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   Table of Contents - Current issue
Coverpage
January-June 2020
Volume 3 | Issue 1
Page Nos. 1-62

Online since Thursday, July 2, 2020

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REVIEW ARTICLE  

Role of surgery in recurrent high-grade glioma: Current evidence p. 1
Ujwal Yeole, Arivazhagan Arimappamagan
DOI:10.4103/IJNO.IJNO_7_20  
While the management protocol for de novo glioblastoma is well established, the role of surgery in recurrent high-grade glioma (HGG) is not yet clear. In the light of recent developments in radio and chemotherapy modalities, it has become essential to recognize true disease progression from its mimics. This article discusses the recent literature on the challenges in identifying recurrence in HGG, modalities to diagnose, indications for surgery, and the outcomes in contemporary studies. The factors identified in prognostication have been discussed.
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ORIGINAL ARTICLES Top

Implementation of molecular markers in glioma histology reporting: A survey p. 8
Amitava Ray
DOI:10.4103/IJNO.IJNO_8_20  
Purpose: The purpose of this study is to judge the extent of implementation of the Indian Society of Neuro-Oncology (ISNO) guidelines for the incorporation of molecular markers in glioma histopathological reporting. Materials and Methods: This study was conducted electronically. A form was created on Google Forms and the link was shared on E-mail and WhatsApp to members of the Neurological Society of India and ISNO. Results: One hundred doctors replied to the questionnaire, and the majority worked in large tertiary care hospitals in big cities. However, practitioners from smaller tier 2 and tier 3 cities also participated. Sixty-eight percent of those who responded were neurosurgeons and more than two-thirds of all respondents had a specific interest in neuro-oncology. More than 90% thought that molecular markers added value to histopathology alone, but a much smaller number (12%) had the infrastructure to test all the markers. Only 10% relied on histopathology exclusively, without performing any molecular tests. Lack of adequate infrastructure and the additional cost that was usually borne by the patient were the two largest roadblocks in its wider acceptance. There was also an overwhelming majority of clinicians who thought that the current pathology reports should change and indicate not only the tumor type but include active pathways and suggest the best options for treatment. Conclusion: In spite of the roadblocks, there has been a fair amount of success in clinicians successfully testing for molecular markers in gliomas. As testing becomes more specific and sensitive and treatment becomes targets to specific molecular pathways, analysis of molecular pathways will become integral to glioma histopathology.
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Mitochondrial DNA content in tumor tissue and blood of patients with glioblastoma – A reliable biomarker? p. 12
Palavalasa Sravya, AS Uday Krishna, Vani Santosh, Arivazhagan Arimappamagan
DOI:10.4103/IJNO.IJNO_12_20  
Introduction: Recent studies have shown that mitochondrial DNA (mtDNA) content in the tumor tissue is associated with patient survival in glioblastoma (GBM). However, mtDNA content in the blood of patients with GBM and its variation during treatment has not been documented. Hence, we assessed mtDNA content in blood and tumor tissue of GBM patients, its association with survival, and the variation of mtDNA content in blood with treatment. Materials and Methods: GBM tissue obtained from 20 patients, 2 ml blood collected from the same patients at the time of presentation and following radiation therapy (RT), 2 ml blood obtained from 20 healthy volunteers were assessed for mtDNA content using quantitative real-time polymerase chain reaction (comparative ct method). The mtDNA content is expressed as the mtDNA/nuclear gene ratio. Results: The mean mtDNA copy number in the GBM tissue was 492.3819, while in the blood of patients, it was 41.76 ± 19.45. In healthy volunteers' blood, it was 55.97 ± 5.78 (P = 0.04). The median overall survival was 13 months in patients with high tumor mtDNA content and 10 months in patients with low tumor mtDNA content (P = 0.04). Patients with low-mtDNA content in the blood had a relatively higher content in the tumor tissue (correlation coefficient − 0.26; P = 0.27). No significant difference was noted between mtDNA content in preoperative blood (41.76 ± 19.45) and post-RT blood sample (44.16 ± 12.83) (P = 0.6). Conclusion: High GBM tumor mtDNA copy number is associated with better overall survival. mtDNA content in the blood is lower in GBM patients when compared with healthy volunteers. mtDNA content in the blood of the patients did not vary following surgery and RT.
