Primary intracranial synovial sarcoma: A case report and review of literature.

Background: Primary intracranial synovial sarcomas (PrISS) are unusual dural based mesenchymal tumors seen most commonly in the supratentorial compartment. They can mimic a spontaneous intracranial hemorrhage or a high-grade glioma on imaging. Case Description: A 31-year-old male presented with headache and right hemiparesis for 2 weeks. CT brain revealed a left frontal spontaneous intracerebral hemorrhage. PrISS revealed a heterogeneously ring enhancing solid cystic lesion with attachment to convexity dura. Intraoperatively, it mimicked a high-grade glioma. Histopathology report showed features of a synovial sarcoma, which was later confirmed with IHC. Classical SYT-SSX2 translocation was confirmed only on RTPCR after fluorescent in situ hybridization (FISH) was negative for same. Whole body positron emission tomography (PET-CT) did not show any extracranial tumor. Despite radiotherapy, there were recurrence and tumor progression at 6 months and the patient succumbed 11 months later. Conclusion: PrISS is an unusual aggressive intracranial neoplasm that carries a worse prognosis when compared nonintracranial synovial sarcomas. Molecular cytogenetics (FISH and RTPCR) are essential for confirming the diagnosis, though FISH seems to have a lower sensitivity and can yield false negative results as was noted in this case.

Establishment and Characterization of Brain Cancer Primary Cell Cultures From Patients to Enable Phenotypic Screening for New Drugs.

Aim: Desmoplastic infantile ganglioglioma (DIG), is a rare tumor arising mainly during the first 2 years of life. Molecular characterization of these benign yet rapidly proliferating tumors has been limited to evaluating a few mutations in few genes. Our aim was to establish a live cell culture to enable the understanding of the cellular processes driving the non-malignant growth of these tumors. Methods: Tumor tissue from a rare non-infantile 8-year-old female DIG patient was dissociated and digested using collagenase to establish live cultures. Both 2D monolayer and 3D neurospheres were successfully cultured and characterized for proliferative potential, intrinsic plasticity, presence of cancer stem cells and the expression of stem cell markers. Cells cultured as 3D were embedded as tissue blocks. Immunohistochemistry was performed in both tissue and 3D sections for markers including synaptophysin, vimentin, neurofilament and MIB-1. Mutation analysis by NGS was performed using a-100 gene panel. Results: Using immunohistochemistry, the 3D cultures were shown to express markers as in the original DIG tumor tissue indicating that the spheroid cultures were able to maintain the heterogeneity found in the original tumor. Cells continued proliferating past passage 10 indicative of immortalization. Enrichment of cancer stem cells was observed in neurospheres by FACS using CD133 antibody and RT-PCR. Mutation analysis indicated the presence of germline mutations in three genes and somatic mutations in two other genes. Conclusion: A spontaneous cell line-like cell culture with high percentage of stem cells has been established from a DIG tumor for the first time.

Exosomal PTEN as a Predictive Marker of Aggressive Gliomas.

Background: Liquid biopsies have emerged as convenient alternative diagnostic methods to invasive biopsies, by evaluating disease-specific biomarkers and monitoring the disease risk noninvasively. Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) is a potent tumor suppressor, and its deletion/mutations are common in gliomas. Objective: Evaluate the feasibility of non-invasive detection of PTEN and its downstream genes in serum exosomes of glioma patients. Materials and methods: PTEN, Yes-associated-protein 1 (YAP1), and lysyl oxidase (LOX) transcript expression were monitored through polymerase chain reaction (PCR) in serum exosomes and their paired tumor tissues. The impact of PTEN and its axis genes expression on the overall survival (OS) was monitored. Results: Out of the 106 glioma serum samples evaluated, PTEN was retained/lost in 65.4%/34.6% of the tumor samples while it was retained/lost in 67.1%/32.9% of their paired exosomal fractions. PTEN expression in both tissue and paired exosomal fractions was observed in 48.11% of the samples. Sanger sequencing detected three mutations (Chr10: 89720791(A>G), Chr10:89720749(C>T), and Chr10:89720850(A>G). Both PTEN-responsive downstream genes (YAP1) and LOX axis were upregulated in the PTEN-deficient samples. PTEN loss was associated with poor survival in the glioma patients (hazard ratio (HR) 0.68, confidence interval (CI): 0.35-1.31, P = 0.28). The OS of the exosomal PTEN cohort coincided with the tumor-tissue PTEN devoid group (HR 1.08, CI: 0.49-2.36, P = 0.85). While, old age yielded the worst prognosis; gender, location, and grade were not prognostic of OS in the multivariate analysis. Conclusions: PTEN and its responsive genes YAP1 and LOX can be detected in serum exosomes and can serve as essential tools for the non-invasive evaluation/identification of aggressive gliomas.

