RESUMO
AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.
Assuntos
Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Cromossomos Humanos Par 14/genética , Glioma/genética , Glioma/patologia , Metilação de DNA , Feminino , Humanos , Masculino , Monossomia , Neurocitoma/genética , Neurocitoma/patologia , Oligodendroglioma/genética , Oligodendroglioma/patologiaRESUMO
AIMS: Previous data suggest that expression of transcription factors FoxG1 and Olig-2 can separate hotspot histone H3 family member 3A (H3F3A)-mutant tumours in paediatric glioma. We evaluated their prognostic potential and feasibility for identifying H3F3A-mutant tumours among IDH-mutant/wild-type gliomas. METHODS: Immunohistochemistry of FoxG1/Olig-2 and α-thalassaemia/mental-retardation-syndrome-X-linked gene (ATRX) in 471 cases of diffuse gliomas and molecular determination of IDH, H3F3A, MGMT and 1p/19 codeletion status. RESULTS: Mean percentage of FoxG1-positive tumour cells increased from 17% in WHO grade II to over 21% in grade III to 37% in grade IV tumours, whereas mean Olig-2 indices decreased from 29% to 28% to 17% respectively. FoxG1 indices were similar in astrocytic and oligodendroglial tumours, whereas Olig-2 indices were increased in oligodendrogliomas compared to astrocytic tumours (n = 451, P < 0.0001). FoxG1-positive nuclei were significantly reduced in IDH and H3F3A K27-mutant tumours, whereas Olig-2-positive nuclei were significantly reduced in IDH-wild-type and H3F3A G34-mutant tumours. Among IDH-mutant tumours, mean Olig-2 index was significantly higher in 1p/19q codeleted tumours (mean: 43%) compared to IDH-mutant tumours with ATRX loss (mean: 23%, P < 0.0001). A significantly better outcome was first suggested for FoxG1low tumours (n = 212, log rank P = 0.0132) and Olig-2high tumours (n = 203, log-rank P = 0.0011) based on classification and regression tree determined cutoffs, but this was not confirmed by multivariate analysis including IDH mutation, WHO grade, ATRX status and age. CONCLUSIONS: While the combined FoxG1/Olig-2 profile may discriminate H3F3A K27- and G34-mutant tumours and define a prognostically favourable subset in IDH-mutant gliomas, our data show that labelling indices of these transcription factors overlap with adult IDH-mutant and wild-type tumour classes.
Assuntos
Neoplasias Encefálicas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Glioma/metabolismo , Isocitrato Desidrogenase/genética , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Criança , Feminino , Fatores de Transcrição Forkhead/genética , Glioma/genética , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas do Tecido Nervoso/genética , Fator de Transcrição 2 de Oligodendrócitos/genética , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: To assess the diagnostic performance of normalized and non-normalized diffusion kurtosis imaging (DKI) metrics extracted from different tumor volume data for grading glioma according to the integrated approach of the revised 2016 WHO classification. MATERIALS AND METHODS: Sixty patients with histopathologically confirmed glioma, who provided written informed consent, were retrospectively assessed between 01/2013 and 08/2016 from a prospective trial approved by the local institutional review board. Mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were assessed by two blinded physicians from four different volumes of interest (VOI): whole solid tumor including (VOItu-ed) and excluding perifocal edema (VOItu), infiltrative zone (VOIed), and single slice of solid tumor core (VOIslice). Intra-class correlation coefficient (ICC) was calculated to assess inter-rater agreement. One-way ANOVA was used to compare MK between 2016 CNS WHO tumor grades. Friedman's test compared MK and MD of each VOI. Spearman's correlation coefficient was used to correlate MK with 2016 CNS WHO tumor grades. ROC analysis was performed on MK for significant results. RESULTS: The MK assessment showed excellent inter-rater agreement for each VOI (ICC, 0.906-0.955). MK was significantly lower in IDHmutant astrocytoma (0.40±0.07), than in 1p/19q-confirmed oligodendroglioma (0.54±0.10, P=0.001) or IDHwild-type glioblastoma (0.68±0.13, P<0.001). MK and 2016 WHO tumor grades were strongly and positively correlated (VOItu-ed, r=0.684; VOItu, r=0.734; VOIed, r=0.625; VOIslice, r=0.698; P<0.001). CONCLUSIONS: Non-normalized MK values obtained from VOItu and VOIslice showed the best reproducibility and highest diagnostic performance for stratifying glioma according to the integrated approach of the recent 2016 WHO classification.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Glioma/diagnóstico por imagem , Glioma/patologia , Biópsia , Neoplasias Encefálicas/genética , Meios de Contraste , Estudos de Viabilidade , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Compostos Organometálicos , Estudos Retrospectivos , Organização Mundial da SaúdeRESUMO
