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The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridiz...

The gliomagenesis remains not fully established and their etiological factors still remain obscure. Polyomaviruses were detected and involved in several human tumors. Their potential implication in gliomas has been not yet surveyed in Africa and Arab World. Herein, we investigated the prevalence of six polyomaviruses (SV40, JCPyV, BKPyV, MCPyV, KIPyV, and WUPyV) in 112 gliomas from Tunisian patients. The DNA sequences of polyomaviruses were examined by PCR assays. Viral infection was confirmed by DNA in situ hybridization (ISH) and/or immunohistochemistry (IHC). The relationships between polyomavirus infection and tumor features were evaluated. Specific SV40 Tag, viral regulatory, and VP1 regions were identified in 12 GBM (10.7%). DNA ISH targeting the whole SV40 genome and SV40 Tag IHC confirmed the PCR findings. Five gliomas yielded JCPyV positivity by PCR and DNA ISH (2.7%). However, no BKPyV, KIPyV, and WUPyV DNA sequences were identified in all samples. MCPyV DNA was identified in 30 gliomas (26.8%). For GBM samples, MCPyV was significantly related to patient age (p = 0.037), tumor recurrence (p = 0.024), and SV40 (p = 0.045) infection. No further significant association was identified with the remaining tumor features (p > 0.05) and patient survival (Log Rank, p > 0.05). Our study indicates the presence of SV40, JCPyV, and MCPyV DNA in Tunisian gliomas. Further investigations are required to more elucidate the potential involvement of polyomaviruses in these destructive malignancies.

Purpose of the study Epstein-Barr virus (EBV) has been involved in the development of some tumors, including Burkitt's lymphoma and Hodgkin's lymphoma. However, its potential role in glioma tumorigenesis remains debated. In this study, we investigated the EBV infection in gliomas from Tunisian patients. Patients and methods We conducted a retrospective study of 112 gliomas on archival material. The EBV DNA sequence was analyzed by polymerase chain reaction (PCR). Latent membrane protein 1 (LMP1) was detected by immunohistochemistry. In situ hybridization was used to detect EBV encoded small RNA (EBER). Clinicopathological features were recorded. Survival analysis was carried out using the Kaplan-Meier method and the Log-Rank test to compare EBV-positive and EBV-negative patients. Results Overall, there were twenty-four EBV-positive gliomas (21.4%). EBV DNA was identified in 24 cases. LMP1 and EBER were detected in four EBV DNA-positive cases. All EBV-positive cases were glioblastomas multiforme (GBM). Median overall survival and recurrence-free survival of EBV-negative patients were better than those of EBV-positive patients (Log Rank p = 0.006). Conclusion Altogether, these findings support the occurrence of EBV infection in Tunisian GBM. Furthermore, when compared to EBV-negative tumors, EBV infection seems to be associated with the worst patient prognosis. Advanced molecular studies are recommended to confirm these results and to shed further light on the potential role of EBV in these devastating tumors.

Summary Purpose Three cases of histopathologically confirmed central neurocytoma (CN) are presented, emphasizing diagnostic imaging issues: conventional magnetic resonance imaging with Proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) findings of CN. Materials and methods Patients age ranged from 17 to 32 years, Imaging include a CT scan and MR examination with DWI and proton MRS on a 1.5-T system. DWI and subsequent apparent diffusion coefficient (ADC) were obtained in all. Single voxel MRS was performed prior to surgery using a point resolved spectroscopy sequence (PRESS) with short 35 ms and long echotime (TE) 144 ms, associated with a two-dimensional chemical Shift Imaging (2D-CSI) with 144 ms TE (one case). Histopathological examination included immunostaining with synaptophysin. Results With the long TE, a variable amount of glycine with markedly increased choline, very small to almost complete loss of N -acetylaspartate and creatine, and inverted triplet of alanine-lactate were observed in all three patients. Increased glutamate and glutamine complex (Glx) was also observed in all with short TE. DWI demonstrated variable low ADC which appeared well correlated with the tumor signal intensity and cell density: the most homogeneous and highly dense cellular tumor with increased nucleus to cytoplasm ratio demonstrated the lower ADC. Histological pattern was typical in two cases and demonstrated an oligodendroglioma-like pattern in one case. Positivity for synaptophysin confirmed the neuronal origin in all. Conclusion The demonstration within an intraventricular tumor of both glycine and alanine on MRS along with high choline, bulky Glx and restricted diffusion appear diagnostic of CN.

