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   Table of Contents - Current issue
Coverpage
January-March 2014
Volume 57 | Issue 1
Page Nos. 1-163

Online since Thursday, April 17, 2014

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EDITORIAL  

From Editor's desk p. 1
Misra Misra
DOI:10.4103/0377-4929.130836  
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ORIGINAL ARTICLES Top

Histomorphological features of pancreas and liver in chronic alcoholics - an analytical study in 390 autopsy cases p. 2
Pallavi Agrawal, Kim Vaiphei
DOI:10.4103/0377-4929.130842  
Introduction: Chronic pancreatitis and liver disease are two conditions that commonly co-exist in chronic alcoholics with variable incidences. Aim: To evaluate frequency pancreatitis in patients with a history of chronic alcohol abuse. Materials and Methods: A total of 390 autopsies over 11 year's period were included in the study. Gross and microscopic assessment of liver and pancreas were performed. Available clinical and laboratory parameters were recorded. Results: Age ranged from 22 to 65 years with a mean age of 45.32 years. All 390 consecutive patients included in the study were males. Majority of the patients had primarily presented with alcohol related liver diseases whereas few had presented with features of pancreatitis. Micronodular cirrhosis was present in 292 cases. Features of chronic pancreatitis were observed in 42 cases and 8 of these cases had associated changes of acute hemorrhagic pancreatitis. Prevalence of pancreatitis was more in cirrhotics as compared to non-cirrhotics, and acute pancreatitis was mostly seen in non-cirrhotics. Dominant pattern of fibrosis was perilobular followed by periductal, intralobular and diffuse. Conclusion: Chronic pancreatitis as evidence by the presence of parenchymal fibrosis was more frequently observed in alcoholic cirrhosis cases than that in non-cirrhotic alcoholic liver disease, thereby suggesting common underlying pathobiology in the development of fibrosis in liver as well as in pancreas.
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Mutation profiling in gallbladder cancer in Indian population p. 9
Niraj Kumari, Christopher L Corless, Andrea Warrick, Carol Beadling, Dylan Nelson, Tanay Neff, Narendra Krishnani, Vinay Kumar Kapoor
DOI:10.4103/0377-4929.130849  
Aim: Gallbladder cancer is an aggressive malignancy usually diagnosed at late stage. The molecular genetics of this cancer is heterogeneous and not well established. Mutation profiling of gallbladder cancer was performed through massarray technology with an aim to identify molecular markers involved in the tumor pathogenesis that can be helpful as markers for early diagnosis and targets for therapy. Materials and Methods: Forty nine cases of gallbladder cancer were screened through Sequenom Massarray technology for 390 mutations across 30 genes in formalin fixed paraffin embedded archived tissues and the results of mutation profiling was correlated with tumor characteristics. Mutations were observed in 9 of 49 cases across four genes - TP53 (four cases), CTNNB1 (two cases), PIK3CA (two cases), and KRAS (one case). Six of these cases were well differentiated but of eight of them belonged to stage II to IV disease. Six cases had associated gallstones. Conclusion: The mutation frequency found in gallbladder cancer is comparable to the data available in literature. Identification of PIK3CA and KRAS mutations would help in formulating more efficacious targeted approach for management. Studies with large number of cases would help in exploring more targets and better classification of these cancers at genetic level.
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CagA+ H. pylori filtrate induces cytokine IL-8 secretion by esophageal squamous carcinoma EC 109 cells via a p38 pathway p. 13
Guan Xiao Ying, LI Wen Sheng, Zhang Li Xia, Wang Hong Tao
DOI:10.4103/0377-4929.130866  
Background: The relationship between Helicobacter pylori (Hp) infection and the risk of esophageal squamous cell carcinoma is unclear. Aim: The purpose was to investigate the effects of CagA+ Hp on esophageal squamous carcinoma Ec 109 cells in vitro and explore the molecular mechanisms underlying these effects. Materials and Methods: Ec 109 cells were treated with CagA+ Hp filtrate at a concentration of 1.0 mg/mL or 50 μg/mL in vitro, proliferation and apoptosis of Ec 109 cells were assayed, the secretion of IL-8 was measured by ELISA, and the levels of Src homology-2 domain-containing phosphatase (SHP-2) mRNAs was assayed by RT-PCR.. Furthermore, after pretreatment of Ec109 cells with the specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, the p38 pathway was detected. Results: CagA+ Hp filtrate enhanced both the proliferation and apoptosis of Ec 109 cells. In addition, cytokine IL-8 release was significantly increased, and the expression of SHP-2 mRNA declined sharply in the CagA+ Hp group. Furthermore, after pretreatment of Ec109 cells with the specific p38 MAPK inhibitor SB203580, Ec109 cells proliferation and IL-8 secretion were inhibited. Conclusions: Our results suggest that CagA+ Hp filtrates could induce proliferation and the secretion of IL-8 by Ec109 cells in vitro. IL-8 secretion was induced through the activation of the p38 MAPK signal pathway.