OBJECTIVES: In progressive glioblastoma, salvage treatment remains unstandardized, response is highly variable, and detailed analysis of individual approaches is mandatory. Re-irradiation is an established option in the therapy of progressive glioblastoma. Thus, we analysed outcome and prognostic parameters of patients with re-irradiated glioblastoma treated at our institution since 1998. MATERIALS AND METHODS: In a total of 51 patients, clinical and treatment parameters were collected and analysed retrospectively. Re-irradiation protocols included radiosurgery, hypofractionated radiotherapy or normofractionated radiotherapy. Outcome was analysed regarding prognostic factors in this highly selected cohort. RESULTS: Median overall survival after primary diagnosis was 28.8 months. Patients re-irradiated with single-dose stereotactic radiosurgery or hypofractionated regimes showed a superior overall survival after primary diagnosis compared to normofractionated treatment. Positive prognostic factors included a smaller gross tumour volume and younger age. A methylated MGMT promoter approached statistical significance as a positive factor regarding overall survival after re-irradiation. Further well-known prognostic factors as extension of the initial resection and the concomitance of temozolomide with the initial radiation treatment only appeared relevant in a subgroup of four long-term survivors. CONCLUSIONS: The favourable results regarding overall survival are probably due to patient selection for re-irradiation. If technically feasible, stereotactic radiosurgery or hypofractionated regimes should be preferred. In this highly selected re-irradiation cohort, only some of the well-known prognostic factors of the primary tumour setting were found to influence overall survival significantly. In contrast, also some patients presenting with unfavourable predictive parameters showed an encouraging course of disease and thus should not be excluded from re-irradiation.
Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Radiocirurgia , Reirradiação , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , TemozolomidaRESUMO
Tumors of the inner ear and adjacent structures often present with hearing loss, tinnitus and vertigo due to compression of the traversing cranial nerves. More than 90% of the tumors of the inner ear with or without expansion into the cerebellopontine angle are histologically diagnosed as vestibular schwannomas. Less common tumorous lesions include ectopic meningiomas located in the petrous bone, glomus tympanicum paragangliomas or endolymphatic sac tumors (ELST) originating in the vestibular recess. Most tumors are sporadic, but hereditary disorders have to be considered. Bilateral vestibular schwannomas are indicative of neurofibromatosis type 2 and ELST in conjunction with other abdominal tumors indicates von Hippel-Lindau disease. The neuropathological diagnostics and grading guides the subsequent therapy of these mostly benign lesions.
Assuntos
Neoplasias da Orelha/patologia , Doenças do Labirinto/patologia , HumanosRESUMO
Pituicytoma is an exceptionally rare low-grade glioma (WHO grade I) of the neurohypophysis and infundibulum. We are reporting the case of a 48-year-old man who presented with severe Cushing's syndrome. Endocrinological evaluation unequivocally confirmed pituitary-dependent Cushing's syndrome (=Cushing's disease). Cranial MR-imaging displayed a conspicuous area in the dorsal and basal pituitary gland and a minimal bulging of the pituitary gland paramedian of the pituitary stalk on the right side. Transsphenoidal inspection revealed a small tumor in the basal and dorsal pituitary gland. Surprisingly, the definite postoperative histopathological diagnosis of the removed tumor was pituicytoma and not pituitary adenoma. Hence, the microadenoma responsible for Cushing's disease was not yet removed and persistent hypercortisolism necessitated transsphenoidal re-operation. During re-operation, hemihypophysectomy was performed on the right side. The non-tumorous specimen of the adeno-hypophysis showed signs of Crooke's hyalinization consistent with Cushing's disease. Undetectable postoperative ACTH- and cortisol levels provided clear evidence that the underlying ACTH-source was successfully removed during re-operation. Coincidence of pituicytoma and pituitary-dependent Cushing's disease has not previously been reported.