Background Angiomatous meningiomas (AMs) represent a rare subtype of meningiomas in which the vascular component prevail. They represent less than 1% of all intracranial tumors and approximately 2.1% of all meningeal tumors (Hasselblatt et al., 2004). The purpose of this study was to determine the clinical characteristics, radiological features and prognosis of AMs based on a Tunisian multicenter experience in the management of 58 successive cases of intracranial AMs. To the best of our knowledge, this is the largest series reported to date. Methods We retrospectively reviewed 58 patients of AM treated in the departments of Neurosurgery of The Tunisian National Institute of Neurology, Sahloul University Hospital and Fattouma Bourguiba University Hospital from January 2001 to December 2015. Clinical characteristics, radiographic features and treatment modality, in the form of radical surgery, were noted. Statistical analysis was done with regards to recurrence free survival (RFS) and overall survival (OS) using Kaplan-Meier survival analysis. Results The median age of the patients on admission was 53.0 years (8–78). Twenty-two patients were males and thirty-six were females. The median duration of symptoms prior to presentation was six months. Signs of increased intracranial pressure were the most common presenting symptom followed by seizures, motor weakness and cranial nerves paresis. Cystic changes were observed in 50% of cases, moderate to severe peritumoral edema in 81% of cases and multiple signal voids suggestive of blood vessels in 86.2% of cases. Forty-two patients underwent Simpson I excision (72.4%) while fourteen had Simpson II excision (24.1%). A Simpson III resection was realized in two patients (3.5%). The surgical resection was hemorrhagic in 63.8% of cases and in 13.8% of cases, several blood transfusions were necessary to maintain hemodynamic stability. No adjunctive treatment was administered. Six out of the fifty-six patients of the Simpson I/II groups recurred while one of the two patients with Simpson III resection had tumor regrowth. Median duration of RFS was 103 months. Second surgery was realized in all cases with no subsequent recurrence. The extent of tumor resection and the location were found to correlate with the risk of developing recurrences (P =0.001). Conclusions AMs represent a rare subtype of meningioma characterized by variable cystic components, large peritumoral edema and multiple areas of vascular signal voids. The mainstay of the treatment is gross total resection, ideally following a preoperative embolization. The fate of the tumor remnant after incomplete tumor resection still needs to be evaluated and we do not recommend the systematic use of post-operative adjuvant RT in all cases. As local recurrence can develop many years after initial treatment, Long-term follow-up is mandatory.

Background The meningeal hemangiopericytoma (MHPC) is a vascular tumor arising from pericytes. Most intracranial MHPCs resemble meningiomas (MNGs) in their clinical presentation and histological features and may therefore be misdiagnosed, despite important differences in prognosis. Materials and methods We report 8 cases of MHPC and 5 cases of MNG collected from 2007 to 2011 from the Neuro-Surgery and Histopathology departments. All 13 samples were re reviewed by two independent pathologists and investigated by immunohistochemistry (IHC) using mesenchymal, epithelial and neuro-glial markers. Additionally, we screened all tumors for a large panel of chromosomal alterations using multiplex ligation probe amplification (MLPA). Presence of the NAB2-STAT6 fusion gene was inferred by immunohistochemical staining for STAT6. Results Compared with MNG, MHPCs showed strong VIM (100% of cases), CD99 (62%), bcl-2 (87%), and p16 (75%) staining but only focal positivity with EMA (33%) and NSE (37%). The p21 antibody was positive in 62% of MHPC and less than 1% in all MNGs. MLPA data did not distinguish HPC from MNG, with PTEN loss and ERBB2 gain found in both. By contrast, STAT6 nuclear staining was observed in 3 MHPC cases and was absent from MNG. Conclusions MNG and MHPC comprise a spectrum of tumors that cannot be easily differentiated based on histopathology. The presence of STAT6 nuclear positivity may however be a useful diagnostic marker.

