Volume 33, No. 1/2014(January/February)
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Editorial
Clinical Neuropathology 1-2014
Johannes A. Hainfellner
Page No. 1
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (1-5)
Clinical Neuropathology 1-2014
Johannes A. Hainfellner
Original
Clinical Neuropathology practice news 1-2014: Pyrosequencing meets clinical and analytical performance criteria for routine testing of MGMT promoter methylation status in glioblastoma
Matthias Preusser, Anna S. Berghoff, Claudia Manzl, Martin Filipits, Andreas Weinhäusel, Walter Pulverer, Karin Dieckmann, Georg Widhalm, Adelheid Wöhrer, Engelbert Knosp, Christine Marosi, and Johannes A. Hainfellner
Page No. 6
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (6-14)
Clinical Neuropathology practice news 1-2014: Pyrosequencing meets clinical and analytical performance criteria for routine testing of MGMT promoter methylation status in glioblastoma
Matthias Preusser1,3, Anna S. Berghoff1,3, Claudia Manzl2, Martin Filipits1,3, Andreas Weinhäusel4, Walter Pulverer4, Karin Dieckmann5,3, Georg Widhalm6,3, Adelheid Wöhrer3,7, Engelbert Knosp6,3, Christine Marosi1,3, and Johannes A. Hainfellner3,7
1Department of Medicine I, Medical University of Vienna, Vienna, 2Division of Pathology, Medical University of Innsbruck, Innsbruck, 3Comprehensive Cancer Center – CNS Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, 4Molecular Diagnostics, Austrian Institute of Technology, 5Department of Radiotherapy, 6Department of Neurosurgery, and 7Institute of Neurology, Medical University of Vienna, Vienna, Austria
Testing of the MGMT promoter methylation status in glioblastoma is relevant for clinical decision making and research applications. Two recent and independent phase III therapy trials confirmed a prognostic and predictive value of the MGMT promoter methylation status in elderly glioblastoma patients. Several methods for MGMT promoter methylation testing have been proposed, but seem to be of limited test reliability. Therefore, and also due to feasibility reasons, translation of MGMT methylation testing into routine use has been protracted so far. Pyrosequencing after prior DNA bisulfite modification has emerged as a reliable, accurate, fast and easy-to-use method for MGMT promoter methylation testing in tumor tissues (including formalinfixed and paraffin-embedded samples). We performed an intra- and inter-laboratory ring trial which demonstrates a high analytical performance of this technique. Thus, pyrosequencing- based assessment of MGMT promoter methylation status in glioblastoma meets the criteria of high analytical test performance and can be recommended for clinical application, provided that strict quality control is performed. Our article summarizes clinical indications, practical instructions and open issues for MGMT promoter methylation testing in glioblastoma using pyrosequencing.Correspondence to:
Johannes A. Hainfellner, MD
Institute of Neurology & Comprehensive Cancer
Center –
CNS Tumors Unit (CCC-CNS),
Medical University of Vienna
Währinger Gürtel 18-20, 1090 Vienna, Austria
Email: [email protected]
Original
Embryonal tumor with multilayered rosettes: Diagnostic tools update and review of the literature
Johnatan Ceccom, Franck Bourdeaut, Najat Loukh, Valerie Rigau, Serge Milin, Romulus Takin, Wilfrid Richer, Emmanuelle Uro-Coste, Jerome Couturier, Anne Isabelle Bertozzi, Olivier Delattre and Marie Bernadette Delisle
Page No. 15
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (15-22)
Embryonal tumor with multilayered rosettes: Diagnostic tools update and review of the literature
Johnatan Ceccom1, Franck Bourdeaut2,3,4, Najat Loukh1, Valerie Rigau5, Serge Milin6, Romulus Takin1, Wilfrid Richer3, Emmanuelle Uro-Coste1,7, Jerome Couturier2, Anne Isabelle Bertozzi8, Olivier Delattre2,3, and Marie Bernadette Delisle1,7
1Rangueil Pathology Department, University Hospital of Toulouse, Toulouse, 2Laboratory of Genetics and Biology of Tumors, 3INSERM U830, 4Department of Pediatric Oncology, Curie Institute, Paris, 5Pathology Laboratory, University Hospital of Montpellier, Montpellier, 6Pathology Department, Jean Bernard University Hospital of Poitiers, Poitiers, 7INSERM CRCT U1037, and 8Department of Hematology-Oncology, University Hospital of Toulouse, Toulouse, France
