Shipra Agarwal

Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy

Abstract: Background. Infectious diseases remain among the major morbid events in patients with end‐stage renal disease (ESRD) on renal replacement therapy (RRT). In developing countries, tuberculosis (TB) has been found to occur more frequently in these patients than in the general population. Efficacy of isoniazid (INH) chemoprophylaxis has been seen in other situations, such as human immunodeficiency virus infection. However, studies on INH prophylaxis in ESRD patients on RRT are limited.

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

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.

Molecular profile of oligodendrogliomas in young patients.

Several studies on molecular profiling of oligodendrogliomas (OGs) in adults have shown a distinctive genetic pattern characterized by combined deletions of chromosome arms 1p and 19q, O6-methylguanine-methyltransferase (MGMT) methylation, and isocitrate dehydrogenase 1 (IDH1) mutation, which have potential diagnostic, prognostic, and even therapeutic relevance. OGs in pediatric and young adult patients are rare and have been poorly characterized on a molecular and biological basis, and it remains uncertain whether markers with prognostic significance in adults also have predictive value in these patients. Fourteen cases of OGs in young patients (age, ≤ 25 years) who received a diagnosis over 7 years were selected (7 pediatric patients age ≤ 18 years and 7 young adults aged 19-25 years). The cases were evaluated for 1p/19q status, MGMT promoter methylation, p53 mutation, and IDH1 mutation. None of the pediatric cases showed 1p/19q deletion. In young adults, combined 1p/19q loss was observed in 57% and isolated 1p loss in 14% of cases. The majority of cases in both subgroups (71% in each) harbored MGMT gene promoter methylation. TP53 and IDH1 mutations were not seen in any of the cases in both the groups. To our knowledge, this is the first study to show that molecular profile of OGs in pediatric and young adult patients is distinct. Further large-scale studies are required to identify additional clinically relevant genetic alterations in this group of patients.

Spectrum of cardiac tumors excluding myxoma: Experience of a tertiary center with review of the literature

The aim of this study was to determine the histological spectrum of operated cardiac tumors, excluding myxoma, at a tertiary center in India. Between 1995 and 2010, we encountered 188 cases of operated cardiac tumors that had been subjected to histopathological examination. Morphological characterization was done by light microscopy along with histochemical stains. Immunohistochemistry using a panel of antibodies, i.e., vimentin, desmin, myogenin, smooth muscle actin (SMA), epithelial membrane antigen (EMA), cytokeratins, factor VIII-related antigen, S100-protein, synaptophysin, chromogranin, Bcl2, MIB-1, leukocyte common antigen (LCA), CD 3, CD20, CD34, and CD 99 (MIC-2) was performed wherever applicable. Out of the 188 cases, 184 were primary cardiac tumors, including 170 cases of benign cardiac tumors. Among the benign tumors, myxomas were the most frequent ones (168 cases), followed by fibroma (2 cases). Primary malignancy was diagnosed in 14 cases, including undifferentiated sarcomas, primitive neuroectodermal tumor, rhabdomyosarcoma non-Hodgkin lymphoma, angiosarcoma, synovial sarcoma, and leiomyosarcoma. Metastatic (secondary) tumors were seen in four cases, including one each of adenocarcinoma, choriocarcinoma, renal cell carcinoma, and alveolar soft part sarcoma. Hence, out of the total of 188 cases, 20 were non-myxoma cardiac tumors (NMCTs), including 2 benign tumors, 14 malignant tumors, and 4 metastatic tumors. In our series, the majority of cardiac tumors were primary in nature. The malignant primary tumors outnumbered benign ones, excluding myxomas, and the most common malignant histology was undifferentiated sarcoma, as opposed to the literature.

The evolution of the Banff classification schema for diagnosing renal allograft rejection and its implications for clinicians.

Till the early 1990s there was no standardized international classification of renal allograft biopsies resulting in considerable heterogeneity in reporting among the various centers. A group of dedicated renal pathologists, nephrologists, and transplant surgeons developed a schema in Banff, Canada in 1991. Subsequently there have been updates at regular intervals. The following review presents the evolution of the Banff classification and its utility for clinicians.

Primary intracranial squamous cell carcinoma arising in an epidermoid cyst—A case report and review of literature

Primary intracranial squamous cell carcinoma is extremely rare, with most of the cases arising from malignant transformation of an epidermoid or a dermoid cyst. We report here a case of a 45-year-old male patient who presented with 1-month history of intermittent headache and recent onset of altered sensorium. Imaging revealed a midline posterior fossa mass lesion compressing the fourth ventricle and causing hydrocephalus. A provisional diagnosis of dermoid cyst was considered. Histopathological examination revealed a squamous cell carcinoma possibly arising from an underlying epidermoid cyst. This entity is being reported for its rarity.

