Pilocytic astrocytoma in adults: Histopathological, immunohistochemical and molecular study with clinical association.

Pilocytic astrocytoma is the most common primary CNS neoplasm in children and adolescents, rare after the first two decades of life. While some authors report a favorable prognosis in the adult age group with the tumor, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. This work investigated genetic alterations involving the 7q34 region in BRAF gene in 21 adult individuals with pilocytic astrocytoma, by FISH. In addition, was identified the immunohistochemical expression of BRAFV600E, correlating these findings with histopathological and clinical ones. BRAF-KIAA1549 fusion appeared in only one case, while in two other cases were found deletions related to the FAM131B-BRAF fusion, suggesting that maybe the latter is more frequently in this population. Through the evaluation of immunoreactivity, 71% of the cases were considered positive and 29% negative. Cases considered positive for BRAFV600E immunoreactivity can potentially be treated through drug therapy with BRAF inhibitors; however, it is always recommended to carry out a molecular study for diagnostic confirmation. This is the first Brazilian study that aimed to investigate possible genetic alterations in the BRAF gene in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals.

Pathophysiological evaluation of pilocytic astrocytoma in adults: Histopathological and immunohistochemical analysis.

Pilocytic astrocytoma is a central nervous system tumor of slow growth, which represents 5 % of all gliomas and most often develops in the cerebellum (42-60 %), but can also arise in other neural areas, such as the optic pathway or hypothalamus (9-30 %); brainstem (9 %); spinal cord (2 %). In the pediatric population, this tumor is the second most common cause of neoplasms and, on the other hand, in adults, it is often rare, probably due to its aggressiveness in these individuals. Studies reveal that the origin of pilocytic astrocytoma is characterized by a fusion between the BRAF gene and the KIAA1549 locus, and the application of the immunohistochemistry technique for the analysis of BRAF protein expression can be a valuable tool for diagnostic purposes. Due to the relative rarity of this disease in adults, there are few publications on the most effective diagnostic and treatment strategies for this tumor. The general objective of this study was to analyze the histopathological and immunohistochemical characteristics of pilocytic astrocytoma in these patients. For this, a retrospective study of patients aged over 17 years with a diagnosis of pilocytic astrocytoma was carried out at the Department of Pathology of UNIFESP/EPM, from 1991 to 2015. In order to define BRAF positivity in the immunohistochemical analysis, at least three consecutive fields with more than 50 % immunostaining were used as criteria and, thus, it was inferred that the 7 cases analyzed were considered positive for the cytoplasmic marker BRAF V600E. Histopathological analysis associated with BRAF immunostaining is of paramount importance as a diagnostic method in these cases. However, future molecular studies will be necessary both for a better understanding of the aggressiveness and prognostic of this tumor and for research involving specific therapies for pilocytic astrocytoma in adults.

The involvement of the MAPK pathway in pilocytic astrocytomas.

Pilocytic astrocytomas are the primary tumors most found in the first two decades of life, accounting for around 15% of all brain tumors. Research at the molecular level of pilocytic astrocytoma makes possible to compose an overview of what is known about the origin and development of the tumor. It is known that there are alterations in the Mitogen Activated Protein Kinase (MAPK) signaling pathway that are important auxiliary markers in diagnosis. This study seeks to list the main points about the involvement of this pathway in tumor formation in pilocytic astrocytoma. A review was conducted in search of published studies available in NCBI, PubMed, MEDLINE, Scielo and Google Scholar. The most frequent alteration is the gene fusion between BRAF and KIAA1549 genes, found in approximately 90% of pediatric cases. The second most common event is the BRAFV600E mutation, also often found in children than in adult cases. The molecular origin of pilocytic astrocytomas is related to alterations in the MAPK pathway, which acts with several functions in the brain such as memory formation, pain perception, induction of cortical neurogenesis, and midbrain and cerebellum development. Alterations in this pathway can be therapeutic targets in the treatment of patients with pilocytic astrocytoma. The MAPK pathway is extremely important and knowledge about its involvement in astrocytic tumors is essential for a better approach to the patient.

Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study.

PURPOSE: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. METHODS: It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. RESULTS: The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ([Formula: see text] + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. CONCLUSION: We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.

Meningiomas: A review of general, histopathological, clinical and molecular characteristics.