Embryonal tumor with multilayered rosettes (ETMR), including embryonal tumor with abundant neuropil and true rosettes (ETANTR), and ependymoblastoma (EBL) constitute a distinct entity of the primitive neuroectodermal tumor (PNET) family. The presence of a focal amplification at chromosome region 19q13.42 associated with an up-regulation of the oncogenic miRNA cluster C19MC suggests that they may represent a histological spectrum of a single biological entity. Their histopathological spectrum is wide, including medulloepithelioma, their location may be supra- or infra-tentorial, their prognosis is poor. Recent data on molecular subgroups of PNETs have led to new insights on diagnosis and treatment of these tumors. Subsequently, LIN28A immunoexpression was identified as a highly specific marker for ETMR. In this study, we report 4 cases diagnosed initially as ETANTR with CGH-array data, including 19q13.42 gain with absence of other amplicons, particularly of the MYC gene family, and inconstant gain of whole chromosome 2. Immunohistochemical positive expression of LIN28A and absence of Olig2 expression were observed. We summarize the literature on ETMR, pointing out on the nosological evolution of this entity and the findings on genetic hallmarks of this particular tumor. Our results emphasize the usefulness of immunohistochemistry as a highly sensitive and fast diagnostic tool for ETMR and for genetic data, especially for 19q13.42 locus. Biological features may offer new therapeutic options for these embryonal tumors that do not usually respond to conventional treatments of PNETs.Correspondence to:
Marie Bernadette Delisle, MD, PhD
Service d’Anatomie Pathologique et Histologie-Cytologie
CHU Rangueil
1 Avenue Jean Poulhès, TSA 50032
31059 Toulouse Cedex 9, France
Email: [email protected]
Original
IgA/Kappa-restricted crystal storing histiocytosis involving the central nervous system characterized by proteomic analysis
Brent A. Orr, Gary L. Gallia, Ahmet Dogan and Fausto J. Rodriguez
Page No. 23
Abstract
IgA/Kappa-restricted crystal storing histiocytosis involving the central nervous system characterized by proteomic analysis
Brent A. Orr1, Gary L. Gallia2, Ahmet Dogan3, and Fausto J. Rodriguez4
1Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, 2Department of Neurosurgery, The Johns Hopkins School of Medicine, Baltimore, MD, 3Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, and 4Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
Crystal storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of crystalline material in the cytoplasm of histiocytes. Involvement of the central nervous system (CNS) with CSH is extremely rare. Herein, we report a case of crystal storing histiocytosis involving the CNS. Using immunohistochemistry and mass spectrometry we demonstrate that the disease resulted from an IgA-κ restricted plasma cell dyscrasia. CNS-CSH represents a rare clinicopathologic entity with an indolent course, usually lacking systemic manifestations.Correspondence to:
Brent A. Orr MD, PhD
Department of Pathology
St. Jude Children’s Research Hospital
262 Danny Thomas Place, Memphis, TN 38105-3678, USA
Email: [email protected]
Original
Predominantly periventricular necrotizing encephalitis due to toxoplasmosis: two unusual cases and review of literature
Seth Lummus and Bette K. Kleinschmidt-DeMasters
Page No. 29
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (29-37)
Predominantly periventricular necrotizing encephalitis due to toxoplasmosis: two unusual cases and review of literature
Seth Lummus1 and Bette K. Kleinschmidt-DeMasters1,2,3
Departments of 1Pathology, 2Neurology, and 3Neurosurgery, University of Colorado Health Sciences Center, Aurora, CO, USA
Ventriculitis or periventriculitis as a predominant pattern of tissue involvement in cerebral toxoplasmosis was always a rare event, even at the height of the acquired immunodeficiency syndrome (AIDS) era. Ventriculitis on premortem neuroimaging or at autopsy in AIDS patients chiefly led to differential diagnoses of primary central nervous system lymphoma (PCNSL) or cytomegalovirus ventriculitis, not toxoplasmosis. Usually cerebral toxoplasmosis manifests as multifocal, necrotizing, hemorrhagic foci of cerebritis or abscesses. We report two non-AIDS patients with cerebral toxoplasmosis that presented with predominant ventriculitis/periventriculitis, with diagnosis in both cases made only at postmortem examination. A 90-year-old woman, with autoimmune