Assuntos
Hipersecreção Hipofisária de ACTH/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Glioma/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuro-HipófiseRESUMO
BACKGROUND: The erythropoietin receptor (EpoR) is expressed widely throughout the human CNS, including the choroid plexus. Recent studies have shown that EpoR is also expressed in various human tumors, including carcinomas, meningiomas and gliomas. Thereby, the Epo-EpoR pathway plays a role in inhibition of apoptosis and tumor growth, infiltration, angiogenesis and metastasis as well as treatment resistance and is a potential target in oncological treatment. Lower levels of EpoR have been associated with shorter survival in high grade gliomas and higher risk of tumor recurrence in meningiomas. METHODS: Since the EpoR status in human choroid plexus tumors (CPT) is not known, we investigated 57 CPT from 43 cases including 14 recurrent tumors and compared them with 23 samples of normal choroid plexus (CP). CPT samples consisted of choroid plexus papillomas/CPP (n = 41), atypical CPP (n = 15) and choroid plexus carcinoma/CPC (n = 1). EpoR expression was determined by immunohistochemistry using semi-quantitative scoring for staining intensity and was validated in exemplary cases using western blot and RT-PCR. RESULTS: EpoR expression was observed in all samples of normal and neoplastic CP with significantly lower expression levels in CPT (p < 0.001). CONCLUSION: No significant correlation was found between EpoR expression and age, gender, WHO grade, number of mitosis or tumor recurrence. EpoR expression in CPT is in line with its expression in normal CP and with previous reports on EpoR expression in other glial neoplasms. Association of EpoR levels in CPT with survival, as known in astrocytic gliomas, remains to be determined.
Assuntos
Neoplasias do Plexo Corióideo/metabolismo , Plexo Corióideo/metabolismo , Receptores da Eritropoetina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Anaplastic astrocytomas presenting as gliomatosis cerebri in neonates are extremely rare. Tumours in newborns are mostly of neuroectodermal origin. CASE REPORT: We report about a female newborn at term [birth weight 3 600 g (P 90), head circumference 35 cm (P 95) APGAR 9/10/10] with an intracerebral partially clotted bleeding in the left parieto-occipital region. The bleeding was expansive leading to axial and lateral cerebral herniation. The intracerebral bleeding in the left occipital region was surgically removed. Macroscopically no solid tumour was seen, but small fragments of an anaplastic astrocytic tumour (WHO grade III) were diagnosed histologically. After surgery, no remaining tumour was visible in the MRI. 6 weeks later, a recurrent tumour (4×4 cm) was found in the area of the initial bleeding. Further treatment was initially refused by the parents. The child was readmitted to our hospital at the age of 11 months in good clinical condition and presented with left-sided hemiparesis, right-sided hemianopsia and intermittent strabismus convergens alternans. Because of the good clinical condition further therapeutic treatment was initiated. Due to the final extension of the tumour into the temporal, parietal and occipital lobes, a gliomatosis cerebri WHO III was diagnosed. An extended partial hemispherectomy was done. After neurosurgery, no further neurological failures occurred. In the follow-up examination, MRI showed no relapse of the tumour. Chemotherapy according to the HIT SKK protocol was initiated. A relapse did not occur over a follow-up of 2 years. CONCLUSION: This is a rare case report of a congenital gliomatosis cerebri WHO grade III, treated with partial hemispherectomy, leading to a good clinical and neurological long-term outcome.
Assuntos
Astrocitoma/congênito , Astrocitoma/cirurgia , Neoplasias Encefálicas/congênito , Neoplasias Encefálicas/cirurgia , Hemorragia Cerebral/congênito , Hemorragia Cerebral/cirurgia , Hemisferectomia , Neoplasias Neuroepiteliomatosas/congênito , Neoplasias Neuroepiteliomatosas/cirurgia , Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Córtex Cerebral/patologia , Córtex Cerebral/cirurgia , Hemorragia Cerebral/diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/diagnóstico , Exame Neurológico , ReoperaçãoRESUMO
AIMS: Secreted protein, acidic and rich in cysteine (SPARC) is a regulator of cell-matrix interaction and has been associated with tumour stage and patient survival in various malignancies. As no large-scale study has yet been undertaken, we investigated human brain and astrocytomas for SPARC expression and associations with tumour grade, proliferation, vascular density and patient survival. METHODS: A spectrum of 188 WHO grade I-IV astrocytic tumours and 24 autopsy cases were studied by immunohistochemistry for SPARC, MIB-1 proliferation index and CD31-positive vessels. SPARC protein expression was confirmed by quantitative real-time polymerase chain reaction and Western blot in 13 cases. RESULTS: In normal brain, SPARC is expressed in cortical marginal glia, cerebellar Bergmann glia and focally in white matter but is absent in neurones or vessels. High SPARC expression levels in the cytoplasm of astrocytic tumour cells decreased with the grade of malignancy but showed an increase with grade of malignancy in tumour vessels. SPARC negatively correlated with tumour proliferation but not with vascular density. While cytoplasmic SPARC staining was not associated with survival, vascular SPARC showed a significant association in the group of grade II-IV tumours (P = 0.02) and also in grade II astrocytomas alone (P = 0.01) with vascular SPARC associated with worse prognosis. CONCLUSIONS: SPARC is highly expressed in astrocytomas and decreases with tumour progression. We confirm an association of increased SPARC expression and decreased proliferation. While there is no association between the level of SPARC in the tumour cells and patient survival, increased tumour vascular SPARC expression is associated with decreased patient survival.
