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Featured researches published by Mehar Chand Sharma.


Neurosurgical Review | 2006

Neurocytoma: a comprehensive review

Mehar Chand Sharma; Prabal Deb; Suash Sharma; Chitra Sarkar

Central neurocytomas (CN) are uncommon tumors of the central nervous system, most descriptions of which available in the literature are in the form of isolated case reports and small series. Owing to this rare incidence, diagnosis and management of this neoplasm remain controversial. Usually, these tumors affect lateral ventricles of young adults and display characteristic neuroimaging and histomorphologic findings. Neurocytomas often mimic oligodendrogliomas when confirmation of diagnosis rests on immunohistochemistry, ultrastructure, and genetic studies. Extraventricular neurocytomas, situated entirely within the brain parenchyma and spinal cord, have also been reported. Typically, CN are associated with a favorable outcome although cases with more aggressive clinical course with recurrences are not unknown. MIB-1 labeling index (LI) of >2% often heralds poor prognosis and tumour recurrence. Safe maximal resection is presently considered the ideal therapeutic option, with best long-term prognosis in terms of local control and survival. The role of adjuvant radiotherapy apparently seems to benefit patients with incomplete resection and in atypical neurocytoma. Utility of other therapeutic regimen, however, remains shrouded in controversy. Epidemiology, histogenesis, clinical profile, histology, neuroimaging and therapeutic modalities of neurocytomas have been comprehensively reviewed, with special emphasis on CN and extraventricular neurocytomas and their atypical counterparts.


Journal of Neuro-oncology | 2002

Are childhood and adult medulloblastomas different? A comparative study of clinicopathological features, proliferation index and apoptotic index.

Chitra Sarkar; Pulakesh Pramanik; Asis Kumar Karak; Partho Mukhopadhyay; Mehar Chand Sharma; Varindera Paul Singh; Veer Singh Mehta

Childhood medulloblastomas have been suspected to be biologically different from adult tumors, though comparative studies are sparse in the literature. The present study aims to establish any differences or nexus in the biological characteristics between childhood and adult medulloblastomas. A total of 181 medulloblastomas were studied with respect to clinical and histological characteristics, MIB-1 labeling index (MIB-1 LI), apoptotic index (AI), ratio of apoptotic to LI, p53 and Bcl-2 protein expressions. Two-thirds (112) of the 181 medulloblastomas occurred in children (≤15 years) and 69 in adults (>15 years). Childhood tumors were more commonly of classical histology and midline location while the desmoplastic variant and lateral location occurred more frequently in adults. Adult medulloblastomas were biologically less aggressive, having lower growth rate parameters (mean MIB-1 LI 19.1 ± 15.7; AI 3.73 ± 2.71 and AI : LI 0.207 ± 0.162) as compared to childhood tumors (mean MIB-1 LI 28.3 ± 20.4; AI 2.86 ± 2.14 and AI : LI 0.108 ± 0.111). p53 and Bcl-2 protein expressions were infrequent in all groups of tumors. No difference was noted in any of the parameters when classical and desmoplastic medulloblastomas were compared as a whole. But when compared between the age groups, an interesting observation (hitherto unreported in English literature) was that both classical and desmoplastic variants of childhood medulloblastomas had higher LI, lower AI and lower AI : LI ratio than their counterparts in adults, indicating that differences in growth rates cannot be attributed to differences in the frequency of occurrence of the histological variants in the two age groups. Thus, this study conclusively shows that there is a biological difference between childhood and adult medulloblastomas which is independent of standard histology and appeared to be associated more with age-related factors. This also warrants less-aggressive therapy for adult medulloblastoma.


