Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway.

Abstract:

:Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the granule cell hypertrophy in LDD is secondary to activation of mammalian target of rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major regulator of cell growth. Histopathologically, in addition to the classical findings of LDD, we observed prominent vascular proliferation and vacuolization of the white matter in many of the lesions. Four patients met diagnostic criteria for CD, and many of the remaining patients had some clinical features of CD. Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in the large ganglionic cells forming the lesions, indicating activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD. These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic inhibition of mTOR.

authors

Abel TW,Baker SJ,Fraser MM,Tihan T,Nelson JS,Yachnis AT,Bouffard JP,Mena H,Burger PC,Eberhart CG

doi

10.1093/jnen/64.4.341

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

341-9

issue

4

eissn

0022-3069

issn

1554-6578

journal_volume

64

pub_type

杂志文章,评审
  • Retroperitoneal ganglioneuroblastoma: a kaleidoscope of neuronal degeneration. A light and electron microscopic study.

    abstract::The light and electron microscopic features of an unique retroperitoneal ganglioneuroblastoma in a four-year-old female are described. The unprecedented concurrence of Hirano, zebra, membranous cytoplasmic (MCB), and Pick bodies in the same population of neoplastic, sympathetic ganglion cells provides further evidence...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197601000-00002

    authors: Powers JM,Balentine JD,Wiśniewski HM,Terry RD

    更新日期:1976-01-01 00:00:00

  • Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. III. bergmann fiber anomalies.

    abstract::Bergmann fibers and the distribution of Golgi epithelial cells were significantly altered in staggerer, reeler and double mutant (affected by both staggerer and reeler conditions). However, the Bergmann fiber anomalies in double mutant were not identical to those of either staggerer or reeler. A comparison of these an...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197705000-00003

    authors: Yoon CH

    更新日期:1977-05-01 00:00:00

  • Primary brain lymphoma cell turnover differs in patients with and without AIDS: relationships to bcl-2 expression and host cell reaction.

    abstract::Primary central nervous system lymphomas (PCNSLs) are more resistant to radiotherapy and chemotherapy in AIDS (A-PCNSLs) than in non-AIDS patients (NA-PCNSLs). We investigated 23 A-PCNSLs and 24 NA-PCNSLs. Lymphoma cell kinetics (i.e. proliferation [mitotic index, MIB-1 and PCNA labeling indices], apoptosis and turnov...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199910000-00005

    authors: Christov C,Adle-Biassette H,Lechapt E,Poron F,Gray F,Gaulard P,Gherardi RK

    更新日期:1999-10-01 00:00:00

  • Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation.

    abstract::In the central nervous system, tuberous sclerosis complex (TSC) is characterized by a range of lesions including cortical tubers, white matter heterotopias, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). Recent studies have implicated an important role for the TSC genes TSC1 and TSC2, in a sig...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.12.1236

    authors: Chan JA,Zhang H,Roberts PS,Jozwiak S,Wieslawa G,Lewin-Kowalik J,Kotulska K,Kwiatkowski DJ

    更新日期:2004-12-01 00:00:00

  • Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression.

    abstract::Recent studies have shown that deficient functioning of glutamate transporters (GTs) in Alzheimer disease (AD) might lead to neurodegeneration. The main objectives of the present study were to determine which GT subtype is most affected in AD and to asses to what extent altered GT function is associated with abnormal ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199708000-00008

    authors: Li S,Mallory M,Alford M,Tanaka S,Masliah E

    更新日期:1997-08-01 00:00:00

  • Restoration of blood-nerve barrier in neuropathy is associated with axonal regeneration and remyelination.

    abstract::We investigated the temporal course of blood-nerve barrier (BNB) breakdown during the evolution of tellurium neuropathy, ricin neuropathy, and Wallerian degeneration following nerve transection or nerve crush. Blood-nerve barrier permeability was assessed with a 4,000-molecular weight fluoresceinated dextran from thre...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199111000-00004

    authors: Bouldin TW,Earnhardt TS,Goines ND

    更新日期:1991-11-01 00:00:00

  • Neuropathologic, biochemical, and molecular characterization of the frontotemporal dementias.

