摘要:

In recent years, antineuronal autoantibodies of varying antigenic specificity have come to be associated with a number of paraneoplastic neurologic disorders. Anti‐Hu is a polyclonal complement‐fixing IgG directed against a 35 to 40 kilodalton protein concentrated in the nuclei of neurons throughout the central and peripheral neuraxes. Its elaboration at high titer in serum and cerebrospinal fluid is invariably associated with a neurologic syndrome characterized chiefly by subacutely evolving sensory neuropathy and an array of central disturbances that include bulbar and cerebellar dysfunction, limbic encephalitis and motor neuron disease. The manufacture of anti‐Hu IgG is triggered in a great majority of cases by underlying small cell carcinomas of pulmonary origin, typically limited in stage and otherwise silent, that aberrantly express the native neuronal antigen or an antigenically indistinguishable epitope. Both neoplastic and diseased neural tissues contain lymphocytes of B and T lineage specifically cognizant of the Hu antigen as well as concentrated anti‐Hu IgG bound to tumor cells and neurons, respectively. These observations suggest that an immune response serving initially to limit the growth and spread of its inciting neoplasm comes subsequently to be misdirected against the nervous system of the host, resulting in autoimmunologically‐mediated neurologic injury. Clinical, neuropathologic and immunologic data derived from a series of 71 sero‐confirmed cases of the anti‐Hu‐associated paraneoplastic sensory neuronopathy/encephalomyelitis compl

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00747.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Multiple sclerosis (MS) is generally considered to be an autoimmune disorder with myelin as the target and with several unidentified viruses playing ancillary roles, possibly through molecular mimicry. Although this paradigm has led to important progress on potential mechanisms of myelin loss, neither a target antigen in myelin nor a triggering mechanism has yet been identified, leaving the etiology of MS still unknown. Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. A host immune response targeting proteins expressed at low levels from viral DNA latent in the central nervous system (CNS) might underlie a focal demyelinating disease such as MS. A shift from autoimmunity to a latent‐virus model is not a trivial substitution of target antigens. This shift would expand the search for a definitive laboratory test for MS and could lead to improved therapeutic and preventive approache

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00748.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Thep53tumor suppressor gene is frequently mutated in glioblastomas. Mutations within thep53gene often result in aberrant expression of the p53 protein leading to protein accumulation within the nucleus of the cells which can be detected by immunochemistry. Many studies have correlated alterations of p53 protein expression withp53gene mutations. Positive staining of tumor cells for p53 protein has been widely assumed, perhaps incorrectly, to signify the presence ofp53gene mutations. This study compared the immunostaining patterns for p53 protein in 37 glioblastomas with the molecular genetic data obtained by the single strand conformation polymorphism assay.p53gene mutations were detected in 46% (17 of 37) of glioblastomas, while 65% (24 of 37) of glioblastomas were positive for protein accumulation by immunohistochemistry. Although 30 of 37 glioblastomas analyzed showed concordance for p53 protein expression andp53gene mutations, a subset of seven glioblastomas showed discordant accumulation of the p53 protein in the absence of any detectablep53gene mutations. The mdm‐2 gene was assessed in 17 glioblastomas for gene rearrangements or amplification, but none were found. This result suggests that a mechanism other thanp53gene mutation can result in altered p53 protein expressio

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00749.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

To detect DNA sequences of herpes simplex virus (HSV) in neural and non‐neural tissue sections in disseminated human neonatal HSV infection, a solution polymerase chain reaction (PCR) protocol was developed which amplified HSV thymidine kinase and host genomic DNA sequences that were hybridized with sequence‐specific probes in Southern blots. Serial sections of formalin‐fixed, paraffin embedded autopsy tissues were tested by PCR and compared to histology and HSV antigen detection. The sensitivity, specificity and reproducibility of this PCR protocol were determined on uninfected and HSV‐infected mouse tissues and on HSV DNA from infected tissue culture cells. Samples estimated to contain as few as 60 copies of preserved HSV DNA target sequence gave a positive PCR result. In nine neonates that died during acute HSV infection, all non‐neural tissues and a minority of neural tissues with histological lesions had HSV antigen; when DNA could be amplified, HSV DNA sequences were detected by PCR. Together, these findings indicate a direct role for virus in the pathogenesis of these lesions. In the same cases, some or all brain samples were negative for HSV antigen, but nevertheless had HSV DNA sequences detected by PCR. The possible explanations for this finding are discussed. In one neonate dying seven weeks after birth, HSV sequences were found in brain lesions in the absence of HSV antigen; neither HSV DNA nor antigen were found in non‐neural tissues, suggesting a latent HSV infection in brain. It is practical to apply PCR methods to detect minute quantities of viral DNA in formalin‐fixed, paraffin embedded autopsy tissues. With careful selection of conditions, suitable controls and meticulous attention to technique, specific results can be obtained, and can be correlated with histology and immunohistochemical

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00750.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

In early 1987, I was approached by Professor Klaus Joachim Zülch, with a proposal that I convene at an early date a meeting in Houston, Texas, for the purpose of considering recent research developments that might have an influence on the classification of brain tumors. It was further considered that a review of this nature might ultimately necessitate revision of the WHO “Blue Book” ofHistological Typing of Tumours of the Central Nervous System.Among the group which met in Houston in March 1988 were members of the original Collaborating Centre who were still active and other neuropathologists from around the world who had expertise in these mat