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Paraganglioma of the urinary bladder: A clinicopathologic spectrum of a series of 14 cases emphasizing diagnostic dilemmas p. 19
Santosh Menon, Pankaj Goyal, Pallavi Suryawanshi, Hemant Tongaonkar, Amit Joshi, Ganesh Bakshi, Sangeeta Desai
DOI:10.4103/0377-4929.130873  
Background: Paraganglioma (PG) of the urinary bladder is a rare neuroendocrine neoplasm, accounting for < 0.1% of all bladder tumours. Distinction from urothelial carcinoma is imperative as management and prognosis vary markedly. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. Materials and Methods: All cases of PG of urinary bladder diagnosed at our institute from 2002-2012 were retrieved and diagnosis confirmed in accordance with WHO classification. Clinical and treatment details were obtained from hospital medical records. Results: Fourteen cases of PG of urinary bladder including 5 consult cases were analysed. These included 11 transurethral resections ± partial cystectomies, 2 partial cystectomies and 1 radical cystectomy. Two out of the 5 consult cases had been submitted with a diagnosis of urothelial carcinoma and 1 with that of a rhabdomyosarcoma. Age ranged from 15-84 years (median, 43 years) with a male to female ratio of 1:2.5. Presenting symptoms were haematuria, dysuria and flank pain; only 1 case had antecedent hypertension. Histologically, typical 'zellballen' (72%), diffuse (21%) and ribbon-like (7%) growth patterns amidst a richly vascularised stroma were seen. Muscularis propria invasion and necrosis was present in 72% and 21%, respectively. Substantial cautery artifacts led to misdiagnosis in the 3 erroneous cases. Tumour cells were positive for chromogranin, synaptophysin; sustentacular cells were S-100 positive. Follow up was available in 6 patients; median follow-up was 29 months (8-120 months). One patient developed distant metastasis in cervical lymph node 10 years after diagnosis; remaining were alive without evidence of disease. Conclusions: Paraganglioma of the urinary bladder is a rare tumor and may be misdiagnosed as urothelial cancer especially on TURBT, but a high index of suspicion, careful search for the characteristic histological features and supportive immunohistochemical studies should lead to a correct diagnosis
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The correlation between p16 expression and INK4a locus mutation with grades and stages in oral squamous cell carcinoma p. 24
Soudabeh Sargolzaei, Sareh Farhadi, Bahram Kazemi, Mojgan Bandehpour, Mohammad Javad Kharazifard
DOI:10.4103/0377-4929.130877  
Objective: p16INK4a is a tumor suppressor gene playing a critical role. Researches have indicated the gene to be altered in oral squamous cell carcinoma. Present studies have tried to assess the correlation between p16INK4a expression and INK4a locus mutation in relation to grades and stages of this tumor. Materials and Methods: Expression of p16INK4a was studied immunohistochemically in 58 oral squamous sell carcinoma samples and INK4a locus mutation was determined by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE). Results: Expression of p16INK4a was higher in stage1 compared to stage 2, 3, and 4 (P = 0.234). The difference was not significant in grade 1, 2, and 3 (P = 0.671). The average values of total score (TS) were significantly higher in stage1 compared to stage 2, 3, and 4 (P = 0.035). The average values of complete score (CS) were higher in stage 1 compared to stage 2, 3, and 4 (P = 0.061). The research did not show a significant correlation between lymph node involvement and p16INK4a expression (P = 0.491). It seems that 5.1% (3/58) of samples have mutation in INK4a locus. Conclusion: Loss of p16INK4a expression occurred in initial stages of oral squamous cell carcinoma. Evaluation of TS and CS for p16INK4a might be a useful clinical indicator concerning the tumor. However, gene mutation is believed to have minor rate of genetic alteration in carcinogenesis.
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Heparin: Induced thrombocytopenia: Incidence and laboratory approach to diagnosis in Indians p. 31
Jyoti Kotwal, Sanjeev Chaudhary, Madakshira Gopal Manoj, Shahbaz Hasnain, Velu Nair, Manoj Luthra
DOI:10.4103/0377-4929.130886  
Background and objectives: One of the most common complications of heparin administration is heparin-induced thrombocytopenia (HIT) which can also lead to catastrophic thrombotic events. The problem of identifying the cause of thrombocytopenia, as due to heparin, in patients with multiple co-morbid conditions is very essential for management. Thus, the laboratory investigations for diagnosis of HIT play a pivotal role. The objective of the study was to arrive at the incidence of HIT in ethnic Indian population and provide a decision after analysis of tests used to diagnose HIT. Materials and Methods: 125 consecutive patients (Power of study being 80%) undergoing open heart surgery and receiving unfractionated heparin were taken as subjects. Blood samples were collected a day before the surgery and days 1, 3, 5 and 7 after surgery. The cases were categorized into probable and unlikely groups depending on the clinical presentation and degree fall of platelet count. Anti-heparin PF4-associated antibodies were detected using rapid-ID gel microtyping system and ELISA tests. HIT was also tested using functional assays:- heparin-induced platelet aggregation test (PAT) and the rapid luminographic assay of heparin-induced ATP release. Results: Of the 125 patients, 11 patients were clinically labeled as probable HIT and 29 patients were clinically labeled as unlikely HIT. There were seven confirmed cases of HIT cases that were positive for one functional and one immunological assay. Only one case of HITT was encountered. Accordingly, the incidence of HIT was found to be 5.6 % and that of HITT to be 0.8%. ELISA tests were positive in 21 cases (17%) which demonstrated the presence of anti-HPF4 antibodies in non-HIT cases as well. It was found that the rapid gel test had sensitivity comparable to functional assay with better specificity than ELISA. Interpretation and conclusions: Incidence of HIT in ethnic Indian population is 5.6%. Patients with a drop of >50% in platelet count should be perused as a likely candidate of HIT. These cases should be subjected to the ID-HPF4 antibody assay as this is a rapid test, can be done for individual cases, and has better specificity and similar sensitivity than ELSIA. Cases with clinically probable HIT and a positive ID-HPF4 assay can be taken as confirmed cases of HIT. However, cases clinically unlikely for HIT and a positive ID-HPF4 assay should be subjected to another test to establish the diagnosis of HIT.
