Volume 27, No. 6/2008(Nov/Dec)
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 Clinical Neuropathology
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Index 2008
Tumor
Ganglioglioma originating in the cerebellum with a large cyst – a case report and review of the literature
H. Tokunaga, K. Sunami, N. Wagai, H. Murai, Y. Nagai, T. Tanizawa, Y. Nakatani and Y. Iwadate
Abstract
H. Tokunaga1, K. Sunami1, N. Wagai1, H. Murai2, Y. Nagai3, T. Tanizawa3, Y. Nakatani3 and Y. Iwadate2
1Department of Neurosurgery, JFE Kawatetsu Chiba Hospital, 2Department of Neurological Surgery, 3Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan
Here we report a rare case of cerebellar ganglioglioma accompanied by a large cyst, and present a review of the reported 28 cases with cerebellar ganglioglioma. An otherwise healthy 46-year-old woman complained of gradual headache and truncal ataxia. MRI revealed a huge cystic lesion with a mural nodule in the left cerebellar hemisphere. The tumor was resected totally. Histologically, it was composed of neuronal and glial elements, and was accordingly diagnosed as ganglioglioma.Correspondence to:
Y. Iwadate, MD, PhD; Department of Neurological Surgery Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan
Email: iwadatey@faculty.chiba-u.jp
Tumor
Occipital pilomyxoid astrocytoma in a 14-year-old girl – case report
A.M. Buccoliero, C.F. Gheri, V. Maio, D. Moncini, F. Castiglione, F. Garbini, M. Sanzo, A. Taddei, L. Genitori and G.L. Taddei
Abstract
A.M. Buccoliero1, C.F. Gheri1, V. Maio1, D. Moncini1, F. Castiglione1, F. Garbini1, M. Sanzo2, A. Taddei3, L. Genitori2 and G.L. Taddei1
1Department of Human Pathology and Oncology, 2Division of Neurosurgery, “Anna Meyer” Pediatric Hospital, 3Department of General Surgery, University of Florence, Florence, Italy
Pilomyxoid astrocytoma is a recently described tumor. Its most typical morphological characteristics are an angiocentric astrocytic proliferation embedded in a myxoid background. The behavior seems to be unfavorable due to the reported high rate of local recurrence. The earlier studies indicated that pilomyxoid astrocytoma typically affects young children and arises in the hypothalamic/chiasmatic region. We report a case of a 14-year-old patient with a 6-year history of absence seizure. Magnetic resonance imaging showed a right occipital lesion of approximately 3 cm in diameter. The patient underwent the surgical procedure with gross total excision. Histologically, the tumor was mainly composed of a monomorphous population of bipolar elongated piloid cells radially arranged around thin-walled blood vessels in a prominent myxoid background. There were focal hemorrhagic foci but no bona fide evidence of tumor necrosis or mitoses. Rosenthal fibers and eosinophilic granular bodies were not observed. The postoperative course was uneventful. No adjuvant therapy was administered. The patient is alive and well at 18-month follow-up. The case presented provides evidence that pilomyxoid astrocytoma can occur at a later age and can arise in regions different from hypothalamic/chiasmatic.Correspondence to:
A.M. Buccoliero; Department of Human Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 85, 50134 Florence, Italy
Email: ambuccoliero@unifi.it
Tumor
Detecting chromosomal alterations at 1p and 19q by FISH and DNA fragment analysis – a comparative study in human gliomas
H. Broholm, P.W. Born, D. Guterbaum, H. Dyrbye and H. Laursen
Abstract
H. Broholm, P.W. Born, D. Guterbaum, H. Dyrbye and H. Laursen
Laboratory of Neuropathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Histological classification of gliomas is important for treatment and as a prognostic predictor, but classification by histology alone can be a challenge. Molecular genetic investigations, in particular the combined loss of the short arm of chromosome 1 and the long arm of chromosome19 (LOH1p/ 19q), has become a significant predictor of outcome in oligodendrogliomas. 