RESUMO
Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.
Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical do Grupo I , Malformações do Desenvolvimento Cortical , Consenso , Epilepsia/diagnóstico , Epilepsia/patologia , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico , Neuroimagem , Estudos RetrospectivosRESUMO
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.
Assuntos
Biomarcadores Tumorais/análise , Glioma/metabolismo , Glioma/patologia , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adolescente , Adulto , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/metabolismo , Epilepsia/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Proteínas de Ligação a RNA/genética , Estudos Retrospectivos , Adulto JovemRESUMO
Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Cartilagem/patologia , Glioma/genética , Glioma/patologia , Histonas/genética , Feminino , Humanos , Metaplasia/patologia , Pessoa de Meia-Idade , MutaçãoRESUMO
OBJECTIVE: Microglial abnormalities have been reported in pathologic specimens from patients with tuberous sclerosis complex (TSC), a genetic disorder characterized by epilepsy, intellectual disability, and autism. However, the pathogenic role of microglia in epilepsy in TSC is poorly understood, particularly whether microglia defects may be a primary contributor to epileptogenesis or are secondary to seizures or simply epiphenomena. In this study, we tested the hypothesis that Tsc1 gene inactivation in microglia is sufficient to cause epilepsy in mouse models of TSC. METHODS: Using a chemokine receptor, Cx3cr1, to target microglia, conventional Tsc1Cx3cr1-Cre CKO (conditional knockout) mice and postnatal-inducible Tsc1Cx3cr1-CreER CKO mice were generated and assessed for molecular and histopathologic evidence of microglial abnormalities, mechanistic target of rapamycin 1 (mTORC1) pathway activation, and epilepsy. RESULTS: Tsc1Cx3cr1-Cre CKO mice exhibited a high efficiency of microglia Tsc1 inactivation, mTORC1 activation, increased microglial size and number, and robust epilepsy, which were rapamycin-dependent. However, Cre reporter studies demonstrated that constitutive Cx3cr1 expression affected not only microglia, but also a large percentage of cortical neurons, confounding the role of microglia in epileptogenesis in Tsc1 Cx3cr1-Cre CKO mice. In contrast, postnatal inactivation of Tsc1 utilizing a tamoxifen-inducible Cx3cr1-CreER resulted in a more-selective microglia Tsc1 inactivation with high efficiency, mTORC1 activation, and increased microglial size and number, but no documented epilepsy. SIGNIFICANCE: Microglia abnormalities may contribute to epileptogenesis in the context of neuronal involvement in TSC mouse models, but selective Tsc1 gene inactivation in microglia alone may not be sufficient to cause epilepsy, suggesting that microglia have more supportive roles in the pathogenesis of seizures in TSC.
Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Microglia/patologia , Esclerose Tuberosa/patologia , Esclerose Tuberosa/fisiopatologia , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Antagonistas de Estrogênios/farmacologia , Regulação da Expressão Gênica/genética , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fosfopiruvato Hidratase/metabolismo , Sirolimo/farmacologia , Estatísticas não Paramétricas , Tamoxifeno/farmacologia , Esclerose Tuberosa/tratamento farmacológico , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo , Gravação em VídeoRESUMO
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.
Assuntos
Epilepsia/patologia , Malformações do Desenvolvimento Cortical/patologia , Lobo Occipital/patologia , Adolescente , Criança , Epilepsia/classificação , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Feminino , Humanos , Hipóxia-Isquemia Encefálica , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Lobo Occipital/cirurgia , Estudos Retrospectivos , Adulto JovemRESUMO
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 BRAF(V600E) 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.
Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Glioma/patologia , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Adulto , Astrocitoma/genética , Gânglios da Base/patologia , Neoplasias Encefálicas/genética , Feminino , Quarto Ventrículo/patologia , Glioma/genética , Humanos , Masculino , Neoplasias Neuroepiteliomatosas/genética , Lobo Parietal/patologia , Estudos Retrospectivos , Formação de Roseta , Adulto JovemRESUMO
AIMS: 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. METHODS: The clinical data and clinicopathological findings of nine cases with AG histological features were described. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Adolescente , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/complicações , Criança , Pré-Escolar , Epilepsia/etiologia , Feminino , Glioma/complicações , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
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.
