Volume 29, No. 4/2010(July/August)
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 Clinical Neuropathology
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Editorial
Clinical Neuropathology, Vol. 29 – No. 4/2010
J. Hainfellner
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010
J. Hainfellner
Original contribution
Cerebral amyloid angiopathy and microhemorrhages after amyloid beta vaccination: case report and brief review
E. Uro-Coste, G. Russano de Paiva, C. Guilbeau-Frugier, N. Sastre, P.J. Ousset, N.A. da Silva, V. Lavialle-Guillotreau, B. Vellas and M.-B. Delisle
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (209-216)
Cerebral amyloid angiopathy and microhemorrhages after amyloid beta vaccination: case report and brief review
E. Uro-Coste1,2, G. Russano de Paiva1, C. Guilbeau-Frugier1, N. Sastre3, P.J. Ousset3, N.A. da Silva4, V. Lavialle-Guillotreau1, B. Vellas3 and M.-B. Delisle1,2
1Service d’Anatomie Pathologique et Histologie Cytologie, CHU Rangueil and Faculté de Médecine Rangueil, 2INSERM, IFR150, I2MR, Equipe 15, 3Gerontopole CMRR, Department of Internal Medicine and Clinical Gerontology, CHU Purpan-Casselardit, and 4Service de Neuroradiologie, CHU Purpan, Toulouse, France
After the interruption of the international multicenter Phase 2 clinical trial with active immunotherapy based on synthetic Abeta42 (AN1792), few reports about the neuropathological findings in those patients and those from the Phase 1 clinical trial were published. These reports described some pathological similarities among the patients such as a reduction in the burden of amyloid plaques, the reactions of microglia/macrophages and the persistence of neurofibrillary tangles and neuropil threads. In addition, a lymphocytic inflammatory infiltrate as well as white matter lesions were present in some cases with meningoencephalitis. In both animal models of vaccination, as well as some vaccinated patient samples, there appears to be a correlation between vaccination and hemorrhages. Subsequently, two series reports concerning 8 patients from the Phase 1 initial trial showed that immunization with Abeta42 seemed to result in clearance of amyloid plaques, but did not prevent progressive neurodegeneration and that it increased vessel wall amyloid angiopathy as well as cortical microhemorrhages. Recent clinical data gave further encouraging results regarding vaccination in humans demonstrating that long term follow-up of patients from the second clinical trial revealed reduced functional decline, at least, in antibody responders. Here we describe a patient diagnosed with Alzheimer’s disease who also participated in the Phase 2 clinical trial. A neuropathological examination confirmed Alzheimer’s disease without meningoencephalitis and revealed a severe amyloid angiopathy with frequent microhemorrhages, the decrease of amyloid load being difficult to ascertain. Our results are in agreement with previous studies and confirm the presence of severe amyloid angiopathy after vaccination. The latter may be a transient phenomenon depending on the degree of immune response and the pathological stage of the disease when the patient underwent treatment. In addition, our vaccinated case also demonstrated microhemorrhages and microinfarcts which were already noticed to occur with a higher density in immunized Alzheimer’s disease patients.Correspondence to:
M.-B. Delisle, MD, PhD
Service d’Anatomie et Cytologie Pathologiques
Hôpital de Rangueil, 1
Avenue J. Poulhès, TSA 50032
31059 Toulouse, Cedex 9, France
Email: delisle.b@chu-toulouse.fr
Original contribution
Intracerebral amyloidoma: case report and review of the literature
H. Foreid, C. Barroso, T. Evangelista, A. Campos and J. Pimentel
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (217-222)
Intracerebral amyloidoma: case report and review of the literature
H. Foreid1, 2, C. Barroso1, T. Evangelista1, 2, A. Campos3 and J. Pimentel1, 2
1Laboratory of Neuropathology, Department of Neurosciences, Serviço de Neurologia, CHLN EPE-Hospital de Santa Maria, 2Neurological Clinical Research Unit, Institute of Molecular Medicine and 3Department of Neurosciences, Serviço de Neurocirurgia, CHLN EPE-Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal
Intracerebral amyloidoma (ICA) is a type of monoclonal immunoglobulin deposition disease (MIDD) which is accompanied by an overexpression and fibrillary assembly of monoclonal light chains, ultimately leading to nodular deposits of light chains in the form of amyloid light chain (AL-amyloid). The diagnosis is made by the histological demonstration of intracerebral masses harboring the classical staining and birefringence features of amyloid. We aim to report a case of ICA and review histological features of previous cases. A 51-year-old man with epilepsy and cognitive decline was admitted for epileptic seizures. A brain magnetic resonance imaging (MRI) disclosed periventricular enhancing lesions, hypointense on T1 and heterogeneous on T2-weighted images. A brain stereotactic biopsy was performed. The neuropathological examination revealed several congophilic nodules, allowing the diagnosis of ICA. The immunohistochemical study was positive for transthyretin (TTR), and both lambda and kappa immunoglobulin light chains. No inflammatory infiltrates were seen. Although a plasma cell clone may play a major role in the etiopathogeny of ICA, plasma cells were scarce or even absent when reviewing histological reports. ICA has a poorly understood patgogenesis. ICA may simulate malignant neoplasms, hence the need for a definite histological diagnosis.Correspondence to:
J. Pimentel, PhD
Laboratory of Neuropathology
Hospital de Santa Maria
Av. Egas Moniz
1649-035 Lisbon, Portugal
Email: josepimentel@fm.ul.pt
Original contribution
Calcifying pseudoneoplasm (fibro osseous lesion) of neuraxis (CAPNON) – a case report
I. Mohapatra, R. Manish, A. Mahadevan, C. Prasad, S. Sampath and S.K. Shankar
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (223-226)
Calcifying pseudoneoplasm (fibro osseous lesion) of neuraxis (CAPNON) – a case report
I. Mohapatra1, R. Manish2, A. Mahadevan1, C. Prasad3, S. Sampath2 and S.K. Shankar1
Departments of 1Neuropathology, 2Neurosurgery, and 3Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India
Calcifying pseudoneoplasm of neuraxis (CAPNON) is a rare but distinctive lesion of the central nervous system. These are benign lesions that mimic ossified vascular lesions clinically and radiologically, and can be cured by complete resection. We report a case in a 48 year old male with complex partial seizures who had a right temporobasal calcified lesion that clinically and radiologically mimicked an oligodendroglioma. Histopathology revealed a large necrotic lobulated mass with admixture of chondromyxoid zones, nodular fibrovascular stroma, metaplastic calcification and ossification in varying proportions.Correspondence to:
Dr. S.K. Shankar, Prof. and Head
Department of Neuropathology
National Institute of Mental Health & Neurosciences
Bangalore 560 029, India
Email: shankarsk2004@gmail.com
Original contribution
Paraganglioma of the filum terminale: review and report of the first case analyzed by CGH
A. Gutenberg, C. Wegner, S.M. Pilgram-Pastor, B. Gunawan, V. Rohde and A. Giese
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (227-232)
Paraganglioma of the filum terminale: review and report of the first case analyzed by CGH
A. Gutenberg1, C. Wegner2, S.M. Pilgram-Pastor3, B. Gunawan4, V. Rohde1 and A. Giese1
Departments for 1Neurosurgery, 2Neuropathology, 3Neuroradiology and 4Pathology, Georg August University Göttingen, Germany
Objective: As a rare tumor paraganglioma of the filum terminale is of diagnostic challenge. A thorough review of all published cases most often reveals a benign course if complete surgically resection is achieved. We report on the first molecular cytogenetic analyses performed on filum termiale paragangliomas. Clinical presentation: A 52-year-old man suffered from low back pain for many years that gradually worsened and was aggravated by sitting and bending. The pain radiated dorsally into both legs. Magnetic resonance imaging (MRI) with and without Gd-DTPA revealed a 12 mm sized, intradural oval mass at the level of L3 with slightly increased T2-signal and a rim of low signal on T2-weighted sequences. The tumor enhanced remarkably after Gd-DTPA. Intervention: The patient underwent a left sided hemilaminectomy of L3. Durotomy revealed a well-delineated, firm and highly vascularized reddish tumor. The proximal terminal filum entered the tumor at the proximal pole and exited its distal pole. Coagulation and dissection of the terminal filum allowed in toto removal of the tumor. DNA was isolated from the formalin-fixed and paraffin-embedded specimen. The tumor was analyzed by comparative genomic hybridization, providing a normal DNA profile without any chromosomal copy number changes. Conclusion: The origin of paragangliomas of the CNS and especially of the filum terminale is still unclear. If no complete surgical resection can be achieved, molecular cytogenetic analysis is of additional value to prognostification of paragangliomas of the filum terminale.Correspondence to:
Dr. med. A. Gutenberg
Department of Neurosurgery
Georg August University
37099 Göttingen, Germany
Email: agutenberg@med.uni-goettingen.de
Original contribution
Intravascular large B-cell lymphoma of central nervous system – a report of two cases and literature review