1p/19q alterations can be investigated by fluorescence in situ hybridization (FISH), but controversies persist in the interpretation of results. Another technique is polymerase chain reaction (PCR) analysis using microsatellites as primers and capillary electrophoresis or southern blot as detection method. The objective of the present study was to compare the accuracy, reliability and feasibility of detecting chromosomal changes at 1p/19q with PCR microsatellite analysis and FISH in glial tumors in the clinical laboratory, where often only small formalin-fixed paraffin-embedded samples are available. Commercial DNA and normal cortex were used for comparison. The material comprised 41 glial tumors including 10 oligodendrogliomas (WHO Grades II and III, 5 each), 10 mixed oligoastrocytomas (WHO Grades II and III, 5 each), 10 astrocytomas (WHO Grades II and III, 5 each), and 11 glioblastomas (WHO Grade IV). Our data confirmed a correlation between FISH and LOH fragment analysis in classical oligodendrogliomas and in mixed oligoastrocytomas. Disparity was found among the glioblastomas, where fragment analysis showed 1p/19q loss in three cases, with no changes detected by FISH. The fragment analysis seems reliable and implementable for LOH 1p/19q investigation without patient-related control material.Correspondence to:
H. Broholm, MD; Laboratory of Neuropathology, 6301, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, 2100 Æ, Kopenhagen, Denmark
Email: hbroholm@rh.dk
Tumor
Poor reliability and reproducibility of PCR-based testing of O6-methylguanine-DNA methyltransferase gene (MGMT) promoter methylation status in formalin-fixed and paraffin-embedded neurosurgical biopsy specimens
M. Preusser, L. Elezi and J.A. Hainfellner
Abstract
M. Preusser1, L. Elezi2 and J.A. Hainfellner2
1Department of Internal Medicine I, Medical University, 2Institute of Neurology, Medical University of Vienna, Austria
Objective: To analyze the reliability and reproducibility of PCR-based testing of O6-methylguanine-DNA methyltransferase gene (MGMT) promoter methylation status in formalin-fixed and paraffin-embedded (FFPE) neurosurgical biopsy specimens. Materials: We used 6 FFPE neurosurgical temporal lobe specimens of children and young adults with drug-resistant epilepsy. Histopathologically, all specimens showed CNS tissue with gliosis but no tumor tissue. Methods: For MGMT promoter methylation analysis, we used methylation specific PCR (MGMT MSP). In all 6 tissue specimens, 4 repetitive runs of MGMT MSP were performed. Results: We obtained conclusive results only in 13/24 (54.2%) MGMT MSP analyses. In 5/13 (38.5%) successful MSP runs, the results indicated presence of a methylated MGMT promoter. In only 1/6 specimens, MSP yielded consistent results in all 4 repetitive runs. Conclusions: In our hands, MGMT MSP shows poor reliability and reproducibility of test results on FFPE neurosurgical tissue specimens. A more reliable method for diagnostic MGMT promoter methylation testing needs to be identified and validated by systematic testing of intra- and interlaboratory reliability and reproducibility. Alternatively, methods of tissue fixation that do not impair DNA quality but at the same time warrant high quality histopathology could facilitate molecular diagnostics.Correspondence to:
J.A. Hainfellner, MD; Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
Email: Johannes.hainfellner@meduniwien.ac.at.
Tumor
Angiocentric glioma: presentation of two cases with dissimilar histology
D. Arsene, C. Ardeleanu, I. Ogrezeanu and L. Danaila
Abstract
D. Arsene1,2, C. Ardeleanu1, I. Ogrezeanu3 and L. Danaila4
1Department of Histopathology, “Victor Babes” Institute of Pathology, 2Department of Neuropathology and Anatomic Pathology, National Institute of Neurology and Neurovascular Diseases, 3“Bagdasar-Arseni” Clinical Emergency Hospital, 42nd Neurosurgery Unit, National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania