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What regulates hepcidin in poly-transfused β-Thalassemia Major: Erythroid drive or store drive? p. 39
Richa Chauhan, Sunita Sharma, Jagdish Chandra
DOI:10.4103/0377-4929.130891  
Background: Hepcidin, a key regulator of iron homeostasis, is increased by iron overload and inflammation while suppressed by hypoxia. In spite of iron overload in β-Thalassemia Major (β-TM), a paradoxical decrease in hepcidin is observed. Aim: To assess the opposing effects of enhanced erythropoiesis due to anemia and iron overloading on hepcidin in β-TM patients. Setting and Design: This prospective observational study was done at our tertiary care hospital. Materials and Methods: Eighty-three pediatric polytransfused (> 20 transfusions) patients of β-TM were compared with 70 children who served as controls. Serum assays for ferritin, transferrin receptors (sTfR) and hepcidin were performed. Statistical analysis: Independent Student t test was used to compare variables between both the groups. A Pearson correlation coefficient was used to find any correlation between ferritin, sTfR and hepcidin. Results: The mean value of hepcidin in β-TM children was 13.88±10.68 ng/ml (range, 0.9-60 ng/ml) and showed significant negative correlation with sTfR (r = -0.296, P < 0.0066). However, there was no correlation of hepcidin with ferritin. Ferritin and sTfR were significantly elevated in β-TM children compared to controls (P < 0.001). The mean serum hepcidin/ferritin index in the study group (0.00552) was significantly lower (P value < 0.001) than the controls (0.378) thus indicating inappropriate levels of hepcidin to iron overload. Conclusion: In polytransfused β-TM children increased iron demand dominates over iron overload in regulating hepcidin. In spite of excessive iron load, the inappropriate hepcidin levels may further contribute to iron overload enhancing iron toxicity.
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Establishing a normal reference range for thromboelastography in North Indian healthy volunteers p. 43
Arulselvi Subramanian, Venencia Albert, Renu Saxena, Deepak Agrawal, Ravindra Mohan Pandey
DOI:10.4103/0377-4929.130896  
Background: Thromboelastography (TEG) is relatively recent assay to analyze the coagulation state of a blood sample, providing a continuous visualization of physical changes occurring during blood coagulation. There is a paucity of published literature on assessment of coagulation status using TEG in Indian population. Aim: The primary aim of the following study is to establish normal reference values for TEG in North Indian healthy volunteers and secondary aim is to compare them with conventional plasma-based routine coagulation tests and the manufacturers reference range. Materials and Methods: A total of 200 healthy volunteers comprised of 100 males and 100 females of age groups between 20 and 50 years, were enrolled over a period of 1 year, i.e., 2011-2012. Thromboelastometry (TEM) was performed on TEM-A automated thromboelastometer (Framar Biomedica, Rome, Italy), using whole blood non-additive (360 µl). TEG parameters analyzed were r-time, k-time, α-angle, maximal amplitude (MA). Prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count was performed for all volunteers. The 95% reference range was calculated as (mean-1.96 standard deviation [SD]) to (mean + 1.96 SD). Results: Our reference values for 95% of 200 volunteers were r-time: 1.8-14.2 min, k-time: 0.7-7.3 min, α-angle: 27.3-72.3° and MA: 32.1-87.9 mm. Maximum clot strength was higher in women compared with men, however statistically insignificant. Overall 14.5% (29/200) of the volunteers had at least one abnormal parameter while 74% (149/200) had deranged TEG values using the manufacturer's reference range. Statistically significant variation was seen in r-time for 84.8% (P < 0.001), for k-time, in 87.1% (P < 0.001), for α-angle in 83.7% (P < 0.001) and for MA in 84% (P < 0.001), between the manufacturer and our reference range. Conclusion: The efficacy of classical coagulation test has been well-established; on the contrary TEG is a fairly recent assay and its utility for patient management remains to be demonstrated. We observed TEG to be oversensitive in determining coagulopathy where there is no clinical presentation. The manufacturer's reference values may not be appropriate for different ethnicity. TEG may give an overall representation of hemostasis; however, it cannot replace the conventional coagulation tests. We recommend the determination of normal TEG values by each laboratory for their target population.
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C-reactive protein in patients with Guillain Barré syndrome p. 51
Chetana Vaishnavi, Prashant Kapoor, Chitra Behura, Shrawan Kumar Singh, Sudesh Prabhakar
DOI:10.4103/0377-4929.130897  
Context: C-reactive protein (CRP) is an acute phase reactant, widely used as a biomarker for various infectious and inflammatory conditions. Guillain-Barrι syndrome (GBS) is an acute, autoimmune, polyradiculoneuropathy, triggered by infectious agents such as Campylobacter jejuni. GBS is generally precipitated 1-3 weeks following C. jejuni infection which suggests a humoral immunopathogenic mechanism. Aims: Basal CRP levels were estimated in sera of patients with GBS and compared with adequate controls. Settings & Design: The study population was divided into 4 groups: (i) GBS group included 45 newly diagnosed GBS patients; (ii) Neurological control (NC) group comprised of 59 patients with non-paralytic neurological symptoms/disorders; (iii) Non-neurological controls (NNC) comprised of 43 patients having no neurological symptoms and (iv) Healthy controls (HC) comprised of 101 healthy subjects. Materials and Methods: CRP was evaluated using slide latex agglutination test (LAT) and enzyme linked immunosorbent assay (ELISA). Statistical Analysis: Statistical analysis was done by the Chi-square test. Results: CRP by LAT was positive in 24.4% GBS group, 34% NC group and 44% NNC group. The range of titer in CRP positive samples in the three patient groups (GBS, NC, NNC) was at concentration of 0.6 mg/dl to 19.2 mg/dl. Similar results were also obtained by ELISA in the patient groups. None of the HC subjects was positive for detectable levels of CRP. High basal level of CRP was detected in patients with GBS. Conclusion: Autoimmune conditions like GBS can stimulate the production of a high level of inflammation resulting in an increase in the CRP production.
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Prevalence of Chlamydia trachomatis in women attending sexually transmitted disease clinics in the Colombo district, Sri Lanka p. 55
Gunasekera Henadira Appuhamilage Kamani Mangalika, Silva Koththigoda Cankanamge, Dhammike Priyadarshana, Prathapan Shamini, Mananwatte Sujatha, Weerasinghe Geeganage, Abeygunasekera Nalaka
DOI:10.4103/0377-4929.130898  
Background: In Sri Lanka little is known about the prevalence of Chlamydia trachomatis (CT) infection. Objective was to determine the prevalence of CT in female patients attending sexually transmitted disease (STD) clinics in the Colombo district. Materials and Methods: A descriptive cross-sectional study was carried out for the prevalence of CT in all female patients (n = 168) more than 18 years of age, attending two STD clinics in the Colombo district from January to May 2012. Endocervical swabs were collected and tested for CT using the Amplicor CT/NG polymerase chain reaction assay. Results: Prevalence of CT in females attending the STD clinics in the Colombo district was 8.3%. Mean age of those infected with CT was 32.9 years (SD ± 8.2). Majority of females with CT infections were Sinhalese and married. There was no significant association with age, ethnicity or being married or not. Females who did not attend school, or had their education only up to Grade 5 were significantly found to have six times the risk of having CT infection (95% CI = 1.8-22.6). A significant association was found with number of sexual partners but not with commercial sex work or past history of STD. Conclusions: Prevalence of CT was moderately high in this population.
