RESUMO
Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommon histopathological and clinical features. Here we report seven SMARCB1-deficient intracranial tumors sharing distinct clinical, histopathological and molecular features. Median age of the four females and three males was 40 years (range 15-61 years). All tumors were located in the pineal region. Histopathologically, these tumors displayed spindled and epithelioid cells embedded in a desmoplastic stroma alternating with a variable extent of a loose myxoid matrix. All cases showed loss of nuclear SMARCB1/INI1 protein expression, expression of EMA and CD34 was frequent and the Ki67/MIB1 proliferation index was low in the majority of cases (median 3%). Three cases displayed heterozygous SMARCB1 deletions and two cases a homozygous SMARCB1 deletion. On sequencing, one tumor showed a 2 bp deletion in exon 4 (c.369_370del) and one a short duplication in exon 3 (c.237_276dup) both resulting in frameshift mutations. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-SNE analysis and hierarchical clustering analysis, however, all tumors grouped closely together and showed similarities with ATRT-MYC. After a median observation period of 48 months, three patients were alive with stable disease, whereas one patient experienced tumor progression and three patients had succumbed to disease. In conclusion, our series represents an entity with distinct clinical, histopathological and molecular features showing epigenetic similarities with ATRT-MYC. We propose the designation desmoplastic myxoid tumor (DMT), SMARCB1-mutant, for these tumors.
Assuntos
Neoplasias Encefálicas/genética , Mutação/genética , Glândula Pineal , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Proteína SMARCB1/genética , Adolescente , Adulto , Fatores Etários , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumor Rabdoide/mortalidade , Taxa de Sobrevida , Adulto JovemRESUMO
Pediatric tumors of the central nervous system composed of oligoid tumor cells showing diffuse leptomeningeal spread without a primary mass lesion seem to represent a novel tumor entity. The terms "diffuse leptomeningeal glioneural tumor" or-preferably-"disseminated oligodendroglial-like leptomeningeal tumor of childhood" (DOGLT) were proposed. Four patients were identified with clinico-neuropathologic findings compatible with DOGLT and a mean follow-up time of 54 months was determined. Seven different biopsies obtained from the four patients were histologically evaluated. Clinical course, diagnostic measures, histopathologic and radiologic features and treatment suggestions were recorded, on the basis of which diagnostic and therapeutic algorithm was proposed. Patients with DOGLT presented with hydrocephalus as first symptom, requiring neurosurgical therapy. Open arachnoid biopsy was necessary to confirm diagnosis. The oligoid cells in a desmoplastic or focally myxoid matrix showed OLIG2-, MAP2-, S-100 and rare HuC/HuD protein-immunopositivity. IDH1 (R132H)- and CD99-immunohistochemistry was negative in all patients. None of the evaluable biopsies of three patients showed chromosome 1p/19q deletion, neither as isolated nor combined allelic loss. Chemotherapy according to the SIOP-LGG 2004 standard induction and consolidation protocol resulted in complete response and partial response, respectively, in 50 % of the patients. However, after discontinuation of chemotherapy, two patients experienced tumor progression and one of them succumbed to the disease after 19 months. Radiological criteria as well as preliminary treatment results are presented after observation of four clinical cases. Prognosis and long-term clinical courses remain to be observed.
Assuntos
Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/terapia , Oligodendroglioma/diagnóstico , Oligodendroglioma/terapia , Criança , Pré-Escolar , Progressão da Doença , Evolução Fatal , Humanos , Lactente , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Radiografia , Resultado do TratamentoRESUMO
Catalase and ABCD3 are frequently used as markers for the localization of peroxisomes in morphological experiments. Their abundance, however, is highly dependent on metabolic demands, reducing the validity of analyses of peroxisomal abundance and distribution based solely on these proteins. We therefore attempted to find a protein which can be used as an optimal marker for peroxisomes in a variety of species, tissues, cell types and also experimental designs, independently of peroxisomal metabolism. We found that the biogenesis protein peroxin 14 (PEX14) is present in comparable amounts in the membranes of every peroxisome and is optimally suited for immunoblotting, immunohistochemistry, immunofluorescence, and immunoelectron microscopy. Using antibodies against PEX14, we could visualize peroxisomes with almost undetectable catalase content in various mammalian tissue sections (submandibular and adrenal gland, kidney, testis, ovary, brain, and pancreas from mouse, cat, baboon, and human) and cell cultures (primary cells and cell lines). Peroxisome labeling with catalase often showed a similar tissue distribution to the mitochondrial enzyme mitochondrial superoxide dismutase (both responsible for the degradation of reactive oxygen species), whereas ABCD3 exhibited a distinct labeling only in cells involved in lipid metabolism. We increased the sensitivity of our methods by using QuantumDots™, which have higher emission yields compared to classic fluorochromes and are unsusceptible to photobleaching, thereby allowing more exact quantification without artificial mistakes due to heterogeneity of individual peroxisomes. We conclude that PEX14 is indeed the best marker for labeling of peroxisomes in a variety of tissues and cell types in a consistent fashion for comparative morphometry.
Assuntos
Proteínas de Membrana/análise , Peroxissomos/química , Peroxissomos/metabolismo , Proteínas Repressoras/análise , Glândulas Suprarrenais/química , Glândulas Suprarrenais/citologia , Animais , Biomarcadores/análise , Encéfalo/citologia , Gatos , Células Cultivadas , Feminino , Humanos , Rim/química , Rim/citologia , Masculino , Camundongos , Ovário/química , Ovário/citologia , Pâncreas/química , Pâncreas/citologia , Papio , Ratos , Testículo/química , Testículo/citologiaRESUMO
Extrapleural solitary fibrous tumors are uncommon mesenchymal neoplasms frequently observed in middle-aged adults and are classified, according to the WHO classification of soft tissue tumors, as part of the hemangiopericytoma tumor group. However, these two entities remain separated in the WHO classification of tumors of the central nervous system. In fact, meningeal solitary fibrous tumors are believed to be benign lesion and only in a minority of cases local relapses have been described, although detailed survival clinical studies on solitary fibrous tumors of meninges are rare. In contrast to hemangiopericytoma, which frequently shows distant extracranial metastases, such an event is exceptional in patients with meningeal solitary fibrous tumors and has been clinically reported in a handful of cases only and their histopathological features have not been investigated in detail. In this report, we describe the detailed clinico-pathological features of a meningeal solitary fibrous tumor presenting during a 17-year follow-up period, multiple intra-, extracranial relapses and lung metastases.
Assuntos
Neoplasias Meníngeas/patologia , Tumores Fibrosos Solitários/secundário , Feminino , Humanos , Meninges/patologia , Pessoa de Meia-Idade , RecidivaRESUMO
Primary Hodgkin's lymphomas of the central nervous system (CNS) as well as cerebral involvement as the first manifestation of a systemic Hodgkin's disease are very rare. CNS involvement usually occurs in patients with advanced or relapsing systemic disease. Because primary CNS Hodgkin's lymphoma may present unexpected and sometimes misleading clinical and neuroradiological features, the description of unusual cases is important for expanding the awareness of this rare disease of the central nervous system. We describe three cases of primary Hodgkin's lymphoma of the CNS with peculiar features. None of the three patients had a previous clinical history of systemic Hodgkin disease. Case 1 and case 2 presented an unusual localization in the cerebellar hemisphere and in the brainstem, respectively. The third case occurred as a temporal lesion in the settings of a Richter transformation of a chronic lymphocytic leukemia.
Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Doença de Hodgkin/complicações , Doença de Hodgkin/patologia , Idoso , Neoplasias Encefálicas/terapia , Feminino , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Intracerebral hemorrhage (ICH) is a frequently disabling or fatal disease. The localization of ICH often allows an etiological association. However, in atypical/lobar ICH, the cause of bleeding is less obvious. Therefore, we present prospective histopathological and radiological studies which were conducted within the diagnostic workup to identify causes for lobar ICH other than hypertension. From 2016 to 2018, 198 patients with spontaneous, non-traumatic ICH requiring neurosurgical monitoring were enrolled in an institutional prospective patient registry. Patients with deep-seated ICH and/or hemorrhagically transformed cerebral infarcts were excluded from further analysis. Data to evaluate the source of bleeding based on histopathological and/or radiological workup were prospectively evaluated and analyzed. After applying the inclusion criteria and excluding patients with incomplete diagnostic workup, a total of 52 consecutive patients with lobar ICH were further analyzed. Macrovascular disease was detected in 14 patients with lobar ICH (27%). In 11 patients, diagnostic workup identified cerebral amyloid angiopathy-related ICH (21%). In addition, five patients with tumor-related ICH (10%) and six patients with ICH based on infectious pathologies (11%) were identified. In four patients, the cause of bleeding remained unknown despite extensive diagnostic workup (8%). The present prospective registry study demonstrates a higher probability to identify a cause of bleeding other than hypertension in patients with lobar ICH. Therefore, a thorough diagnostic work-up in patients with ICH is essential to accelerate treatment and further improve outcome or prevent rebleeding.