B. Mihaljevic, N. Sternic, M. Skender Gazibara, A. Sretenovic, D. Antic, T. Terzic and V. Kostic
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (233-238)
Intravascular large B-cell lymphoma of central nervous system – a report of two cases and literature review
B. Mihaljevic1, N. Sternic2, M. Skender Gazibara3, A. Sretenovic1, D. Antic1, T. Terzic3 and V. Kostic2
1Institute of Hematology, 2Institute of Neurology, Clinical Center of Serbia (CCS) and 3Institute of Pathology, School of Medicine, Belgrade, Serbia
Intravascular large B-cell lymphoma (IVL) is a rare form of diffuse large B cell lymphoma (DBCL) frequently presenting with skin and/or central nervous system (CNS) involvement. IVL involves CNS in 75 – 85% of patients and neurological symptoms include sensory and motor deficits or neuropathies, meningoradiculitis, paresthesia, hypostenia, aphasia, dysarthria, hemiparesis, seizures, transient visual loss, vertigo and impaired cognitive function. Neuroimaging discloses CNS involvement only in half of patients with neurological symptoms because there are no pathognomonic neuroradiological findings for IVL; ischemic foci are the most common presentation pattern and therefore vasculitis is the most common differential diagnosis. According to all mentioned data, diagnosis of CNS IVL requires a histopathological confirmation. Brain biopsy is absolutely indicated in patients with progressive neurological deterioration with unclear abnormalities in cerebral MR imaging. A general policy is that patients with IVL should be considered to have disseminated disease and should be treated with systemic chemotherapy. In younger patients with unfavorable features the high-dose chemotherapy with autologous stem cell transplantation should be used. Nevertheless, the course of IVL is rapidly progressive and ultimately fatal.Correspondence to:
D. Antic, MD, MSci
Institute of Hematology
Clinical Center of Serbia (CCS)
Koste Todorovica 2
11 000 Belgrade, Serbia
Email: tweety@scnet.rs
Original contribution
Analysis of PIK3CA and B-RAF gene mutations in human astrocytomas: association with activation of ERK and AKT
E.A. El-Habr, P. Tsiorva, M. Theodorou, G. Levidou, P. Korkolopoulou, G. Vretakos, L. Petraki, N.V. Michalopoulos, E. Patsouris and A.A. Saetta
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (239-245)
Analysis of PIK3CA and B-RAF gene mutations in human astrocytomas: association with activation of ERK and AKT
E.A. El-Habr1*, P. Tsiorva1*, M. Theodorou1*, G. Levidou1, P. Korkolopoulou1, G. Vretakos2, L. Petraki2, N.V. Michalopoulos1, E. Patsouris1 and A.A. Saetta1
1Department of Pathology, Medical School, National and Kapodistrian University of Athens, and 2Department of Neurosurgery, Metropolitan Hospital, N. Faliro, Athens, Greece
Objective: The analysis of the presence of PIK3CA and B-RAF gene mutations in relation to ERK and AKT activation in diffusely infiltrating astrocytomas, in order to determine their potential role in tumor aggressiveness. Methods: Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP) and sequencing analysis were used for PIK3CA and B-RAF gene mutation detection. pERK and pAKT expression were examined by immunohistochemistry. Results: PIK3CA mutations were found in 2 (3%) cases of glioblastomas whereas none of these cases displayed mutations in exon 15 of B-RAF gene. Neither low grade astrocytomas nor anaplastic astrocytomas revealed any mutations in these genes. Nuclear and cytoplasmic pERK immunoreactivity was displayed in 100% and 82% of cases, respectively. pERK nuclear expression was positively correlated with pERK cytoplasmic expression (p = 0.0067). Moreover, pERK nuclear expression increased in parallel with tumor grade (II, III v/s IV, p = 0.0262). Nuclear and cytoplasmic pAKT immunoreactivity was displayed in 97% and 100% of cases, respectively. Similarly, pAKT nuclear expression was positively correlated with pAKT cytoplasmic expression (p = 0.0074). pAKT cytoplasmic expression increased with increasing tumor grade (II,III v/s IV, p = 0.0930), although the latter relationship was of marginal significance. pAKT cytoplasmic expression was also positively correlated with pERK nuclear expression (p = 0.0156). Conclusions: Our study reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins. Moreover, the correlation of pERK nuclear and pAKT cytoplasmic expression with tumor grade suggests the possible crucial role of the activation of these proteins in human gliomagenesis.Correspondence to:
E.A. El-Habr
D. Glinou 7, N. Iraklio 14122, Athens, Greece
Email: elhabere@yahoo.com
Original contribution
Hyaline astrocytic inclusions in pediatric epilepsy: report of two cases
J. Adam, M. Polivka, R. Kaci, C. Godfraind and F. Gray
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (246-253)
