Recurrence-associated chromosomal anomalies in meningiomas: Single-institution study and a systematic review with meta-analysis

•WHO grade II or III and loss of heterozygosity (LOH) on 1p, and 14q are responsible for recurrence of a sporadic meningioma.•WHO grading has greater impact on further tumour behaviour than molecular findings.•Sparse reporting of the rate of resection prevents full meta-analysing

Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features

List of genes differentiating between pilocytic astrocytomas by different clinical features (DOCX 117 kb

The molecular pattern of histopathological progression to anaplastic meningioma – A case report

Meningiomas (MGs) are the most frequent primary tumours of the central nervous system (CNS) and exhibit a large spectrum of histological types and clinical phenotypes. The WHO classification of CNS tumours established strict diagnostic criteria of the benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3) subtypes. Combined with the resection rate, WHO grading has the most crucial role as the prognostic factor. Additionally, such biomarkers as Ki-67/MIB-1, progesterone receptors and phosphor-histone H3 were correlated with MG progression. Recently, it was suggested that the aggressive behaviour of some MGs is attributed to molecular alterations, regardless of their histopathology. The analysis of loss of heterozygosity (LOH) at chromosomes 1, 9, 10, 14 and 22 was performed. The presented case of WHO Grade 2 MG initially exhibited LOH at chromosomes 10, 14 and 22. In the first recurrence, the tumour genetic profiling revealed additional LOH at chromosome 1p and atypical histopathology. During the second recurrence, an aggressive phenotype was observed and tumour progressed to an anaplastic form. Considering the appearance of the tumour relapses, the set of molecular changes overtook the histopathological progression. The genetic and histopathological imbalance in the tumour progression in secondary anaplastic MGs has not been previously described. The evolution of genetic and histopathological changes was presented in the same patient. In the future, the individualised therapy of potentially more aggressive forms of MGs could be based on certain chromosome aberrations

Spektroskopia rezonansu magnetycznego w wewnątrzczaszkowych nowotworach pochodzenia glejowego

Background and purpose To determine in vivo magnetic resonance spectroscopy (MRS) characteristics of intracranial glial tumours and to assess MRS reliability in glioma grading and discrimination between different histopathological types of tumours. Material and methods Analysis of spectra of 26 patients with glioblastomas, 6 with fibrillary astrocytomas, 4 with anaplastic astrocytomas, 2 with pilocytic astrocytoma, 3 with oligodendrogliomas, 3 with anaplastic oligodendrogliomas and 17 control spectra taken from healthy hemispheres. Results All tumours’ metabolite ratios, except for Cho/Cr in fibrillary astrocytomas (p = 0.06), were statistically signiflcantly different from the control. The tumours showed decreased Naa and Cr contents and a high Cho signal. The Lac-Lip signal was high in grade III astrocytomas and glioblastomas. Reports that Cho/Cr ratio increases with glioma's grade whereas Naa/Cr decreases were not confirmed. Anaplastic astrocytomas compared to grade II astrocytomas had a statistically significantly greater ml/Cr ratio (p = 0.02). In pilocytic astrocytomas the Naa/Cr value (2.58 ± 0.39) was greater, whilst the Cho/Naa ratio was lower (2.14 ± 0.64) than in the other astrocytomas. The specific feature of oligodendrogliomas was the presence of glutamate/glutamine peak Glx. However, this peak was absent in two out of three anaplastic oligodendrogliomas. Characteristically, the latter tumours had a high Lac-Lip signal. Conclusions MRS in vivo cannot be used as a reliable method for glioma grading. The method is useful in discrimination between WHO grade I and WHO grade II astrocytomas as well as oligodendrogliomas from other gliomas.Wstęp i cel pracy Ustalenie charakterystyki spektroskopii magnetycznego rezonansu jądrowego (magnetic resonance spectroscopy – MRS) u chorych z nowotworami wewnątrzczaszkowymi pochodzenia glejowego oraz ocena przydatności tego badania w diagnostyce różnicowej typów histologicznych glejaków. Materiał i metody Przeprowadzono analizę widm MRS nowotworów u 26 chorych z glejakami wielopostaciowymi, 6 z gwiaździakami włókienkowymi, 4 z gwiaździakami anaplastycznymi, 2 z włosowatokomórkowymi, 3 ze skąpodrzewiakami, 3 ze skąpodrzewiakami anaplastycznymi oraz 17 widm kontrolnych pochodzących ze zdrowych półkul mózgu. Wyniki Wszystkie wskaźniki metaboliczne w przypadkach nowotworów, z wyjątkiem Cho/Cr w gwiaździakach włókienkowych (p = 0,06), różniły się znamiennie od tych w grupie kontrolnej. Nowotwory wykazywały zmniejszoną zawartość Naa i Cr oraz wysoki sygnał Cho. Sygnał Lac-Lip był wysoki w gwiaździakach III stopnia wg WHO i glejakach wielopostaciowych. Nie udało się potwierdzić doniesień, że wskaźnik Cho/Cr rośnie, a wskaźnik Naa/Cr maleje wraz ze wzrostem stopnia złośliwości glejaka. Gwiaździaki anaplastyczne wykazywały znamiennie wyższy wskaźnik ml/Cr (p = 0,02) w porównaniu z gwiaździakami II stopnia wg WHO. W gwiaździakach włosowatokomórkowych wartość Naa/Cr (2,58 ± 0,39) była większa, a Cho/Naa mniejsza (2,14 ± 0,64) niż w innych gwiaździakach. Skąpodrzewiaki charakteryzowała obecność szczytu glutaminianu/glutaminy (Glx), którego jednak nie obserwowano w 2 spośród 3 przypadków skąpodrzewiaków anaplastycznych. Dla tych ostatnich symptomatyczna była obecność silnego sygnału Lac-Lip. Wnioski Badanie MRS in vivo nie jest niezawodną metodą różnicującą glejaki wewnątrzczaszkowe. Wydaje się użyteczne w diagnostyce różnicowej gwiaździaków I i II stopnia wg WHO oraz w odróżnianiu skąpodrzewiaków od pozostałych glejaków