It has become increasingly evident that morphologically similar gliomas may have distinct clinical phenotypes arising from diverse genetic signatures. To date, glial tumours from the Tunisian population have not been investigated. To address this, we correlated the clinico-pathology with molecular data of 110 gliomas by a combination of HM450K array, MLPA and TMA-IHC. PTEN loss and EGFR amplification were distributed in different glioma histological groups. However, 1p19q co-deletion and KIAA1549:BRAF fusion were, respectively, restricted to Oligodendroglioma and Pilocytic Astrocytoma. CDKN2A loss and EGFR overexpression were more common within high-grade gliomas. Furthermore, survival statistical correlations led us to identify Glioblastoma (GB) prognosis subtypes. In fact, significant lower overall survival (OS) was detected within GB that overexpressed EGFR and Cox2. In addition, IDH1R132H mutation seemed to provide a markedly survival advantage. Interestingly, the association of IDHR132H mutation and EGFR normal status, as well as the association of differentiation markers, defined GB subtypes with good prognosis. By contrast, poor survival GB subtypes were defined by the combination of PTEN loss with PDGFRa expression and/or EGFR amplification. Additionally, GB presenting p53-negative staining associated with CDKN2A loss or p21 positivity represented a subtype with short survival. Thus, distinct molecular subtypes with individualised prognosis were identified. Interestingly, we found a unique histone mutation in a poor survival young adult GB case. This tumour exceptionally associated the H3F3A G34R mutation and MYCN amplification as well as 1p36 loss and 10q loss. Furthermore, by exhibiting a remarkable methylation profile, it emphasised the oncogenic power of G34R mutation connecting gliomagenesis and chromatin regulation.

The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection. 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient’s survival. In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021). We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.

Background PA is a grade I glial tumor that mostly occurs in children. However, although apparently similar to paediatric PA, adult PA presents a different clinical follow-up that could arise from specific molecular alterations. A variety of genetic alterations have been identified as diagnostic or prognostic glioma molecular markers. Material and methods We describe a right infratentorial tumor that occurred in a 58-year-old man. Neuroimaging and neuropathological examination suggested PA as an initial diagnosis. The tumor was completely resected. Unexpectedly, two years later, a rapidly growing tumor on the operative site was observed with a second location in the pineal region. Immunohistochemical reactions (IHC), Multiplex ligation probe amplification (MLPA) and fluorescence in situ hybridization (FISH) was performed in both primary and relapse tumor. Results Neuroimaging and neuropathological examinations suggested an unusual diagnosis for adult patients: a recurrent PA. Both MLPA and FISH analysis contribute to diagnostic confirmation by KIAA1549: BRAF fusion detection. Additional genetic results revealed interesting findings that justified the tumor aggressivity. Conclusion Molecular analysis of adult PA cases should be routinely combined with histopathological and neuroimaging examination to further refine prognostic diagnoses.

Background: Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. Materials and Methods: We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Results: Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. Conclusions: This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

Oligodendrogliomas are the tumors of normal glial cells of brain called oligodendrocytes. They represent a small proportion of childhood brain tumors and are infrequently encountered in the posterior fossa. CT scan and MRI are very helpful for the preoperative management of oligodendrogliomas. However, due to the rarity and non-specific imaging features, it may be difficult to differentiate oligodendroglioma from astrocytoma especially in an infratentorial location. The short- and long-term outcome and the exact treatment protocol of posterior fossa oligodendroglioma is yet to be established. We report a rare case of an oligodendroglioma of the vermis in an 8-year-old female with a brief review of the literature.