hemolytic anemia and large granular lymphocytic leukemia diagnosed 2 1/2 years prior, presented with altered mental status. Neuroimaging revealed a necrotic 5.4 × 4.6 × 3.5 cm mass extending across corpus callosum and involving both periventricular frontal horn regions, diagnosed as “butterfly” glioblastoma or possible PCNSL. No consideration of infection was raised, care was withdrawn. A 44-year-old woman with systemic lupus erythematous (SLE) treated with prednisone presented with fever and generalized malaise with rapid progression to agitation and confusion. Infection was suspected, but never confirmed on extensive premortem workup. Brain autopsy in both patients revealed severe necrotizing toxoplasmosis virtually confined to periventricular regions. In the first case, necrosis extended across the corpus callosum. Large numbers of organisms were found microscopically, reflecting their immunocompromised, and untreated, status. Cerebral toxoplasmosis should be included in the differential diagnosis when encountering patients with necrotizing ventriculitis, even in the non-AIDS immunosuppressed population.Correspondence to:
Bette K. Kleinschmidt-DeMasters, MD
University of Colorado Health Sciences Center
Department of Pathology, B-216
4200 E. 9th Ave., Aurora, CO 80262, USA
Email: [email protected]
Original
Spinal lobular capillary hemangioma with an intramedullary component
Ricardo Gonzalez, Julian Spears, Aditya Bharatha and David G. Munoz
Page No. 38
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (38-41)
Spinal lobular capillary hemangioma with an intramedullary component
Ricardo Gonzalez1, Julian Spears2, Aditya Bharatha3, and David G. Munoz4
1National University of Colombia, Faculty of Medicine, Department of Pathology, Bogota DC, Colombia, 2Department of Surgery, Division of Neurosurgery, 3Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada and 4Department of Laboratory Medicine and Pathobiology, St. Michaels Hospital and University of Toronto, Toronto, Ontario, Canada
Capillary hemangiomas are benign vascular neoplasms rarely involving the spinal cord, where their usual location is extramedullary. A 59-year-old man presented with a 7-month history of progressive numbness which began in the left lower extremity and progressed across the lower back, right flank, trunk and into the right lower extremity with associated pressure and pain in his lower back. On magnetic resonance imaging, there was an avidly-enhancing thoracic intradural lesion that contained an extramedullary intradural component posteriorly, with an apparent intramedullary component anteriorly. Laminectomy of T7 – 8 was performed, and intradural exploration revealed a highly vascular-appearing tumor below the arachnoid, which was not completely dissected because it was densely adherent to the spinal cord. The pathological diagnosis was lobular capillary hemangioma with extra- and intramedullary components. We suggest this lesion should be considered in the differential diagnosis of spinal cord tumors with an intramedullary component.Correspondence to:
Dr. David G. Munoz
St. Michael’s Hospital
30 Bond Street, Toronto, Ontario, M5B 1W8, Canada
Email: [email protected]
Original
PD1 (CD279) and PD-L1 (CD274, B7H1) expression in primary central nervous system lymphomas (PCNSL)
Anna Sophie Berghoff, Gerda Ricken, Georg Widhalm, Orsolya Rajky, Johannes A. Hainfellner, Peter Birner, Markus Raderer, and Matthias Preusser
Page No. 42
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (42-49)
PD1 (CD279) and PD-L1 (CD274, B7H1) expression in primary central nervous system lymphomas (PCNSL)
Anna Sophie Berghoff1,2,3, Gerda Ricken1,3, Georg Widhalm3,4, Orsolya Rajky2,3, Johannes A. Hainfellner1,3, Peter Birner3,5, Markus Raderer2,3, and Matthias Preusser2,3
1Institute of Neurology, 2Department of Medicine I, 3Comprehensive Cancer Center, 4Department of Neurosurgery, and 5Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria
Background: Primary central nervous system lymphoma (PCNSL) is a malignant brain tumor with limited treatment options and shows prominent infiltration by tumor infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Programmed death 1 (PD1; CD279) and its ligand PD-L1 (B7H1, CD274) promote escape of tumor cells from immune surveillance in several tumor types, but no data are available on PCNSL. Agents inhibiting PD1 and PD-L1 are showing compelling antitumor activity in current clinical trials in solid and hematological cancers. Methods: We investigated PD1 (clone NAT ab52587) and PD-L1 (clone 5H1) expression in large neurosurgical resection specimens of 20 immunocompetent historical PCNSL patients using immunohistochemistry. Results: We found expression of PD1 and/or PD-L1 on tumor cells, TILs, or TAMs in a total of 18/20 (90%) of PCNSL cases. In 12/20 (60%) cases, intratumoral PD1-positive TILs were present (low density: 9/20, 45%; moderate density: 2/20, 10%; high density: 1/20, 5%) with additional peritumoral accumulation of PD1-positive lymphocytes in all of 12 cases with evaluable adjacent brain tissue on the tissue section. PD-L1 expressing intratumoral TAMs were found in 4/20 (20%) tumors. In 2/20 (10%) and 4/20 (20%) specimens, we observed striking PD-L1 or PD1 expression on PCNSL tumor cells, respectively. Median number of CD8-positive TILs was 517/mm2 (range 75 – 2,470) and did not correlate with PD1 or PD-L1 expression (p > 0.05, Kruskal- Wallis test). Conclusions: PD1 and PDL1 are immunohistochemically detectable in PCNSL and may be involved in creating an immunosuppressive microenvironment. Specific immune checkpoint inhibitors may be considered for experimental therapy approaches in this disease.Correspondence to:
Matthias Preusser, MD
Department of Medicine I and
Comprehensive Cancer Center CNS Unit (CCC-CNS)
Medical University of Vienna
Waehringer Guertel 18-20, 1090 Vienna, Austria
Email: [email protected]
Appendix Table S1 – S6
Walter Pulverer, Manuela Hofner, Matthias Preusser, Elisabeth Dirnberger, Johannes A. Hainfellner and Andreas Weinhaeusel
Page No. 50
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (50-60)
A simple quantitative diagnostic alternative for MGMT DNA-methylation testing on RCL2 fixed paraffin embedded tumors using restriction coupled qPCR
Walter Pulverer1, Manuela Hofner1, Matthias Preusser2, Elisabeth Dirnberger3, Johannes A. Hainfellner3, and Andreas Weinhaeusel1
1Molecular Diagnostics, Austrian Institute of Technology, 2Department of Medicine I and Comprehensive Cancer Center CNS Unit, and 3Institute of Neurology, Medical University Vienna, Vienna, Austria
Background: MGMT promoter methylation is associated with favorable prognosis and chemosensitivity in glioblastoma multiforme (GBM), especially in elderly patients. We aimed to develop a simple methylation-sensitive restriction enzyme (MSRE)-based quantitative PCR (qPCR) assay, allowing the quantification of MGMT promoter methylation. Methods: DNA was extracted from non-neoplastic brain (n = 24) and GBM samples (n = 20) upon 3 different sample conservation conditions (–80 °C, formalin-fixed and paraffin-embedded (FFPE); RCL2-fixed). We evaluated the suitability of each fixation method with respect to the MSRE-coupled qPCR methylation analyses. Methylation data were validated by MALDITOF. Results: qPCR was used for evaluation of alternative tissue conservation procedures. DNA from FFPE tissue failed reliable testing; DNA from both RCL2-fixed and fresh frozen tissues performed equally well and was further used for validation of the quantitative MGMT methylation assay (limit of detection (LOD): 19.58 pg), using individual’s undigested sample DNA for calibration. MGMT methylation analysis in non-neoplastic brain identified a background methylation of 0.10 ± 11% which we used for defining a cut-off of 0.32% for patient stratification. Of GBM patients 9 were MGMT methylationpositive (range: 0.56 – 91.95%), and 11 tested negative. MALDI-TOF measurements resulted in a concordant classification of 94% of GBM samples in comparison to qPCR. Conclusions: The presented methodology allows quantitative MGMT promoter methylation analyses. An amount of 200 ng DNA is sufficient for triplicate analyses including control reactions and individual calibration curves, thus excluding any DNA qualityderived bias. The combination of RCL2-fixation and quantitative methylation analyses improves pathological routine examination when histological and molecular analyses on limited amounts of tumor samples are necessary for patient stratification.Correspondence to:
Andreas Weinhaeusel
Molecular Diagnostics
Austrian Institute of Technology
Muthgasse, 1190 Vienna, Austria
Email: [email protected]
Original
Is mutation p.Arg168Gly in TPM3 gene responsible for Type 1 fiber hypoplasia and cap structure formation?