RESUMO
Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, characterized pathologically by α-synuclein aggregates preferentially found in oligodendroglial cells. DNA methylation has emerged as a mechanism of regulation of α-synuclein expression. Reduced 5-methylcytosine (5-mC) DNA methylation of α-synuclein has been found in the brains of patients with Parkinson's disease (PD). 5-hydroxymethylcytosine (5-hmC) methylation is another epigenetic modification of DNA. It is involved in the de-methylation of DNA, gene regulation, and DNA repair mechanisms. Here, we examined sections of human paraffin-embedded brain tissue from the cerebellum and brain stem, including the substantia nigra pars compacta, of patients with PD (n = 8) and MSA (n = 8) as well as age-matched controls (n = 8). The neocortical tissue of PD patients (n = 10) and controls (n = 10) was also examined. Using immunohistochemistry, we analyzed the expression of 5-mC and 5-hmC with an automatic, rater-independent semi-quantification method. We found a significant upregulation of 5-mC, but not 5-hmC, in cortical sections from PD patients. The brain stem and substantia nigra, and in particular the dopaminergic neurons, showed unchanged levels of both 5-mC- and 5-hmC-immunoreactivity in all groups. In the cerebellum, 5-mC was significantly decreased only in MSA patients in the granule cell layer; in contrast, 5-hmC was significantly upregulated in the cerebellar white matter of both PD and MSA patients. Our study showed different levels of expression of total 5-mC and 5-hmC methylation across different brain regions in PD and for the first time in MSA. Our results indicate that 5-mC may be relevant in MSA. The underlying mechanism of the differential 5-mC and 5-hmC expression remains unclear.
Assuntos
5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Encéfalo/metabolismo , Atrofia de Múltiplos Sistemas/metabolismo , Doença de Parkinson/metabolismo , 5-Metilcitosina/análise , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ependymoma with YAP1-MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1-MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo-rosettes, small to medium-sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot-like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1-MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1-11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow-up, 4.84 years). In this to date, largest series of ependymomas with YAP1-MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings.
Assuntos
Ependimoma/genética , Ependimoma/patologia , Neoplasias Supratentoriais/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Lactente , Masculino , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Estudos Retrospectivos , Neoplasias Supratentoriais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAPRESUMO
We report on a 7-year-old girl with a phenotype combining mandibuloacral dysplasia (MAD), progeria, and rigid spine muscular dystrophy. Mild proximal weakness, contractures, and rigidity of the spine were the primary findings. Although present since birth, dysmorphic manifestations typical for MAD and progeroid features became more prominent with time, and the full clinical phenotype was recognizable at early school age. Her phenotype was caused by a homozygous mutation in LMNA (c.1411C > T, which predicts p.R471C) inherited from the heterozygous, consanguineous, unaffected parents. This mutation has only been reported in compound heterozygous state and was associated with a milder phenotype. Some LMNA mutations are known to cause MAD and overlapping phenotypes (MAD spectrum) in an autosomal recessive pattern. The p.R471C homozygous LMNA mutation causes a severe phenotype of the MAD spectrum. This case extends the clinical spectrum of MAD and further expands the phenotypic range of lamin A/C associated diseases.