Cerebral hytatid cysts (HC) are extremely rare, forming 2% of all intra cranial space occupying lesions even in counties where the disease is endemic. HC diagnosis is usually based on a pathognomonic computed tomography (CT) pattern. In order to assess the value of MR we reviewed the CT (n=25) and magnetic resonance (MR, n=4 including diffusion and proton magnetic resonance spectroscopy in 1) imaging of 25 patients with pathologically confirmed cerebral hydatid disease. 19 HC were seen in children under 16 years. All were supra tentorial with 22 in the middle cerebral artery territory. HC was solitary in 18 cases, unilocular in 23 and multi-vesicular in 2 with heavily calcified pericyst in 1. 2 cysts were intra ventricular and 1 intra aqueducal. The most typical features were well defined, smooth thin walled spherical or oval cystic lesions of CSF density and/or signal with considerable mass effect (20/25). Surrounding oedema with complete or incomplete rim enhancement was seen in 3 cases which were labelled as complicated and/or infected cysts. Although CT is diagnostic of hydatid disease in almost all cases (22/25), MRI including diffusion and spectroscopy precisely demonstrate location, number, cyst capsule, type of signal and enhancement and allows diagnosis of atypical or complicated HC and appears more helpful in surgical planning.

Calcification of the cervical ligamentum flavum is a rare entity observed exclusively in Japanese people. We report a new case in a 65-year-old man from Tunisia who presented with symptoms of cervical myelopathy with mild tetra paresis, sensory abnormalities and dysuria. Magnetic resonance imaging (MRI) showed a posterior compression of the spinal cord at C3-C4. CT-scan showed a calcification of the ligamentum flavum at level C3-C4, compressing the left postero-lateral aspect of the spinal cord. C3-C4 laminectomy was performed with removal of abnormal ligamentum flavum tissue. The postoperative course was uneventful and all symptoms resolved. Calcification of the cervical ligamentum flavum is a rare entity; the diagnosis is easy but the pathogenesis remains unclear. Literature regarding this pathology is reviewed.

Desmoplastic infantile ganglioglioma is a rare intracranial tumor of infancy, characterized by solid and cystic component, voluminous size and supratentorial location. These tumors are diagnosed usually below the age of 2 years. We report 1 case of desmoplastic ganglioglioma in 13-year-old male. Computed tomography and magnetic resonance imaging diagnosed supratentorial mixed cystic and solid tumor, which presented as a large cystic component with intense contrast enhancement of a mural nodule. The tumor was surgically removed, and histology revealed desmoplastic ganglioglioma. The patient had a good follow up. This observation emphasizes the possibility of desmoplastic ganglioglioma in older infants. It mustn't be considered as a specific entity of very young age infant and must be recognized in older infant because it may be misdiagnosed as malignant glioma. Despite the pseudo malignant appearance, these tumors have a good prognosis after surgery and when excision is complete they don't led to recurrences.

Primary malignant melanoma of the central nervous system is an uncommon localization, first reported by Hirsberg in 1906. Since then, to our knowledge, only 39 cases have been reported in the literature. We present a case of primary intradural extra-medullary melanoma which developed in a 51-Year-old man who complained of pain in the lower cervical spine, difficulties in micturition and sexual impotence. The diagnosis was suspected at the MRI which showed a lesion with a paramagnetic signal and was confirmed by the histological examination. The resection was complete and the course has been satisfactory after 19 months follow-up.

The authors report the case of a 24 years-old man who had a first tumor in the right maxilla diagnosed as Ewing's sarcoma and treated by chemotherapy and radiotherapy. A second tumor appeared in the skull vault twenty seven months later. The histological diagnosis after removal of the lesion was IgG Lambda plasmacytoma. The revision of the histological cut of the maxillary tumor retained the same diagnosis. The patient is without evidence of local recurrence and systemic diffusion of the disease two years after treatment. The authors insist on the necessity of immunochemistry to establish the diagnosis.

The authors report, after a follow-up period of two years, a case of intramedullary congenital epidermoid cyst treated surgically. The patient, a 21 year-old man, presented with a seven year history of motor disturbances of his left lower limb and more recent urinary incontinence. The diagnosis of an intramedullary tumor was provided by a myelogram and a post-myelogram CT. In the absence of a dermal sinus or vertebral dysraphic anomalies, the epidermoid nature of the mass was an operative and histological finding. The main data from the literature are commented: frequency, topography, clinical diagnosis, and radiologic or M.R.I. imaging. Intracapsular removal of the mass seems to result, as in the presently reported case, in a satisfactory outcome.