Anna Fidzianska, Agnieszka Madej-Pilarczyk and Irena Hausmanowa-Petrusewicz
Page No. 61
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (61-64)
Is mutation p.Arg168Gly in TPM3 gene responsible for Type 1 fiber hypoplasia and cap structure formation?
Anna Fidzianska, Agnieszka Madej-Pilarczyk and Irena Hausmanowa-Petrusewicz
Neuromuscular Unit, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland
Congenital fiber type disproportion with delayed fiber type maturation and the appearance of cap structures were analyzed in a child with p.Arg168Gly mutation in TPM3 gene. Very narrow myotube-like Type 1 fibers with single nuclei decorated by cap structures seem to be a result of a failure in fusion process and mature fiber formation. Repeated mutations in exon 5 of TPM3 gene giving cap structures may be a different consequence of the loss of specific isoform normally operating in the fusion process and sarcomer formation.Correspondence to:
Anna Fidzianska, MD
Dr Neuromuscular Unit
Mossakowski Medical Research Center
Polish Academy of Sciences
Pawinskiego St. 5, 02-106 Warsaw, Poland
Email: [email protected]
Original
Olfactory dysfunction related to TDP-43 pathology in amyotrophic lateral sclerosis
Takahiro Takeda, Toshiki Uchihara, Shunji Kawamura and Takashi Ohashi
Page No. 65
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (65-67)
Olfactory dysfunction related to TDP-43 pathology in amyotrophic lateral sclerosis
Takahiro Takeda1,3,4, Toshiki Uchihara3, Shunji Kawamura2, and Takashi Ohashi1
1Department of Neurology, 2Department of Pathology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, 3Department of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, and 4Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan
Aims: To clarify a possible contribution of TDP-43 pathology to odor dysfunction in amyotrophic lateral sclerosis patients. Case report: An 83-year-old woman suffered from muscle weakness, which started to deteriorate during the previous half year. In addition to her pyramidal signs, lower motor involvement was shown by needle electromyography; this upper and lower motor neuron involvement was suggestive of probable ALS. She presented with severe odor impairments but relatively preserved cognitive functions. Her autopsy findings revealed TDP-43-positive inclusions in the spinal motor neurons and cerebral limbic system without significant tau or α-synuclein deposits. Discussion: This case showed evidence suggesting that olfactory dysfunction was probably related to limbic TDP-43 pathology and was possibly independent of her Alzheimer pathology. Olfactory dysfunction does not necessarily indicate the presence of tau or α-synuclein pathology and could be an early sign of ALS with the limbic involvement of TDP-43 pathology even when cognitive functions are preserved.Correspondence to:
Takahiro Takeda, MD
Department of Neurology
Tokyo Women’s Medical University
8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
Email: [email protected]
Original
Immunohistochemical study of pseudohypertrophy of the inferior olivary nucleus
Katsuhiko Ogawa, Satoshi Kamei, Kazuaki Ichihara, Kenji Uehara, Yoshio Suzuki, Toshiki Uchihara, Hirokazu Yoshihashi and Ja-Mun Chong
Page No. 68
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (68-75)
Immunohistochemical study of pseudohypertrophy of the inferior olivary nucleus
Katsuhiko Ogawa1, Satoshi Kamei1, Kazuaki Ichihara1, Kenji Uehara1, Yoshio Suzuki2, Toshiki Uchihara3, Hirokazu Yoshihashi4, and Ja-Mun Chong5
1Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, 2Department of Pathology, Asahi General Hospital, Chiba, 3Laboratory of Structual Neuropathology, Tokyo Metropolitan Institute for Medical Science, Tokyo, 4Department of Neurology, Toshima Hospital, Tokyo, and 5Department of Laboratory Medicine, Toshima Hospital, Tokyo, Japan