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Study of virulence factors of uropathogenic Escherichia coli and its antibiotic susceptibility pattern p. 61
Seema Mittal, Madhu Sharma, Uma Chaudhary
DOI:10.4103/0377-4929.130899  
Context: Urinary tract infection (UTI) is one of the most common nosocomial infections, caused by Escherichia coli. This study determined the presence of virulence factors in the organism and correlates it with the multi-drug resistance (MDR). Aims: The aim of the following study is to assess the virulence factors of uropathogenic E. coli and antibiotic susceptibility pattern. Settings and Design: This was a prospective study conducted in the Department of Microbiology in PT. B. D. Sharma, PGIMS, Rohtak. Subjects and Methods: The study was conducted over a period of 1 year. Urine samples received were processed as per standard microbiological procedures. Virulence factors such as hemolysin, hemagglutination, cell surface hydrophobicity, serum resistance, gelatinase and siderophore production were studied. The antimicrobial susceptibility was done as per Clinical and Laboratory Standard Institute Guidelines. Statistical Analysis Used: The data was analyzed by using SPSS(Statistical Package for the social sciences) IBM Corporation version 17.0. A two sided P ≤ 0.05 was considered to be significant. Results: Hemolysin production was seen in 47.4%, hemagglutination in 74.8%, cell surface hydrophobicity in 61%, serum resistance in 59%, gelatinase in 67.5% and siderophore production in 88% isolates. Nitrofurantoin was found to be most effective followed by, gatifloxacin and gentamicin. Twenty nine percent (29.62%) isolates were MDR. Conclusions: Therefore, the knowledge of virulence factors of E. coli and their antibiotic susceptibility pattern will help in better understanding of the organism and in the treatment of UTI.
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Multidrug resistant NDM-1 metallo-beta-lactamase producing Klebsiella pneumoniae sepsis outbreak in a neonatal intensive care unit in a tertiary care center at central India p. 65
Atul Khajuria, Ashok Kumar Praharaj, Mahadevan Kumar, Naveen Grover, Amit Aggarwal
DOI:10.4103/0377-4929.130900  
Objective: The objective of the following study is to detect genes encoding carbapenem resistance in Klebsiella pneumoniae sepsis outbreak in a neonatal intensive care unit (NICU). Materials and Methods: Antibiotic sensitivity test was performed by standard Kirby Bauer disc diffusion technique and minimum inhibitory concentrations of antibiotics was determined by VITEK-2. Polymerase chain reaction (PCR) assays and sequencing was used to determine the presence of beta-lactamase encoding genes. Conjugation experiments were performed to determine the transferability of beta-lactamase. Isolate relatedness were determined by repetitive-element PCR (REP), enterobacterial repetitive intergenic consensus (ERIC) PCR and random amplified polymorphic deoxyribonucleic acid (RAPD). Results: All the isolates were completely resistant to the second and third generation cephalosporins tested as well as carbapenems. Susceptibility profiling of the isolates indicated that 100% retained susceptibility to tigecycline and colistin. Conjugation experiments indicated that blaNDM-1 was transferable and likely through a plasmid-mediated event. All the isolates showed the presence of blaNDM-1 with co association of bla CTX-M-15 . REP-PCR, ERIC-PCR and RAPD revealed a single clonal type circulating in NICU environment. Conclusion: Co-production of NDM-1 with CTX-M-15 in K. pneumoniae isolates was detected for the first time in our NICU. Transmission of plasmid carrying these resistant genes to other members of Enterobacteriaceae will increase the incidence of multidrug resistance. Early detection of these genes will help in prevention and adequate infection control by limiting the spread of these organisms.
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BRIEF COMMUNICATIONS Top

Tuberculous neuritis: A rare sequel of a common disease p. 69
Bhushan M Warpe, Sandhya V Poflee, Nandu P Pande, Anuradha V Shrikhande
DOI:10.4103/0377-4929.130902  
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis is an infectious disease that continues to be a significant health problem in a developing country like India. The cause of peripheral neuropathy associated with tuberculosis is controversial. Possibilities include the toxic effects of anti-tuberculous chemotherapy (especially, rifampicin, streptomycin & ethambutol), immune mediated neuropathy, direct invasion of nerves, vasculitic neuropathy, compressive neuropathy, and meningitic reaction. This report describes an unusual finding of tuberculous granulomas in the peripheral nerve (Greater auricular nerve) of a patient ,who presented with a painful neck swelling. Granulomas were present in Greater auricular nerve (C2,C3) biopsy specimen associated with tuberculous peri-neuritis, but with no more specific indications of the mechanism of the neuropathy.