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00751.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The new edition of the World Health Organization (WHO) book on ‘Histological Typing of Tumours of the Central Nervous System’ reflects the progress in brain tumour classification which has been achieved since publication of the first edition in 1979. Several new tumour entities have been added, including the pleomorphic xanthoastrocytoma, central neurocytoma, the infantile desmoplastic astrocytoma/ganglioglioma, and the dysembryoplastic neuroepithelial tumour. The list of histological variants has also been expanded. In line with recent morphological and molecular data on glioma progression, the glioblastoma is now grouped together with astrocytic tumours. The classification of childhood tumours has been largely retained, the diagnosis primitive neuroectodermal tumour (PNET) only being recommended as a generic term for cerebellar meduiloblastomas and neoplasms that are histologically indistinguishable from medulloblastoma but located in the CNS at sites other than the cerebellum. The WHO grading scheme was revised and adapted to new entities but its use, as before, remains optio

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00752.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This review deals with one of the newly adopted entities in the second edition of the histologic typing of CNS tumours by the World Health Organization: pleomorphic xanthoastrocytoma and reviews the clinical features, gross and microscopic characteristics as well as the common and some of the unusual variants of this tumor. The steps and events leading to the recognition of the basic character of this neoplasm and its designation as an independent entity are recollected and a few characteristic MRI scans and photomicrographs of pleomorphic xanthoastrocytomas are provided.

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00753.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The desmoplastic infantile ganglioglioma and desmoplastic cerebral astrocytoma of infancy are rare neoplasms arising in the cerebral hemispheres within the first two years of life which are defined by a combination of distinctive clinicopathologic features. The tumours are massive, partially cystic and invariably occur in a supratentorial location. Involvement of multiple lobes is common with a predilection for frontoparietal areas. In one series of 22 desmoplastic infantile gangliogliomas, all patients presented between 2 and 24 months of age (mean = 6 months; median = 4 months) with a male to female ratio of 1.4: 1. In the nine reported cases of the desmoplastic cerebral astrocytoma of infancy, all patients presented between 1.5 and 14 months of age (mean = 6.8 months; median = 6 months) with a male to female ratio 0.8: 1. The hallmark feature of both neoplasms is an abundant and often dense desmoplasia, imparting a characteristic firmness to the neoplasms. In the desmoplastic infantile gangliogliomas, astroglial and neuronal tumour cells in addition to variable numbers of more primitive, mitotic cells comprise the neoplastic neuroepithelial populations. In contrast, the neuroepithelial component of the desmoplastic infantile astrocytomas is restricted to neoplastic astrocytes. Despite the large size, cellular pleomorphism and cellular atypia, prognosis following successful surgical resection in both types of tumours is quite favorable. The longest followup data is available for the desmoplastic infantile gangliogliomas. With the median interval of 8.7 years (range 1 to 14.5 years) following surgery for 14 patients in this series, there were no deaths due to tumour or any evidence of tumour recurrence. Likewise for the astrocytomas, with a median followup of 1.5 years (≥5.5 years), there was no evidence of tumour recurrenc

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00754.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Dysembryoplastic neuroepithelial tumours (DNTs) are a group of supratentorial cortical benignant lesions that superficially resemble mixed oligoastrocytomas, oligodendrogliomas or astrocytomas. Clinically these tumours are associated with partial seizures beginning before the age of 20 years, with no neurologic deficit and no stigmata of phacomatosis. In the revised WHO classification, DNTs have been incorporated among the category of neuronal and mixed neuronoglial tumours. This classification describes a histologic variant characterized by the following criteria: cortical location, multinodular architecture ‐ the nodule being made of multiple variants looking like astrocytomas, oligodendrogliomas or oligo‐astrocytomas, foci of dysplastic cortical disorganization and the presence of a glioneuronal element showing a columnar structure perpendicular to the cortical surface. A study of 14 cases for which only a specific glioneuronal element could be identified demonstrated that this specific element is sufficient for diagnosing DNTs and that the spectrum of DNTs includes a simple form with a unique glioneuronal element. Preoperative imaging follow‐up data, in the series of 23 simple and complex forms, indicated that DNTs are perfectly stable. However, these tumours may show a high MIB1 labeling

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00755.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The central neurocytoma is a supratentorial, often calcified brain tumour affecting young adults and is typically located in the lateral ventricles in the region of the foramen of Monro. Clinically, the tumour causes signs of increased intracranial pressure, visual and mental disturbances and, occasionally, pyramidal or endocrine symptoms. By light microscopy, the tumour is composed of small round cells in a delicate fibrillary matrix. Tumour cells consistently show features of neuronal differentiation by electron microscopy (synapses, dense‐core vesicles, presynaptic clear vesicles, specialized synaptic junctions) and immunoreactivity for synaptophysin and other neuronal marker proteins. The tumour can be totally removed in nearly half of the cases. After incomplete surgical resection neurocytomas may recur but because of their low proliferation potential, radio‐ or chemotherapy are not generally recommended. Postoperative recurrence‐free survival times of up to 19 years have been reported. Neurocytomas constitute nearly one half of supratentorial intraventricular tumours in adults but amount to less than 1% of all tumours of the central nervous system and its cove

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00756.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY