A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies. Methods: We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility. Results: ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-ß and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs. Conclusions: Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS)-Does it Really Exist?

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS) is a rare variant of the CLIPPERS spectrum with less than ten reports published so far. There is ongoing discussion regarding whether SLIPPERS is a disease entity on its own or just an acronym encompassing many underlying diagnoses, such as sarcoidosis, vasculitis and anti-glial fibrillary acidic protein (GFAP)-associated disease. A 40-year-old woman presented with episodes of language and attention impairment. Magnetic resonance imaging (MRI) revealed T2/FLAIR hyperintense lesions in the subcortical white matter associated with a micronodular, curvilinear perivascular contrast-enhancement. Alternative diagnoses were excluded. There was a remarkable response to steroids. A relapse occurred after six years, and the biopsy showed perivascular T-cell lymphocytic infiltrate, without granulomas, vasculitis, or neoplasia. There was complete resolution of the relapse after steroids. This case represents the longest reported follow-up of a patient diagnosed with SLIPPERS, and brain biopsy after 6 years did not suggest alternative diagnoses. This report contributes to the discussion regarding the possibility that exclusive supratentorial CLIPPERS-like pathology might be an isolated disease entity, but more biopsy-proven cases with a longer follow-up are needed to support this hypothesis. Recently, GFAP astrocytopathy has been characterized and might correspond to a significant number of cases previously diagnosed as CLIPPERS or SLIPPERS.

Case Report: Evolutionary Clinical-Radiological Features of a Diffuse Hemispheric Glioma, H3 G34 Mutant with Over 5 Years of Survival.

Diffuse hemispheric glioma (DHG), H3 G34 mutant was included in the 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System recently published. Given the recent inclusion in the current classification and its rarity in adult patients, there are scarce data on clinical-radiological characteristics, survival, and outcome. The authors report the case of a 35-year-old female with DHG, H3 G34-mutant characteristics and outcomes with an unusual presentation, recurrence, and prolonged survival. In conclusion, our case report demonstrates relevant details that should be observed in patients with suspicion or confirmation of the diagnosis of DHG, H3 G34 mutant, not only in the initial presentation but also in the evolution to ensure more personalized treatment.

Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival.

Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohistochemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median peripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.

Crotalphine Attenuates Pain and Neuroinflammation Induced by Experimental Autoimmune Encephalomyelitis in Mice.

Multiple sclerosis (MS) is a demyelinating disease of inflammatory and autoimmune origin, which induces sensory and progressive motor impairments, including pain. Cells of the immune system actively participate in the pathogenesis and progression of MS by inducing neuroinflammation, tissue damage, and demyelination. Crotalphine (CRO), a structural analogue to a peptide firstly identified in Crotalus durissus terrificus snake venom, induces analgesia by endogenous opioid release and type 2 cannabinoid receptor (CB2) activation. Since CB2 activation downregulates neuroinflammation and ameliorates symptoms in mice models of MS, it was presently investigated whether CRO has a beneficial effect in the experimental autoimmune encephalomyelitis (EAE). CRO was administered on the 5th day after immunization, in a single dose, or five doses starting at the peak of disease. CRO partially reverted EAE-induced mechanical hyperalgesia and decreased the severity of the clinical signs. In addition, CRO decreases the inflammatory infiltrate and glial cells activation followed by TNF-α and IL-17 downregulation in the spinal cord. Peripherally, CRO recovers the EAE-induced impairment in myelin thickness in the sciatic nerve. Therefore, CRO interferes with central and peripheral neuroinflammation, opening perspectives to MS control.

Granule cell dispersion is associated with hippocampal neuronal cell loss, initial precipitating injury, and other clinical features in mesial temporal lobe epilepsy and hippocampal sclerosis.