Neuro-oncology | 2009

Pediatric glioblastomas: A histopathological and molecular genetic study

Vaishali Suri; Prasenjit Das; Ayushi Jain; Mehar Chand Sharma; Sachin A Borkar; Ashish Suri; Deepak Gupta; Chitra Sarkar

Glioblastoma multiforme (GBM) occurs rarely in children. Relatively few studies have been performed on molecular properties of pediatric GBMs. Our objective in this study was to evaluate the genetic alterations in pediatric GBM (age < or = 18 years) with special reference to p53, p16, and p27 protein expression, alterations of the epidermal growth factor receptor (EGFR), and deletion of the phosphate and tensin homolog gene (PTEN). Thirty cases of childhood GBMs reported between January 2002 and June 2007 were selected, and slides stained with hematoxylin and eosin were reviewed. Immunohistochemical staining was performed for EGFR, p53, p16, and p27, and tumor proliferation was assessed by calculating the MIB-1 labeling index (LI). Fluorescence in situ hybridization analysis was performed to evaluate for EGFR amplification and PTEN deletion. Histopathological features and MIB-1 LI were similar to adult GBMs. p53 protein expression was observed in 63%. Although EGFR protein overexpression was noted in 23% of cases, corresponding amplification of the EGFR gene was rare (5.5%). Deletion of the PTEN gene was also equally rare (5.5%). One case showed polysomy (chromosomal gains) of chromosomes 7 and 10. Loss of p16 and p27 immunoexpression was observed in 68% and 54% of cases, respectively. In pediatric de novo/primary GBMs, deletion of PTEN and EGFR amplification are rare, while p53 alterations are more frequent compared to primary adult GBMs. Frequency of loss of p16 and p27 immunoexpression is similar to their adult counterparts. This suggests that pediatric malignant gliomas are distinctly different from adult GBMs, highlighting the need for identification of molecular targets that may be adopted for future novel therapeutic strategies.


Pathology & Oncology Research | 2004

Subependymal giant cell astrocytoma - a clinicopathological study of 23 cases with special emphasis on histogenesis

Mehar Chand Sharma; Angela Mercy Ralte; Shailesh Gaekwad; Vani Santosh; S. K. Shankar; Chitra Sarkar

Subependymal giant cell astrocytomas (SEGAs) are relatively rare tumors but occur commonly in the setting of the familial syndrome of tuberous sclerosis complex (TSC). In view of its varied morphology, i.e. resemblance to astrocytic and ganglion cells, its histogenesis remains controversial. We studied 23 cases of SEGA, 19 from our own institute and 4 from NIMHANS, Bangalore. These 19 cases of SEGAs were collected over a period of 23 years (1979 to 2001), and accounted for 0.16% of intracranial tumors and 0.51% of all gliomas reported at our center. The majority of patients presented with visual disturbances (19÷23, 82.6%) in the form of decreased vision (60.8%) and blindness (21.7%), generalized tonic clonic seizures (43.4%) and focal motor seizures (4.37%). Age ranged from 4 to 37 years (mean 13.2 years) with male predominance (M:F 2.2:1), and the duration of symptoms varied from 1 month to 96 months (mean 17.2 months). Lateral ventricular involvement was the most common site (91.3%), followed by the third ventricle (8.6%). Nine patients (39.1%) had stigmata of tuberous sclerosis (6 at the time of diagnosis and 3 in the follow-up period). Two patients died due to surgical complications, while the rest were alive and well in the follow-up period ranging from 3 to 264 months (mean 37.1 months). Two patients experienced recurrences, one two years and another 22 years after surgery. Microscopic examination showed varied histology consisting of sweeping bundles of spindle cells, gemistocyte and ganglion-like cells with interspersed inflammatory cell component. The inflammatory cell component on special staining turned out to be an admixture of mast cells and T lymphocytes. Six cases showed areas of necrosis and/or mitosis, but were not indicative of aggressive nature of this tumor. Immunoreactivity for GFAP, NF, S-100, NSE and synaptophysin indicates that this is a hybrid tumor with glial and neuronal differentiation. None of the tumors was immunopositive for HMB-45. The significance of the presence of T lymphocytes and mast cells is not clear. It could be related to tumor immunology and may indicate a favorable prognosis.