    abstract::The frontotemporal dementias (FTDs) are a heterogeneous group of neurodegenerative disorders that are characterized clinically by dementia, personality changes, language impairment, and occasionally extrapyramidal movement disorders. Historically, the diagnosis and classification of FTDs has been fraught with difficul...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/64.5.420

    authors: Mott RT,Dickson DW,Trojanowski JQ,Zhukareva V,Lee VM,Forman M,Van Deerlin V,Ervin JF,Wang DS,Schmechel DE,Hulette CM

    更新日期:2005-05-01 00:00:00

  • Brain structures selectively targeted by canine distemper virus in a mouse model infection.

    abstract::Paramyxoviruses such as measles virus or canine distemper virus are etiological agents for acute and chronic encephalitis (measles inclusion body encephalitis, subacute sclerosing panencephalitis and chronic distemper encephalitis or old dog encephalitis). The mechanisms by which viral injury leads to neurological dis...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199309000-00005

    authors: Bernard A,Fevre-Montange M,Bencsik A,Giraudon P,Wild TF,Confavreux C,Belin MF

    更新日期:1993-09-01 00:00:00

  • Prominent Vascular and Perivascular Eosinophilic Infiltrates Heralding CNS Mycosis Fungoides.

    abstract::Brain parenchymal involvement of mycosis fungoides (MF) is very rare. This study reports a patient with known cutaneous MF (under treatment) who presented with a CNS syndrome and multiple brain lesions. Brain biopsy demonstrated massive eosinophilic infiltrates but no MF cells. Despite treatment, new lesions developed...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0000000000000245

    authors: Schowinsky J,Leppert M,Ney D,Kleinschmidt-DeMasters BK

    更新日期:2015-10-01 00:00:00

  • Therapy of a murine model of pediatric brain tumors using a herpes simplex virus type-1 ICP34.5 mutant and demonstration of viral replication within the CNS.

    abstract::To develop improved therapies for medulloblastoma, we studied the ability of a neuroattenuated HSV-1 ICP34.5 mutant (variant-1716) to replicate within and destory an authentic medulloblastoma cell line known as Med 283 (D283) using immunohistochemistry, in situ hybridization, and viral titrations. In vitro studies sho...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199612000-00010

    authors: Lasner TM,Kesari S,Brown SM,Lee VM,Fraser NW,Trojanowski JQ

    更新日期:1996-12-01 00:00:00

  • Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

    abstract::Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31821350b0

    authors: Waddell LB,Lemckert FA,Zheng XF,Tran J,Evesson FJ,Hawkes JM,Lek A,Street NE,Lin P,Clarke NF,Landstrom AP,Ackerman MJ,Weisleder N,Ma J,North KN,Cooper ST

    更新日期:2011-04-01 00:00:00

  • Selective nuclear shrinkage of oligodendrocytes lacking glial cytoplasmic inclusions in multiple system atrophy: a 3-dimensional volumetric study.

    abstract::Glial cytoplasmic inclusions (GCIs) are a pathologic hallmark of multiple system atrophy (MSA), but their pathogenetic roles need to be clarified. To determine possible roles of GCIs in individual cells, serial optical sections obtained by confocal microscopy were reconstructed to yield 3-dimensional (3D) images of th...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181b67678

    authors: Uyama N,Uchihara T,Mochizuki Y,Nakamura A,Takahashi R,Mizutani T

    更新日期:2009-10-01 00:00:00

  • Inclusion-body myositis: newest concepts of pathogenesis and relation to aging and Alzheimer disease.

    abstract::We review the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic criteria of s-IBM. We discuss the possible pathogenic role of several themes, such as 1) increased amyloid-beta precursor protein (AbetaPP) and of its fragment ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章,评审

    doi:10.1093/jnen/60.1.1

    authors: Askanas V,Engel WK

    更新日期:2001-01-01 00:00:00

  • Remyelination After Cuprizone-Induced Demyelination Is Accelerated in Juvenile Mice.

    abstract::Remyelination capacity decreases with age in adult mice, but data comparing remyelination capacity after toxic demyelination in developing mice versus adult mice are not available. We treated 3-week-old and adult C57BL/6 mice with cuprizone for 1 to 5 weeks and studied demyelination/remyelination and cellular reaction...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0000000000000214

    authors: Pfeifenbring S,Nessler S,Wegner C,Stadelmann C,Brück W

    更新日期:2015-08-01 00:00:00

  • Downregulation of the potassium chloride cotransporter KCC2 in vulnerable motoneurons in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.