Assuntos
Astrocitoma/metabolismo , Vasos Sanguíneos/metabolismo , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Proliferação de Células , Osteonectina/metabolismo , Adulto , Astrocitoma/irrigação sanguínea , Astrocitoma/patologia , Vasos Sanguíneos/patologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Movimento Celular , Citoplasma/metabolismo , Citoplasma/patologia , Feminino , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologia , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
We present the case of a 69-year old patient with a contrast enhancing, partially cystic lesion of the right temporal lobe, involving the ventricle and extending into the occipital lobe. The resected tumor showed histological features of a glioblastoma with granular cell astrocytoma features, lacking amplification of the EGFR gene region and IDH1R132H mutation. Literature review of 59 cases showed a 12-month overall survival of 11.7% for high-grade and 40% for low-grade granular cell astrocytomas. In 35% more than one cerebral lobe was affected. These extended mass effects may explain the worse prognosis despite the relatively bland histology of the granular cell component.
Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Idoso , Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Feminino , Glioblastoma/diagnóstico , Humanos , Lobo Temporal/patologiaRESUMO
Herein, we report the case of a 72-year-old male with an exceedingly rare manifestation of a low-grade lymphoma in the brain associated with light chain deposition disease (LCDD). The patient presented with epileptic seizures. Magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense lesions in the right parietal lobe that were suspicious of vasculitis, low-grade glioma, or neurosarcoidosis. In the cerebrospinal fluid (CSF), but not in the serum, highly elevated IgG was found. A stereotactic biopsy of one cerebral lesion was performed. Histopathology revealed a low grade lymphoplasmacytic B-cell lymphoma with light chain deposition disease (LCDD). Bone marrow biopsy and laboratory workup did not show any systemic involvement. LCDD exclusively affecting the brain is an exceedingly rare finding. It can be associated with low-grade B-cell lymphoma. This is the first report of LCDD exclusively affecting the brain in an elderly patient. Compared with the two younger patients previously reported, the course of the disease was of a slow-evolving nature. In constellations of highly elevated IgG in CSF and multiple white matter lesions, LCDD should be considered as underlying pathology.
Assuntos
Encefalopatias/diagnóstico , Encefalopatias/imunologia , Neoplasias Encefálicas/diagnóstico , Imunoglobulina G/líquido cefalorraquidiano , Cadeias Leves de Imunoglobulina/metabolismo , Linfoma de Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Idoso , Biomarcadores/líquido cefalorraquidiano , Biópsia , Medula Óssea/patologia , Encefalopatias/líquido cefalorraquidiano , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/patologia , Humanos , Linfoma de Células B/líquido cefalorraquidiano , Linfoma de Células B/patologia , Linfoma não Hodgkin/líquido cefalorraquidiano , Linfoma não Hodgkin/patologia , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: We report about endoscope-assisted surgery of epidermoid cysts in the posterior fossa focusing on the application of neuro-endoscopy and the clinical outcome in cases of recurrent epidermoid cysts. MATERIAL AND METHODS: 25 consecutively operated patients with an epidermoid cyst in the posterior fossa were retrospectively analysed. Surgeries were performed both with an operating microscope (OPMI Pentero or NC 4, Zeiss Company, Oberkochen, Germany) and endoscopic equipment (4 mm rigid endoscopes with 30° and 70° optics; Karl Storz Company, Tuttlingen, Germany) under continuous intraoperative monitoring. Surgical reports and DVD-recordings were evaluated for identification of adhesion areas and surgical details. RESULTS: 7 (28%) of the 25 patients were recurrences of previously operated epidermoid cysts. Mean time to recurrence was 17 years (8-22 years). In 5 cases the endoscope was used as an adjunctive tool for inspection/endoscope-assisted removal of remnants. The effective time of use of the endoscope was limited to the end stage of the procedure, but was very effective. CONCLUSION: In a modern operative setting and with the necessary surgical experience recurrent epidermoid cysts may be removed with excellent clinical results. The combined use of microscope and endoscope offers relevant advantages in demanding anatomic situations.
Assuntos
Encefalopatias/cirurgia , Fossa Craniana Posterior/cirurgia , Endoscopia/métodos , Cisto Epidérmico/cirurgia , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIMS: Little is known about the immune response of the brain to invasive meningiomas. The present study was based upon the hypothesis that the microglial/macrophagic response towards brain-invasive meningiomas is dependent on the intactness of the pial-glial basement membrane. METHODS: We immunostained sections from 40 brain-invasive meningiomas that were graded according to World Health Organization (WHO) 2007 criteria. Thirty-three tumours were histologically WHO grade II (18, 'otherwise benign', and 15, 'otherwise atypical'), and seven, grade III. Microglial/macrophagic cells were labelled with antibodies directed against major histocompatibility complex class II, CD68, CD14 and CD163. Anti-collagen IV was used to visualize basement membranes. RESULTS: Twenty-five per cent (10/40) meningiomas (1/18 WHO grade II 'otherwise benign', 3/15 grade II 'otherwise atypical' and 6/7 WHO grade III) contained microglial/macrophagic cells at the tumour-brain border. The presence of these cells correlated with the absence of the pial-glial basement membrane (BM) and with WHO grade III. The monocytic response was of two kinds: one consisted of a dense layer of mononuclear cells at the tumour-brain border in nine cases, the other of an elevated number of microglial cells expressing CD14 or CD163 (two cases). CONCLUSIONS: The immune response at the tumour-brain interface correlates with the absence of the pial-glial BM and with malignancy grade. It remains to be established whether the mononuclear cells at the tumour-brain border are native microglia or blood-derived macrophages.
Assuntos
Neoplasias Encefálicas/imunologia , Encéfalo/imunologia , Macrófagos/imunologia , Meningioma/imunologia , Microglia/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Membrana Basal/imunologia , Encéfalo/metabolismo , Genes MHC da Classe II , Humanos , Imuno-Histoquímica , Receptores de Lipopolissacarídeos/metabolismo , Pessoa de Meia-Idade , Monócitos/imunologia , Pia-Máter/imunologia , Receptores de Superfície Celular/metabolismoRESUMO
AIMS: The Epo-EpoR pathway plays a role in tumour growth, metastasis and treatment resistance and is a potential target in oncological treatment. As the EpoR status in human meningiomas is unknown, our aim was to characterize EpoR expression in these tumours. METHODS: We examined 131 meningioma samples of all WHO grades from 116 patients by immunohistochemistry for EpoR. Among these, 25 meningiomas showed brain invasion and 29 patients had a further tumour recurrence. A group of 20 patients without tumour recurrence served as controls. In 12 cases we were able to compare both the primary and the following recurrent tumours. The presence of EpoR in meningiomas was confirmed by RT-PCR and Western blot. RESULTS: EpoR was expressed in all meningiomas. Statistical analysis revealed that the mean expression levels of EpoR were significantly lower in primary tumours with known recurrence compared with a recurrence-free control group. Additional matched pair analysis in individual cases showed no significant differences between primary and recurrent tumours. No significant correlation between EpoR expression and WHO grade, age, sex or brain invasion was detected. Using specific primer pairs for RT-PCR, we were able to detect all three known isoforms of EpoR: the full-length isoform EpoR-F, the truncated isoform EpoR-T and the soluble isoform EpoR-S. CONCLUSIONS: Our results demonstrate the expression of EpoR in meningiomas. Lower EpoR mean levels might be a useful marker for a higher recurrence risk, but further studies are needed to clarify the influence of EpoR on recurrences and the role of the different isoforms.