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Post chemotherapy blood and bone marrow regenerative changes in childhood acute lymphoblastic leukemia a prospective study p. 72
Rashmi Kushwaha, Ashutosh Kumar, Kamal Aggrawal, Neha Nigam, Archana Kumar
DOI:10.4103/0377-4929.130903  
Context: This study was done to assess the Serial peripheral blood and bone marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. Aims: To assess the therapy related serial bone marrow changes in patients of Acute Lymphoblastic Leukemia. Settings and Design: Prospective study, carried out in Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March 2012. A total of 60 cases were studied Materials and Methods: History, complete hemogram, bone marrow examination at pretherapy (Day-0), intratherapy (Day-14), and end of induction chemotherapy (Day-28) were done. Peripheral blood smears were evaluated at regular interval to assess clearance of blast cells. Statistical analysis used: The statistical analysis was done using SPSS (Statistical Package for Social Sciences) Version 15.0 statistical Analysis Software. The values were represented in Number (%) and Mean ± SD. The following Statistical formulas were used: Mean, standard deviation, Chi square test, Paired "t" test, Student 't' test, Level of significance P Results: Incidence of ALL-L1 (46.7%) and ALL-L2 (53.3%) was equal. ALL-L2 patients had poor survival.Day 0 (D-0) bone marrow was hypercellular with flooding of marrow by leukemic cells. High levels of tumor load at D'0' were associated with poor survival. 14 th day of Induction phase showed significant decrease in hemoglobin and TLC as compared to D '0' parameters. D28 showed marrow regeneration. Cellularity, Blast%, and Leukemic Index showed significant drop from day '0' to day 14 due to myelosupression, whereas regeneration reflected by increased cellularity as per day 28 marrow. Lymphocytosis (>20%) at end of induction chemotherapy had better survival and longer remission.Risk of mortality was directly proportional to blast clearance and was a major independent prognostic factor for achievement of complete remission. Conclusions: A bone marrow examination at the end of induction chemotherapy provides information whether patient has achieved remission with regeneration of cells or still has residual leukemia. If the patient is in remission, maintenance treatment is started and if not more intensive chemotherapy or bone marrow transplantation may be embarked upon.
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Your dilemma, my identity: Unusual immunogenetic profiles of pediatric B cell acute lymphoblastic leukemia p. 78
Anurag Gupta, Manu Goyal, Koteswara Rao Nidamanuri, Palanki Satya Dattatreya
DOI:10.4103/0377-4929.130904  
B-cell acute lymphoblastic leukemia (B-ALL) is characterized by CD19 expression, which is one of the most important prerequisites, along with expression of CD10, CD22 and/or CD79a. Rearrangements involving MLL gene are seen in CD10 B-ALL (pro-B cell origin) and t(9;11)(p21;q23) is most commonly reported in acute myeloid leukemia (AML), where it is known to carry very good prognosis in pediatric AMLs and rarely in acute lymphoblastic leukemia (ALL). We report a case of CD10 + , CD19 pediatric ALL with rearrangements of MLL gene as a result of t(9;11)(p21;q23), thus conferring a very poor prognosis. The case emphasizes use of comprehensive panel of antibodies for flow cytometric immunophenotyping and cytogenetic correlation for correct diagnosis and prognostication.
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Early dengue diagnosis by nonstructural protein 1 antigen detection: Rapid immunochromotography versus two the enzyme-linked immunosorbent assay kits p. 81
Selvaraj Stephen, Marie Victor P Charles, Velmurugan Anitharaj, Civamany Deepa, Sivaraman Umadevi
DOI:10.4103/0377-4929.130905  
Dengue is known for its serious life-threatening complications. New rapid kits available recently in India target circulating non-structural protein (NS1) antigen from day one onwards. The sensitivity and specificity of a newly introduced rapid combo kit against two conventional ELISA kits is assessed. The performance of this kit is quite satisfactory since excellent agreement of 94.26% was observed with particular reference to NS1 antigen detection among all three kits namely Rapid SD Bioline dengue Duo (SD Korea), InBios DENV Detect NS1 ELISA, USA and dengue Early ELISA, Panbio, Australia. The false positivity of the rapid kit is very low since its specificity as for as NS1 antigen detection is concerned is 98.33%. The use of combination kit helps to detect additional cases of dengue, which are negative for NS1 antigen but positive for IgM and/or IgG antibodies, thus facilitating early diagnosis in remote areas and small laboratorie
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CASE REPORTS Top

Myoepithelial carcinoma of palate: Case report p. 85
Balakrishnan Thayumanavan, Nandimandalam Venkata Vani
DOI:10.4103/0377-4929.130906  
Myoepithelial carcinoma is an uncommon malignant salivary gland neoplasm with a predilection for parotid gland. However, its occurrence in minor salivary glands is considerably less with only 28 cases being reported in the literature. We report a case of myoepithelial carcinoma of palate in a 50-year-old woman. Computed tomography and magnetic resonance imaging revealed an extensive lesion in the palate. Microscopically, the tumor exhibited a wide spectrum of cytomorphologic features that overlap with other salivary gland tumors. Immunohistochemistry served as an adjunct in the diagnosis of the lesion. Clinical, radiographic, and histopathologic correlation along with immunohistochemical profile enabled to arrive at a diagnosis of myoepithelial carcinoma.
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Case of pulmonary pneumocytoma: A probable cytological diagnosis with histopathological confirmation p. 89
Mayank Gupta, Jigar Shah, Marie Therese Manipadam, Vinay M Rao
DOI:10.4103/0377-4929.130909  
Pneumocytoma is a rare benign tumor of the lung that usually presents as a solitary pulmonary nodule. It is believed to arise from the primitive undifferentiated respiratory epithelium. We report a case of pulmonary pneumocytoma that was suspected on needle aspiration smears and confirmed histologically. This case describes the cytological features of pneumocytoma that are rarely described in textbooks.
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Multifocal pulmonary mucinous cystic neoplasm with ovarian type stroma, a new finding in an extremely rare case report p. 92
Bita Geramizadeh, Bijan Ziyaian, Shima Khaleghi
DOI:10.4103/0377-4929.130910  
Primary pulmonary mucinous cystic neoplasm is a rare tumor and there are only a few case reports in the English literature. Herein we report a very unusual multifocal pulmonary mucinous neoplasm. Microscopic sections revealed ovarian type stroma which was diffusely positive for estrogen receptor, same as its pancreaticobiliary counterpart. To the best of our knowledge such a presentation of pulmonary mucinous neoplasm has not been previously reported in the English literature.
