaning lower epileptogenicity. Slow repetitive spike, repetitive spike, and paroxysmal fast tend to occur in more severe FCD patients which mean a great possibility of epileptogenicity.

Fibrocartilaginous embolism is a rare cause of anterior spinal cord infarction. We report a case of anterior spinal cord infarction caused by a fibrocartilaginous embolism of 3 months duration in a 23-year-old man. Ten days after a trivial strike to the neck and back, he had sudden back pain, weakness of the upper and lower extremities, developed dyspnea and became unconscious. Cervical MRI showed an enlargement of the lower medulla and cervical cord with abnormal signals in the ventral portion. The follow-up MRI performed 2 months later showed atrophy of the above lesion. On histopathological examination, there was a recent, extensive infarct in the cervical cord and lower medulla. The lesion was symmetrical, and predominantly involved the anterior part of the spinal cord. Moreover, many basophilic, alcian blue-positive emboli in the arteries and veins of the lesion were detected. This is the first autopsy case of anterior spinal cord infarction caused by a fibrocartilaginous embolism that has been confirmed in China. The clinicopathological features of this case are reviewed in this paper.

To evaluate the alteration of subunits composition in NMDA receptor and the alterations of the expression and distribution of NMDA receptors and parvalbumin (PV)-positive neurons in focal cortical dysplasia (FCD) cortices.Twenty cases of FCD samples (including all four subtypes of FCD) obtained during epilepsy surgery and 4 controls were analysed by immunohistochemical staining for NR1, NR2A/B and PV.Increased expression of NR1 was detected in the giant neurons and dysmorphic neurons in FCD; while pronounced expression of NR2A/B was detected in immature neurons, giant neurons and dysmorphic neurons of FCD, especially in somata and processes of the immature neurons. Compared with the controls, FCD cortices showed prominent scattered arrangement of PV positive neurons and fibers, dramatically decreased number of PV positive interneurons and PV background staining, especially in foci of FCD II subtype.There are increased expressions of NR1 and NR2A/B subunits in FCD abnormal neurons, as well as scattered and reduced expressions of PV positive neurons and fibers in FCD cortices.

To study the expression of P-glycoprotein, multi-drug resistance associated protein and major vault protein in pathologic brain specimens, and to investigate their roles in the pathogenesis of refractory epilepsy.Immunohistochemical study was performed in pathology specimens from 18 cases of refractory epilepsy (including 5 cases of focal cortical dysplasia, 3 cases of tuberous sclerosis, 5 cases of ganglioglioma and 5 cases of dysembryoplastic neuroepithelial tumor).Both the P-glycoprotein and major vault protein were localized in microvascular endothelium of the lesions. Major vault protein was also seen in balloon cells and some neuronal cells. On the other hand, multi-drug resistance associated protein was mainly localized in the neuronal component of the lesions. In general, the expression of P-glycoprotein and major vault protein in tumoral tissue was higher than that in non-tumoral tissue. The expression of multi-drug resistance associated protein and major vault protein was also different in the neoplastic glial cells of ganglioglioma and dysembryoplastic neuroepithelial tumor.P-glycoprotein, multi-drug resistance associated protein and major vault protein contribute to the pathogenesis of refractory epilepsy. They may however have different roles, with different cellular localization.

Neurenteric cysts are uncommon cystic lesions lined by endodermal-derived epithelium, which are rarely found in the CNS, especially in the intracranial region. Although recurrences and disseminations of these cysts have been reported, only one case of intracranial malignant transformation has previously been described. Here we report a cerebellopontine angle neurenteric cyst in a 26-year-old woman. The cyst wall was lined by columnar epithelium with atypical nuclei and high MIB-1 index. In addition, stromal invasion was found in the subepithelial areas, which shows malignant features. Dissemination was speculated on MRI 6 months after total excision of the original cyst.

To study the clinicopathologic features, immunophenotype and histogenesis of dysembryoplastic neuroepithelial tumor (DNT).Fourteen cases of DNT were retrieved from the archival files of the Department. The histopathologic features and immunohistochemical findings were retrospectively studied. The long-term follow-up data were analyzed.Eleven of the 14 cases studied were located in the temporal lobe. Histologically, the tumor consisted of a heterogeneous admixture of neuronal and glial cells (including 1 simple form case, 8 complex form cases and 5 non-specific form cases). The specific glioneuronal element was seen in 9 cases. Variable degrees of cortical dysplasia (CD) were found in 10 out of the 11 cases which had sufficient tissue samples for thorough histologic examination. The morphologic appearance of CD included the presence of heterotopic neurons in molecular layer and/or white matter (7 cases), persistent subpial granular cell layer (4 cases), dyslamination (10 cases) and cellular abnormalities. Immunohistochemically, the oligodendroglial-like cells expressed Olig2. Some of which were positive for nestin, MAP-2, neurofilament and glial fibrillary acidic protein, but negative for NeuN. Long-term follow up revealed that 12 patients had class I postoperative seizure and 2 patients had class II seizure. No tumor recurrence was detected.DNT is frequently associated with CD. The morphologic diagnosis can be confirmed by immunohistochemical study using a panel of antibodies.

