The mediastinum harbors a mixed bag of tumors, which may create significant diagnostic dilemmas. These tumors have widely variable therapeutic and prognostic implications. Correct pre-operative cytological diagnosis may obviate the need of surgical excision of many of these lesions. A stepwise algorithmic approach such as clinical history, radiological localization, salient cytomorphology and ancillary test helps in correct diagnosis of these tumors. This paper discusses the stepwise diagnostic algorithm for fine needle aspiration cytology diagnosis of mediastinal tumors.

Context: Pyogenic granuloma (PG) is one of the most common reactive vascular lesions in the oral mucosa, which has been divided into the lobular capillary hemangioma (LCH) and the non lobular type (non-LCH) as two distinct entities, on the basis of some investigations. Aims: This study aims to compare the proliferative and angiogenic activity of two histological types of PG to determine whether they have two distinct types of biological behavior. Settings and Design: In this retrospective cross-sectional study, immunostaining was performed on 10 cases of each type of PG. Materials and Methods: About 4μm sections were cut from formalin-fixed paraffin-embedded blocks and each specimen was stained with both anti-CD31 and anti-Ki-67 antibodies simultaneously. Labeling index (LI) was determined for both types by counting Ki-67 and CD31 positive cells separately and simultaneously in 1000 stromal and luminal cells. Micro vessel count (MVC), the mean number of micro vessels in five areas at Χ200 magnification, was also determined for both groups. Statistical Analysis: The results were statistically compared using the Mann-Whitney U-test. Results: Ki-67 LI in LCH (5.4 ± 2.4) was higher than non-LCH (3.9 ± 3.9). The percentage of CD31 positive cells in LCH (28.5 ± 22) was lower than non-LCH (37.1 ± 20.8) and simultaneously immunostaining for both markers in LCH type (2.4 ± 2.1) was higher than non-LCH (1.2 ± 1). The MVC was approximately 77.35 ± 34.6 and 82.6 ± 42.7 in the lobular areas of LCH and central areas of non-LCH PG, respectively. These differences were not statistically significant. Conclusions: These results demonstrate a higher proliferation activity in endothelial cells of LCH PG than in non-LCH.

Background: Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012), SAP (P = 0.003), serum bilirubin (P = 0.001), AST/ALT ratio (P = 0.03), steatosis (P < 0.001), ballooning degeneration of hepatocytes (P < 0.001), portal inflammation (P < 0.001), Mallory hyaline (P = 0.001), ductular proliferation and fibrosis (P < 0.001) showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory's hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

Background: Accuracy of intraoperative frozen section diagnosis is an important part of quality control in surgical pathology. In this study we try to evaluate the frozen section diagnosis in our center, a referral center in southern Iran. Materials and Methods: During the four-year-period of study, all the frozen sections in the affiliated hospitals of Shiraz University of Medical Sciences were evaluated. Discrepant cases were studied to find out reasons for their inaccuracies. Results: In the four years, 759 frozen sections have been done, 25 of which showed discordant results. The most common site of frozen section and discrepancy was in central nervous system tumors. The reason for inaccuracy in frozen section diagnosis in 52% of cases was proved to be interpretative, 44% sampling error and the remainder due to lack of clinical information of the pathologist. Conclusion: Accuracy of our intraoperative consultation is comparable with other centers in Western countries. Most of the discrepancies can be prevented by providing more clinical information for the pathologist and more accurate sampling.

Background: Studies suggest that nuclear factor kappa-B (NFκB) activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. Materials and Methods: This study examines the expression and activity of NFκB in situ in antral biopsies of 42 consecutive patients with immunohistochemical techniques. Results: NFκB was highly expressed in the gastric epithelial cells. The number of cells showing activated NFκB correlated with the activity of gastritis (P < 0.05), a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. There was also a strong inverse association with the presence and grade of atrophy. Conclusion: This correlation is direct evidence of the importance of NFκB dependent signal transduction for neutrophil influx in gastritis. The role of NFκB appears to be only in the initial stages of gastritis, there is no role for the molecule in the development of chronic inflammation or atrophy.

Background: Pediatric hepatic malignancies are rare, accounting for 1-4% of all solid childhood tumors. The histopathology of childhood hepatic tumors guides the treatment and prognosis, and is the cornerstone for precise diagnosis. Until now, there has been no documented study on pediatric liver tumor cases from this center; in this report, we show our experience about the common types of childhood hepatic tumors during five years (2002-2007) and compare them with other studies. Materials and Methods: During five years (2002-2007), all the hepatic tumors of childhood (under 18 year-old) from the pathology file of Namazi Hospital of Shiraz University of Medical Sciences are recorded. This includes both resected specimens and biopsies. All the slides were reviewed and the pathologic diagnosis was confirmed. Results: We detected 53 liver tumor cases in children (below 18 years of age). Among these tumors, 36 (67.9%) were malignant. Male to female ratio was 1.5 to 1. Hepatoblastoma was the most common liver tumor in this age group accounting for 22 patients (41.5%). The second most common primary tumor was hepatocellular carcinoma (HCC), with five patients. Another malignant tumor was embryonal sarcoma. Benign tumors included adenoma, mesenchymal hamartoma, vascular tumors, focal nodular hyperplasia, and inflammatory pseudo tumor. There were also seven metastatic tumors during these five years. Conclusions: The spectrum of hepatic tumors in children is different from that found in the older age group (adults) and also different in different populations.

Background: Immunity status, individual response to disease and types of antibodies produced are well known to vary from person to person, place to place and probably from population to population. A broad spectrum of specific auto antibodies that have so far been associated with specific rheumatic diseases, as noted in Western literature, has been well taken as a reference standard all over the world. There is neither research work nor any data correlating the auto antibodies and their antinuclear antibody (ANA) patterns with the immunoprofile in the Indian population to date. Aims: To understand a definite association between ANA patterns and specific antibodies in the serum in the Indian study population and to document similarities / differences with the West. Settings and Design: This prospective and retrospective double blind study was undertaken on the South Indian population referred for ANA testing by Indirect Immunofluorescence method and by immunoline methods. Materials and Methods: Serum samples of patients from a random South Indian population who sought medical help for rheumatic disease were subjected for ANA testing by indirect immunofluorescence (IIF) method and line immunoassay during the study period of 27 months. Serum samples were processed in dilution of 1:100 using HEp - 2010 / liver biochip (Monkey) (EUROIMMUN AG). The serum samples which were further processed for line immunoassay were treated in 1:100 dilution on nylon strips coated with recombinant and purified antigens as discrete lines with plastic backing (EUROIMMUN AG) coated with antigens nRNP / Sm, Sm, SSA, Ro-52, SSB, Scl-70, PM-Scl, PCNA, Jo-1, CENP-B, dsDNA, nucleosomes, histones, ribosomal protein-P, anti-mitochondrial antibodies (AMA-M2) along with a control band. The analysis was done by comparing the intensity of the reaction with positive control line by image analysis. Results: The antinuclear antibody indirect immunofluorescence (ANA - IIF) patterns obtained were projectable to visualize a certain spectrum of specific antibodies such as homogenous (45.5%) with dsDNA, nucleosomes, histones, SSA / Ro-52, RIB and RNP / Sm, speckled pattern (35.6%) with Sm, RNP, SSA/Ro-52, SSB, Sm and RIB; nucleolar pattern with Scl-70, Sm, RNP and centromere pattern with CENP-B. The methodology indicated that, cytoplasmic pattern noted in ANA also needs to be correlated with primate liver in a biochip, which should prompt further decision for a request for line immunoassay and it is preferable for two pathologists to report independently and sign out a consensus ANA report for better predictive value. Conclusions: As a definite correlation between the ANA patterns and the group of antibodies was detected by line immunoassay, one could predict presence of certain specific auto antibodies for a particular ANA pattern identified. This may restrict one from requesting for line immunoassay, which is expensive and economizes on the cost of laboratory investigations in a developing country like India. Thus, screening of sera by ANA-IIF method alone may suffice and probably reduce the expense of detailed immunological work-up with minimal loss in diagnostic accuracy. This study, the first of its kind in India, provides database and reference for the Indian subpopulation.