    abstract::The balance between excitatory and inhibitory synaptic inputs is critical for the physiological control of motoneurons. The maintenance of a low-intracellular chloride concentration by the potassium chloride cotransporter 2 (KCC2) is essential for the efficacy of fast synaptic inhibition of mature motoneurons in respo...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181f4dcef

    authors: Fuchs A,Ringer C,Bilkei-Gorzo A,Weihe E,Roeper J,Schütz B

    更新日期:2010-10-01 00:00:00

  • PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury.

    abstract::The long-term disabilities associated with spinal cord injury (SCI) are primarily due to the absence of robust neuronal regeneration and functional plasticity. The inability of the axon to regenerate after SCI is contributed by several intrinsic factors that trigger a cascade of molecular growth program and modulates ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlaa147

    authors: Bhowmick S,Abdul-Muneer PM

    更新日期:2021-01-20 00:00:00

  • Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: a clinicopathologic study of 53 cases.

    abstract::Pediatric and NF2-associated meningiomas are uncommon and poorly characterized in comparison to sporadic adult cases. In order to elucidate their molecular features, we analyzed MIB-1, progesterone receptor (PR), NF2, merlin, DAL-1, DAL-1 protein, and chromosomal arms 1p and 14q in 53 meningiomas from 40 pediatric/NF2...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/60.10.994

    authors: Perry A,Giannini C,Raghavan R,Scheithauer BW,Banerjee R,Margraf L,Bowers DC,Lytle RA,Newsham IF,Gutmann DH

    更新日期:2001-10-01 00:00:00

  • Malignant peripheral nerve sheath tumor invasion requires aberrantly expressed EGF receptors and is variably enhanced by multiple EGF family ligands.

    abstract::Aberrant epidermal growth factor receptor (EGFR) expression promotes the pathogenesis of malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with neurofibromatosis type 1, but the mechanisms by which EGFR expression promotes MPNST pathogenesis are poorly understood. We hypothesized...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3182859939

    authors: Byer SJ,Brossier NM,Peavler LT,Eckert JM,Watkins S,Roth KA,Carroll SL

    更新日期:2013-03-01 00:00:00

  • Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice.

    abstract::Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/nen.0b013e318040ad5c

    authors: Huizinga R,Heijmans N,Schubert P,Gschmeissner S,'t Hart BA,Herrmann H,Amor S

    更新日期:2007-04-01 00:00:00

  • Astrocytic proteins in the dorsal and ventral roots in amyotrophic lateral sclerosis and Werdnig-Hoffmann disease.

    abstract::Abnormalities were detected by two-dimensional gel electrophoresis in the protein composition of both the dorsal and ventral roots of three of six patients who succumbed to amyotrophic lateral sclerosis (ALS). The abnormalities consisted of a cascade of acidic protein spots on silver-stained gels which were shown by i...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198411000-00005

    authors: Brock TO,McIlwain DL

    更新日期:1984-11-01 00:00:00

  • Alterations of the microvascular network in sclerotic hippocampi from patients with epilepsy.

    abstract::The main hallmarks of human hippocampal sclerosis are neuronal loss and gliosis; reductions in microvasculature labeling in the cornu Ammonis 1 in this condition have been detected using alkaline phosphatase histochemistry. To determine whether the reduction in alkaline phosphatase activity is coupled with a loss of b...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181b08622

    authors: Kastanauskaite A,Alonso-Nanclares L,Blazquez-Llorca L,Pastor J,Sola RG,DeFelipe J

    更新日期:2009-08-01 00:00:00

  • Medulloblastoma with glial and rhabdomyoblastic differentiation. A myoglobin and glial fibrillary acidic protein immunohistochemical and ultrastructural study.

    abstract::This is a report of an unusual, densely cellular, midcerebellar neoplasm in a seven-year-old boy. Although clinically consistent with a medulloblastoma, immunohistochemistry and electron microscopy demonstrated glial and rhabdomyoblastic differentiation in the tumor. We discuss the differential diagnosis of this tumor...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198311000-00004

    authors: Dickson DW,Hart MN,Menezes A,Cancilla PA

    更新日期:1983-11-01 00:00:00

  • Neutralizing antibodies to IL-18 ameliorate experimental autoimmune neuritis by counter-regulation of autoreactive Th1 responses to peripheral myelin antigen.

