bromochloroacetic-acid and Central-Nervous-System-Neoplasms

Atypical teratoid/rhabdoid tumor (ATRT) and choroid plexus tumors (CPT) represent, so far, 2 well defined types of CNS neoplasm on the basis of their histological features and clinical presentation (10). While CPTs are intraventricular epithelial tumors arising from choroid plexus epithelium, the cellular origin of ATRTs is still unknown. Inactivating mutations of the hSNF5/INI-1 gene located in the chromosomal region 22q11.2 are regarded as a crucial step in the molecular pathogenesis of ATRTs; the genetic changes associated with CPTs are largely unknown. However, the recent finding of inactivation of hSNF5/INI-1 in choroid plexus carcinomas and papillomas (9, 18) points to a closer relationship between these 2 entities. This is supported by the occurence of choroid plexus carcinomas (CPC) in the setting of families with rhabdoid predisposition syndrome (RPS), (19) caused by germ line inactivation of the INI1 gene.

Topics: Central Nervous System Neoplasms; Choroid Plexus Neoplasms; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Gene Silencing; Humans; Keratins; Mutation; Rhabdoid Tumor; Sequence Analysis, DNA; SMARCB1 Protein; Teratoma; Transcription Factors

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

Topics: Alkaline Phosphatase; Carcinoma, Renal Cell; Central Nervous System Neoplasms; Diagnosis, Differential; Germinoma; Glial Fibrillary Acidic Protein; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Meningioma; Mucin-1; Oligodendroglioma; S100 Proteins; Synaptophysin; Vimentin; Xanthomatosis

The malignant rhabdoid tumor (MRT) has been a controversial lesion since its seminal description. There is no consensus as to whether it represents a distinctive clinicopathological entity or, alternatively, a phenotypic pattern that is potentially common to several disparate neoplasms. MRT of the kidney is a childhood tumor that is associated with uniformly aggressive behavior, but it shows a wide spectrum of histologic, immunophenotypic, and cytogenetic findings. Malignant extrarenal rhabdoid tumors (MERTs) have been observed in pure form over a broader range of patient ages and anatomic locations, but they show substantial morphological and biological homology with renal MRT. Lastly, "composite" extrarenal rhabdoid tumors (CERTs)--in which recognizable "parent" neoplasms are admixed with MERTs--also have been recognized in several topographic sites. In aggregate, these observations suggest that "rhabdoid tumors" are a heterogeneous group of lesions with dissimilar lineages of differentiation. Particularly in CERTs, it is likely that the rhabdoid phenotype represents a common end point of clonal evolution in tumors of clearly different origins. Despite these caveats, the authors do support retention of the diagnosis of "rhabdoid tumor," because the affiliated morphological pattern is uniformly attended by aggressive biological behavior despite potential dissimilarities at a subcellular level.

Topics: Abdominal Neoplasms; Central Nervous System Neoplasms; Child, Preschool; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Kidney Neoplasms; Male; Mucin-1; Rhabdoid Tumor

The intermediate filament distribution pattern in cells and tissues of vertebrates reflects their differentiation or functional specialization state, their histogenesis, and their malignant transformation. In the case of cytokeratins, the characteristic epithelial intermediate filaments representing a complex group of about 30 polypeptides, extensive attention has been given to their expression in diverse epithelial and epithelioid cells. However, little is known about their distribution during fetal development and in neuroectodermal cells. This review specifically focuses on the data concerning cytokeratin expression in intracranial and intraspinal tissues, as expressed alone or as coexpressed with other intermediate filament proteins. Furthermore, the expression pattern of individual cytokeratin polypeptides was investigated by immunocytochemistry in diverse human and animal tissues using a broad panel of monoclonal antibodies. Only the cytokeratins typical of simple epithelia with the primary keratin pair 8/18 as a significant component have been detected in neuroectodermal tissues such as the choroid plexus and ciliary body epithelia, the retinal pigment epithelium, the subcommissural organ, and the ependymal cell clusters in fetal pineal gland (only in humans) as well as in various "unspecialized" ependymal cells of brain ventricles and spinal cord ependyma. Focal cytokeratin 19 expression in rat ciliary body and ventricle ependyma represents a rare exception. In addition, a group of intracranial and intraspinal tissues with controversial histogenesis express solely the cytokeratins 8 and 18: endocrine pituitary cells, arachnoid cells, and corneal endothelium. In most cases of tissues with neuroectodermal derivation, coexpression of cytokeratins and vimentin, or triple expression of cytokeratin, vimentin, and GFAP (fetal and neonatal choroid plexus of humans, rat and guinea pig ependymal cells in the neighborhood of the subcomissural, folliculostellate cells of human and guinea pig pituitary) is detectable. The coexpressions are discussed in the light of several hypotheses based on morphological and functional data concerning intermediate filament protein expression. Both the occurrence of more than one intermediate filament protein and the individual cytokeratin composition in the corresponding tumors of neuroectodermal origin reflect, in principle, the patterns found in their normal tissues. In the fetal neuroectodermal tissues studied, the cytoke