OBJECTIVES: In this review, the main histological and molecular characteristics of meningiomas will be addressed, as well as the aspects most related to clinical conditions, treatment, and survival of patients, enabling a better understanding of these tumors behavior. METHODS: This study was conducted with the search for published studies available on NCBI, PubMed, MEDLINE, Scielo and Google Scholar. Relevant documents have been identified and 50 articles were selected. RESULTS: The main points about meningiomas were characterized, as well as the histological presence of spontaneous necrosis in grade I and brain invasion as diagnostic criteria, their molecular origin related to deletion of chromosome 22 and mutations in theNF2 and TERT genes, in addition to their clinical characteristics. The preferential treatment remains the total resection of the tumor. CONCLUSION: The information about meningiomas is well known and necessary, but it is expected that more work will emerge related to the behavior of these tumors, and that the scientific community will obtain more clarity about the best ways to conduct the patients treatment.

Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup.

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MBSHH, MBWNT, MBGRP3, or MBGRP4). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, TP53 mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90%) were classified into MBSHH (47.7%), MBWNT (16.1%), MBGRP3 (15.4%), and MBGRP4 (20.8%). GNAS presented the highest expression levels, with higher expression in MBSHH. TP53, MYCN, SOX2, and MET were also up-regulated in MBSHH, whereas PTEN was up-regulated in MBGRP4. GNAS, TP53, and PTEN low expression was associated with the unfavorable patient outcome only for MBSHH (P = 0.04, P = 0.01, and P = 0.02, respectively). TP53 mutations were detected in 28.57% of MBSHH cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of GNAS, TP53, and PTEN improves the patient prognostication in MBSHH subgroup and can be easily incorporated in the 22-gene panel without any additional costs.

Grade I meningiomas with atypical characteristics: a worse prognosis.

OBJECTIVE: The study reviewed the histology of cases of grade I meningiomas with spontaneous necrosis, grade I without necrosis and grade II meningiomas, to evaluate the histological and immunohistochemical factors of the patients' prognosis, while correlating the clinicopathological features with the clinical follow-up of the patients. METHODS: A review of 47 cases from the Department of Pathology of UNIFESP was performed and the samples were submitted to immunohistochemical examination with the p53 protein, Ki-67 cell proliferation factor and progesterone receptor markers. RESULTS: A greater expression was found in the progression of several degrees of aggressiveness for p53 and Ki-67, and a higher frequency of progesterone receptors in the lower degrees. CONCLUSIONS: The group of grade I meningiomas with spontaneous necrosis showed histological and immunohistochemical indexes that approximate those of the grade II meningioma. This suggests a worse prognosis for grade I meningiomas with necrosis.

Grade I meningiomas with atypical characteristics: a worse prognosis / Meningiomas grau I com características atípicas: um pior prognóstico

ABSTRACT The study reviewed the histology of cases of grade I meningiomas with spontaneous necrosis, grade I without necrosis and grade II meningiomas, to evaluate the histological and immunohistochemical factors of the patients' prognosis, while correlating the clinicopathological features with the clinical follow-up of the patients. A review of 47 cases from the Department of Pathology of UNIFESP was performed and the samples were submitted to immunohistochemical examination with the p53 protein, Ki-67 cell proliferation factor and progesterone receptor markers. A greater expression was found in the progression of several degrees of aggressiveness for p53 and Ki-67, and a higher frequency of progesterone receptors in the lower degrees. The group of grade I meningiomas with spontaneous necrosis showed histological and immunohistochemical indexes that approximate those of the grade II meningioma. This suggests a worse prognosis for grade I meningiomas with necrosis.

RESUMO O objetivo do estudo foi realizar a revisão histológica de casos de meningiomas grau I com necrose espontânea, grau I sem necrose e grau II para avaliar os fatores histológicos e imunohistoquímicos de prognóstico dos pacientes, correlacionando informações no âmbito clínico-patológico com o seguimento clínico dos pacientes. Foi realizada revisão de 47 casos do Departamento de Patologia da UNIFESP e as amostras foram submetidas a exame imunohistoquímico com os marcadores proteína p53, fator de proliferação celular Ki-67 e receptor de progesterona. Verificou-se maior expressão na progressão dos diversos graus de agressividade para p53 e Ki-67 e maior frequência de receptores de progesterona nos menores graus. O grupo dos meningiomas grau I com necrose espontânea apresentou índices histológicos e imuno-histoquímicos que se aproximam dos meningiomas grau II. Isto sugere um pior prognóstico dos meningiomas grau I com necrose.

Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma.

Medulloblastoma is the most frequent malignant brain tumor in children. Four medulloblastoma molecular subgroups, MBSHH , MBWNT , MBGRP3 and MBGRP4 , have been identified by integrated high-throughput platforms. Recently, a 22-gene panel NanoString-based assay was developed for medulloblastoma molecular subgrouping, but the robustness of this assay has not been widely evaluated. Mutations in the gene for human telomerase reverse transcriptase (hTERT) have been found in medulloblastomas and are associated with distinct molecular subtypes. This study aimed to implement the 22-gene panel in a Brazilian context, and to associate the molecular profile with patients' clinical-pathological features. Formalin-fixed, paraffin-embedded (FFPE) medulloblastoma samples (n = 104) from three Brazilian centers were evaluated. Expression profiling of the 22-gene panel was performed by NanoString and a Canadian series (n = 240) was applied for training phase. hTERT mutations were analyzed by PCR followed by direct Sanger sequencing and the molecular profile was associated with patients' clinicopathological features. Overall, 65% of the patients were male, average age at diagnosis was 18 years and 7% of the patients presented metastasis at diagnosis. The molecular classification was attained in 100% of the cases, with the following frequencies: MBSHH (n = 51), MBWNT (n = 19), MBGRP4 (n = 19) and MBGRP3 (n = 15). The MBSHH and MBGRP3 subgroups were associated with older and younger patients, respectively. The MBGRP4 subgroup exhibited the lowest 5-year cancer-specific overall survival (OS), yet in the multivariate analysis, only metastasis at diagnosis and surgical resection were associated with OS. hTERT mutations were detected in 29% of the cases and were associated with older patients, increased hTERT expression and MBSHH subgroup. The 22-gene panel provides a reproducible assay for molecular subgrouping of medulloblastoma FFPE samples in a routine setting and is well-suited for future clinical trials.

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation.

High grade gliomas (HGG) are one of the leading causes of cancer-related deaths in children, and there is increasing evidence that pediatric HGG may harbor distinct molecular characteristics compared to adult tumors. We have sought to clarify the role of microsatellite instability (MSI) in pediatric versus adult HGG. MSI status was determined in 144 patients (71 pediatric and 73 adults) using a well established panel of five quasimonomorphic mononucleotide repeat markers. Expression of MLH1, MSH2, MSH6 and PMS2 was determined by immunohistochemistry, MLH1 was assessed for mutations by direct sequencing and promoter methylation using MS-PCR. DNA copy number profiles were derived using array CGH, and mutations in eighteen MSI target genes studied by multiplex PCR and genotyping. MSI was found in 14/71 (19.7%) pediatric cases, significantly more than observed in adults (5/73, 6.8%; p = 0.02, Chi-square test). MLH1 expression was downregulated in 10/13 cases, however no mutations or promoter methylation were found. MSH6 was absent in one pediatric MSI-High tumor, consistent with an inherited mismatch repair deficiency associated with germline MSH6 mutation. MSI was classed as Type A, and associated with a remarkably stable genomic profile. Of the eighteen classic MSI target genes, we identified mutations only in MSH6 and DNAPKcs and described a polymorphism in MRE11 without apparent functional consequences in DNA double strand break detection and repair. This study thus provides evidence for a potential novel molecular pathway in a proportion of gliomas associated with the presence of MSI.

EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines.

PURPOSE: The epidermal growth factor receptor (EGFR) is amplified and overexpressed in adult glioblastoma, with response to targeted inhibition dependent on the underlying biology of the disease. EGFR has thus far been considered to play a less important role in pediatric glioma, although extensive data are lacking. We have sought to clarify the role of EGFR in pediatric high-grade glioma (HGG). EXPERIMENTAL DESIGN: We retrospectively studied a total of 90 archival pediatric HGG specimens for EGFR protein overexpression, gene amplification, and mutation and assessed the in vitro sensitivity of pediatric glioma cell line models to the small-molecule EGFR inhibitor erlotinib. RESULTS: Amplification was detected in 11% of cases, with corresponding overexpression of the receptor. No kinase or extracellular domain mutations were observed; however, 6 of 35 (17%) cases harbored the EGFRvIII deletion, including two anaplastic oligodendrogliomas and a gliosarcoma overexpressing EGFRvIII in the absence of gene amplification and coexpressing platelet-derived growth factor receptor alpha. Pediatric glioblastoma cells transduced with wild-type or deletion mutant EGFRvIII were not rendered more sensitive to erlotinib despite expressing wild-type PTEN. Phosphorylated receptor tyrosine kinase profiling showed a specific activation of platelet-derived growth factor receptor alpha/beta in EGFRvIII-transduced pediatric glioblastoma cells, and targeted coinhibition with erlotinib and imatinib leads to enhanced efficacy in this model. CONCLUSIONS: These data identify an elevated frequency of EGFR gene amplification and EGFRvIII mutation in pediatric HGG than previously recognized and show the likely necessity of targeting multiple genetic alterations in the tumors of these children.