Rosette-forming glioneuronal tumors: a report of two cases.

Rosette-forming glioneuronal tumor, a mixed glial and neuronal tumor, is a relatively new entity in tumors of the central nervous system, included in 2007 classification published by World Health Organization (WHO). It was initially described to occur in and around the fourth ventricle; however, recent case series have reported other locations also. Their occurrence in supratentorial and spinal locations has recently been reported. We report two cases of rosette-forming glioneuronal tumors, one in the midbrain and one in a suprasellar location, and review the literature.

Decompressive surgery for severe cerebral venous sinus thrombosis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is one of the common causes of stroke in young people. Mortality in CVST, in addition to progressive thrombosis, is related to elevated intracranial pressure causing transtentorial herniation. The role of decompressive surgery in CVST is not well established. AIMS: We report our experience with decompressive surgery in CVST and review the literature. SETTINGS AND DESIGN: This is a retrospective study carried out in the Stroke Unit of a multispeciality tertiary care hospital in south India. MATERIALS AND METHODS: The medical records of patients admitted with the diagnosis of CVST between December 2003 and July 2009 were reviewed. The clinical presentation, etiology, medical management, indications for surgery and outcomes were assessed for patients undergoing decompressive surgery. The sensorium was assessed using the Glasgow Coma Scale (GCS), while the outcome was assessed using the modified Rankin scale (mRS). Descriptive statistics were used as appropriate. RESULTS: One hundred and six patients were admitted with the diagnosis of CVST during the study period. Eleven patients (10%) underwent decompressive surgical procedure. Indications for surgery included a low GCS at admission with large infarct on the computed tomography scan, mass effect and midline shift, clinical and radiological signs of transtentorial herniation, deterioration in the sensorium in spite of anti-edema measures and postthrombolysis hematoma. Eight patients (73%) had a good outcome while three patients (27%) died. Of the patients who died, two had a low GCS and bilaterally nonreactive pupils before the surgery while one had thrombosis of the deep venous system. CONCLUSION: Decompressive surgery for patients with large cerebral venous infarcts is a life-saving procedure. Patients with CVST who develop clinical and radiological features of transtentorial herniation either at presentation or during the course of medical management may benefit from decompressive surgery.

Olfactory ensheathing cell tumor.

Olfactory ensheathing cells (OECs) are found in the olfactory bulb and olfactory nasal mucosa. They resemble Schwann cells on light and electron microscopy, however, immunohistochemical staining can distinguish between the two. There are less than 30 cases of olfactory groove schwannomas reported in the literature while there is only one reported case of OEC tumor. We report an OEC tumor in a 42-year-old male and discuss the pathology and origin of this rare tumor.

Exosomes as a biomarker platform for detecting epidermal growth factor receptor-positive high-grade gliomas.

OBJECTIVE High-grade glial brain tumors are often characterized by an elevated expression of the tumorigenic epidermal growth factor receptor variant III ( EGFRvIII). The authors sought to establish a clinically adaptive protocol as a noninvasive diagnostic tool for EGFRvIII detection through serum exosomes. METHODS Purity of serum exosome/RNA was confirmed by electron microscopy and flow cytometry and through an RNA bioanalyzer profile. EGFRvIII amplification was initially established by semiquantitative polymerase chain reaction in tumor tissues and exosomes. Diagnostic performance of EGFRvIII transcript in tissue versus exosome was determined using a 2 × 2 clinical table approach. Overall survival was determined using Kaplan-Meier analysis. RESULTS The EGFRvIII transcript was detected in 39.5% of tumor tissue samples and in 44.7% of their paired serum exosome samples; 28.1% of biopsy tumors coexpressed wild-type EGFR and EGFRvIII. Tissue EGFRvIII amplification served as the reference-positive control for its paired serum expression. The overall clinical sensitivity and specificity of semiquantitative exosome EGFRvIII polymerase chain reaction detection assay in serum were 81.58% (95% CI 65.67%-92.26%) and 79.31% (95% CI 66.65%-88.83%), respectively. Age, sex, tumor location, and side of the body on which the tumor was located had no effect on the detection rate of exosomal EGFRvIII transcript. EGFRvIII expression either in exosomes or tissue correlated with poor survival. CONCLUSIONS The authors established a serum-based method for detection of EGFRvIII in high-grade brain tumors that might serve as an optimal noninvasive method for diagnosing EGFRvIII-positive high-grade gliomas.