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Androgen - secreting steroid cell tumor of the ovary p. 94
Paras Ratilal Udhreja, Arunima Banerji, Devangi P Desai, Jignesh B Vaishnani
DOI:10.4103/0377-4929.130911  
Steroid cell tumors (SCTs), not otherwise specified of the ovary are rare subgroup of sex cord tumors, which account for less than 0.1% of all ovarian tumors and also that will present at any age. The majority of these tumors produce steroids with testosterone being the most common. A case of a 28-year-old woman who presented with symptoms of virilization is reported. Although SCTs are generally benign, there is a risk for malignant transformation. Surgery is the most important and hallmark treatment.
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Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma p. 98
Lipika Lipi, Ritesh Sachdev, Dheeraj Gautam, Jasbir Singh, Ishani Mohapatra
DOI:10.4103/0377-4929.130912  
A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein) and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin) with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.
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Pleomorphic xanthoastrocytoma with anaplastic features: A case report p. 101
Sadiya Niamathullah, S Sivaselvam, Mitra Ghosh, Siddhartha Ghosh
DOI:10.4103/0377-4929.130913  
Pleomorphic xanthoastrocytoma has been considered as an astrocytic tumor with relatively favorable prognosis. It corresponds to WHO Grade-II neoplasm. Recently, several patterns with relatively poor prognosis have been recorded and a new concept of "PXA with anaplastic features" has been proposed. The present case is about a 9-year-old girl who presented with symptoms of recurrent headache, seizures and poor academic performance. MRI revealed left fronto-parietal irregular enhancing mass lesion with callosal involvement and right mid-brain arteriovenous malformation. Clinical and radiological examination was suggestive of a high grade glial neoplasm/PNET. A diagnosis of high grade glial neoplasm was rendered on the squash smears submitted for frozen sections based on the presence of spindle cells, admixed with pleomorphic bizarre, giant cells with multilobated nuclei showing few atypical mitosis and abundant eosinophilic cytoplasm. Frontal craniotomy with debulking of the tumor was performed and permanent sections revealed a biphasic glial neoplasm with spindle cells arranged in fascicles admixed with bizarre multinucleated giant cells showing abundant vacuolated and lipidized cytoplasm, nuclear hyperchromasia with intranuclear inclusions. Eosinophilic granular bodies, mitosis of 7/10 HPF, micro vascular proliferation, necrosis and invasion into the underlying brain parenchyma were noted. With these histomorphological findings a diagnosis of pleomorphic xanthoastrocytoma with anaplastic features was rendered.
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Clear cell papillary cholangiocarcinoma: A case report with review of literature p. 105
Rachna Khera, Shantveer G Uppin, Megha S Uppin, Challa Sundaram
DOI:10.4103/0377-4929.130914  
Clear cell papillary cholangiocarcinoma is a rare variant of intrahepatic cholangiocarcinoma with only nine reported cases in the literature. This tumor needs to be differentiated from clear cell variant of hepatocellular carcinoma and other metastatic clear cell carcinomas. This tumor is known to have better prognosis compared to conventional intrahepatic cholangiocarcinoma. Hence, it is important to correctly diagnose this entity and differentiate it from other histologic mimics. We describe clinical, histopathological, and immunohistochemical findings of one such rare case in a 66-year-old gentleman who was incidentally detected to have an intrahepatic tumor at routine ultrasound examination.A review of all the similar cases reported so far in the literature is also provided.
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Cytokeratin - positive rib osteosarcoma metastasizing to the small intestine p. 109
Hiroko Kuwabara, Kazuhiko Fujita, Masako Yuki, Isao Goto, Toshiaki Hanafusa, Yuro Shibayama
DOI:10.4103/0377-4929.130915  
Osteosarcoma (OS) is a malignant tumor in which osteoid or bone is produced directly by tumor cells. Some OS cells are positive for cytokeratin (CK) and epithelial membrane antigen by immunohistochemistry (IHC) and this may lead to a misdiagnosis of metastatic carcinoma, particularly when the tumor location is unusual. On the other hand, gastrointestinal metastasis of OS is rare. We present the case of a 67-year-old Japanese man with a small intestinal intussusception due to metastasis of a CK-positive rib OS. The tumor cells were positive for CK, osteopontin and osteonectin by IHC and a diagnosis of a CK-positive chest wall OS metastasizing to the small intestine was considered. Osteoid or bone formation was histologically absent and therefore chest wall OS had to be differentially diagnosed from metastatic carcinoma of unknown origin. A postmortem histological analysis confirmed a rib OS. Awareness of CK-positive OS is important for making a correct diagnosis and for disease management and an immunohistochemical analysis of the tumor for expression of osteopontin and osteonectin may be used to support the diagnosis. In addition, this case shows that rib OS can metastasize to the gastrointestinal tract, albeit rarely, which may induce an intestinal intussusception.
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Pelvic mature cystic teratoma with neuroendocrine carcinoma: Report of a rare association and review of literature p. 113
Mukund N Sable, Debojit Nath, Sunil Chumbar, Chandan J Das, Pratyusha Priyadarshini, Kavneet Kaur, Richa Ranjan, Siddhartha Datta Gupta, Prasenjit Das
DOI:10.4103/0377-4929.130916  
Extra-gonadal malignant transformation of teratoma is rare and there are only a few reports available citing malignancy arising in the non-germ cell components. We hereby report a case of a 35-year-old female, who presented with lower backache with a radiologically identifiable mass lesion in the pre-sacral region. Clinical and radiological findings suggested the possibility of a cystic teratoma. Histopathological examination and relevant immunohistochemical tests detected a mature cystic teratoma with features of a grade 2 neuroendocrine tumor in it. Like the index case, most of the previously reported cases of teratoma with malignant transformation of the somatic components were found in extra-gonadal site. This case is being reported to emphasize that any extra-gonadal mass in reproductive age group, even if it appears radiologically and per-operatively benign, must be subjected to histopathological examination to rule out possibility of malignant transformation of the germ cell or non-germ cell components.