Spinal cord compression secondary to epidural bilharzioma: case report.

A case of an epidural granuloma due to Schistosoma mansoni compressing the spinal cord at T7-T9 is presented. The patient, a 35-year-old Brazilian man, started complaining of recurrent back pain since 2003. A magnetic resonance imaging (MRI) scan showed a large epidural mass extending from T7 to T9 and causing mild spinal cord compression. Through a bilateral laminectomy the bilharzioma was subtotally removed without significant bleeding. The histopathology confirmed the diagnosis of granuloma due to S. mansoni. The patient recovered completely. Although the MRI is nonspecific, this differential diagnosis should be included in homogeneous epidural lesions without bone involvement, more than ever in endemic countries or during the evaluation of travelers to those regions.

Clinical features and surgical outcome of patients with indolent brain tumors and epilepsy

INTRODUCTION: In this study the authors review the outcomes of 22 patients with medically refractory epilepsy and slow growth brain tumors. OBJECTIVES: Evaluate the clinical, electrophysiological, operative, and histopathological features. PATIENTS AND RESULTS: The majority of the tumors were located in the temporal lobe (n = 20) and involved the cortical gray matter. The most frequent tumors were gangliogliomas (n = 9), astrocytomas grade I and II (n = 6), dysembryoplastic neuroepithelial tumors (n = 5) and ganglioneuroma (n = 2). The biological behavior of the tumors was strikingly indolent, as indicated by a long preoperative history of chronic seizures (mean, 14 years). Mean follow-up time after resection was 27 months, and according to EngelÆs classification, 85 percent were seizure-free, 10 percent showed a reduction of seizure frequency of at least 90 percent, and 5 percent had reduction in seizure frequency at least 75 percent. CONCLUSION: The data indicate that neoplasms associated with pharmacoresistent epilepsy constitute a distinct clinicopathological group of tumors that arise in young patients, involve the cortex, and exhibit indolent biological behavior for many years. Complete surgical removal of these tumors, including the epileptogenic area, can achieve excellent seizure control.

INTRODUÇÃO: Neste estudo os autores avaliaram retrospectivamente 22 pacientes tratados cirurgicamente com diagnóstico de epilepsia refratária e tumor cerebral de crescimento lento. OBJETIVOS: Avaliar os aspectos clínicos, eletrofisiológicos, cirúrgicos e histopatológicos. PACIENTES E RESULTADOS: A maioria dos tumores estava localizada no lobo temporal (n = 20) com envolvimento da substância cinzenta. Ganglioglioma foi o tumor mais frequente (n = 9), seguido do astrocitoma grau I e II OMS (n = 6), tumor neuroepitelial disembrioplástico (DNET) (n = 5) e ganglioneuroma (n = 2). O comportamento biológico dos tumores foi estritamente indolente como indicado pela longa história pré-operatória de (média, 14 anos). O tempo de acompanhamento pós-operatório médio foi de 27 meses e de acordo com a Classificacão de Engel, 85 por cento ficaram sem crises (Classe I), 10 por cento obtiveram redução maior de 90 por cento das crises (Classe II), e 5 por cento tiveram redução menor que 75 por cento (Classe III). CONCLUSÃO: Os dados indicam que neoplasias associadas à epilepsia crônica refratária constituem um grupo de tumores com características clinico-patológicas distintas que se iniciam em pacientes jovens, envolvem o córtex e apresentam comportamento biológico indolente. A ressecção cirúrgica completa destes tumores, incluindo a zona epileptogênica, levou ao controle total das crises na maior parte dos casos estudados.