Objective and importance: Angiocentric glioma (AG) is a recently described tumor of the brain which was included as a distinct entity in the 2007 WHO classification. To date only 26 cases have been reported in the literature. We describe two additional cases of this possibly confusing lesion of the brain. Emphasis is put on variations in the histopathological picture. Clinical presentation: The patients (20- and 55-year-old males) presented with seizures and headaches, respectively. Imaging examination showed a small cortical-subcortical tumor in each case. Both tumors were totally removed. Material and methods: Paraffin blocks from the two cases were examined with classical histopathology stainings and immunohistochemistry for GFAP, vimentin, EMA, neurofilament protein, synaptophysin, S100 protein, CD31, CD34, FVIII, smooth muscle actin and Ki67. Results: The tumor proliferation was restricted around small intraparenchymal vessels. Immunohistochemistry demonstrated positivity for glial and negativity for vascular or neuronal markers. The cell shape and arrangement was different in the two cases. Conclusions: AG is a peculiar tumor of uncertain histogenesis but with certain glial reactivity. Histopathology is variable but restricted, for unknown reasons, to perivascular areas. Apparently, a better prognosis than for other gliomas is distinctive. Further studies are needed in order to expand the information regarding the clinical behavior and therapeutic approach of this tumor type.Correspondence to:
Dr. D. Arsene; “Victor Babes” Institute of Pathology, Splaiul Independentei Nr. 99-101, Sect 5, Bucharest, Romania
Email: dorelarsene@yahoo.com
Tumor
A case of an elderly adult presenting with obstructive hydrocephalus secondary to a rare hemorrhagic suprasellar pilocytic astrocytoma
R.F. Sekula Jr., E.M. Marchan, M.R. Quigley, A.M. Frederickson and C. Pu
Abstract
R.F. Sekula Jr.1, E.M. Marchan1, M.R. Quigley1, A.M. Frederickson1 and C. Pu2
1Department of Neurosurgery and 2Department of Neuropathology, Allegheny Neuroscience Institute, Allegheny General Hospital, Drexel University College of Medicine, Pittsburgh, PA, USA
In this report, we present a 65-year-old man who presented with signs and symptoms consistent with impending brain herniation. Emergent imaging revealed a hyperdense mass in the suprasellar region. Urgent surgery was performed and final pathology eventuated a pilocytic astrocytoma. Although rare cases of suprasellar pilocytic astrocytoma in children and adults have been reported, we report an interesting case of a hemorrhagic suprasellar pilocytic astrocytoma in an elderly adult (without prior anticoagulant use) causing impending brain herniation secondary to obstructive hydrocephalus.Correspondence to:
R.F. Sekula Jr., MD; Assistant Professor of Neurological Surgery, Department of Neurosurgery, Allegheny General Hospital, Drexel University College of Medicine, 420 East North Ave. Suite 302, Pittsburgh, PA 15212, USA
Email: raymondsekula@yahoo.com
Infectious disease
Aspergillus terreus brain abscess mimicking tumor progression in a patient with treated glioblastoma multiforme
D.M. Damek, K.O. Lillehei and B.K. Kleinschmidt-DeMasters,
Abstract
D.M. Damek1,2, K.O. Lillehei2 and B.K. Kleinschmidt-DeMasters1,2,3
Departments of 1Neurology, 2Neurosurgery, 3Pathology, University of Colorado, Health Sciences Center, Aurora, CO, USA
Objective: To detail a case of Aspergillus terreus brain abscess in a patient undergoing treatment for malignant glioma. Central nervous system aspergillosis usually occurs in patients with hematopoietic neoplasms or post transplantation, not in those with solid tumors. Most systemic invasive mold infections are attributable to Aspergillus fumigatus or Aspergillus flavus. Patient and methods: The patient had received external beam radiation, temozolomide chemotherapy, and high-dose steroids, and had lymphopenia, but not sustained neutropenia. She developed a brain mass that mimicked tumor progression by neuroimaging criteria; infection was not a consideration. Results: Brain biopsy showed fungal cerebritis and cultures grew A. terreus, a variant being reported with greater frequency as a pathogen in patients with risk factors for aspergillosis. Conclusion: Brain tumor patients who receive steroids to control their peritumoral edema may be particularly susceptible to cerebral A. terreus infection, especially when they additionally develop the lymphopenia commonly associated with temozolomide.Correspondence to:
B.K. Kleinschmidt-DeMasters, MD; Department of Pathology, UCD-School of Medicine, P.O. Box 6510, 12605 E. 16th Avenue, Room 3017, Aurora, CO 80045, USA
Email: BK.DeMasters@uchsc.edu
Neurodegeneration