Context: Rheumatoid arthritis (RA) has a heterogeneous course, spanning from mild forms tending to remission and reacting well to treatment, to aggressive forms resistant to classical therapeutic measures. Reliable predictive parameters of the disease course in RA are needed. Raised levels of Rheumatoid Factors (RFs) are associated with RA and that this RF is found in IgM, IgA and IgG classes (isotypes). Aims: To figure out the value of RF isotypes titers as predictors for RA processes and outcomes. Materials and Methods: Fifty three RA patients were enrolled in this study. The patients were diagnosed based on ACR criteria. Blood sample was taken from each patient at time of attending; sera were separated immediately and kept frozen at -70^oC until used. Disease Activity Score (DAS) was calculated using DAS28-3 formula. Radiographs were read by expert radiologists. Sandwich Enzyme-linked Immunosorbent Assay (ELISA) was used for the separate quantitative detection of RF of the IgG, IgM and IgA classes in serum. Statistical Analysis Used: Chi-square, Pearson's correlation coefficient and ROC statistical analyses was performed using SPSS version 15.0. Results: Among the 53 RA patients who were enrolled in this study, there were statistically significant positive correlations between the presence of radiological joint changes with serum levels of IgG-RF, IgM-RF and IgA-RF as measured by calculation of area under curve (0.772, 0.703 and 0.769, respectively). However, no correlation could be found between those RF isotypes with any of other disease processes and outcomes. Conclusions: These results may indicate the importance of the titers of those isotypes as good predictors of erosive RA and may reflect a causal relationship between their titers and joint damage during the course of RA.

Context: Counting of newly formed microvessel may prove to be a useful tool in the early detection of metastatic potential and selection of patients for whom antiangiogenesis drugs might be beneficial. Aims: We designed this study to assess the significance of microvessel quantification in colorectal cancer with respect to different clinicopathological variables. Materials and Methods: Forty archived paraffin-embedded colorectal adenocarcinoma samples and their resection margins were enrolled in our study. Thin paraffin-embedded sections (3-5 ΅m thick) of both tumor and resection margins were prepared for each respective biopsy and were used to detect endothelial cell (EC) surface expression of PECAM-1 and vWF by immunohistochemistry technique. Statistical Analysis: For the comparison between tumor and resection margin regarding the investigated parameters, the t-test of significance was conducted. The association between surface expression of PECAM-1 and vWF along with tumor differentiation, depth of invasion and lymph node metastasis was performed by Chi-square (χ² ) and ANOVA test as well as 95% confidence interval. On the other hand, the association between the investigated parameters and tumor stage as well as tumor size was performed by student t-test. The correlations between the two investigated parameters in respect to various clinicopathological parameters were calculated by correlation coefficient (r). Statistical significance was defined as P < 0.05. All statistical analyses were performed using SPSS statistical package for social and medical science version 15.0. Results: Based on the current outcome, there were significant differences in microvessel density based on PECAM-1 or vWF immunostaining when each tumor sample was compared to its respective resection margin (P < 0.001 and P < 0.001, respectively). In addition, tumors ≥3 mm ³ in size demonstrated a significant increase in their microvessel density compared to their counterparts whether PECAM-1 or vWF immunostaining was applied (P < 0.001 and P < 0.001, respectively). Moreover, when tumor samples were analyzed based on their depth of invasion, for intratumoral microvessel count, exclusively, vWF immunostaining analysis demonstrated significant differences among the three groups: submucosa into muscularis propria (SMP), tumor reaches serosa (SE) and tumors invade other organs (OR), since the latter came up with the highest microvessel count (P < 0.05). When tumor lymph node metastases were questioned, exclusively, vWF immunostaining were significantly differentiated among N0, N1 and N2 groups (P < 0.05). Concerning the possible correlations between the two investigated parameters in respect to various histopathological variables, both PECAM-1 and vWF immunostaining demonstrated significant positive correlations in tumor samples (r = 0.37), whereas in resection margins, these correlations were absent. Although, PECAM-1 and vWF immunostaining revealed significant and positive correlations within tumor differentiation (WD: r = 0.56, MD: r = 0.57 and PD: r = 0.89) as well as with tumor stage (A-B: r = 0.39 and C-D: r = 0.31), still, they seem to correlate significantly and exclusively within SE group (r = 0.74), tumors <3 mm ³ in size (r = 0.66), N0 (r = 0.36) and N1 (r = 0.85) groups. However, PECAM-1 and vWF immunostaining revealed significant but negative correlation exclusively within N2 group (r = -0.38). Conclusion: In conclusion, microvessel count could be useful as a predictor for tumor metastases in patients with colorectal adenocarcinoma. Possible interpretations of the current outcome are explained thoroughly in the text.

