Rett Syndrome as a minicolumnopathy
M.F. Casanova, D. Buxhoeveden, A. Switala and E. Roy

Oligodendroglioma: CD44 as a possible prognostic opportunity
A.M. Buccoliero, A. Caldarella, L. Arganini, P. Mennonna, F. Ammanati, A. Taddei and G.L. Taddei

Histological and immunohistochemical study of a neuroblastoma in a dog
M.T. Capucchio, D. Lotti, E. Cornaglia, F. Valenza and D. Schiffer

Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients
M. Szybka, J. Bartkowiak, K. Zakrzewski, L. Polis, P. Liberski and R. Kordek

Recurrent and atypical meningiomas – a multiparametric study using Ki67 labelling index, AgNOR and DNA Feulgen staining
F. Ferraraccio, M. Accardo, F. Giangaspero and L. Cuccurullo

Vein of Galen malformation combined with atrial septal defect in a neonate
T. Hortobágyi, Á. Szüts, M. Csenki, T. Harkany, Z. Zádor, M. Katona and I. Bódi

Intracranial giant cell arteritis with fatal middle cerebral artery territory infarct
L. Browne, O. Hardiman, H. O’Dwyer and M. Farrell

Distal muscular dystrophy of the Miyoshi type
H. Yildiz, U. Emre, Ö. Coskun, U. Ergün, H.T. Atasoy and L.E. Inan

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Clinical Neuropathology, Volume 22, No. 4/2003 (163-168)

Rett Syndrome as a minicolumnopathy

M.F. Casanova, D. Buxhoeveden, A. Switala and E. Roy

Medical College of Georgia, Augusta, GA, USA 

Objective: Rett syndrome is a progressive neurological disorder affecting primarily females. It is characterized by the early regression of acquired language, cognitive functions, social skills, and purposeful hand function. Patients with Rett syndrome are often misdiagnosed as autistic. Recent reports of minicolumnar abnormalities in the brains of autistic and Asperger’s syndrome prompted us to search for similar pathology in Rett syndrome. Material: The patient population consisted of 5 Rett syndrome patients (mean age = 14.4 ± 4.0 years) and 17 controls (mean age = 14.6 ± 9.5 years). Tissue was celloidin embedded, sectioned at 35 um and Nissl stained. Images (100×) were taken from Brodmann’s areas 9, 21, and 22 from layer III of the left hemisphere. Method: Columnar width measurements for these images were obtained with computerized image analysis using previously published algorithms. Each area was analyzed separately with univariate ANOVA, including diagnosis as a fixed factor and age (linear and quadratic terms), and sex as covariates. Results: Diagnosis dependent effects were statistically significant only in area 21 (p = 0.009) even when taking into account a Bonferroni correction for the multiple comparisons. Conclusion: Both the regional nature of the changes as well as differences in mean cell spacing differentiates the abnormal minicolumnar morphometry of Rett syndrome from that of autism.
  

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Clinical Neuropathology, Volume 22, No. 4/2003 (169-175)

Oligodendroglioma: CD44 as a possible prognostic opportunity

A.M. Buccoliero¹, A. Caldarella¹, L. Arganini¹, P. Mennonna²,
F. Ammanati², A. Taddei³ and G.L. Taddei¹

¹Dipartimento di Patologia Umana e Oncologia, Università degli Studi di Firenze, ²Unità operativa di Neurochirurgia, Policlinico di Careggi, and
³Dipartimento di Area Critica Medico-Chirurgica, Sezione Chirurgia Generale e D.C., Università degli Studi di Firenze, Firenze, Italy

CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a wide variety of non-neoplastic and neoplastic cells. CD44 has been considered to be implicated in tumoral growth and in metastatic potential. We studied the immunohistochemical expression of CD44 standard in 30 oligodendrogliomas (19 primary lesions and 11 recurrences) in order to verify its possible prognostic role. Twelve primary oligodendrogliomas (63%) and 8 recurrences (73%) were CD44-positive. Three of 9 (33%) primary oligodendrogliomas with a Smith grade A-B and 9 of 10 (90%) primary oligodendrogliomas with a Smith grade C-D were found to be in CD44H-positive (p = 0.020). Three of 9 (33%) primary oligodendrogliomas that had not relapsed and 9 of 10 (90%) successively relapsed primary lesions were found to be CD44H-positive (p = 0.020). Median survival of the patients with a CD44H-positive lesion was 84 months; median survival of the patients with a CD44H-negative lesion was 91 months. We conclude that CD44H could have prognostic value regarding the occurrence of relapses.
  