Assuntos
Homozigoto , Lamina Tipo A/genética , Distrofias Musculares/genética , Distrofias Musculares/fisiopatologia , Mutação , Criança , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/fisiopatologia , Feminino , Humanos , Fenótipo , Progéria/fisiopatologia , Coluna Vertebral/anormalidadesRESUMO
Allgrove or triple A syndrome is a rare autosomal recessive disorder that can present with a variable range of multi-system manifestations, including optic atrophy, cerebellar ataxia, upper and lower motoneuron signs and various neuropathic abnormalities. These cases are a diagnostic challenge, particularly when the eponymous combination of achalasia, Addisonianism and alacrima is incomplete. Therefore, it is in the differential diagnosis for multisystem conditions and should be known to pathologists who diagnose disorders of skeletal muscle. Here, we describe new findings in skeletal muscle histology from the case of a boy of consanguineous Turkish origin whose achalasia provided the only specific clinical clue to the diagnosis. These include myocyte nuclear abnormalities with partially abnormal anti-lamin A/C immunohistochemistry and altered nuclear ultrastructure but without overt abnormalities of nuclear pore morphology. In this case, the condition was associated with a hitherto unreported c.762delC mutation in the nucleoporin gene AAAS.
Assuntos
Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/patologia , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/patologia , Músculo Esquelético/patologia , Núcleo Celular/patologia , Criança , Consanguinidade , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Células Musculares/patologia , Mutação , Proteínas do Tecido Nervoso/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genéticaRESUMO
Background: The aim of this study was to investigate the potential of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive. Methods: Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of 18F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test. Results: TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001). Conclusions: The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of 18F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Lesões por Radiação/diagnóstico por imagem , Radioterapia/efeitos adversos , Tirosina/análogos & derivados , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Lesões por Radiação/etiologia , Lesões por Radiação/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Tirosina/metabolismo , Adulto JovemAssuntos
Vértebras Lombares/cirurgia , Linfoma de Células T Periférico/cirurgia , Segunda Neoplasia Primária/cirurgia , Neurilemoma/cirurgia , Raízes Nervosas Espinhais/cirurgia , Adulto , Humanos , Laminectomia/métodos , Vértebras Lombares/patologia , Linfoma de Células T Periférico/patologia , Masculino , Segunda Neoplasia Primária/patologia , Neurilemoma/patologia , Raízes Nervosas Espinhais/patologiaRESUMO
OBJECTIVE: To investigate whether the occurrence or clearance of microhemorrhages in cerebral amyloid angiopathy (CAA)-related vascular inflammation can be modified by immunosuppressive treatment. METHODS: Clinical and radiologic follow-up for more than 5 years of a patient with histopathologically confirmed CAA-related vascular inflammation treated with a prolonged and tapered regimen of IV cyclophosphamide and oral steroids. RESULTS: Under long-term immunosuppressive treatment, a reduced number of cortical micobleeds was observed on repeat MRIs because of both the prevention of new microbleeds and the clearance of those existing at baseline. CONCLUSIONS: Sustained immunosuppression should be considered and systematically investigated as a treatment option for cortical microbleeds in CAA and related inflammatory phenotypes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence. This is a single observational study without controls.
RESUMO
April 2004: A 53-year-old woman presented with a large club-shaped intra- and extraspinal tumor of the C6 nerve root which had intradurally grown through the enlarged C5-6 neural foramen and focally infiltrated the dura mater. Microscopy revealed a melanin-pigmented tumor with spindle-shaped and epithelioid cells and scattered psammoma bodies, a so-called psammomatous melanotic schwannoma (PMS). More than half of the patients with PMS have Carney complex, a genetically heterogeneous multiple neoplasia syndrome of autosomal-dominant inheritance, which in our patient, however, could not be detected unequivocally. Prognosis of all melanotic schwannomas (MSs) is not good with local recurrences or metastases in over 40% of cases. In our case, frequent versicular nuclei with distinct nucleoli, occasional mitoses and apoptoses and increased focal MIB-1 labeling indices prompted us to diagnose a malignant PMS. However, histologic criteria for malignancy in MSs are not clearly defined and there is no reliable histopathological indicator of malignant clinical behavior in MSs. Therefore, designation of "PMS with malignant histologic features" may be more appropriate. Since tumor recurrences and metastases im MSs may occur after more than 5 years, long-term follow-up of affected patients is required. One year after operation our patient showed no signs of tumor recurrence or metastases.