To investigate the clinicopathologic features of focal cortical dysplasia (FCD) in patients with refractory epilepsy.The clinical, radiologic and pathologic features of 38 cases of FCD receiving surgical treatment in 2005 were reviewed retrospectively.The mean age of disease onset was 9.2 years. The disease lasted for 11.9 years on average and often presented as complex partial seizure. Radiologic examination revealed hippocampal sclerosis, or abnormal signals in the grey matter in 21 cases. According to Palmini's classification system, the following pathologic subgroups were identified: FCD type IA (3/38), FCD type IB (20/38), FCD type IIA (5/38) and FCD type IIB (5/38). The remaining 5 cases were classified as mild cortical dysplasia. Topographically, FCD type II was often seen in the extratemporal region (8/10), predominantly in the frontal lobe (5/8). Dual pathology was identified only in cases with FCD type IB. Immunohistochemical study showed that the giant neurons, immature neurons and dysmorphic neurons were strongly positive for NeuN. A small number of balloon cells expressed nestin.FCD is a common cause of refractory epilepsy. FCD type IB is the predominant pathologic subtype. Associated hippocampal sclerosis is sometimes seen. Clinicopathologic differences between FCD type I and FCD type II are observed.

To study the loss of heterozygosity (LOH) at chromosomes 1p or 19q in oligodendroglial tumors.Twenty-eight cases of oligodendroglial tumors were enrolled into the study. Real-time quantitative polymerase chain reaction-based microsatellite analysis was performed on paraffin-embedded tumor tissues in order to study the status of chromosomes 1p and 19q.Among the 28 cases of oligodendroglial tumors, 24 cases (85.7%) showed 1p LOH, while 18 cases (64.3%) showed 19q LOH and 17 cases (60.7%) showed LOH of both 1p and 19q. LOH at 1p or 19q was present in 25 (89.3%) of the 28 cases.Real-time quantitative polymerase chain reaction-based microsatellite analysis is a rapid and specific way in detecting LOH in paraffin-embedded tumor tissues. LOH at 1p or 19q is present in majority of the oligodendroglial tumors studied.

Leigh syndrome is a mitochondrial disease of infancy and early childhood and is rare in adults. We report an autopsy case of adult Leigh syndrome of 15 years duration in a 32-year-old man with a familial history of the disease. His initial symptom was clumsiness followed by dullness, and dysphasia and dysarthria appeared in the last 3 months. His brother had similar symptoms and died at the age of 27 years. His sister is also demented. Cranial MRI revealed abnormal signals in the bilateral putamen and tegmentum of the brainstem. Neuropathologically, there were symmetrical, well-demarcated necrotizing lesions with proliferation of capillaries in the putamen, caudate nucleus and thalamus, as well as in the periaqueductal gray matter of the midbrain and tegmentum of the pons. It seems that the lesions in the putamen were more severe and older than those of the brainstem, the latter having numerous macrophage infiltrations. Neuronal loss and gliosis were also observed in the substantia nigra and cerebellar cortex. This is the first autopsy-confirmed familial adult Leigh syndrome in China. The clinicopathological features are presented together with a literature review.

Papillary glioneuronal tumor (PGNT) has recently been identified as a new variant of mixed neuronal-glial tumors. We report the clinical and pathological features of PGNT in two Chinese patients. One patient was a 35-year-old man who suffered from intractable seizures for 16 years. Another was a 26-year-old woman who presented with headache for 2 years. In both patients, magnetic resonance imaging showed well demarcated, mixed cystic and solid tumor in the temporal lobe. Histology of the excised tumors revealed a pseudopapillary architecture surrounded by a glial component and intervening areas were occupied by neuronally differentiated cells. No cortical dysplasia was found in the neighboring cortex in one of them. The glial component showed immunoreactivity with glial fibrillary acidic protein and S-100 protein. Neuronally differentiated cells were immunolabeled by antisynaptophysin, NF, NeuN and MAP2 antibodies. Some small cells surrounding the surface of the pseudopapillae and in the compact area were immunopositive for Olig2. The MIB-1 labeling index was < 3%. The tumor did not recur within the follow-up periods of 50 months and 13 months, and the patient with temporal lobe epilepsy became seizure-free after surgery.