A patient with MV2 subtype of sporadic Creutzfeldt-Jakob disease and atypical clinical presentation
D, Guerrero, N. Martínez-Velilla, M.C. Caballero, M.T. Mendióroz, T. Tuñón,, J. Masdeu, A. Rodríguez, J. Armstrong and I. Ferrer
Abstract
D, Guerrero1, N. Martínez-Velilla2, M.C. Caballero1,3, M.T. Mendióroz4, T. Tuñón1,3,5, J. Masdeu6, A. Rodríguez7, J. Armstrong7 and I. Ferrer7
1Biomedical Research Center-Neurological Tissue Bank of Navarra, 2Department of Geriatrics, Navarra Hospital, 3Ciberned, 4Department of Neurology, Virgen del Camino Hospital, 5Department of Pathology, Navarra Hospital, 6University of Navarra, Pamplona, Navarra, 7Institute of Neuropathology, Idibell-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
We report the case of a 71-year-old woman with progressive dementia over the course of 4 years, characterized by prominent pyramidal signs and by the lack of ataxia and other cerebellar signs. Creutzfeldt-Jakob disease (CJD) was not suspected during the patient’s life. Autopsy brain tissue showed severe spongiform encephalopathy with kuru-like, but not florid, plaques in neocortex and cerebellum. Massive synaptic diffuse and plaque-like PrPSc deposition was found in the cerebral cortex, striatum, cerebellum and brainstem. Genetic analysis revealed no PRNP gene mutations and methionine/valine heterozygosity (MV) at codon 129. The pathogenic scrapie prion protein (PrPSc) pattern detected by Western blot was Type 2. However, this pattern showed a single unglycosylated band in contrast to the doublet described for MV2 subtype of sCJD with kuru plaques. In summary, this is an autopsy case report of a particular presentation of MV2 subtype of sCJD.Correspondence to:
D. Guerrero, PhD; Biomedical Research Center-Neurological Tissue Bank of Navarra, Irunlarrea, 3, Pamplona, 31008, Navarra, Spain
Email: dguerres@cfnavarra.es
Mitochondrial disease
The G11778A LHON mutation does not enhance ethambutol cytotoxicity in a cybrid model
R. Pommer, S. Schoeler, C. Mawrin, R. Szibor and E. Kirches
Abstract
R. Pommer1, S. Schoeler1, C. Mawrin2, R. Szibor3 and E. Kirches1
Institutes of 1Neuropathology and 3Forensic Medicine, Otto von Guericke University Magdeburg, 2Institute of Neuropathology, Friedrich Schiller University Jena, Germany
Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder, leading to a selective loss of retinal ganglion cells (RGC) and degeneration of the optic nerve, which results in severe visual impairment or even blindness. The primary causes are point mutations of the mitochondrial DNA (mtDNA), associated with aminoacid exchanges in complex I of the electron transport chain (ETC), which are thought to disturb oxidative ATP generation in the mitochondria. The major side effect of the antibiotic ethambutol, commonly used in tuberculosis therapy, is a retinopathy, which may lead to selective RGC loss, if not detected in an early stage. Moreover, LHON was reported to be elicited by ethambutol in some mutation carriers. Objective: The present study intended to measure a possible synergism between mitochondrial dysfunction, caused by the most common LHON mutation (G11778A) and caused by ethambutol, which may lead to a higher cytotoxicity of the drug in LHON cells. Material: An NT2/D1 teratoma-derived LHON cybrid line and the parental cells. Method: Determination of ethambutol toxicity in both lines, using a microtiter tetrazolium assay, luminometric measurement of ATP/ADP ratios and determination of mtDNA copy numbers by Realtime PCR. Results: Short-term ethambutol toxicity occurred only at mmolar concentrations, far beyond the estimated plasma peak concentrations of patients under antibiotic therapy. No significant difference occurred between both cell lines. The ATP/ADP ratios in the cybrids were surprisingly low, but showed no correlation with the mutational status of drug-treated cells. The mtDNA copy number of treated LHON and parental cells did not differ significantly. Conclusions: Ethambutol shows no synergism with the most common primary LHON mutation with respect to mitochondrial energy production or mtDNA replication in cybrid cells, although the issue of ATP decline should be further addressed in neuronally differentiated cybrids with complete OXPHOS dependency.Correspondence to:
Dr. E. Kirches; Institut für Neuropathologie, Otto-von-GuerickeUniversität, Leipziger Straße 44, 39120 Magdeburg, Germany
Email: Elmar.kirches@medizin.uni-magdeburg.de
Myology
Altered distribution of lamin and emerin in muscle nuclei of sIBM patients
A. Fidzianska, Z. Glinka, A. Kaminska, and I. Niebroj-Dobosz
Abstract
A. Fidzianska1, Z. Glinka1, A. Kaminska1,2 and I. Niebroj-Dobosz1
1Neuromuscular Unit MRC, Polish Academy of Sciences, 2Department of Neurology, Medical University of Warsaw, Poland
Objective: Sporadic inclusion body myositis (sIBM) is a chronic acquired inflammatory myopathy. The cause of sIBM remains unknown and its pathogenesis is controversial. There is a hypothesis [Karpati and Carpenter 1993] that the rimmed vacuoles result from nuclear breakdown, and IBM filaments are formed from components of the nuclear matrix. Material and methods: For nuclear membrane protein detection, six IBM patients were studied using immunohistochemical and immunochemical techniques. Results: It was demonstrated that in the interior of 10 – 15% myonuclei emerin and lamin A/C inclusions appeared constantly. This finding indicated an abberant localization of lamin A/C epitopes, the presence of presumptive lamin A (67 KDu) and emerin as in the affected nuclei. Conclusion: We support the suggestion that truncated, changed lamin A protein takes part in nuclear disintegration and rimmed vacuole formation.Correspondence to:
A. Fidzianska, MD, PhD; Neuromuscular Unit, Medical Research Center, Polish Academy of
Sciences, Pawinskiego 5 str., 02-106 Warsaw, Poland
Email: neurmyol@cmdik.pan.pl
Myology
Dynamin 2-related centronuclear myopathy: Clinical, histological and genetic aspects of further patients and review of the literature
M. Jeub, M. Bitoun, P. Guicheney,, K. Kappes-Horn, K. Strach, K.F. Druschky, J. Weis and D. Fischer,
Abstract
M. Jeub1, M. Bitoun2,3, P. Guicheney2,3,4, K. Kappes-Horn1, K. Strach5, K.F. Druschky6, J. Weis7 and D. Fischer1,8
1Muskellabor, Department of Neurology, University Hospital of Bonn, Germany, 2Institut National de la Santé et de la Recherche Médicale, U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 3Université Pierre et Marie Curie-Paris 6, UMR S582, IFR14, 4AP-HP, Groupe Hospitalier Pitié-Salpêtrière Hospital, Paris, France, 5Department of Radiology, University Hospital of Bonn, 6Department of Neurology, Klinikum Karlsruhe, 7Institute of Neuropathology, RWTH University Hospital, Aachen, Germany, and 8Department of Neurology, University Hospital Basel and Department of Neuropediatrics, University Children’s Hospital, Basel, Switzerland
Centronuclear myopathy (CNM) is a slowly progressive congenital myopathy with characteristic histopathological findings of chains of centrally located myonuclei in a large number of muscle fibers. Recently, different missense mutations in the dynamin 2 gene (DNM2, 19p13.2) have been shown to cause autosomal dominant CNM. We re-evaluated patients with a histopathological diagnosis of CNM and report on the clinical phenotype, the biopsy findings and the genetic results of these patients and review the current literature. Two of the three patients showed an unusually late disease onset (> 40 years). Interestingly, intramuscular nerve fascicles found in the muscle biopsy of a patient harboring the E368K DNM2 mutation contained nerve fibers with disproportionately thin myelin sheaths. Schwann cells of unmyelinated nerve fibers showed abnormal plasma membrane and basal lamina protrusions, indicating peripheral nerve involvement.Correspondence to:
Dr. med. D. Fischer; Neurologische Klinik, Universitätsspital Basel, Petersgraben 4, 4031 Basel, Switzerland
Email: fischerdi@uhbs.ch
History of Neuropathology
125th anniversary of the Institute of Neurology (Obersteiner Institute) in Vienna. “Germ Cell” of Interdisciplinary Neuroscience
G. Kreft, G.G. Kovacs, T. Voigtländer, C. Haberler, J.A. Hainfellner, H. Bernheimer and H. Budka
Abstract
G. Kreft, G.G. Kovacs, T. Voigtländer, C. Haberler, J.A. Hainfellner, H. Bernheimer and H. Budka
Euro-CNS News
Society News of the European Confederation of Neuropathological Societies
