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ABSTRACT: AIMS: To identify and validate clinico-pathologic factors including molecular sub-grouping that correlate with outcome in Indian patients with medulloblastoma. METHODS: Patients with medulloblastoma accrued and treated post-operatively on prospective clinical trials with available tumor tissues (either fresh-frozen or paraffin blocks) were identified from a prospective neuro-oncology database. Molecular sub-classification was done by mRNA expression levels of select protein-coding marker genes by real-time reverse transcriptase polymerase chain reaction. Univariate and multivariate analysis was done to identify factors associated with poor outcomes. RESULTS: Electronic search identified 40 patients with complete clinical details and analyzable tissues. The median age of the study cohort was 10 years (inter-quartile range 8-14 years) with a predominant male distribution (n = 29). Post-operative adjuvant therapy was based on conventional clinico-pathologic risk-stratification. Twenty six (65%) patients were classified as high-risk, including 10 (25%) with metastatic disease at presentation. Molecular analysis identified four distinct sub-groups viz. WNT (n = 10), SHH (n = 6), C (n = 11), and D (n = 13) as per consensus classification. There was substantially high incidence (55%) of metastases at presentation in molecular sub-group C. With a median follow-up of 26 months (inter-quartile range 9-40 months), the 5-year (+standard error) event-free survival and overall survival for the entire cohort was 53.2% (+9.7%) and 62.1% (+9.3%) respectively. On univariate analysis, risk-strata (average-risk vs high-risk metastatic, p = 0.017); histology (classical vs anaplastic, p = 0.016); and molecular sub-groups (WNT vs C, p = 0.003, and WNT vs SHH, p = 0.005) were significant prognostic factors. Cox regression analysis identified molecular sub-group C as the worst prognostic factor independently associated with significantly poor survival (p = 0.015). CONCLUSION: Molecular sub-group C, high-risk metastatic disease, and anaplastic histology are associated with significantly poorer outcomes in Indian patients with medulloblastoma consistent with published data from the western world.
Neuro-Oncology 06/2012; 14(suppl 1-10.1093/neuonc/nos093):i82-105. · 5.72 Impact Factor
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ABSTRACT: Glioblastoma progenitor or stem cells residing in the stem-cell niche in the subventricular zones (SVZ) can initiate or promote tumorigenesis. They can also migrate throughout the brain, resulting in disease progression. Irradiation of potential cancer stem-cell niche in the SVZ may influence survival. To analyze radiotherapy dose-volume parameters to the SVZ that correlate with survival in adequately treated patients with newly diagnosed glioblastoma, 40 adults with histopathologically proven supratentorial glioblastoma with available baseline imaging treated with postoperative conventionally fractionated focal conformal radiotherapy plus chemotherapy, available radiotherapy planning dataset, and documented event of progression or death or minimum 6-month follow-up were included in this retrospective study. Dose-volume parameters to the SVZ were extracted from treatment planning system and analyzed in relation to survival outcomes. Mean ipsilateral and contralateral SVZ volumes were 5.6 and 6.4 cc, respectively. With median follow-up of 15 months (interquartile range 12-18 months), median [95 % confidence interval (CI)] progression-free survival (PFS) and overall survival (OAS) was 11 months (95 % CI 8.9-13.0 months) and 17 months (95 % CI 11.6-22.4 months), respectively. Older age (>50 years), poor recursive partitioning analysis (RPA) class, and higher than median of mean contralateral SVZ dose were associated with significantly worse PFS and OAS. Multivariate analysis identified RPA class, Karnofsky performance status, and mean ipsilateral SVZ dose as independent predictors of survival. Increasing mean dose to the ipsilateral SVZ was associated with significantly improved OAS. Irradiation of potential cancer stem-cell niche influences survival outcomes in patients with newly diagnosed glioblastoma.
Journal of Neuro-Oncology 05/2012; 109(1):195-203. · 3.21 Impact Factor
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ABSTRACT: Primary cutaneous marginal zone lymphomas (PCMZL) have a wide range of morphology from tumors with monocytoid B cells to those composed entirely of plasma cells and the T-cell rich variants. We report a 60-year-old male with a PCMZL rich in plasma cells of the foot with a lymphoepithelioid-like pattern of dissemination to the lymph nodes posing problems in the diagnosis. The patient had a lesion on the dorsum of the foot which histologically revealed dense perivascular collections of lymphoid cells and plasma cells amidst fibrous tissue. Though the plasma cells did show light chain restriction, CD20 and CD3 did not reveal an overwhelming B/T-cell population and hence a diagnosis of a reactive process was offered. Subsequently the patient developed inguinal nodes with diffuse loss of architecture and replacement by epithelioid histiocytes and reactive T cells with few large B cells (lymphoepithelioid-like pattern). On pathology review it was realized that the two lesions may be related and clonality studies were asked for. The skin lesion showed clonally rearranged IgH receptor while the T-cell receptor rearrangement was negative. The patient developed disseminated disease and received six cycles of chemotherapy with partial response and 6 years after the initial presentation was alive with nonprogressive disease. Thus, the polymorphous background in PCMZL is evolving and an immunocytoma-like tumor can show a T-cell rich or Lennert's like growth pattern of spread and early recognition these odd patterns may aid in appropriate management of patients.
Indian Journal of Pathology and Microbiology 04/2012; 55(2):222-6. · 0.68 Impact Factor
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ABSTRACT: HER2/neu gene status in breast cancers can be evaluated by targeting protein and gene - immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH). Recent studies have shown chromogenic in-situ hybridization (CISH) as a relatively cheaper alternative.