Immunohistochemical expression of p16(INK4A) in normal uterine cervix, nonneoplastic epithelial lesions, and low-grade squamous intraepithelial lesions.

OBJECTIVES: In this study, the authors analyzed the immunoexpression of p16 in high-risk human papillomavirus DNA-negative normal and nonneoplastic cervical epithelia, in low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, and squamous cell carcinoma. MATERIALS AND METHODS: A retrospective study, in which 58 normal cervical hysterectomy samples, 56 nonneoplastic cervical biopsies, 88 CIN 1, 33 CIN 2, 32 CIN 3, and 47 invasive squamous cell carcinoma biopsies, were evaluated for p16 immunoexpression. Human papillomavirus tests were also performed. RESULTS: p16 immunohistochemistry seems to reveal possible different biological subgroups of lesions among morphologically similar mildly dysplastic cervical epithelia. CONCLUSION: Distribution patterns of p16 protein might be useful to predict different outcomes in CIN 1.

Metaphase and array comparative genomic hybridization: unique copy number changes and gene amplification of medulloblastomas in South America.

Tumors of the central nervous system are the second most frequent malignancy of childhood, accounting for the majority of cancer-related deaths in this age group. Among these tumors, medulloblastomas (MB) remain in need of further genomic characterization toward understanding of pathogenesis and outcome predictors. Eight pediatric embryonal brain tumors were analyzed: five MB (one being desmoplastic), one PNET, one medulloepithelioma, and one ependymoblastoma. Analyses identified genomic imbalances, including the gain of 16p and the nonsyntenic coamplification of MYCN and TERT loci. More detailed FISH analysis showed that coamplification of MYCN and TERT in one of the MBs manifested as dispersed nuclear speckling, consistent with the presence of double minute chromosomes. There was considerable cell-to-cell copy number heterogeneity present, but it was clear that both genes were amplified concordantly. The amplification of oncogenes seems to play an important role in the pathogenesis of MB, and the association between MYCN and TERT amplifications and poor prognosis has not been well recognized. The uncharacteristic pattern of genomic imbalances detected in MB tumors may be a reflection of the characteristics of these tumors occurring in South America.

Gemistocytes in astrocytomas: are they a significant prognostic factor?

Our aim was to retrospectively evaluate the influence of gemistocytic astrocytes, cellular proliferation indices, immunoexpression of proteins p53 and bcl-2 in the clinical outcome of 39 patients with WHO grade II and III astrocytomas with the presence of gemistocytes. The mean proportion of gemistocytes was 18.7% and the mean proliferative index was 3.3%. Immunoexpression of p53 was detected in 29 cases (74.4%) and all cases (100%) were positive for bcl-2. The median overall survival was 97.2 months and the progression-free survival was 43.1 months. Estimated 1-, 5- and 10-year overall survival rates were 94.3%, 69.5% and 46.4%; 1-, 5- and 10-year progression-free survival rates were 91.1%, 26.1% and 13.1%. Out of 24 who presented clinical and neuroimaging worsening, characterized as tumor progression or recurrence, 16 had histological confirmation and were also analyzed. We could not detect significant differences when comparing all the indices between WHO grade II and III and also between the first and second biopsies. We also could not detect significant differences in progression-free and overall survival when analyzing the gemistocyte index and the immunohistochemical labeling indices p53, bcl-2 and MIB-1, as well as patientsa9 age (median value, up to 34 vs. over 34 years) and histological grade (II or III). Our finding confirms recent reports that question the role of gemistocytes as a prognostic factor in diffuse astrocytomas. The significance and role of gemistocytes in astrocytomas has yet to be defined and warrants further study.

Mild hypothermia reduces polymorphonuclear leukocytes infiltration in induced brain inflammation.