The correlation of clinical and chromosomal alterations of benign meningiomas and their recurrences

Meningiomas (MGs) are the frequent benign intracranial tumors. Their complete removal does not always guarantee relapse-free survival. Recurrence-associated chromosomal anomalies in MGs haves been proposed as prognostic factors in addition to the World Health Organisation (WHO) grading, tumor size and resection rate. The aim of this study was to evaluate the frequency of deletions on chromosomes in sporadic MGs and to correlate them with the clinical findings and tumor behaviour. Along with survival, the tumor recurrence was the main endpoint. Chromosomal loss of heterozygosity (LOH) was studied. 46 benign MGs were subjected to the analysis, complete tumor resection was intended and no early mortalities were observed. Incomplete removal was related to parasagittal location and psammomatous hisptopathology (p<0.01). Chromosomal alterations were present in 82.6% of cases; LOH at 22q (67.4%) and 1p (34.8%) were the most frequent and associated with male sex (p=0.04). Molecular findings were not specific for any of the histopathologic grade. Tumor recurrence (14 of 46) correlated with tumor size (≥35mm), LOH at 1p, 14q, coexistence of LOH at 1p/14q, 10q/14q, ‘complex karyotype’ status (≥2 LOHs excluding 22q), patient age (younger <35), and Simpson grading of resection rate (≥3 of worse prognosis). The last 3 variables were independent significant prognostic factors in multivariate analysis and of the same importance in recurrence prediction (Receiver Operating Characteristic curves comparison p>0.05). Among the cases of recurrence, tumor progression was observed in 3 of 14. In 2 cases, LOH on 1p and/or coexistence of LOH 1p/14q correlated with anaplastic transformation

Successful elimination of non-neural cells and unachievable elimination of glial cells by means of commonly used cell culture manipulations during differentiation of GFAP and SOX2 positive neural progenitors (NHA) to neuronal cells

<p>Abstract</p> <p>Background</p> <p>Although extensive research has been performed to control differentiation of neural stem cells – still, the response of those cells to diverse cell culture conditions often appears to be random and difficult to predict. To this end, we strived to obtain stabilized protocol of NHA cells differentiation – allowing for an increase in percentage yield of neuronal cells.</p> <p>Results</p> <p>Uncommitted GFAP and SOX2 positive neural progenitors – so-called, Normal Human Astrocytes (NHA) were differentiated in different environmental conditions to: only neural cells consisted of neuronal [MAP2+, GFAP-] and glial [GFAP+, MAP2-] population, non-neural cells [CD44+, VIMENTIN+, FIBRONECTIN+, MAP2-, GFAP-, S100β-, SOX2-], or mixture of neural and non-neural cells.</p> <p>In spite of successfully increasing the percentage yield of glial and neuronal <it>vs</it>. non-neural cells by means of environmental changes, we were not able to increase significantly the percentage of neuronal (GABA-ergic and catecholaminergic) over glial cells under several different cell culture testing conditions. Supplementing serum-free medium with several growth factors (SHH, bFGF, GDNF) did not radically change the ratio between neuronal and glial cells – i.e., 1,1:1 in medium without growth factors and 1,4:1 in medium with GDNF, respectively.</p> <p>Conclusion</p> <p>We suggest that biotechnologists attempting to enrich <it>in vitro </it>neural cell cultures in one type of cells – such as that required for transplantology purposes, should consider the strong limiting influence of intrinsic factors upon extracellular factors commonly tested in cell culture conditions.</p

Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. It is invariably fatal and displays a short clinical disease stage. The key event in sCJD is the propagation of a beta-sheet rich conformer of the physiological PrPC protein, known as PrPSc. Neuropathological disease characteristics include gliosis, neuronal loss and spongiform degeneration; disease clinical manifestations refer to mental and visual disabilities, cognitive impairment, gait or limb ataxia, myoclonus and mutism. Definite sCJD diagnosis requires post-mortem brain material histopathological examination. However, highly certain pre-mortem differential diagnosis is desired to exclude other treatable disorders and to reduce disease transmission risks. Detection and/or quantification of cerebrospinal fluid (CSF) biomarkers reflecting neuronal damage and PrPC misfolding in the diseased brain significantly enhance pre-mortem diagnosis. Previously established and newly identified biomarkers are used towards this direction. Increased CSF Neurofilament light chain (NFL) concentrations have been reported in several neurological disorders, including prion diseases. In the present study, we analyzed CSF NFL levels in two independent patient cohorts, consisting of highly suspected sCJD cases that were further classified as sCJD or non-CJD according to established diagnostic criteria. CSF NFL concentrations were increased in sCJD compared to non-CJD cases in both cohorts (area under the curve (with 95% confidence interval) equal to 0.89 (0.82 to 0.97) and 0.86 (0.77 to 0.96), respectively. CSF NFL was associated neither to age nor to sex but correlated with total-tau concentrations in both cohorts. Overall, our data provide independent validation of CSF NFL utility in sCJD differential diagnosis