Assuntos
Neoplasias do Ventrículo Cerebral/diagnóstico , Glioma/diagnóstico , Terceiro Ventrículo/patologia , Adulto , Neoplasias do Ventrículo Cerebral/cirurgia , Neoplasias do Plexo Corióideo/diagnóstico , Neoplasias do Plexo Corióideo/cirurgia , Feminino , Glioma/cirurgia , Humanos , Pessoa de Meia-Idade , Papiloma do Plexo Corióideo/diagnóstico , Papiloma do Plexo Corióideo/cirurgia , Terceiro Ventrículo/cirurgiaRESUMO
Focal Cortical Dysplasia (FCD) is a frequent cause of drug-resistant focal epilepsy in children and young adults. The international FCD classifications of 2011 and 2022 have identified several clinico-pathological subtypes, either occurring isolated, i.e., FCD ILAE Type 1 or 2, or in association with a principal cortical lesion, i.e., FCD Type 3. Here, we addressed the DNA methylation signature of a previously described new subtype of FCD 3D occurring in the occipital lobe of very young children and microscopically defined by neuronal cell loss in cortical layer 4. We studied the DNA methylation profile using 850 K BeadChip arrays in a retrospective cohort of 104 patients with FCD 1 A, 2 A, 2B, 3D, TLE without FCD, and 16 postmortem specimens without neurological disorders as controls, operated in China or Germany. DNA was extracted from formalin-fixed paraffin-embedded tissue blocks with microscopically confirmed lesions, and DNA methylation profiles were bioinformatically analyzed with a recently developed deep learning algorithm. Our results revealed a distinct position of FCD 3D in the DNA methylation map of common FCD subtypes, also different from non-FCD epilepsy surgery controls or non-epileptic postmortem controls. Within the FCD 3D cohort, the DNA methylation signature separated three histopathology subtypes, i.e., glial scarring around porencephalic cysts, loss of layer 4, and Rasmussen encephalitis. Differential methylation in FCD 3D with loss of layer 4 mapped explicitly to biological pathways related to neurodegeneration, biogenesis of the extracellular matrix (ECM) components, axon guidance, and regulation of the actin cytoskeleton. Our data suggest that DNA methylation signatures in cortical malformations are not only of diagnostic value but also phenotypically relevant, providing the molecular underpinnings of structural and histopathological features associated with epilepsy. Further studies will be necessary to confirm these results and clarify their functional relevance and epileptogenic potential in these difficult-to-treat children.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Displasia Cortical Focal , Malformações do Desenvolvimento Cortical , Criança , Adulto Jovem , Humanos , Pré-Escolar , Estudos Retrospectivos , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/genética , Metilação de DNA , Epilepsia/genética , Epilepsia Resistente a Medicamentos/patologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: To investigate the clinical and radiological characteristics of cortical vein thrombosis for early diagnosis and treatment. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Veias Cerebrais , Trombose Intracraniana/diagnóstico , Trombose Venosa/diagnóstico , Adulto , Fatores Etários , Córtex Cerebral/irrigação sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: PI3K pathway, at least in part, involves in the occurrence of MCD, and may play an important role in the pathogenesis.