Objective: Pathogenesis of pseudohypertrophy of the inferior olivary nucleus (PH-IO) was analyzed based on immunohistochemical study. Methods: Immunostained medullas with PH-IO were observed with confocal laser microscopy. Results: αB-crystallin (αBC) was frequently expressed in the neurons and co-localized with microtubule-associated protein 2 (MAP2). The neurons were occasionally positive for SMI-31. αBC and SMI-31 were co-localized in some neurons. Synaptophysin (SYP)-immunoreactive dots were present around MAP2-positive hypertrophic neurons and hypertrophic thick neurites. Periphery-stained Lys-Asp-Glu-Leu (KDEL)-positive neurons were shown. Central chromatolytic neurons were found with Klüver-Barrera staining, which indicated that the rough endoplasmic reticulum (ER) was distributed to the periphery of the cytoplasm. Conclusions: αBC prevents microtubule disassembly and phosphorylation of the neurofilaments under stressful conditions. Our results indicated that αBC protected microtubules and neurofilaments in PH-IO. The retrograde transport of KDEL receptors from the Golgi complex to the ER is increased under stressful conditions. We considered that KDEL receptors were retro-transported to ER, and then the ER containing KDEL receptors was distributed to the periphery of the cytoplasm. PH-IO showed various immunohistochemical changes due to trans-synaptic degeneration.Correspondence to:
Katsuhiko Ogawa, MD
Division of Neurology, Department of Medicine
Nihon University School of Medicine
30-1 Oyaguchi-kamimachi,
Itabashi-ku, Tokyo 173-8610, Japan
Email: [email protected]
Original
XIAP immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy
Yasuhiro Kawamoto, Hidefumi Ito, Masafumi Ihara and Ryosuke Takahashi
Page No. 76
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (76-83)
XIAP immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy
Yasuhiro Kawamoto1,2, Hidefumi Ito3, Masafumi Ihara4, and Ryosuke Takahashi1
1Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, 2Department of Neurology, Seijinkai Rakusaishimizu Hospital, Kyoto, 3Department of Neurology, Wakayama Medical University, Wakayama, and 4Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan
X-linked inhibitor of apoptosis protein (XIAP) selectively binds to caspases-3, -7 and -9, and inhibits the activities of these caspases. To elucidate the role of XIAP in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. In normal brains, several types of neurons were immunostained for XIAP, and XIAP-immunopositive oligodendrocytes were scattered throughout the cerebral and cerebellar white matter. In the MSA brains, neuronal XIAP immunoreactivity was spared even in the severely-affected lesions, and glial cytoplasmic inclusions (GCIs), neuronal cytoplasmic inclusions (NCIs) and dystrophic neurites were all intensely immunoreactive for XIAP. A semiquantitative analysis of mid-pons sections double-immunostained for XIAP and α-synuclein demonstrated that the average percentages of XIAP-immunopositive GCIs and NCIs in the pontine nucleus were 70.2% and 82.2%, respectively. Our results suggest that a widespread accumulation of XIAP may occur in brains with MSA, and that XIAP may be partially associated with the pathogenesis of MSA.Correspondence to:
Yasuhiro Kawamoto, MD, PhD
Department of Neurology, Faculty of Medicine
Kyoto University
54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan
Email: [email protected]
Original
An acardiac twin with advanced development of the brain: a histologic and volumetric study
Katsuyuki Yamaguchi and Koichi Honma
Page No. 84
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 (84-90)
An acardiac twin with advanced development of the brain: a histologic and volumetric study
Katsuyuki Yamaguchi and Koichi Honma
Department of Pathology, Dokkyo University School of Medicine, Tochigi, Japan