Assuntos
Neoplasias Encefálicas/metabolismo , Meningioma/metabolismo , Recidiva Local de Neoplasia/metabolismo , Receptores da Eritropoetina/metabolismo , Adulto , Fatores Etários , Idoso , Western Blotting , Neoplasias Encefálicas/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Meningioma/diagnóstico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Prognóstico , Isoformas de Proteínas/metabolismo , Receptores de Progesterona/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores SexuaisRESUMO
AIMS: Currently, clinical trials using WT1 (Wilms tumour gene) peptide vaccines are conducted in haematopoietic malignancies and solid cancers. Single reports showed that the Wilms tumour gene product WT1 is also expressed in astrocytic neoplasms. Our aim was to investigate WT1 expression in a large cohort of various neuroepithelial tumours of different World Health Organization (WHO) grades and in normal central nervous system (CNS) tissue specimens to test its potential value as a diagnostic marker. METHODS: Specimens were assessed by RT-PCR, Western blotting and immunohistochemistry. The samples investigated in our study consisted of 334 human neuroepithelial tumours, among those 33 oligodendrogliomas, 219 astrocytomas (including 105 glioblastomas) and 47 ependymomas. RESULTS: Our results showed a de novo WT1 expression in neuroepithelial tumours. In diffuse astrocytomas and ependymomas, WT1 expression increased significantly with the grade of malignancy. In contrast, no significant difference was seen between WHO grade-II and -III oligodendrogliomas. Controlling for WHO grade, the comparison of oligodendrogliomas with ependymal and astrocytic tumours showed higher expression values for the latter. CONCLUSIONS: Our study shows that WT1 is expressed de novo in numerous neuroepithelial tumours and increases with the grade of malignancy. These results suggest an important role of WT1 in tumourigenesis and progression in human brain tumours.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Neuroepiteliomatosas/diagnóstico , Proteínas WT1/metabolismo , Adulto , Western Blotting , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Criança , Células Endoteliais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/metabolismo , Neoplasias Neuroepiteliomatosas/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Proteínas WT1/genética , Adulto JovemRESUMO
AIMS: Most brain diseases are complex entities. Although animal models or cell culture experiments mimic some disease aspects, human post mortem brain tissue remains essential to advance our understanding of brain diseases using biochemical and molecular techniques. Post mortem artefacts must be properly understood, standardized, and either eliminated or factored into such experiments. Here we examine the influence of several premortem and post mortem factors on pH, and discuss the role of pH as a biochemical marker for brain tissue quality. METHODS: We assessed brain tissue pH in 339 samples from 116 brains provided by 8 different European and 2 Australian brain bank centres. We correlated brain pH with tissue source, post mortem delay, age, gender, freezing method, storage duration, agonal state and brain ischaemia. RESULTS: Our results revealed that only prolonged agonal state and ischaemic brain damage influenced brain tissue pH next to repeated freeze/thaw cycles. CONCLUSIONS: pH measurement in brain tissue is a good indicator of premortem events in brain tissue and it signals limitations for post mortem investigations.
Assuntos
Encéfalo , Preservação de Órgãos , Adulto , Idoso , Idoso de 80 Anos ou mais , Química Encefálica , Isquemia Encefálica , Pré-Escolar , Criopreservação , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Controle de Qualidade , Bancos de Tecidos , Adulto JovemRESUMO
Nerve injuries may result in sensory and motor deficits when not treated appropriately. Especially the surgical management of nerve defects still represents a challenge for the surgeon. In these cases the grafting of autologous nerves represents the only reasonable approach. Due to the side effects associated with this method (sacrifice of donor nerves, neuroma formation in the harvesting area, limited availability of donor nerves, etc.), numerous alternatives were proposed in order to avoid the transplantation of autologous tissue. This review provides a general view on the state of the art of how to supply gaping injuries in the peripheral nerve. Furthermore new approaches emphasizing tubulization techniques for the reconstruction of lost nerve tissue are described with a special focus on various materials with their advantages and disadvantages.