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Short-term results of treatment outcome and toxicities following gamma knife surgery in cerebellopontine angle tumors p. 19
Nishant Lohia, Arti Sarin, Manoj Kumar Semwal, Virender Suhag, Sukhvir Singh, Sankalp Singh, Pankaj Goyal, Tejas Pandya
DOI:10.4103/IJNO.IJNO_21_19  
Introduction: About 5% to 10% of all intracranial neoplasms are located at the cerebellopontine (CP) angle. The most common of these is the vestibular schwannoma (VS). Aims and Objectives: The primary objective was to assess treatment outcomes in CP angle tumor post-Gamma Knife radiosurgery (GKS). Secondary objectives were the assessment of dose conformity and gradient indices for target coverage and organs-at-risk sparing along with the assessment of hearing function preservation post-GKS. We also assessed facial and trigeminal nerve function and quality of life (QoL) post-GKS. Materials and Methods: This was a retrospective study carried out in a tertiary care center of North India for 2 years and 3 months. All patients were followed up for 24 months posttreatment with a minimum follow-up at least 12 months. Tumor expansion was assessed post-GKS along with hearing preservation rates, facial and trigeminal nerve function and QoL. Results: No significant relationship between age, sex, and study variables was made out. The target tumor coverage ranged from 94% to 100%, with a mean of 97.24%. The conformity index ranged from 1.17 to 1.92, and the gradient index ranged from 1.35 to 1.73. Tumor expansion occurred in 52% of the patients (13) 6 months after GKS, though the increase in size was minimal with a standard deviation of 0.59 and did not result in any clinical deterioration of patients. Positive correlation was seen between maximum tumor size and loss of hearing function. The hearing preservation rate at 12 months post-GKS is 80%. This study also showed that GKS for VS has little impact in the deterioration of the function of the trigeminal and facial nerve and the general QoL. Conclusion: The radiation changes after GKS are generally seen after 6–12 months post-GKS and about 3–5 years are required to ascertain tumor control and any meaningful change in hearing levels and other toxicities. Thus, a longer period of follow-up is needed to validate the findings of this study.
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Bioinformatics analysis of SOX2 gene expression in gliogenesis p. 26
Shouhartha Choudhury
DOI:10.4103/IJNO.IJNO_4_20  
Background: Glioblastoma is the most aggressive cerebral tumor is invariable and lethal. The previous stem cell experiment reported the glioblastoma is expressed in neural cells. SOX2 gene has self-renewal ability in the neural stem cells. The SOX2 gene is a master regulator involved in sustaining self-renewal in neural stem cells. Therefore, the study of the SOX2 gene is essential to explore the aberrant growth of glioblastoma. The SOX family characterized by the DNA-binding domain (high-mobility group [HMG] domain) is involved in the developmental process in mammals. Objective: The present study objective was to investigate the SOX family in mammals. The SOX family plays an essential role during the developmental process in mammals. Therefore, the investigation of the SOX family in the mammalian genome is now mandatory to explore the specific function of the SOX2 gene. Methods: In this study, the author performed powerful bioinformatics and computational technique to the current knowledge of the SOX family in particular organisms. Results: The present study findings confirmed the presence of SOX2 gene in both organisms. The author took a closer look at the SOX family and analyzed genes known so far those that have a different functional domain. The findings provide evidence of the SOX family and their HMG domain in between Homo sapiens and Mus musculus. The conserved domain, motifs, phylogeny, Chromosome location, and gene expression hypothesized that the SOX2 gene is expressed in neural stem cells. Conclusion: The findings concluded that the SOX family is associated with the developmental process in mammals. In contrast, the SOX2 gene expression controls the proliferation of neural stem cells. The downregulated expression of SOX2 gene leads to the loss of tumorigenicity. These observations support the hierarchical model of glioblastoma controlled by SOX2 gene, which would be the ultimate target for glioblastoma therapy.