Pathology | 1998

A study of proliferative markers in central neurocytoma

Mehar Chand Sharma; Annapurna Rathore; Asis Kumar Karak; Chitra Sarkar

Summary To gain a better insight into the biological behavior of central neurocytomas, various proliferative indices were studied in these tumors and correlated with the histological features as well as the clinical outcome. Twenty cases of neurocytoma were selected over a 16 year period (1980–1995), which accounted for 0.28% of all intracranial tumors reported at this centre. Treatment consisted of surgical resection (total 14, subtotal six) followed by radiotherapy. Except for five patients who died of surgical complications, the remaining 15 were all alive and well during the follow‐up period, varying from six months to 72 months (average 32 months). Thirteen tumors showed benign histological characteristics (Group I) while seven showed mitoses + necrosis (Group II). The proliferative index was assessed in formalin‐fixed paraffin‐embedded tissue of 17 cases using the silver nucleolar organiser region (AgNOR) technique and immunohistochemical staining for proliferating cell nuclear antigen (PCNA‐PC10 antibody) and Ki‐67 antigen (MIB‐1 monoclonal antibody). The AgNOR counts ranged from 1.2 to 2.6 (mean 1.9±0.4), PCNA labeling index (LI) from 0.1 to 5.5 (mean 2.5±1.8) and MIB‐1 LI from 0.1 to 3 (mean 0.8±0.02). There was no significant difference in any of these parameter values between histological Groups I and II, except that MIB‐1 LI tended to be higher in Group II tumors. Further, there was no significant correlation between these proliferative indices and the mitotic rate of the tumors as well as the survival of the patients. A longer follow‐up will be required to determine the relationship between proliferative markers and outcome as well as to bring out any heterogeneity in their biological behavior. Since these are relatively rare tumors, multicentric pooling of data will be required to reach a definitive consensus regarding their biological aggressiveness and consequentially, the use of radiotherapy in their treatment. The present report is a contribution in this direction.Abbreviations: AgNOR, silver nucleolar organiser region; GFAP, glial fibrillary acidic protein; LI, labeling index; NSE, neuron‐specific enolase; PCNA, proliferating cell nuclear antigen.


Surgical Neurology | 1999

Choroid plexus papilloma: a clinicopathological study of 23 cases

Chitra Sarkar; Mehar Chand Sharma; Shailesh Gaikwad; Chanda Sharma; Virender Pal Singh

BACKGROUND Choroid plexus papillomas (CPPs) are rare, accounting for less than 1% of all intracranial tumors in adults. However, they are relatively more common in childhood and constitute 1.5 to 4% of intracranial tumors. DESCRIPTION They are most often located in the lateral ventricle, followed by the fourth and third ventricles and, rarely, in the cerebellopontine angle. The radiological appearance of a CPP as a cyst with a mural nodule is a curiosity. Bone formation is rare in CPPs and only 6 cases have been described in the literature. Neuromelanin production is also extremely rare and only 2 cases have been reported to date. CONCLUSION In the present communication, 23 cases of CPP are analyzed and rare clinical, pathological, and radiological features are described.


Neurology India | 2005

Glioblastoma multiforme with long term survival

Prabal Deb; Mehar Chand Sharma; Ashok Kumar Mahapatra; Deepak Agarwal; Chitra Sarkar

Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of (3) > or = 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53 ), cyclin-dependant kinase-inhibitors (p27 and p16 ) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases.


Pediatric Radiology | 2011

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

Jyoti Bajpai; Shivanand Gamnagatti; Rakesh Kumar; Vishnubhatla Sreenivas; Mehar Chand Sharma; Shah Alam Khan; Shishir Rastogi; Arun Malhotra; Rajni Safaya; Sameer Bakhshi

BackgroundHistological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy.ObjectiveTo establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease.Materials and methodsThirty-one treatment-naïve osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006–2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out.ResultsBoth pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume.ConclusionIn osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma.


Neuro-oncology | 2013

Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing

Shipra Agarwal; Mehar Chand Sharma; Prerana Jha; Pankaj Pathak; Vaishali Suri; Chitra Sarkar; Kunzang Chosdol; Ashish Suri; Shashank Sharad Kale; Ashok Kumar Mahapatra; Pankaj Jha

BACKGROUND Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas. MATERIALS AND METHODS Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations. RESULTS Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells. CONCLUSIONS IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.