We describe a rare case of an acardiac twin (acardius anceps) with advanced brain development. Complete serial sections of the brain were made for microscopic observation and volumetric analysis. The cerebral surface showed unusual gyri and sulci with absence of the right olfactory bulb. Cortical lamination was almost normal, except for the insula where polymicrogyria and leptomeningeal neuroglial heterotopia were seen. The latter was also observed in the basal forebrain. Partial agenesis of the corpus callosum was noted with a very thick left cingulate gyrus. The anterior commissure did not cross the midline. Subcortical structures including basal ganglia, diencephalon, and brainstem/cerebellum appeared grossly normal, but hypo- or dysplasic changes were observed in some regions. The ventricles were enlarged and the left internal carotid artery was absent. In addition, porencephalic foci were located in the right temporal and parietal lobes. On comparative volumetry, the total brain was normal, but brain structures showed variable volumetric changes, with higher volume in the ventricles, diencephalon, and archi-/paleopallium, and lower volume in the periventricular germinal layer, basal ganglia, cerebral cortex, and brainstem/cerebellum. These observations showed that brain development can proceed nearly normally in acardia if blood flow is relatively preserved.Correspondence to:
Dr. K. Yamaguchi
Department of Pathology
Dokkyo University School of Medicine
880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan
Email: [email protected] and [email protected]
Letter to the Editor
Dumbbell-shaped intraspinal solitary fibrous tumor extending into the thoracic cavity
Lutao Yuan, Xin Chen, Hengli Tian and Shiwen Chen
Page No. 91
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 – Letters to the editor
Dumbbell-shaped intraspinal solitary fibrous tumor extending into the thoracic cavity
Lutao Yuan, Xin Chen, Hengli Tian and Shiwen Chen
Department of Neurosurgery, Shanghai Sixth Peoples Hospital, Shanghai Jiaotong University, Shanghai, China
Correspondence to:
Shiwen Chen, MD
Department of Neurosurgery
Shanghai Sixth Peoples Hospital
Shanghai Jiaotong University
No. 600 Yishan Road, Xuhui District, Shanghai, China
Email: [email protected]
Letter to the Editor
Primary fourth ventricular B-cell lymphoma in an immunocompetent patient
Andrew J. Fabiano, Susanna Syriac, Robert A. Fenstermaker and Jingxin Qiu
Page No. 94
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 – Letters to the editor
Primary fourth ventricular B-cell lymphoma in an immunocompetent patient
Andrew J. Fabiano1,2, Susanna Syriac3, Robert A. Fenstermaker1,2 and Jingxin Qiu3
1Department of Neurosurgery, Roswell Park Cancer Institute, 2Department of Neurosurgery, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, and 3Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA
Correspondence to:
Andrew J. Fabiano MD
Department of Neurosurgery
Roswell Park Cancer Institute
Elm and Carlton Streets, Buffalo, NY 14263, USA
Email: [email protected]
Letter to the Editor
Pediatric fronto-orbital cemento-ossifying fibroma: a report of two cases
Ishita Pant, Sujata Chaturvedi, Rakesh Kumar Dua, Gurbachan Singh and Rima Kumari
Page No. 98
Abstract
Clinical Neuropathology, Vol. 33 – No. 1/2014 – Letter to the editor
Pediatric fronto-orbital cemento-ossifying fibroma: a report of two cases
Ishita Pant1, Sujata Chaturvedi1, Rakesh Kumar Dua3, Gurbachan Singh3 and Rima Kumari2
1Department of Pathology, 2Department of Neuroradiology, Institute of Human Behaviour and Allied Sciences, Delhi, India and 3Department of Neurosurgery, Guru Teg Bahadur Hospital, Delhi, India
Correspondence to:
Dr. Ishita Pant
Department of Pathology, IHBAS Hospital
Dilshad Garden, Delhi-110 095, India
Email: [email protected] and [email protected]
Euro-CNS News
Society News of the European Confederation of Neuropathological Societies
Page No. 101
Abstract
Society News of the European Confederation of Neuropathological Societies