Assuntos
Epilepsia/metabolismo , Malformações do Desenvolvimento Cortical/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Proteínas de Ciclo Celular , Criança , Epilepsia/patologia , Feminino , Ganglioglioma/metabolismo , Ganglioglioma/patologia , Humanos , Masculino , Malformações do Desenvolvimento Cortical/patologia , Fosfoproteínas/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Esclerose Tuberosa/metabolismo , Esclerose Tuberosa/patologia , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To investigate the immunohistochemical expression of isocitrate dehydrogenase 1 gene (IDH1) R132H in glioma and its diagnostic utility. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioma/metabolismo , Glioma/patologia , Isocitrato Desidrogenase/metabolismo , Adolescente , Adulto , Idoso , Astrocitoma/metabolismo , Astrocitoma/patologia , Criança , Diagnóstico Diferencial , Feminino , Gliose/metabolismo , Gliose/patologia , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Mutação , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To investigate the diagnostic significance of D2-40 and annexin-1 in the ependymal tumors. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Anexina A1/metabolismo , Neoplasias Encefálicas/diagnóstico , Ependimoma/diagnóstico , Glicoproteínas de Membrana/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Ependimoma/metabolismo , Ependimoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Mucina-1/metabolismo , Papiloma do Plexo Corióideo/diagnóstico , Papiloma do Plexo Corióideo/metabolismo , Papiloma do Plexo Corióideo/patologia , Adulto JovemRESUMO
OBJECTIVE: To study the clinicalpathologic features of intracranial multiple lesions. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , Neoplasias Neuroepiteliomatosas/diagnóstico , Toxoplasmose Cerebral/diagnóstico , Tuberculose do Sistema Nervoso Central/diagnóstico , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Criança , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/cirurgia , Feminino , Glioma/patologia , Glioma/cirurgia , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/patologia , Histiocitose Sinusal/cirurgia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/cirurgia , Estudos Retrospectivos , Toxoplasmose Cerebral/patologia , Toxoplasmose Cerebral/cirurgia , Tuberculose do Sistema Nervoso Central/patologia , Tuberculose do Sistema Nervoso Central/cirurgia , Adulto JovemRESUMO
Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.
Assuntos
Degeneração Lobar Frontotemporal/complicações , Doença dos Neurônios Motores/complicações , Transtornos Parkinsonianos/complicações , Tauopatias/complicações , Adulto , Idoso , Astrócitos/metabolismo , Astrócitos/patologia , Astrócitos/ultraestrutura , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/ultraestrutura , Citoplasma/metabolismo , Citoplasma/patologia , Citoplasma/ultraestrutura , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/patologia , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Emaranhados Neurofibrilares/ultraestrutura , Neuroglia/metabolismo , Neuroglia/patologia , Neuroglia/ultraestrutura , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/ultraestrutura , Tauopatias/metabolismo , Tauopatias/patologia , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
OBJECTIVE: To study the immunohistochemical expression and diagnostic significance of CD34 in brain tumors of patients with refractory epilepsy. METHODS: 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. RESULTS: 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. CONCLUSIONS: CD34 preferred to staining for GG and PXA. Which represent a valuable tool for distinguishing GG, PXA and DNT, oligoastrocytoma, glioblastoma.
Assuntos
Antígenos CD34/metabolismo , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Epilepsia/etiologia , Ganglioglioma/metabolismo , Neoplasias Neuroepiteliomatosas/metabolismo , Astrocitoma/complicações , Astrocitoma/patologia , Astrocitoma/cirurgia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Diagnóstico Diferencial , Ganglioglioma/complicações , Ganglioglioma/patologia , Ganglioglioma/cirurgia , Glioblastoma/complicações , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/cirurgiaRESUMO
OBJECTIVE: To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes. METHODS: A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF. RESULTS: Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05). CONCLUSIONS: Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Neurônios/imunologia , Neurônios/patologia , Teratoma/imunologia , Teratoma/patologia , Adolescente , Adulto , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoantígenos/metabolismo , Feminino , Humanos , Masculino , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/imunologia , Receptores de N-Metil-D-Aspartato/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
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.
Assuntos
Ângulo Cerebelopontino/patologia , Defeitos do Tubo Neural/patologia , Adulto , Antígeno Carcinoembrionário/análise , Núcleo Celular/patologia , Epitélio/metabolismo , Epitélio/patologia , Feminino , Proteína Glial Fibrilar Ácida/análise , Humanos , Imuno-Histoquímica , Queratinas/análise , Imageamento por Ressonância Magnética , Mitose , Mucina-1/análise , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/cirurgia , Proteínas S100/análiseRESUMO
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.