    abstract::Experimental autoimmune neuritis (EAN) is a demyelinating disease of the peripheral nervous system (PNS). This acute inflammatory disease is mediated by CD4+ T cells and bears significant similarities to the Guillain-Barré syndrome of humans. In the present study, we investigated the function of IL-18 in T cell-mediat...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/61.7.614

    authors: Yu S,Chen Z,Mix E,Zhu SW,Winblad B,Ljunggren HG,Zhu J

    更新日期:2002-07-01 00:00:00

  • TAR DNA-Binding protein 43 accumulation in protein aggregate myopathies.

    abstract::Protein aggregate myopathies, including myofibrillar myopathies and sporadic inclusion body myositis (sIBM), are characterized by abnormal protein aggregates composed of various muscular and ectopic proteins. Previous studies have shown the crucial role ofdysregulated transcription factors such as neuron-restrictive s...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181996d8f

    authors: Olivé M,Janué A,Moreno D,Gámez J,Torrejón-Escribano B,Ferrer I

    更新日期:2009-03-01 00:00:00

  • Targeting vascular amyloid in arterioles of Alzheimer disease transgenic mice with amyloid β protein antibody-coated nanoparticles.

    abstract::The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that uses a monoclo...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318225038c

    authors: Poduslo JF,Hultman KL,Curran GL,Preboske GM,Chamberlain R,Marjańska M,Garwood M,Jack CR Jr,Wengenack TM

    更新日期:2011-08-01 00:00:00

  • Developmental changes in neurotransmitter receptor binding in the human periaqueductal gray.

    abstract::The periaqueductal gray (PAG) plays a central role in the integration of defense responses to threatening or stressful stimuli. Little is known about the neurochemical development of the human PAG around the time of birth, when the fetus makes the transition to extrauterine life and independent defense responses are n...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199604000-00003

    authors: Reddy SC,Panigrahy A,White WF,Kinney HC

    更新日期:1996-04-01 00:00:00

  • BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants.

    abstract::Recent studies highlight the importance of BRAF alterations resulting in mitogen activated protein kinase (MAK/ERK) pathway activation in low-grade CNS tumors. We studied 106 low-grade CNS neoplasms in a cohort of primarily pediatric patients to identify the prevalence and clinicopathologic significance of these alter...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31823f2cb0

    authors: Lin A,Rodriguez FJ,Karajannis MA,Williams SC,Legault G,Zagzag D,Burger PC,Allen JC,Eberhart CG,Bar EE

    更新日期:2012-01-01 00:00:00

  • Podoplanin: a marker for reactive gliosis in gliomas and brain injury.

    abstract::Reactive astrogliosis is associated with many pathologic processes in the central nervous system, including gliomas. The glycoprotein podoplanin (PDPN) is upregulated in malignant gliomas. Using a syngeneic intracranial glioma mouse model, we show that PDPN is highly expressed in a subset of glial fibrillary acidic pr...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0000000000000150

    authors: Kolar K,Freitas-Andrade M,Bechberger JF,Krishnan H,Goldberg GS,Naus CC,Sin WC

    更新日期:2015-01-01 00:00:00

  • Dendritic vacuolization in the central nervous system of rats after long-term voluntary consumption of ethanol.

    abstract::Adult male rats were housed in a colony environment for six months, with ad lib access to anise-flavored 10% ethanol in water. Animals were then removed from the colony, and their consumption of alcohol during a period in isolated housing was measured. Individual rats were scored as high, moderate, and low consumers. ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198309000-00009

    authors: Goldstein B,Maxwell DS,Ellison G,Hammer RP

    更新日期:1983-09-01 00:00:00

  • Primitive neuroectodermal tumors of the cerebral hemispheres in two siblings with TP53 germline mutation.

    abstract::AWe report on two siblings (brother and sister) who developed cerebral PNETs at the age of 5 years and 6 months, respectively. Both children were treated by operation followed by polychemotherapy. The brother also received cranio-spinal irradiation. Nevertheless, the children died about 12 months and 24 months post-op...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199802000-00009

    authors: Reifenberger J,Janssen G,Weber RG,Boström J,Engelbrecht V,Lichter P,Borchard F,Göbel U,Lenard HG,Reifenberger G

    更新日期:1998-02-01 00:00:00