Assuntos
Neurilemoma/patologia , Neoplasias do Sistema Nervoso Periférico/patologia , Neoplasias da Medula Espinal/patologia , Antígenos de Neoplasias , Feminino , Humanos , Antígeno MART-1 , Imageamento por Ressonância Magnética/métodos , Antígenos Específicos de Melanoma , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neurilemoma/metabolismo , Neoplasias do Sistema Nervoso Periférico/metabolismo , Proteínas S100/metabolismo , Neoplasias da Medula Espinal/metabolismoRESUMO
The arterial vascular wall contains a non-neuronal intrinsic cholinergic system. The rate-limiting step in acetylcholine (ACh) synthesis is choline uptake. A high-affinity choline transporter, CHT1, has recently been cloned from neural tissue and has been identified in epithelial cholinergic cells. Here we investigated its presence in rat and human arteries and in primary cell cultures of rat vascular cells (endothelial cells, smooth muscle cells, fibroblasts). CHT1-mRNA was detected in the arterial wall and in all isolated cell types by RT-PCR using five different CHT1-specific primer pairs. Antisera raised against amino acids 29-40 of the rat sequence labeled a single band (50 kD) in Western blots of rat aorta, and an additional higher molecular weight band appeared in the hippocampus. Immunohistochemistry demonstrated CHT1 immunoreactivity in endothelial and smooth muscle cells in situ and in all cultured cell types. A high-affinity [3H]-choline uptake mechanism sharing characteristics with neuronal high-affinity choline uptake, i.e., sensitivity to hemicholinium-3 and dependence on sodium, was demonstrated in rat thoracic aortic segments by microimager autoradiography. Expression of the high-affinity choline transporter CHT1 is a novel component of the intrinsic non-neuronal cholinergic system of the arterial vascular wall, predominantly in the intimal and medial layers.
Assuntos
Colina/metabolismo , Endotélio Vascular/metabolismo , Proteínas de Membrana Transportadoras/biossíntese , Músculo Liso/metabolismo , Idoso , Animais , Artérias/metabolismo , Autorradiografia , Western Blotting , Células Cultivadas , Endotélio Vascular/citologia , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/citologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Ependimoma/patologia , Ependimoma/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Neurocirúrgicos , Prognóstico , Região SacrococcígeaRESUMO
OBJECT: The mismatch repair (MMR) system has previously been implicated in acquired chemoresistance in malignant gliomas in humans. Its impact on the primary chemoresistance in glioblastoma multiforme (GBM) has not been determined in detail, however. METHODS: The authors investigated the expression of both the MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6) at the transcriptional level through reverse transcription-polymerase chain reaction and the hMSH2 protein through Western blot and immunohistochemical analysis of tumor tissue and primary cell cultures of 25 in vitro human de novo GBMs without prior experimental treatment. Results of these analyses were compared with data on in vitro chemoresistance to nine drugs that are in general use in glioma therapy. All MMR genes were expressed in the GBMs, with no significant difference among the individual tumors except in one respect; that is, GBMs showed either relatively high levels or barely detectable levels of hMSH2 messenger (m)RNA and protein expression. All multiresistant tumors demonstrated high hMSH2 expression, and all but two of the sensitive tumors exhibited low hMSH2 mRNA levels. CONCLUSIONS: Analysis of the data indicates that functional alterations of the MMR system are involved in the primary drug resistance in in vitro human malignant gliomas. Analysis of hMSH2 expression might therefore predict therapeutic responses in humans with GBMs.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Pareamento Incorreto de Bases , Western Blotting , Enzimas Reparadoras do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism that causes disease entities such as periodontal and soft tissue abscesses, pulmonary and intraabdominal infections and very rarely intracerebral infections. CASE PRESENTATION: Here, we report the rare case of a previously healthy 25-year-old German man with a cerebellar abscess caused by Fusobacterium nucleatum that resulted in rapid brain death. Toxicological screening showed positivity for amphetamines and cannabis. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in cerebrospinal fluid. CONCLUSIONS: In drug users clinicians should think about rare causes of brain abscesses/meningitis. Early diagnosis is necessary and justifies the use of molecular techniques.
Assuntos
Abscesso Encefálico/microbiologia , Morte Encefálica , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/isolamento & purificação , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Abscesso Encefálico/complicações , Infecções por Fusobacterium/microbiologia , Humanos , MasculinoRESUMO
We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.