Context: Pulmonary hypertension (PH) is a serious and sometimes life-threatening event that occurs as a complication of various cardiopulmonary disorders, of which rheumatic heart disease (RHD) is an important example in our country. The pathogenesis of PH is a complex, multistep process in which "pulmonary endothelial dysfunction" (PED) is widely regarded as the central pathogenetic event. PED is, in turn, influenced by several local and systemic factors, of which nitric oxide synthase 3 (NOS3) and endothelin 1 (ET1) are 2 prime candidates, and are the subject of our study. Aims: Our aim was to study the immunoreactivity of NOS3 and ET1 in the pulmonary vasculature of PH patients of various etiologies, with emphasis on RHD cases. Settings and Design: A retrospective, autopsy-based study. Subjects and Methods: A total of 49 autopsy cases (39 patients and 10 controls) were chosen for our study. Of the 39 patients, 20 had PH secondary to RHD, whereas the remaining 19 patients had non-RHD etiologies as the basis of their PH. Lung sections taken from all the 49 cases were subjected to routine H and E, elastic van Gieson, and immunohistochemical staining (with NOS3 and ET1 separately). The intensity of immunostaining in all the cases and controls were then graded as focal/diffuse and weak/strong. Results: Controls showed positivity for both NOS3 (bronchiolar epithelium) and ET1 (endothelium of pulmonary arteries). Characteristic changes of PH on H and E were seen in 14 out of 19 non-RHD cases, which matched with the number of ET1 positivity cases. Similarly, for the RHD cases, 14 out of 20 cases showed changes of PH on H and E, but only 2 cases showed mild, focal positivity for ET1. Surprisingly, NOS3 positivity was largely absent in both the non-RHD and RHD cases. Conclusions: Our study showed NOS3 negativity and ET1 positivity in the lung vasculature of patients with PH, a conclusion more or less in line with the predominant view of the other investigators in this field. But at the same time, our study could not conclude an unequivocal role of NOS3 in PH, whereas it could, in the case of ET1.

Objectives: Prostaglandins are critical mediators of inflammation and affect both humoral and cell-mediated immune responses. Recent findings show that T and B cells express COX-2 upon activation. The purpose of this study is to investigate the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic tonsillitis and to determine the sites of their expression. In addition, their expression in adult patients is compared with that in child patients. Materials and Methods: Immunohistochemical techniques were used to evaluate the expression of the enzymes COX-1 and COX-2, in chronic tonsillitis tissue specimens from adults (n = 15) and children (n = 15). Results: There was no staining in surface epithelium or reticulated crypt epithelium. COX-1 and COX-2 expressions were observed mainly in the intraepithelial lymphoid cells in reticulated crypt epithelium and subepithelial cells. Also, COX-1 and COX-2 stained cells were found in the germinal center. There was no difference of the expressions of COX-1 and COX-2 among adults and children. The only significant difference noted between the adults and children was that, the adults had rich subepithelial plasma cells. Conclusion: Activated B and T cells express COX-1 and COX-2 in paraffin-embedded tissue sections of chronic tonsillitis. Further studies need to be performed to elucidate expression of COX enzymes and their immunologic role in tonsil diseases. They will play an important role in the treatment of chronic tonsillitis. Additional studies are warranted to study the effects of NSAIDs and selective COX-2 inhibitors in chronic tonsillitis