Forty-three nonconsecutive, randomly selected primary invasive breast cancer cases were evaluated for c-erbB-2 (HER2 protein) by IHC and gene amplification by FISH and CISH. Results of each of the same were compared.
CISH showed approximately 90% and 100% concordance for IHC negative and positive cases, respectively; while approximately 94.4% and 91% concordance with FISH amplified and non-amplified cases, respectively.
This study showed feasibility of incorporation of CISH as a low cost option in routine management of breast carcinoma in the Indian setting. Secondly, reconfirmation of IHC negative and positive cases can be done by CISH.
Indian Journal of Pathology and Microbiology 04/2012; 55(2):175-9. · 0.68 Impact Factor
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ABSTRACT: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma.
Twenty children ≥ 5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ).
The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively.
HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.
International journal of radiation oncology, biology, physics 02/2012; 83(5):1534-40. · 4.59 Impact Factor
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Poonam Panjwani, Sridhar Epari,
Arti Karpate,
Hemlata Shirsat,
Preetha Rajsekharan,
Ranjan Basak,
Tanuja Shet,
Roshni Chinoy,
Roy Chacko,
Sampada Gursale,
Nayana Baraskar,
Sudeep Gupta,
Rohini Hawaldar,
Sangeeta Desai
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ABSTRACT: Determination of HER2 status in breast cancer has become important to identify potential candidates for anti-HER2 therapy. In this study we compared fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for the determination of HER2 status in breast cancer patients referred to a tertiary care referral centre.
A total of 200 cases of invasive breast cancer were evaluated for HER2 status using IHC and FISH and results were compared.
The IHC 3+ (93.9%) and IHC negative (85.9%) cases showed good concordance with the corresponding FISH results; while 66.6 per cent of IHC 2+ cases showed gene amplification by FISH. In addition, hormone receptor expression and HER2 gene status showed a statistically significant inverse association (P<0.05).
These findings reaffirm IHC as a prudent first-step to screen tissue samples for HER2 status and to determine suitability for technically demanding FISH test and the dual coloured FISH as a gold standard for determination of HER2/neu status in IHC equivocal cases of breast carcinoma.
The Indian journal of medical research 09/2010; 132:287-94. · 1.84 Impact Factor
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ABSTRACT: Although cavernous hemangiomas and a few cases of angiosarcoma in the urinary bladder have been described, only a single case of epithelioid hemangioendothelioma of the urinary bladder has been documented in English publications, to date. Therefore, the biologic properties of epithelioid hemangioendothelioma in this location are uncertain. We report the clinical and pathologic findings of a case of primary epithelioid hemangioendothelioma of the urinary bladder in a 17-years-old boy. The tumor was treated by transurethral resection.
Urology 03/2009; 73(6):1259-61. · 2.43 Impact Factor
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ABSTRACT: CASE REPORT: Paragangliomas of the orbit are extremely rare tumors. We report a well-documented case of orbital paraganglioma in a 45-year-old man who presented with proptosis and decreased vision. The patient underwent complete excision of the tumor with preservation of orbital structures. There was total regression of symptoms after surgery and vision was well maintained. COMMENTS: Radiological and pathological features are described and differential diagnoses of this entity are discussed.
Canadian Journal of Ophthalmology 11/2005; 40(5):640-4. · 1.47 Impact Factor
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Neurology India 59(2):319-20. · 0.96 Impact Factor
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ABSTRACT: There is significant inter-observer variation amongst the neuro-pathologists in the typing, subtyping, and grading of glial neoplasms for diagnosis. Centralized pathology review has been proposed to minimize this inter-observer variation and is now almost mandatory for accrual into multicentric trials. We sought to assess the concordance between neuro-pathologists on histopathological diagnosis of glioblastoma.
Comparison of local, institutional, and central neuro-oncopathology reporting in a cohort of 34 patients with newly diagnosed supratentorial glioblastoma accrued consecutively at a tertiary-care institution on a prospective trial testing the addition of a new agent to standard chemo-radiation regimen.
Concordance was sub-optimal between local histological diagnosis and central review, fair between local diagnosis and institutional review, and good between institutional and central review, with respect to histological typing/subtyping. Twelve (39%) of 31 patients with local histological diagnosis had identical tumor type, subtype and grade on central review. Overall agreement was modestly better (52%) between local diagnosis and institutional review. In contrast, 28 (83%) of 34 patients had completely concordant histopathologic diagnosis between institutional and central review. The inter-observer reliability test showed poor agreement between local and central review (kappa statistic=0.12, 95% confidence interval (CI): -0.03-0.32, P=0.043), but moderate agreement between institutional and central review (kappa statistic=0.51, 95%CI: 0.17-0.84, P=0.00003). Agreement between local diagnosis and institutional review was fair.
There exists significant inter-observer variation regarding histopathological diagnosis of glioblastoma with significant implications for clinical research and practice. There is a need for more objective, quantitative, robust, and reproducible criteria for better subtyping for accurate diagnosis.
Neurology India 60(1):61-5. · 0.96 Impact Factor
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ABSTRACT: Papillary tumors of the pineal region (PTPRs) are rare and are recognized as a distinct entity in the recent 2007 World Health Organization (WHO) classification of tumors of nervous system. Till date, only 55 cases have been reported. We report another three patients of PTPRs with characteristic radiological features. Histologically, all the three patients exhibited remarkable uniform histology of epithelioid morphology with variable presence of single to multilayered papillary architecture. Consistent absence of fibrillary matrix was noted in all the three cases. None of the cases showed aggressive histology. A large multicenter study is essential for upfront characterizing the biological behavior, as frequency of these tumors is very low.
Neurology India 59(3):455-60. · 0.96 Impact Factor