PURPOSE: To characterize a 10-year series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) and determine the histopathological characteristic of the association between granule cell dispersion (GCD) and hippocampal neuronal loss. METHODS: The study included 108 MTLE/HS patients. Histopathological analyses were performed in NeuN-stained hippocampal sections for HS pattern, neuronal density, dentate gyrus (DG) pathology, and granule cell layer width. Statistical tests investigated the association between DG pathologies and HS patterns, as well as the correlation of DG width with total hippocampal and subfield-specific neuronal densities. RESULTS: Fifty-six patients (51.9%) presented right HS. All the four ILAE HS patterns were represented (90 Type 1, 11 Type 2, 2 Type 3, and 5 no-HS). Sixty-seven patients (62.0%) presented GCD, 39 (36.1%) normal DG, and 2 (1.9%) narrow DG. GCD was associated with initial precipitating injury, higher numbers of monthly focal seizures and lifetime bilateral tonic-clonic seizures, longer epilepsy duration, and older age at surgery. GCD was prevalent in all HS patterns, except for Type 2 (81.8% normal versus 18.2% GCD, p = 0.005). GCD was associated with total hippocampal and subfield-specific neuronal loss, except for CA1. DG width correlated with total hippocampal (r = -0.201, p = 0.037) and CA4 neuronal densities (r = -0.299, p = 0.002). Patients with HS Type 1 had better surgical outcomes, with 51 (61.4%) seizure-free in the first year post-surgery. CONCLUSIONS: This study confirmed that seizure control in MTLE/HS patients submitted to surgical treatment is comparable worldwide. Moreover, histopathological analyses showed an association between GCD and hippocampal neuronal loss, especially in the CA4 subfield.

An atypical case of neurotoxoplasmosis in immunocompetent patient.

Toxoplasmosis is an infection caused by Toxoplasma gondii, an intracellular protozoan that is often associated with immunocompromised patients and is rare in immunocompetent. A 60-year-old man was admitted with a history of 2 days of headache and right-sided weakness. There was no history of fever, surgeries, or any other comorbid illness. Cerebrospinal fluid showed just mild pleocytosis with 15 cells/mm3, predominantly lymphomononuclear. MRI showed Peripheral enhancing lesion with central diffusion restriction and perivascular enhancing lesion with restricted diffusion with vasogenic edema and leptomeningeal enhancement in the white matter. Viral serologies, tumor markers, protein electrophoresis were normal. The patient was submitted to brain biopsy, revealing necrotic brain parenchyma with predominantly acute inflammation, with diffuse encephalitis pattern, and cysts with bradyzoites (cystozoites) of Toxoplasma gondii in the brain parenchyma. The central nervous system infection by Toxoplasma gondii can present as meningoencephalitis during primary infection in an immunocompetent, although it is rare. Central nervous system lymphoma is the main differential diagnosis of neurotoxoplasmosis by imaging, especially in our case.

Health-Related Quality of Life in Women with Breast Cancer Undergoing Chemotherapy in Brazil.

INTRODUCTION: Breast cancer (BC) is an austere public health problem, representing the most incident and prevalent malignancy among women worldwide. OBJECTIVE: To evaluate the health-related quality of life of women with breast cancer undergoing initial and final stages of chemotherapy treatment. METHODS: It was descriptive, correlational, analytical, prospective cross-sectional study that included 80 women diagnosed with breast cancer undergoing chemotherapy treatment. Health-related quality of life was assessed in two phases. The first one was on the initial day of the treatment and the second, 120 days after started the chemotherapy. RESULTS: Eighty adult women were part of the study, whose average age was 52.54. Overall quality of life decreased due to chemotherapy. It was noted the negative impact that the emotional role, the sexual function and the concern about hair loss on health-related quality of life. It was observed that fatigue, nausea and vomiting, appetite loss, diarrhea were frequent symptoms in comparison between the phases. Sexual function and satisfaction were dissatisfying and worsened during chemotherapy. CONCLUSION: The quality of life related to the health of patients is negatively influenced during chemotherapy treatment, hence, requiring interventions in oncology and research in this sphere.