Objective: This series of six intestinal T cell lymphomas (ITCL) attempts to document enteropathy-associated T cell lymphoma (EATCL) in India. Materials and Methods: A total of six ITCL were selected from 170 gastrointestinal lymphomas in last 10 years. Results: The cases studied included EATCL (4), ITCL with a CD4 positive phenotype (1) and ITCL NK/T cell type (1). Of the four EATCL, two occurred in the ileum, one in right colon and one in duodenum. In three EATCL cases, there was history of celiac disease or lactose intolerance and enteropathic changes were noted in the adjacent mucosa. These tumors had CD3+/CD8+/CD56 (+/-)/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic small cell type (type II EATCL) with a CD3+/CD8-CD56+/CD4-/ Granzyme B+ phenotype. EBER- ISH (Epstein Barr virus coded RNA's- in situ hybridization) revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in three EATCL. Conclusion: ITCL are rare in Indian patients but do occur and comprise a mixture of the enteropathic and non-enteropathic subtypes.

Objective: To determine the frequency and magnitude of discrepancies in the surgical pathological diagnosis of soft tissue lesions on review and second opinion in a histopathology center. Study Design: Cross-sectional, observational. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from April 2006 to May 2007. Materials and Methods: All the cases of soft tissue as well as bone lesions, irrespective of age and gender, which were referred for second opinion or review after being reported elsewhere, were included in the study. A panel of antibodies of soft tissue, epithelial and lymphoid markers was applied according to the requirements of each case. The cases were categorized as category A where there was concurrence between initial diagnosis and diagnosis at review. Category B included cases where there was disagreement in the specific diagnostic entity as per WHO classifications without therapeutic implications. Category C was cases where the category of benign or malignant diagnosis remained the same but there was disagreement in the specific diagnosis with definite therapeutic implications. Category D had diagnosis of benign changed to malignant while category E had cases where diagnosis of malignancy was changed to a benign lesion. Results: During the study period, 34 cases of soft tissue lesions were received for review and second opinion. The mean age of the patients was 39 ΁ 22 years and immunohistochemistry was performed in 21 (62%) of 34 cases. Concurrence between the review and initial diagnosis was seen in 18 (53%) cases (category A). Discrepancy in the diagnosis at review and initial consultation was seen in 16 (47%) cases. There were four (11.8%) cases that were placed in category B as the diagnosis of benign and malignant remained the same but the specific diagnostic entity was changed. Category C included eight (23.5%) cases where the review diagnosis changed the therapeutic modality despite the benign or malignant category remaining unchanged. All the cases in this category required immunohistochemistry as diagnosis of metastatic carcinoma was changed to sarcoma in two cases and diagnosis of sarcoma was changed to carcinoma in three cases. There was only one (2.9%) case in category D where a benign diagnosis was changed to malignant on review and three (8.8%) cases reported as malignant had a revised diagnosis of benign lesion, placing them in category E. Conclusion: In the absence of a quality assurance regulatory body to monitor and overlook the professional competence of practicing surgical pathologists, a mandatory review and second opinion should be undertaken whenever a major therapeutic endeavor is to be undertaken, regardless of the cost for the ultimate benefit of the patient.

Context: Lymphatic invasion and nodal metastasis play a major role in the spread and prognosis of endometrial adenocarcinoma (EC). Aims: In this study, we investigate tumor lymph-angiogenesis, detected by D2-40, as a predictive marker for the risk of lymph node (LN) metastasis and its relation to other prognostic parameters in EC. Materials and Methods: Fifty-five cases of EC treated with total hysterectomy and pelvic LN dissection were reviewed. All cases were immunostained for D2-40. Positively stained microvessels (MV) were counted in densely lymphovascular foci (hotspots) at X 400 field (0.17 mm2). Statistical Analysis: Statistical analysis was performing using Chi square "X ²" test. Results: Lymphovascular invasion was detected in 20 / 55 patients by D2-40 and 14 / 55 by routine hematoxylin and eosin (H and E). Peritumoral lymphatic vessel (LV) count was significantly higher than intratumoral LV count (17 + 7 versus 5 + 4 / 0.17 mm ² , P < 0.01). Peritumoral D2-40 lymphovascular counts correlated significantly with FIGO grade (P < 0.001), lymphovascular invasion (P = 0.001) and LN metastases (P = 0.005). However, it showed non-significant correlation with peritoneal wash positivity (P = 0.830) and stage of the disease (P = 0.341). Intratumoral lymphovascular invasion detected by D2-40 showed significant correlation with LN metastases (P < 0.01). Conclusions: Our study shows that assessing LVD with D2-40 in the endometrial carcinoma might be a valuable parameter for predicting patients having an increased risk of developing of metastatic disease. In addition, D2-40 increases the frequency of detection of lymphatic invasion relative to routine H and E stain.