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Hepatoid adenocarcinoma of stomach: Case report of a rare histological variant p. 116
Vidisha Mahajan, Neelam Gupta, Saurabh Gupta, Reetika Sharma
DOI:10.4103/0377-4929.130917  
Hepatoid adenocarcinoma of the stomach is a rare form of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. Here, we report a case of a 60-year-old male patient who presented in the outpatient department with pain abdomen and constitutional symptoms. Radiological examination revealed a growth involving the antrum of the stomach while the liver and spleen were normal. The serum alpha fetoproteins were 6590 ng/ml. The patient underwent a partial gastrectomy and microscopic examination of the growth showed two types of histological patterns. Majority of the tumor displayed hepatoid differentiation with adenocarcinomatous foci. Periodic acid Schiff positive intracytoplasmic hyaline globules were seen. The tumor was immunohistochemically positive for alpha fetoprotein. The patient underwent radical gastrectomy, received chemotherapy and has been on follow-up for the past 12 months. Though known to be an aggressive neoplasm early diagnosis of hepatoid adenocarcinoma can help improve the prognosis of the disease.
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Incidentally discovered goblet cell carcinoid clinically presenting as acute intestinal obstruction: A case report with review of literature p. 120
Nishat Afroz, Nida Shamim, Lateef Ahmed Sofi, Syed Amjad Ali Rizvi
DOI:10.4103/0377-4929.130918  
Goblet cell carcinoid (GCC) is a rare variant of carcinoid tumor that exclusively involves the appendix. It usually occurs in 5 th -6 th decade with the most common clinical presentation being acute appendicitis. The natural history of this tumor is intermediate between carcinoids and adenocarcinomas. We here report a case of GCC diagnosed incidentally in a patient presenting with acute intestinal obstruction. Ultrasonographic examination supported the clinical diagnosis of acute intestinal obstruction, following which the patient underwent laparotomy and resection of ileum along with appendix was done. On gross pathological examination, a nodular growth was present on the tip and body of appendix that was yellow in color with a semi-solid to mucoid consistency on cut section. On microscopy, lakes of mucin with few acinar structures floating in them were seen. The submucosa as well as serosa were infiltrated by clusters of goblet cells and well-formed acini, with little atypia. Glands and nests were positive for per-iodic acid Schiff and immunohistochemistry showed focal chromogranin positivity in glandular structures, thereby confirming the diagnosis of GCC. Although the prognosis of GCC is better than adenocarcinomas, it is one of the carcinoids having a poorer outcome when compared with other variants of carcinoid tumor. Therefore, it is important to rule out other differential diagnoses of goblet cell carcinoid, the most important being mucinous adenocarcinomas.
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Krukenberg tumor in a young woman: A rare presentation p. 124
Deepa Hatwal, Chitra Joshi, Sheela Chaudhari, Pawan Bhatt
DOI:10.4103/0377-4929.130919  
Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young age are very rare and reported to be 2% of all the cases. Thirty percent of all ovarian neoplasms occurring during childhood and adolescence are malignant. A 25-year-old woman, parity- 2, presented with abdominal distension, pain in abdomen and amenorrhea. On examination, 18 weeks lump was palpable, firm to hard in consistency, non-tender and mobile. On ultrasonography bilateral ovarian tumors were reported, without any peritoneal free fluid. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Microscopic examination revealed signet ring cells with glandular differentiation, diffusely invading the ovarian parenchyma. Tumor cells exhibited strong, diffuse immunopositivity for CEA with focal strong immunopositivity for CK7 and CK20 and immunonegativity for SATB2. Diagnosis of Krukenberg tumor was made. Endoscopic biopsy confirmed the diagnosis of adenocarcinoma stomach. This case is reported because of its rarity in younger age group.
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Cutaneous amyloidosis and insulin with coexistence of acanthosis nigricans p. 127
Bevinahalli N Nandeesh, T Rajalakshmi, B Shubha
DOI:10.4103/0377-4929.130920  
Skin is one of the important organs affected by amyloidosis which is characterized by extracellular deposition of fibrillary proteins having homogenous, eosinophilic on routine staining with distinct tinctorial properties. Nodular cutaneous amyloidosis is rare and may affect dermis, subcutis and also vascular walls. Nodular amyloid deposits in the deeper dermis occurring at the site of insulin injection are a rare observation, which is described here. This description indicates that cutaneous amyloidosis may be associated with local subcutaneous injections of insulin and may clinically mimic a neoplasm or lipodystrophic lesion.
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Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous differentiation in a case of Von Recklinghausen's disease p. 130
Manas R Baisakh, Nachiketa Mohapatra, Samiran D Adhikary, Debasis Routray
DOI:10.4103/0377-4929.130924  
Malignant peripheral nerve sheath tumor (MPNST) of the adrenal gland is extremely rare. Most of them occur in association with neurofibromatosis, ganglioneuroma or as part of a composite tumor such as pheochromocytoma. Only seven cases of MPNST of the adrenal gland have been reported in the literature till date. Discriminating this entity from other soft tissue sarcomas and gastrointestinal stromal tumor of the adrenal gland has important diagnostic and therapeutic implications. Moreover, the tumor size and pattern of expression for certain immunohistochemical markers may serve as independent predictors of aggressiveness. Herein we present a 24-years-old male with features of Von Recklinghausen's disease who presented with large left adrenal gland malignant peripheral nerve sheath tumor.
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Testicular swelling: A rare manifestation of chronic lymphocytic leukemia presenting with Richter's syndrome p. 133
Bhawna Jha, Jasmita Dass, Ritesh Sachdev, Rahul Bhargava
DOI:10.4103/0377-4929.130925  
Richter syndrome (RS) represents the clinico-pathologic transformation of indolent lymphomas to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. Majority of the patients have a previous diagnosis of Chronic Lymphocytic Leukemia and the median time to transformation is 2-4 years. De novo RS is extremely uncommon. RS frequently arises in the lymph nodes or bone marrow and rarely presents with extra nodal involvement, common sites being the gastrointestinal tract, eye, central nervous system, lung and kidney. Involvement of testis by RS is extremely rare and we came across only one such reported case in the literature. We are reporting this case as our patient presented with de novo RS at an extremely uncommon extra nodal site, testis.