Crotalphine attenuates pain and neuroinflammation induced by experimental autoimmune encephalomyelitis in mice

Multiple sclerosis (MS) is a demyelinating disease of inflammatory and autoimmune origin, which induces sensory and progressive motor impairments, including pain. Cells of the immune system actively participate in the pathogenesis and progression of MS by inducing neuroinflammation, tissue damage, and demyelination. Crotalphine (CRO), a structural analogue to a peptide firstly identified in Crotalus durissus terrificus snake venom, induces analgesia by endogenous opioid release and type 2 cannabinoid receptor (CB2) activation. Since CB2 activation downregulates neuroinflammation and ameliorates symptoms in mice models of MS, it was presently investigated whether CRO has a beneficial effect in the experimental autoimmune encephalomyelitis (EAE). CRO was administered on the 5th day after immunization, in a single dose, or five doses starting at the peak of disease. CRO partially reverted EAE-induced mechanical hyperalgesia and decreased the severity of the clinical signs. In addition, CRO decreases the inflammatory infiltrate and glial cells activation followed by TNF-α and IL-17 downregulation in the spinal cord. Peripherally, CRO recovers the EAE-induced impairment in myelin thickness in the sciatic nerve. Therefore, CRO interferes with central and peripheral neuroinflammation, opening perspectives to MS control.

Temporal horns subependymomas: A report of two cases of an intraventricular neoplasm in an atypical location.

Slow-growing intraventricular masses are sometimes imaging findings in asymptomatic patients. The neuroimaging characteristics frequently help making the correct diagnosis and the treatment decision. Subependymomas usually present as single lesions poorly vascularized, without invasion into adjacent brain parenchyma or cerebrospinal fluid dissemination. Ependymoma is considered the main differential diagnosis. We report two cases of this tumour who share the unusual location: The temporal horns. The lack of enhancement (or heterogeneous when present) and advanced neuroimaging techniques can be very useful in differentiating them from other lesions.

Genetic Variants Related to Cell Cycle and Stability of Telomere in Patients with Glioma.

Background: Glioma, most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. Evaluate the association of polymorphisms related of to the cell cycle, integrity and DNA repair with gliomas, as well as lifestyle habits, comorbidities, survival and response to treatment. Methods: Were studied 303 individuals distributed into: Study Group - 100 patients with gliomas, regardless of the degree of malignancy, and Control Group - 203 individuals without clinical signs of the disease. These polymorphisms were genotyped by TaqMan® SNP Genotyping Assay. Significance level was set at 5%. Results: Smoking, alcohol consumption, systemic arterial hypertension (SAH) and diabetes mellitus (DM) prevailed in patients, compared to controls (P=0.0088, P=0.0001, P=0.0001, P=0.0011, respectively). In the logistic regression analysis, alcohol consumption and SAH were identified as independent risk factors for gliomas (P=0.0001, P=0.0027, respectively). Patients with low-grade gliomas showed survival in one year (92.0±6.8%), compared to patients with high-grade gliomas (24.0±5.3; P=0.011). Conclusion: Polymorphisms involved in cell cycle, telomere protection and stability and DNA repair are not associated with gliomas. On the other hand, alcohol consumption and SAH stand out as independent risk factors for the disease. Low-grade gliomas, response to treatment and the combination of chemotherapy with Temozolomide and radiation therapy show increased survival of patients.

The impact of epilepsy duration in a series of patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis.

PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.

Case Report: Clinical Outcome and Image Response of Two Patients With Secondary High-Grade Glioma Treated With Chemoradiation, PCV, and Cannabidiol.

We describe two patients with a confirmed diagnosis of high-grade gliomas (grades III/IV), both presenting with O6-methylguanine-DNA methyltransferase (MGMT) methylated and isocitrate dehydrogenase (IDH-1) mutated who, after subtotal resection, were submitted to chemoradiation and followed by PCV, a multiple drug regimen (procarbazine, lomustine, and vincristine) associated with cannabidiol (CBD). Both patients presented with satisfactory clinical and imaging responses at periodic evaluations. Immediately after chemoradiation therapy, one of the patients presented with an exacerbated and precocious pseudoprogression (PSD) assessed by magnetic resonance imaging (MRI), which was resolved in a short period. The other patient presented with a marked remission of altered areas compared with the post-operative scans as assessed by MRI. Such aspects are not commonly observed in patients only treated with conventional modalities. This observation might highlight the potential effect of CBD to increase PSD or improve chemoradiation responses that impact survival. Further investigation with more patients and critical molecular analyses should be performed.