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Interlinked expression of tumor attributes: Can their evaluation serve as a noninvasive paradigm for prognosis in glioblastoma? p. 32
Puneet Gandhi, Richa Khare, Nitin Garg, Sandeep K Sorte
DOI:10.4103/IJNO.IJNO_22_19  
Background: Glioblastoma (GB) is one of the deadliest brain cancers with a bleak prognosis. It is characterized by highly proliferating tumor cells influenced by surrounding stroma, with a constant detectable communication between the tumor and its environmental components, which can be assessed in terms of specific proteins. Patients and Methods: To experimentally establish this cellular dialog, we undertook to evaluate plasma expression of three proteins: human telomerase reverse transcriptase (hTERT), chitinase-like protein (YKL-40), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in 66 individuals inclusive of thirty primary and two secondary GB patients and 34 age-matched controls, with reference to proliferation, angiogenesis, and extracellular matrix (ECM) degradation biomarkers. A follow-up at 3 months postsurgery for marker profile was done for GB. Results: Plasma levels of markers were higher in therapy-naive patients than in controls (P < 0.0001). In a 3-month follow-up, these levels were found to be higher in patients who survived for ≤4 months than nine patients who had lower values with better survival. A strong correlation existed between hTERT, YKL-40, and TIMP-1 levels; Cox regression analysis revealed higher levels of these circulating markers as poor prognostic indicators. The sensitivity of these markers increased to 96.9% in combination, thereby improving the accuracy of prognosis. Confounders, i.e. age, site, and extent of resection, had no effect on the prognostication of these markers. Conclusion: These experimental blood-based data define the influence of angiogenesis and ECM remodeling on proliferation of GB relative to poor survival, using a panel of biomarkers. Evaluating the disease outcome noninvasively can pave the way for designing intervention strategy to control angiogenesis and ECM degradation and in turn tumor progression.
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CASE REPORTS Top

Collision tumor: Metastatic renal cell carcinoma to cerebellar hemangioblastoma in Von Hippel-Lindau disease p. 38
Tushar V Soni, Nirmal L Desai
DOI:10.4103/IJNO.IJNO_3_20  
A tumor-to-tumor metastasis, also known as collision tumor, is a rare metastatic process in which primary malignant tumor metastasizes to another tumor. Meningioma has been implicated as the most common intracranial neoplasm to harbor metastasis, with donor tumor is the most common lung or breast tumor. Here, we describe the case of metastasis of renal cell carcinoma (RCC) to capillary hemangioblastoma (HAB) of the cerebellum in a patient of Von Hipple-Landau (VHL) disease. Patients with hereditary cancer syndromes may be at increased risk for the development of tumor-to-tumor metastasis. We review the literature about RCC to HAB metastasis and described the pathological and immunohistochemical findings of both the tumor to distinguish the two and to do clinical diagnosis of VHL syndrome.
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Dual-imaging strategy for the resection of recurrent malignant glioma: Challenges and practical utility p. 42
Salman T Shaikh, Prakash M Shetty, Aliasgar V Moiyadi
DOI:10.4103/IJNO.IJNO_9_20  
Recurrent high-grade gliomas constitute a significant, yet vexing burden of disease in neuro-oncological surgery. Despite evidence supporting the multiple benefits of surgery, radical resection remains difficult in many cases. One of the biggest challenges in its treatment is the difficulty in delineating progressive tumor from the treatment-related changes, namely scarring of prior surgical treatment, pseudoprogression, and radiation-induced gliosis. Neurosurgeons dealing with recurrent gliomas should be familiar with the various adjuncts available. Considering the relative benefits and limitations of each of these techniques, a combined modality approach may be most appropriate in such cases. We describe a case of a recurrent glioma operated using three-dimensional intraoperative ultrasound and 5-Aminolevulinic acid illustrating the role of a dual-imaging approach for malignant gliomas.
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Giant lumbar extraforaminal schwannoma p. 45
Rohit Balasubramanian, Subhash Kale, Vignesh Kanda Kumar, Sagar Ghodasara, Udaykumar Badhe
DOI:10.4103/IJNO.IJNO_13_20  
Schwannomas are dumb-bell shaped benign intradural or extradural spinal canal nerve sheath tumors. Here, we present the rare case of a lumbar canal schwannoma in a middle-aged man. The tumor was completely extraforaminal with scalloping of the bone. Gross total excision was achieved by a lumbar approach.