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Clinical Neuropathology, Volume 22, No. 4/2003 (176-179)

Histological and immunohistochemical study of a neuroblastoma in a dog

M.T. Capucchio¹, D. Lotti², E. Cornaglia¹, F. Valenza¹ and D. Schiffer³

¹Department of Animal Pathology, Faculty of Veterinary Medicine, University of Turin, Grugliasco, ²Private Practitioner in Veterinary Medicine, Revigliasco, Turin, and ³Department of Neuroscience, University of Turin, Turin, Italy

A 13-year-old, male German Shepherd dog was euthanasized for a frontal temporal mass revealed by the MRI. The histological examination showed a proliferation composed of small round undifferentiated cells arranged in sheets or nests and sometimes in pseudorosettes interrupted by hypocellular zones of fibrovascular stroma. Immunohistochemical studies revealed the expression of neuroblastic epitopes. The presented neoplasm has many histological and immunohistochemical features in common with the group of olfactory neuroblastomas reported in man, so it could be classified as primitive neuroectodermal tumor with neuronal differentiation.
 

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Clinical Neuropathology, Volume 22, No. 4/2003 (180-186)

Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients

M. Szybka¹, J. Bartkowiak², K. Zakrzewski³, L. Polis³,
P. Liberski^2,3 and R. Kordek¹

¹Department of Pathology and ²Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University of Lodz and ³Department of Neurosurgery, Institute Polish Mother Memorial Hospital, Lodz, Poland

Microsatellite instability (MSI) is used as a molecular marker for defective DNA mismatch repair (MMR) genes. We report here alterations of MSI in 15 malignant astrocytomas (WHO grade III) and glioblastomas (GBM; WHO grade IV) of pediatric patients (2 – 21 years) and 12 GBM from adults (44 – 68 years) by comparative analysis of BAT25/BAT26 loci and 10 other microsatellite markers. High-level microsatellite instability (MSI-H) occurred in 4 of the 15 pediatric cases (26.7%) and in 1 of the 12 adult GBM cases (8.3%). Low-level microsatellite instability (MSI-L) was observed in 6 pediatric cases (40%) and 8 adult GBM (66.7%). Unstable BAT-25 locus was found in 1 of the MSI-H pediatric cases. Thus, 2 unstable cases showed no instability of this marker. For BAT-26, such a discordance was even more profound: in 1 of MSI-H cases, we obtained no PCR product and the remaining 3 showed no alterations of this marker. MSH2 (Human MutS, Homologue2) protein was detected in all but 3 pediatric cases (1 highly unstable and 2 low-level unstable) and in all adult cases. MLH1 (Human MutL, Homologue 1) protein was detected in all but 2 pediatric cases (1 highly unstable and 1 low-level unstable). Thus, 2 highly unstable pediatric cases showed no detectable MLH1/MSH2 proteins. Our data support earlier observations that MSI occurs predominantly in malignant astrocytic tumors of young patients, which lends support to the hypothesis of different molecular mechanisms of pediatric brain tumors. Surprisingly, we found no significant correlation between the status of 10 microsatellite markers and that of either BAT25 or BAT26 loci or with the expression of MMR genes.
  

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Clinical Neuropathology, Volume 22, No. 4/2003 (187-192)

Recurrent and atypical meningiomas – a multiparametric study using Ki67 labelling index, AgNOR and DNA Feulgen staining

F. Ferraraccio¹, M. Accardo¹, F. Giangaspero² and L. Cuccurullo¹

¹Department of Morphopathology, II University, Naples, and
²Servizio di Anatomia Patologica, Ospedale Bufalini, Cesena, Italy

Objective: Histological analysis has limited value to predict the biological behavior of meningiomas. In this study, we investigated the utility of indicators of cell proliferation in the evaluation of histologically benign meningiomas. Materials and methods: For this purpose, 50 meningothelial meningiomas, 50 atypical meningiomas and 8 primary benign meningiomas with their recurrences were studied. For each case the Ki67 labeling index (LI), DNA ploidy and AgNOR were evaluated and the results quantitatively processed and assessed by computerized image analyzer. Results: The Ki67 labelling showed a low index (11.3%) in typical meningiomas and primary meningiomas (13.6%). In contrast, it was higher in atypical (26.6%) and recurrent meningiomas (28%). Similar results were obtained for the AgNOR granule count which showed that typical and primary meningiomas had mean 1.51 – 1.49, whereas recurring meningiomas and atypical meningiomas had mean values of 1.92 and 1.98, respectively. DNA ploidy revealed in the hyperpolyploid region between 4c – 16c: 7.02% of the nuclei in primary meningiomas, 17.98% of the nuclei in recurring meningiomas and 24.63% of the nuclei in atypical meningiomas. Conclusion: Our results suggest that evaluation of cell proliferation using Ki67 LI, DNA ploidy and AgNOr, integrated with standard histopathology, can provide better information for a correct grading of meningiomas.
 