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis.

OBJECTIVE: The objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. METHODS: The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). RESULTS: There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance - the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001). SIGNIFICANCE: Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS.

Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. METHODS: Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. RESULTS: Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). CONCLUSION: This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS.

Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse.

The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through ß-adrenergic receptors (AR). Here, we wished to define the role played by the ARß3 isoform in this process. This study focused on the ARß3 knockout mice (ARß3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARß3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARß3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARß3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARß3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARß3 inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.

Anaplastic Ganglioglioma of the Pineal Region ­ A Case Report

Introduction Gangliogliomas are tumors commonly found in the temporal lobe and related to seizures; their appearance in the pineal region is rarely described. This report characterizes the first case of anaplastic ganglioglioma of the pineal region. Case Report The authors describe the case of a 32-year-old woman that developed progressive headache. An MRI investigation revealed a pineal tumor. The patient tested negative for biomarkers and underwent surgery through supracerebellar infratentorial approach and achieved gross total resection of the tumor in a challenging location. Pathological analysis revealed a biphasic neoplasm with the following two distinct phenotypes in separate fields: an immature neuronal component with several atypical mitoses and a mature astrocytic component with bipolar cells, microcysts, and eosinophilic bodies. The Ki67/MIB1 proliferation index was 20­30% in localized hotspots. Based on the pathological findings, the tumor was defined as an anaplastic ganglioglioma World Health Organization (WHO) grade III. Discussion/Conclusion Gangliogliomas are classified as glioneural neoplasms based on the histologic findings described as a mixture of neoplastic astrocytes and neurons. Moreover, these tumors represent 0.4­1.3% of tumors of the central nervous system. Authors describe de novo anaplastic ganglioglioma as 1% of the largest series. Gross total resection and adjuvant treatment may play important role in patients' prognostic. In this case, due to the malignant anaplastic component of her tumor, the patient received treatment with temozolamide and radiotherapy after gross total resection of the lesion.

Introdução Gangliogliomas são tumores comumente encontrados no lobo temporal e se relacionam com crises epilépticas; o aparecimento desses tumores na região da pineal é raramente descrito. Este relato caracteriza o primeiro caso de ganglioglioma anaplásico da região da pineal. Relato de Caso Paciente do sexo feminino, 32 anos, apresentou-se com cefaleia de piora progressiva. Investigação com ressonância magnética revelou tumor na região da pineal. Os biomarcadores para tumores da pineal foram negativos e a paciente foi submetida a microcirurgia com o acesso supracerebelar e infratentorial atingindo ressecção total da lesão. A análise patológica revelou neoplasia bifásica com dois fenótipos distintos em campos separados: um componente era composto por células neuronais imaturas com inúmeras mitoses atípicas e o segundo componente era composto por astrócitos maduros, microcistos e corpos eosinofílicos. Foi encontrado um índice proliferativo Ki67/M1B1 de 20­30%. Baseado nos achados anatomopatológicos, o tumor foi definido como ganglioglioma anaplásico grau III da OMS. Discussão/Conclusão Gangliogliomas são classificados como neoplasias glioneurais baseado nos achados histológicos descritos como misto de neoplasia neuronal e glial; esses tumores representam 0,4­1,3% de todos os tumores do sistema nervoso central. Ganglioglioma anaplásico de novo tem sido descrido em 1% nas maiores series de gangliogliomas. Ressecção total da lesão e tratamento adjuvante desempenham um papel importante no prognóstico dos pacientes. Devido ao componente anaplásico do tumor em questão, a paciente foi tratada com temozolamida e radioterapia após ressecção total da lesão.

Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms.

OBJECTIVE: The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer. METHODS: The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases. RESULTS: The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of high-grade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68. CONCLUSION: Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.