Assuntos
Procedimentos Neurocirúrgicos/métodos , Nervos Periféricos/cirurgia , Humanos , Nervos Periféricos/patologiaRESUMO
AIM: Infiltration of autoantigen-specific T cells and monocytes into the central nervous system is essential for the development of both experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). RhoA is one of the best-known members of Rho GTPases, and inhibition of RhoA has been shown to attenuate the progression of EAE. The aim of this study was to investigate the expression of RhoA in brains of EAE rats and MS tissue. METHODS: EAE was induced by immunization with the synthetic peptide gpMBP68-84 in rats, and clinical severity was scored. RhoA expression pattern was investigated in brains of EAE rats at different time points and in different lesions of brain tissue specimens from six MS brains and five neuropathologically unaffected controls by immunohistochemistry. METHODS: In EAE rat brains, accumulation of RhoA(+) cells reached maximal levels around Day 13, correlating to the clinical severity of EAE, and up-regulation lasted until the recovery stage of the disease. Double-labelling experiments showed that the major cellular sources of RhoA were reactive macrophages/microglia. While RhoA(+) cells in normal human brain parenchyma were rarely observed, RhoA expression was found to be spatially associated with MS lesions, showing a marked decrease from active lesions via chronic stages to its near absence in normal-appearing white matter. In addition, major RhoA(+) cells in brain parenchyma of MS were identified to be activated macrophages/microglia. CONCLUSION: Our present data indicated that RhoA may play an important role during the effector phase of EAE and MS. Therefore, RhoA inhibitors might be a therapeutic option for MS patients.
Assuntos
Encéfalo/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Esclerose Múltipla/metabolismo , Proteína rhoA de Ligação ao GTP/biossíntese , Animais , Encéfalo/imunologia , Encéfalo/patologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Microglia/metabolismo , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Ratos , Ratos Endogâmicos LewRESUMO
Herein, we report the case of a 47-year-old man clinically presenting a slow progressive loss of lower extremity functions within 8 weeks followed by an acute neurogenic bladder dysfunction. The patient exhibited high-grade paralysis of both legs with reduced sensation from dermatome Th11 downwards as well as marked spasticity of the lower extremity. Neuroradiological examinations revealed a protruding spinal tumor with extraosseous-intraspinal extension. The resected tumor mass exhibited a highly vascularized tumor with architectural complexity and high cellularity finally leading to the diagnosis of a hemangioendothelioma. Interesting was the fact that the tumor vasculature exhibited many CD68-positive cells protruding into the lumen and, therefore, being part of a partially histiocytoid differentiation which is all the more uncommon in hemangioendothelioma. The time frame of 3 hours between embolization and tumor resection is too short to explain a monocytic intravascular reaction. Usually, hemangioendotheliomas arise from the soft tissue, lungs or liver, but intraspinal manifestations are only rarely observed. Furthermore, the clinical course with a progressive development of a paraparesis due to a hemangioendothelioma is very uncommon.
Assuntos
Hemangioendotelioma/complicações , Hemangioendotelioma/patologia , Compressão da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/patologia , Alcoolismo/complicações , Angiografia Digital , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Terapia Combinada , Descompressão Cirúrgica , Hemangioendotelioma/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paraparesia/etiologia , Radioterapia Adjuvante , Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/terapia , Vértebras Torácicas/patologia , Bexiga Urinaria Neurogênica/etiologiaRESUMO
According to the WHO grading system, myxopapillary ependymomas are assigned to WHO Grade I. However, the clinico-pathological spectrum might be very heterogenous. Herein, we report 4 cases exhibiting lumbar tumor masses, 1 causing muscular atrophy over a 30-year period, 3 displaying clinical history of persisting lumbar pain for only several weeks. All tumors were crooked with dura and spinal roots resulting in incomplete resection in three cases. On histological examination, two tumors were almost acellular and showed polycyclic hyaline and fibrotic extracellular matrix leading to differential diagnoses of chordoma, meningioma, fibrolipoma and ependymoma. Finally, together with the immunohistochemical investigations, electron microscopy led to the diagnosis of myxopapillary ependymoma, WHO Grade I, with massive degenerative changes. The other 2 cases presented with the typical neuropathology of myxopapillary ependymomas but showed local recurrence within 1 and 13 years throughout the whole neuraxis, and in 1 case additional metastases of the 3rd ventricle. Although the morphological feature of these myxopapillary ependymomas was benign, the presented cases showed that the biological behavior of myxopapillary tumors might differ greatly and that these tumors present a serious operative and diagnostic challenge. Myxopapillary ependymomas occur most often in the lumbosacral region. Due to the anatomic complexity of the cauda equina, a complete resection can be technically challenging in this region. However, a gross total resection at the primary surgery is the most predictive factor for the outcome.