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Clinical Neuropathology, Volume 22, No. 4/2003 (193-199)

Vein of Galen malformation combined with atrial septal defect in a neonate

T. Hortobágyi¹, Á. Szüts¹, M. Csenki², T. Harkany³, Z. Zádor¹, M. Katona² and I. Bódi⁴

¹Department of Pathology, ²Pediatrics and ³Medical Chemistry, University of Szeged, Szeged, Hungary, and ⁴Department of Neuropathology, Institute of Psychiatry, King’s College Hospital, London, UK

An arteriovenous fistula (AVF) is an abnormal connection between an artery and a vein, whereby the interconnecting capillary network is missing. Such a malformation frequently occurs in the deep midline regions of the brain, and the subsequent increased flow into the draining vein of Galen substantially dilates in an aneurysmal manner. Congenital forms of the aneurysmal dilatation of the vein of Galen (AVG) often lead to death in the neonatal period, predominantly due to cardiac failure caused by the increased venous inflow as a consequence of the intracerebral arteriovenous shunting. In the presented case a male baby suffered from a rare combination of a cerebral AVF and an atrial septal defect (ASD). He was born at week 38 of pregnancy and subsequently developed tachydyspnoe. Ultrasound (US) and CT scans revealed a large bilateral AVF with dilated basal venous sinuses, hydrocephalus and brain atrophy. In the heart, severe right ventricular hypertrophy, patent ductus arteriosus and an ASD were detectable by US. Neurosurgical consultation rejected the possibility of an operative treatment due to size and localization of the lesion and the existing irreversible brain damage. The child died because of cardiac failure 6 days after birth. Autopsy examination in the brain demonstrated a large conglomerate of dilated blood vessels predominantly in the midline and left occipital lobe, edema and hydrocephalus. In the heart, the ASD detected by US proved to be an ostium secundum-type lesion. Histologically, the conglomerate of vessels revealed features of an AVF and matched the characteristics of AVG. Consequences of chronic ischemic brain injury were also present, with ferruginated neurons suggesting intrauterine damage caused by a congenital AVF. Based on data in the literature, we assume that the left-to-right shunt due to increased venous influx into the heart caused not only cardiomegaly, but may have also interfered with the normal development of the atrial septum leading to an ASD, contributing to the rapid progression of the cardiac failure. 
 

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Clinical Neuropathology, Volume 22, No. 4/2003 (199-203)

Intracranial giant cell arteritis with fatal middle cerebral artery territory infarct

L. Browne, O. Hardiman, H. O’Dwyer and M. Farrell

Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland 

A37 year-old man who developed a fatal middle cerebral territory infarct was found at autopsy, to have widespread granulomatous angiitis involving meningeal and intracranial – extracerebral vessels but not intracerebral vessels or other extra-cranial vessels. The findings are unique and overlap with those of granulomatous angiitis of the nervous system (GANS) and classic giant cell arteritis (GCA). A possible precipitant for this devastating illness was a recent Chlamydia infection. The salient clinical and pathologic differences between GANS and GCA of the nervous system are discussed.
 

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Clinical Neuropathology, Volume 22, No. 4/2003 (204-208)

Distal muscular dystrophy of the Miyoshi type

H. Yildiz¹, U. Emre¹, Ö. Coskun¹, U. Ergün¹, H.T. Atasoy² and L.E. Inan¹

¹Department of Neurology, Ministry of Health, Ankara Resarch Hospital, Ankara, and ²Department of Neurology, Karaelmas University Medical School, Zonguldak, Turkey

Objective: Miyoshi myopathy is an autosomal recessive muscular dystrophy. It is characterized by distal muscle involvement, especially the gastrocnemius and soleus. The disease starts with weakness and atrophy of the calves. Material and methods: Here we report on 2 patients, brother and sister, from a Turkish family. Onset of the disease was at the age of 20 and 26 years of age, respectively. In both siblings, there was an early and predominant involvement of the distal muscles of the lower limbs. Creatine kinase activity was elevated 50- to 100-fold above normal values. Results: Electromyography revealed a myopathic pattern. Histology of the biceps muscles indicated some myopathic changes consistent with muscular dystrophy. Occurrence in only these 2 siblings with no other family members was indicative of an autosomal recessive inheritance. Conclusions: We describe the distinctive clinical features in 2 siblings of a Turkish family with MM as differential diagnosis and histological change.
  

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