Hyaline astrocytic inclusions in pediatric epilepsy: report of two cases
J. Adam1, M. Polivka1, R. Kaci1, C. Godfraind2 and F. Gray1
1Service Central d’Anatomie et de Cytologie Pathologiques, APHP, Hôpital Lariboisière-Université Paris 7, Paris France, and 2Service d’Anatomie Pathologique, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium
Distinctive hyaline inclusion bodies in the cytoplasm of neocortical astrocytes were observed in surgical resection specimens of a frontal epileptic focus, in 2 patients aged 16 and 10 who had suffered intractable partial seizures since the age of 2 years. One case had minimal neurological impairment and no brain malformation on MRI and recovered completely following surgery. The second case had mental retardation and surgery reduced the frequency and generalization of seizures. In both cases, the astrocytic inclusions were strongly eosinophilic, hyaline and refractile. They were PAS negative. Electron microscopy in the first case, confirmed their granular osmiophilic structure. By immunohistochemistry, the inclusions were strongly positive for filamin in the first case, only some were weakly positive in the second case. They also variably expressed other proteins such as alpha-B-crystallin, GFAP, S-100 protein and cytoglobin. We compare our findings with previously reported cases and discuss the clinical significance of the inclusions and the pathophysiologic relevance of filamin A and other proteins accumulation in astrocytes.Correspondence to:
Prof. F. Gray, MD, PhD
Service Central d’Anatomie et de Cytologie Pathologiques
Hôpital Lariboisière
2 rue Ambroise Paré
75475 Paris cedex 10, Paris, France
Email: francoise.gray@lrb.aphp.fr
Original contribution
Dystrobrevin isoform expression in patients with neuromuscular disease
G.P. Ramelli
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (254-261)
Dystrobrevin isoform expression in patients with neuromuscular disease
G.P. Ramelli
Department of Paediatrics, Ospedale San Giovanni Bellinzona, Bellinzona, Switzerland
Objective: The role of dystrobrevin, a cytoplasmic component of the dystrophin-protein complex, in neuromuscular diseases has not been fully elucidated. This study evaluated the expression of dystrobrevin in patients with different neuromuscular diseases. Methods: We compared dystrobrevin isoforms expression in patients with Duchenne and Becker Muscular Dystrophy (DMD and BMD) and patients with other neuromuscular disorders not linked to the dystrophin-associated complex. Results: Both, alpha-dystrobrevin-1 and -2 isoforms are markedly reduced in the muscle of patients with dystrophinopathies irrespective of the age at the time of biopsy. Conversely, alpha-dystrobrevin-1 was preserved in Limb Girdle Muscular Dystrophies (LGMD) type 2I patients with altered glycosylation of alpha-dystroglycan and in patients with alterations of alpha-dystroglycan due to defects in extracellular matrix proteins (laminin-alpha2). Conclusions: Immunolabeling of dystrobrevin could be a useful marker in the diagnostic of neuromuscular diseases.Correspondence to:
Dr. med. G.P. Ramelli
Department of Pediatrics
Ospedale San Giovanni
6500 Bellinzona, Switzerland
Email: gianpaolo.ramelli@eoc.ch
Original contribution
Tubuloreticular inclusions in inclusion body myositis
H.D. Katzberg and D.G. Munoz
Abstract
Clinical Neuropathology, Vol. 29 – No. 4/2010 (262-266)
Tubuloreticular inclusions in inclusion body myositis
H.D. Katzberg1, 2 and D.G. Munoz1, 3
1St. Michael’s Hospital, 2Division of Neurology and 3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Objective: To evaluate whether patients with inclusion body myositis (IBM) can have tubuloreticular inclusions present in muscle endothelial cells. Material and methods: Light microscopy with histochemical staining and electron microscopy of a right quadriceps muscle biopsy were used to identify the pathological features in an 83-year-old patient with a clinical diagnosis of IBM. Results: Light microscopy showed rimmed vacuoles. Immunostaining for HLA-1 revealed widespread membrane labeling and for TDP-43 multiple areas of subsarcolemmal and sarcoplasmic staining. Electron microscopy revealed tubuloreticular inclusions in the cytoplasm of endothelial cells. Electron microscopy also showed the presence of myeloid bodies and aggregates of tubolo filaments in the nucleus and cytoplasm of myocytes which confirmed the diagnosis of inclusion body myositis. Conclusion: Tubuloreticular inclusions may be found in the muscle endothelial cells of patients with a clinical and pathological diagnosis of IBM.Correspondence to:
Dr. D.G. Munoz
St. Michael’s Hospital
30 Bond Street
Toronto, Ontario, M5B 1W8, Canada
Email: munozd@smh.toronto.on.ca
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