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Reporting two cases of second primary brain tumors and how to differentiate from metastasis preoperatively with magnetic resonance imaging p. 48
G Krishna Kumar, Shashi Sekhar Singh, Amit Kumar, Anandh Balasubramaniam, BJ Rajesh, Bharat A Vaswani
DOI:10.4103/IJNO.IJNO_10_20  
The incidence of second primary tumors in adults is increasing due to betterment in the diagnosis and management of first primary tumors. In literature so far, second primary brain tumors are not reported. Glioblastoma has a poor prognosis despite all recent advances in its molecular genetics and treatment. We report two cases of glioblastoma presenting as second primary tumor of the brain. The first patient was a 70-year-old female with seizures who was treated for carcinoma cervix 6 years back. The second patient was a 75-year-old male patient, a known case of colonic carcinoma treated a year back, and he presented with seizure. Both the patients were operated, and biopsy turned out glioblastoma. A solitary brain lesion in the known first primary patient may be a glial tumor which needs proper evaluation since its management differs from metastasis.
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Primary central nervous system lymphoma – Presenting as a posterior fossa extradural mass lesion: A rare entity and literature review p. 52
Amit Singh, G Krishna Kumar, Shashi Sekhar Singh, Karamtoat Sugali Kiran, Bhavani Prasad Ganji
DOI:10.4103/IJNO.IJNO_6_20  
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin's lymphoma (NHL) confined to the brain, leptomeninges, eyes, or spinal cord. Primary NHL of the cranium with extra- and intracranial extension without systemic or skeletal manifestation in an immunocompetent patient is extremely rare. The prognosis of PCNSL is inferior to that of other NHL subtype. We describe a case of 49-year-old woman presented with occipital headache for 1 month, without any deficits. Imaging showed extradural mass lesion in the posterior fossa based at the trocula with minimal inner bony table changes mimicking primary bony tumor, meningioma, lymphoproliferative disorder, or metastatic tumor. We operated upon this patient, and histopathology was suggestive of B-cell NHL. On further evaluation, there was no systemic involvement. The patient was planned for radiotherapy followed by six cycles of chemotherapy with rituximab and bendamustine. There are case reports of cranial vault lymphomas involving frontoparietal/temporal region. So far, no posterior fossa extradural lesion reported till now.
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Metastatic spindle cell tumor in sacrum p. 56
Umesh Chandra Dutta, ML A Rahman, Naznin Rashid, R Barua
DOI:10.4103/IJNO.IJNO_5_19  
Spindle cell tumours metastatic to bone are rare. A gastrointestinal stromal tumor (GIST) with spindle cell histology is one such tumour that may rarely metastasize to bone and pose great diagnostic or therapeutic challenge for the clinicians. Their symptoms are minimal in the early stage and may go unnoticed before being detected. At the time of presentation, the tumor often metastasizes to other parts of the body, rarely to bone. GISTs are defined as spindle cell, epitheloid, or occasionally pleomorphic mesenchymal tumors of the gastrointestinal tract, which express the KIT protein (CD117), and/or DOG1.Cytological and histological features of metastatic GIST are variable. We present here a rare case of metastatic spindle cell tumour (without clinical evidence of primary) involving sacrum with histopathological & immunohistochemical features of GIST.
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Temporal bone giant-cell tumor with secondary aneurysmal bone cyst: A rare case report and review of literature p. 60
Venkateswara Rao Kommu, Sudha S Murthy, Rashmi Sudhir, Swarna Ch Kumari
DOI:10.4103/IJNO.IJNO_1_20  
Giant-cell tumor (GCT) and aneurysmal bone cyst (ABC) are locally aggressive and benign in nature. They usually occur in the extremities of the long bones. Involvement of the skull base or cranial vault is very rare. Both are different in pathologically and cytogenetically. GCT can be associated with ABC, which are likely reactive in nature. To the best of our knowledge, only two cases are reported coexisting GCT with ABC in the cranial vault. Here, we report the third case of coexisting GCT secondary ABC of the temporal bone and the first case of temporal bone coexisting GCT with ABC.
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