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Suprasellar salivary gland-like pleomorphic adenoma p. 136
Kun Yao, Zejun Duan, Yu Bian, Mengyang Wang, Xueling Qi
DOI:10.4103/0377-4929.130926  
Suprasellar salivary gland-Like pleomorphic adenoma is not a common disease and seldom reported so far. We are reporting a case of a 23-year-old man with recurrent suprasellar salivary gland-like pleomorphic adenoma, who underwent an operation of subtotal, subfrontal resection under the wrong pathology diagnosis of benign teratoma in another hospital 4-year-ago. Four years later, he was admitted to our hospital for additional visual loss of the right eye (left, 1.0; right, 0.4) resulting from tumor regrowth. Magnetic resonance imaging revealed that suprasellar extension and compressed optic chiasm resulted in visual disturbance of the patient. The tumor was totally excised and histological examination evidenced the pathological features of intrasellar salivary gland-like pleomorphic adenoma. The patient did not receive any further treatment and he is free from tumor recurrence for 30 months after the operation. From this point of view, clinical prognosis of intrasellar salivary gland-like pleomorphic adenoma was good after total surgical resection.
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Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen's disease p. 139
Vani Gopal, T Mangaiyarkarasi, R Gopal
DOI:10.4103/0377-4929.130927  
Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen's disease. A middle-aged man with a known case of diabetes mellitus and Hansen's disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Patient was operated for cataract and Intraocular lens implanted. Patient developed headache and vomiting on the 4 th post-operative day. Lumbar puncture was carried out and gram stain of cerebrospinal fluid showed Gram-negative bacilli in the direct smear and culture yielded a heavy growth of K. pneumoniae. The patient was treated with antimicrobials according to the susceptibility pattern. He initially showed improvement but later on developed altered sensorium and hypotension. Patient succumbed to infection in spite of all medical attention.
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Blood stream infection by an emerging pathogen Oligella ureolytica in a cancer patient: Case report and review of literature p. 141
Frincy K Baruah, Monica Jain, Mamta Lodha, Rajesh K Grover
DOI:10.4103/0377-4929.130928  
Oligella ureolytica is an emerging bacteria rarely implicated as a human pathogen. It is infrequently recovered from clinical specimens probably because of inadequate processing of non-fermenting oxidase positive Gram negative bacilli. We present here a case of a 30 year old male suffering from right lung adenocarcinoma (moderately differentiated) with multiple abdominal lymph node metastasis with Syringohydromyelia whose blood culture yielded Oligella ureolytica in pure culture. Oligella ureolytica isolation in pure culture and the patient's response to targeted treatment supported that Oligella ureolytica was the true causative agent of the blood stream infection. Early suspicion, diagnosis and treatment with potent antibiotics are needed to prevent further complications resulting from infection with this emerging pathogen.
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Intraductal papillary neoplasm of the bile duct: A rarity p. 144
Munita Meenu Bal, Mahesh Goel, Mukta Ramadwar, Kedar Deodhar
DOI:10.4103/0377-4929.130929  
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Metaplastic breast carcinoma with extensive chondrosarcomatous differentiation p. 146
Sandhya Venkatachala, Alamelu Jayaraman, V Chaitra, S Rjeshkumar
DOI:10.4103/0377-4929.130930  
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Expansile congenital soft-tissue mass: A massive presentation p. 148
Ingale Ingale, Samapika Routray, Supriya M Kheur
DOI:10.4103/0377-4929.130931  
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Isolated adrenal metastasis: A case report p. 150
Sonal Bhandare, Shailesh Shrikhande, Ganesh Bakshi, Kedar K Deodhar
DOI:10.4103/0377-4929.130932  
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Papillary variant of medullary carcinoma thyroid p. 151
Saumya Shukla, Namrata P Awasthi, Nuzhat Husain
DOI:10.4103/0377-4929.130933  
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Methotrexate-induced pneumonitis and myocarditis p. 152
Subhash Yadav, Sridharan Kannan, Pradeep Vaideeswar, Nithya Gogtay, Urmila Thatte
DOI:10.4103/0377-4929.130934  
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Primary small cell carcinoma of the renal pelvis with adenocarcinoma component p. 154
Shuguang Liu, Xing Hua, Haili Zhu, Hong Shen
DOI:10.4103/0377-4929.130935  
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Calcifying fibrous pseudotumor of the mediastinum: A rare case report p. 155
Kriti R Chauhan, Hiral U Shah, Priti P Trivedi, Manoj J Shah
DOI:10.4103/0377-4929.130936  
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Anaplastic lymphoma kinase (ALK) positive diffuse large B cell lymphoma in a 20 year old: A rare entity p. 157
Ritesh Sachdev, Shalini Goel, Sunil Gupta, Nitin Sood
DOI:10.4103/0377-4929.130937  
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Sensitivity testing of Staphylococcus aureus p. 158
Gopal N Agrawal, Arti S Wandre
DOI:10.4103/0377-4929.130938  
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Biofilm production in Gram-positive isolates causing urinary tract infection in a tertiary care hospital p. 159
Pragyan Swagatika Panda, Uma Choudhary, Sarita Yadav, Surya K Dube
DOI:10.4103/0377-4929.130939  
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Pneumocephalus in mixed aerobic and anaerobic (Bacteroides fragilis) meningitis p. 160
Subasree Ramakrishnan, Pramod Krishnan, P Satish Chandra, HB VeenaKumari, S Nagarathna
DOI:10.4103/0377-4929.130940  
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Chronic lymphocytic leukemia developing in a case of chronic myelogenous leukemia: Some observations p. 161
Mayur Parihar, Neeraj Arora, Deepak Kumar Mishra
DOI:10.4103/0377-4929.130942  
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Erratum to chronic lymphocytic leukemia developing in a case of chronic myelogenous leukemia: Accelerated phase: A rare case with review of literature, published in Indian J Pathol Microbiol. Jul-Sep; 56(3):303-5 p. 162
Narender Kumar, Jasmina Ahluwalia, Pankaj Malhotra, Man Updesh Singh Sachdeva
DOI:10.4103/0377-4929.130943  
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