Topics: Central Nervous System; Central Nervous System Neoplasms; Keratins

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly malignant tumor of the central nervous system with poor prognosis. Nowadays, multimodal management, including surgery, chemotherapy (CMT), and radiation therapy (RT), is advocated. However, AT/RT treatment with gamma knife surgery (GKS) was rarely reported. The aim of this study was to assess the efficacy and safety of GKS for the treatment of AT/RT.. Medical records of AT/RT patients who underwent surgery from 2007 to 2014 at the West China Hospital were retrospectively reviewed and statistically analyzed.. Eighteen patients (12 males and 6 females) were presented with AT/RTs. Median age during presentation was 20.5 months (range, 4-179 months). Twelve patients were < 3 years and six patients were > 3 years. Tumor location was supratentorial in seven patients, infratentorial in ten patients, and center area of the brain in one patient. Treatments performed were as follows: surgery alone in two patients, surgery+RT in two patients, surgery+CMT in five patients, surgery+CMT+RT in two patients, and surgery+CMT+RT+GKS in seven patients. The 2-year overall survival (OS) rate and event-free survival (EFS) rate for all 18 consecutive patients were 33.3 and 27.8%, respectively. Cox regression analyses showed that multimodal management combined with GKS was an independent positive prognostic factor for OS.. Although AT/RTs are lethal cancer types, the OS of the disease was improved by using multimodal therapeutic strategies, including surgery, CMT, and RT, combined with GKS.

Topics: Adolescent; Antineoplastic Agents; Central Nervous System Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Infant; Keratins; Male; Mucin-1; Nerve Tissue Proteins; Radiosurgery; Retrospective Studies; Rhabdoid Tumor; Treatment Outcome; Vimentin

Exposure of cells to stress, particularly oxidative stress, leads to misfolding of proteins and, if they are not refolded or degraded, to cytoplasmic protein aggregates. Protein aggregates are characteristic features of a variety of chronic toxic and degenerative diseases, such as Mallory bodies (MBs) in hepatocytes in alcoholic and non-alcoholic steatohepatitis, neurofibrillary tangles in neurons in Alzheimer's, and Lewy bodies in Parkinson's disease. Using 2D gel electrophoresis and mass spectrometry, we identified p62 as a novel MB component. p62 and cytokeratins (CKs) are major MB constituents; HSP 70, HSP 25, and ubiquitinated CKs are also present. These proteins characterize MBs as a prototype of disease-associated cytoplasmic inclusions generated by stress-induced protein misfolding. As revealed by transfection of tissue culture cells overexpressed p62 did not induce aggregation of regular CK filaments but selectively bound to misfolded and ubiquitinated CKs. The general role of p62 in the cellular response to misfolded proteins was substantiated by detection of p62 in other cytoplasmic inclusions, such as neurofibrillary tangles, Lewy bodies, Rosenthal fibers, intracytoplasmic hyaline bodies in hepatocellular carcinoma, and alpha1-antitrypsin aggregates. The presence of p62 along with other stress proteins and ubiquitin in cytoplasmic inclusions indicates deposition as aggregates as a third line of defense against misfolded proteins in addition to refolding and degradation.

Topics: Adaptor Proteins, Signal Transducing; alpha 1-Antitrypsin Deficiency; Animals; Astrocytoma; Central Nervous System Neoplasms; CHO Cells; Cricetinae; Heat-Shock Proteins; Humans; Inclusion Bodies; Keratins; Liver Diseases; Mice; Neurodegenerative Diseases; Protein Binding; Protein Folding; Proteins; Sequestosome-1 Protein; Stress, Physiological; Ubiquitin

This study examined immunohistochemical staining patterns for several meningioma variants involving either the brain or spinal cord of dogs. Formalin-fixed, paraffin-embedded tissue from 15 tumors was obtained. The selected tumor group included seven meningothelial, three transitional, two malignant (anaplastic), one myxoid, one papillary, and one osteomatous meningiomas. Tumors were evaluated for reactivity to the following six immunohistochemical markers: vimentin, pancytokeratin, glial fibrillary acidic protein (GFAP), S100, neuron-specific enolase (NSE), and synaptophysin. Vimentin expression was detected in all meningiomas, and 14 of 15 tumors demonstrated intense vimentin staining in more than 50% of the neoplastic cells. Pancytokeratin expression was present in 11 of 15 neoplasms; however, positive staining frequently was focal and often involved a small percentage of the neoplastic cells. GFAP expression was detected in a single, anaplastic meningioma. Although expression of NSE and S100 was detected in 12 of 25 meningiomas, the intensity of the staining and the percentage of positive neoplastic cells was highly variable. Synaptophysin was uniformly negative. These results will help to establish immunohistochemical profiles for meningiomas that will improve our ability to correctly differentiate these neoplasms of meningeal origin from central nervous system tumors originating from other sites.

Topics: Animals; Brain Neoplasms; Central Nervous System Neoplasms; Dog Diseases; Dogs; Female; Glial Fibrillary Acidic Protein; Immunohistochemistry; Immunophenotyping; Keratins; Male; Meningioma; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin; Vimentin

During the last several decades, immunohistochemical studies of tumors, along with other approaches, have suggested that the clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic changes. However, CNS may provide a different microenvironment for activation and proliferation than other tissues. The tissue-specific distribution of intermediate filament proteins, in particular the keratins, permits their use as marker in histopathology, but several important exceptions are recognized. In this connection, it is of interest that, according to the other reports, glial tumors may be positive for different anti-keratin antibodies. However, the gliomas did not show an immunoreaction in any of the cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumors have particularly re-emphasized the need for new thinking about patterns of classification. The diagnosis of malignant melanoma has been considerably facilitated recently by the introduction of immunohistological labelling with antibodies selective against melanoma antigen (HMB-45). Our results confirmed the necessity of cautious interpretation of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several non-melanotic tumors.

Topics: Adenoma; Antibody Specificity; Biomarkers, Tumor; Central Nervous System Neoplasms; Humans; Immunohistochemistry; Keratins; Neoplasm Metastasis; Neoplasms; Pituitary Neoplasms