Extraventricular neurocytomas: a morphological and histogenetic consideration. A study of six cases

Aims: Various molecular markers have been used for diagnosis, management and prognostication of gliomas. Neurocytomas are close morphological mimics of oligodendrogliomas. While combined 1p/19q deletion has been used as a molecular signature of oligodendroglial tumours, it has also been variably reported to occur in neurocytomas, especially those in extraventricular locations (EVN). In recent studies, presence of IDH1 mutation has shown immense prognostic significance in glial tumours including oligodendrogliomas, but its role in neurocytoma pathogenesis remains unexplored. In this study, EVN cases were analysed for histomorphological features, IDH1 mutation using an antibody for specifically detecting mutant IDH1R132H protein, and 1p/19q deletion by fluorescence in situ hybridisation (FISH) assay. Results: Over a period of 10 years (2000–2009), 60 cases of neurocytoma were diagnosed, of which six were EVN. These six cases were assessed for histomorphology, IDH1 mutation and 1p/19q deletion. Five cases showed atypical histological features. While none showed mIDH1R132H, four of the five atypical cases harboured 1p/19q deletion either in isolation or in combination. The only case which was well-differentiated (typical) did not show 1p/19q loss. Conclusions: EVNs are more commonly associated with aggressive histological features. IDH1 mutations, although frequent in oligodendrogliomas, are not seen in EVN. However, similar to oligodendrogliomas, 1p/19q deletion is found in these tumours. Thus, a potential histogenetic link between oligodendrogliomas and EVN remains debatable. This molecular alteration may also have prognostic connotations, being associated with atypical morphological features. Due to the rarity of these tumours, multicentric pooling of larger studies is needed to have an insight into the impact of these molecular aberrations on their biological behaviour.

Spindle cell oncocytoma of the adenohypophysis: report of a rare case and review of literature.

Spindle cell oncocytoma of the adenohypophysis was first escribed by Roncaroli et al. in 2002, in their multi-institutional eries of 5 cases [1]. Since then ten reports of thirteen cases of this umor have been published in literature bringing the total number f reported cases to eighteen [2–11]. This new entity was included n the WHO classification of tumors of the Central Nervous System n 2007 [12]. In nearly all the cases presentation was akin to a non unctioning pituitary adenoma in an elderly patient, however the ehaviour of these tumors varied as seven of the eighteen published ases showed recurrence with or without morphological features of naplasia in the form of nuclear pleomorphism, frequent mitoses, igh Ki-67 index and/or foci of necrosis [2–8]. We report the nineeenth case of spindle cell oncocytoma (SCO) in a 68-year-old male atient and review the available English literature till date on this umor.

Generic tacrolimus (Pan Graf) in renal transplantation: an experience of 155 recipients in India.

BACKGROUND The safety and efficacy of tacrolimus in transplantation are well established. However, tacrolimus (Pan Graf) has only been available in India for the last 2 years. We conducted this study to assess the safety and efficacy of tacrolimus in living related kidney transplantation. Herein we have reported our experience with tacrolimus as de novo therapy in a living related renal transplant program. MATERIALS AND METHODS One hundred fifty-five consecutive recipients of living donor renal allografts were included in this study after consent and ethical clearance. Immunosuppression consisted of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted according to levels done on a regular basis. All patients were followed for periods ranging from 3 to 33 months. All episodes of graft dysfunction were evaluated by a graft biopsy. We evaluated the effects of this regimen on the incidence of graft rejection, graft survival, patient survival, and new onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV) positive. RESULTS There were 137 male and 18 female patients. The incidence of acute rejection was 3.87%; 17.93% developed new onset diabetes mellitus; and 77.7% of HCV-positive patients and 14.07% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival at the current follow-up was 94.19%. CONCLUSION This generic form of tacrolimus is a safe, effective immunosuppressant in living related renal transplantation.

Epithelial-myoepithelial carcinoma of the lacrimal gland: a rare case

Epithelial-myoepithelial carcinoma is a rare tumor of the salivary gland constituting only 1% of all tumors. It is a low-grade malignancy characterized by a classical biphasic morphology and immunophenotype. In the lacrimal gland, it is extremely rare with only 3 cases reported in the English medical literature. We describe the fourth case of epithelial-myoepithelial carcinoma, the first case in a female patient, and review the available literature.