Over the last 50 years deep hypothermia (23 degrees C) has demonstrated to be an excellent neuroprotective agent in cerebral ischemic injury. Mild hypothermia (31-33 degrees C) has proven to have the same neuroprotective properties without the detrimental effects of deep hypothermia. Mechanisms of injury that are exaggerated by moderate hyperthermia and ameliorated by hypothermia include, reduction of oxygen radical production, with peroxidase damage to lipids, proteins and DNA, microglial activation and ischemic depolarization, decrease in cerebral metabolic demand for oxygen and reduction of glycerin and excitatory amino acid (EAA) release. Studies have demonstrated that inflammation potentiates cerebral ischemic injury and that hypothermia can reduce neutrophil infiltration in ischemic regions. To further elucidate the mechanisms by which mild hypothermia produces neuroprotection in ischemia by attenuating the inflammatory response, we provoked inflammatory reaction, in brains of rats, dropping a substance that provokes a heavy inflammatory reaction. Two groups of ten animals underwent the same surgical procedure: the skull bone was partially removed, the duramater was opened and an inflammatory substance (5% carrageenin) was topically dropped. The scalp was sutured and, for the group that underwent neuroprotection, an ice bag was placed covering the entire skull surface, in order to maintain the brain temperature between 29.5-31 degrees C during 120 minutes. After three days the animals were sacrificed and their brains were examined. The group protected by hypothermia demonstrated a remarkable reduction of polymorphonuclear leukocytes (PMNL) infiltration, indicating that mild hypothermia can have neuroprotective effects by reducing the inflammatory reaction.

MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas.

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) measurements derived from perfusion-weighted imaging (PWI) may be useful to evaluate angiogenesis and preoperatively estimate the grade of a glioma. We hypothesized that rCBV is correlated with vascular endothelial growth factor (VEGF) expression as marker of the angiogenic stimulus in presumed supratentorial low-grade gliomas (LGGs). METHODS: From February 2001 to February 2004, we examined 20 adults (16 men, four women; mean age 36 years; range, 23-60 years) with suspected (nonenhancing) supratentorial LGG on conventional MR imaging. Preoperative MR imaging used a dynamic first-pass gadolinium-enhanced, spin-echo echo-planar PWI. In heterogeneous tumors, we performed stereotactic biopsy in the high-perfusion areas before surgical resection. Semiquantitative grading of VEGF immunoreactivity was applied. RESULTS: Nine patients had diffuse astrocytomas (World Health Organization grade II), and 11 had other LGG and anaplastic gliomas. In patients with heterogeneous tumors on PWI, the high-rCBV focus had areas of oligodendroglioma or anaplastic astrocytoma on stereotactic biopsy, whereas the surgical specimens were predominantly astrocytomas. Anaplastic gliomas had high rCBV ratios and positive VEGF immunoreactivity. Diffuse astrocytomas had negative VEGF expression and mean rCBV values significantly lower than those of the other two groups. Three diffuse astrocytomas had positive VEGF immunoreactivity and high rCBV values. CONCLUSION: Our results confirmed the correlation among rCBV measurements, VEGF expression, and histopathologic grade in nonenhancing gliomas. PWI may add useful data to the preoperative assessment of nonenhancing gliomas. Its contribution in predicting tumor behavior and patient prognosis remains to be determined.

Human papillomavirus DNA detection in male sexual partners of women with genital human papillomavirus infection.

OBJECTIVES: To determine the prevalence of human papillomavirus (HPV) DNA in the male partners of HPV-infected women, assess the concordance of the viral group in the infected pair, define the most affected sites in the male genitalia, and compare diagnostic methods in men. METHODS: Fifty male, stable sexual partners of women positive for HPV DNA by the Hybrid Capture 2 (hc2) test had material brushed from six different anogenital areas for hc2 testing. One week later, patients underwent classic peniscopy, and the lesions were biopsied for histologic analysis and hc2 testing. RESULTS: The brushings were HPV DNA positive in 35 (70%) of the 50 men: 32% in the high-risk HPV group, 14% in the low-risk HPV group, and 24% in both groups. HPV detection per anatomic site was 24% in the glans, 44% in the prepuce internal surface, 30% in the distal urethra, 24% in the prepuce external surface, 12% in the scrotum, and 8% in the anus. Acetowhite lesions were seen in 44 (88%) of the 50 patients. Overall, HPV DNA was detected in 27 (26%) of the 104 biopsy specimens, but histologic examination showed evidence of HPV infection in only 14 (13.5%) of 104 biopsy specimens. In 3 (6%) of 50 patients, hc2 was positive only in the histologic examination. Overall, the prevalence of detectable high-risk HPV DNA among male partners was 60% (30 of 50). CONCLUSIONS: Of the 50 male partners studied, 76% were HPV DNA positive. Histologic examination was an inaccurate method to diagnose HPV DNA infection in men; however, brushings detected HPV in 92.1% of the infected men.