Acta Neuropathologica | 2005

Spindle cell oncocytoma of the adenohypophysis: report of two cases

Sonika Dahiya; Chitra Sarkar; E. Tessa Hedley-Whyte; Mehar Chand Sharma; Nicholas T. Zervas; Epari Sridhar; David N. Louis

Spindle cell oncocytoma of the adenohypophysis is a recently described, spindle and granular cell, S-100 protein-positive, GFAP-negative, neuroendocrine marker-negative, mitochondria-rich neoplasm of uncertain histogenesis that can clinically and radiologically mimic pituitary adenoma. We present two cases of this entity to extend understanding of this unusual tumor. The first case was a 26-year-old man who presented with a 6-month history of progressive headache, blurred vision in the right eye, nausea, vomiting and impotence. Magnetic resonance imaging (MRI) revealed a rounded, 1.5to 2-cm homogeneously enhancing mass in the pituitary region, which involved the right cavernous sinus, impinged on the temporal lobe and expanded the sella. At transsphenoidal exploration, the mass was firm and difficult to dissect. Following this procedure, visual acuity in the right eye worsened and he underwent a right pterional craniotomy with subtotal resection of the tumor, with residual tumor remaining around the carotid artery. The patient received proton beam radiotherapy to a total dose of 54 Gy over a period of 2 months, during which his vision improved significantly. He has been followed with serial MRI, visual and endocrine examinations for 7 years and remains stable, without tumor regrowth. The second case was a 55-year-old woman who presented with headache and progressive visual deterioration over 6 months, worse in the left than right eye, as well as a 10-day history of vomiting. MRI showed a 6.5·3.3·4 cm sellar and parasellar mass. A transsphenoidal gross total excision was performed. The tumor was highly vascular with destruction of the sellar floor. Six months following surgery, her visual acuity is improved and she has no evidence of recurrence. The two tumors were histologically similar. Case 1 was predominantly composed of spindle cells in a fascicular arrangement (Fig. 1A) with foci of oncocytic appearance (Fig. 1B). Case 2, although also largely spindled in appearance, had more polygonal cells that formed ill-defined lobules (Fig. 1C, D). The cells in both cases had abundant, granular eosinophilic cytoplasm and nuclei that were only mildly pleomorphic. Neither mitotic activity nor necrosis was noted. On immunohistochemical evaluation, the tumor cells were positive for both S-100 protein (Fig. 1E) and epithelial membrane antigen, but did not stain for GFAP, pituitary hormones (prolactin, growth hormone, TSH, ACTH, FSH, LH), chromogranin or synaptophysin . The MIB1 index was approximately 1% in case 1 and 8% in case 2. Electron microscopy was performed on case 2, and showed the tumor cells to be rich in mitochondria with scattered rare secretory granules, but without complex membrane interdigitations or desmosomes (Fig. 1F). Only seven spindle cell oncocytomas of the adenohypophysis have been reported to date [5, 10]. These seven patients were older adults (ranging from 53 to 76 years), five presenting with pan-hypopituitarism and four complaining of visual defects. All five of the lesions initially reported [10] were considered benign since they lacked invasion and showed low proliferative activity. The mean follow-up period for this first series was 3 years, with the longest follow-up 68 months; none of the five tumors had recurred or metastasized. Kloub et al. [5], however, reported two cases of spindle cell oncocytoma of the adenohypophysis that recurred, raising a question about the predicted behavior of these lesions. Although the morphological features of the two primary tumors were not predictive of aggressive behavior, the recurrent tumors had high Ki-67 labeling indices (18–20%) in addition to one recurrent case with mitotic activity and necrosis. These higher proliferation S. Dahiya AE E. T. Hedley-Whyte AE D. N. Louis (&) Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA E-mail: [email protected]

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Chitra Sarkar

All India Institute of Medical Sciences

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Vaishali Suri

All India Institute of Medical Sciences

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Ajay Garg

All India Institute of Medical Sciences

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Ashish Suri

All India Institute of Medical Sciences

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Aanchal Kakkar

All India Institute of Medical Sciences

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Pankaj Pathak

All India Institute of Medical Sciences

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Manmohan Singh

All India Institute of Medical Sciences

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Ashok Kumar Mahapatra

All India Institute of Medical Sciences

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Deepali Jain

All India Institute of Medical Sciences

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Prerana Jha

All India Institute of Medical Sciences

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