Diagnosis and treatment of multiple hydatid cysts at the craniovertebral junction. Case report.

Echinococcosis, or hydatid disease, of the craniovertebral junction and skull base is rare. The authors report the occurrence of multiple hydatid cysts at this anatomical location in a young woman who was previously misdiagnosed with tuberculosis. The patient underwent transoral excision of the hydatid cysts followed by posterior decompression and occipitocervical fusion. She was treated postoperatively with albendazole for 12 weeks with a good outcome. The management of spinal hydatid disease is reviewed.

Microendoscopic discectomy for prolapsed lumbar intervertebral disc.

BACKGROUND: Lumbar disc prolapse is a common problem and the current surgical standard for its treatment is a microsurgical discectomy. Microendoscopic discectomy (MED) is a minimally invasive spinal procedure being done successfully for prolapsed intervertebral disc disease. AIMS: We report the technique, outcome and complications seen in 107 cases of prolapsed lumbar intervertebral disc who underwent MED. SETTING AND DESIGN: The study was carried out at the Department of Neurosurgery, at a tertiary hospital in South India and the data was collected prospectively. MATERIALS AND METHODS: 107 patients with prolapsed lumbar intervertebral disc who were seen at our institution between November 2002 and January 2006 were included in the study. Data was collected prospectively. The METRx system (Medtronic Sofamor Danek, Memphis,TN) was used to perform MED. Outcome assessment was done by the modified Macnab criteria. RESULTS: 107 patients (67 males, 40 females) underwent MED for prolapsed lumbar intervertebral disc. Follow up ranged from 2 to 40 months with a mean follow up 12.9 months. Seventy six patients had an excellent outcome, 22 patients had a good outcome, 5 patients had a fair outcome and 3 patients had a poor outcome. One patient with a long dural tear required conversion to a standard microdiscectomy and was excluded from outcome assessment. Complications included dural puncture with K-wire (1), dural tear (2), superficial wound infection (1), discitis (1) and recurrent disc prolapse (2). CONCLUSIONS: Microendoscopic Discectomy (MED) is a safe and effective procedure for the treatment of prolapsed lumbar intervertebral disc.

Desmoplastic fibroma of the frontal bone.

Desmoplastic fibroma is a benign but locally aggressive tumor arising usually from the mandible, pelvis and long bones with a potential for recurrence. We report a case of desmoplastic fibroma of the frontal bone in a young male.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A case report and review of literature.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is identified as a distinct entity that differs considerably in its clinical presentation, immunopathology, radiological findings and response to steroids. We describe a case that presented to us with progressive quadriparesis and lower cranial nerve deficits whose radiological and pathological findings were consistent with CLIPPERS. The patient had a good outcome with long term immunosuppression.

Traumatic aneurysm of the callosomarginal artery.

Intracranial aneurysms are rare complications of head injury. The primary goals in the management of patients harbouring these lesions are early identification and intervention to prevent bleeding or rebleeding. The authors present a case of traumatic false aneurysm of the callosomarginal artery which was diagnosed following head injury and managed successfully with a good outcome.

Arteriovenous fistula of the filum terminale misdiagnosed and previously operated as lower lumbar degenerative disease.

Filum terminale arteriovenous fistula (FTAVF) presenting as a cause of failed back surgery syndrome is a rare entity. We report a 48-year-old male patient who presented with clinical features of a conus medullaris/cauda equina lesion. He had upper and lower motor neuron signs in both the lower limbs with autonomic dysfunction. The patient was misdiagnosed and was operated twice earlier for lumbar canal stenosis and disc prolapse. After reviewing his clinical and radiological findings a diagnosis of FTAVF was made. He underwent surgery and there was a significant improvement in his neurological functions. We discuss the case and review the literature on FTAVF's.