Aims: FibroTest and ActiTest are noninvasive tests used in determining the level of fibrosis and the degree of necroinflammatory activity in the liver. In our study, we aimed to investigate whether these tests could be alternative to liver biopsy. Materials and Methods: Fifty patients were included in the study. Serum samples were obtained and liver needle biopsy was performed on the same day. Levels of fibrosis in FibroTest and levels of activity in ActiTest, both determined via serum biochemical markers, were compared with levels of fibrosis and activity in histopathological examination. For statistical analyses, Mc Nemar chi square test and Spearman's correlation tests were used. Results: There was a significant positive correlation between fibrosis in biopsy and the level of fibrosis in FibroTest in patients with hepatitis B virus (HBV) (rho: 0.67, P < 0.0001). However, no significant correlation was determined between the activity in biopsy and the degree of activity in ActiTest (rho: 0.29, P < 0.05). No significant correlation was determined between both fibrosis and activity established in biopsy and the results of FibroTest and ActiTest in the group of patients with hepatitis C virus (HCV) (rho: 0.22, P < 0.05 and rho: 0.15, P < 0.05, respectively). Conclusion: Our results suggest that novel and safer noninvasive biochemical tests are needed as an alternative to histopathology in patients infected with HBV and HCV. Consequently, we believe that liver biopsy maintains its place as a gold standard in determining the histopathological condition of the liver.

Background: Hashimoto's thyroiditis (HT) is the most common cause of hypothyroidism in those areas of the world where iodine levels are sufficient. Fine-needle aspiration cytology (FNAC) can accurately diagnose this lesion in most of the patients. However, a small percentage of cases may be missed due to inherent limitations of this procedure. Therefore, cytologic clues to increase sensitivity of diagnosis need to be searched for. Aims: To assess whether an eosinophilic infiltration of the thyroid gland has a higher association with HT than colloid goiter. Materials and Methods: The study was a case-control study. Smears obtained by FNAC of 50 case, each of HT (which served as cases) and colloid goiter (which served as controls) were observed. The number of eosinophils and neutrophils per high-power field (HPF) was counted in all the smears. The eosinophil-neutrophil ratio in the smears, diagnosed as HT, was then compared with that of colloid goiter using unpaired t-test. Results: Smears diagnosed as HT was found to have a significantly higher eosinophil-neutrophil ratio than smears diagnosed as colloid goiter (P value 0.0001). Conclusion: Eosinophilic infiltration of the thyroid gland has higher association with Hashimoto thyroiditis.

Introduction: Historically, serum alanine transaminase (ALT) has been used as a surrogate marker in the detection of hepatitis viruses in blood donors. With the availability of newer sensitive technologies for the detection of seroconversion, the value of ALT becomes questionable but continues to be used for this purpose with subsequent discarding of ALT elevated blood units. Objective: The present study aims to evaluate the significance and cost effectiveness of ALT as a surrogate marker for hepatitis C virus infection in healthy asymptomatic blood donors who were serologically negative. Materials and Methods: The study was conducted at clinical laboratory of a tertiary care hospital for a period of one year from November 2006 to October 2007. All donors were screened serologically for hepatitis B, C and HIV I and II, syphilis and malaria and those tested positive were excluded from further evaluation. Gender-wise reference ranges and minimal and markedly raised results for ALT (described respectively as one and two folds increase above reference range) were defined and, accordingly, donors were grouped into three. Two hundred seronegative blood donors were randomly selected from all three groups of ALT results and tested for hepatitis C nucleic acid through Amplicor^; HCV RNA test. The cost of discarding an ALT -only elevated blood unit was also assessed. During the study period, 25117 subjects donated blood. Eight hundred and Results: seventy two donors (3.4%) were positive for one or more serological tests. ALT of all donors ranged from 0-1501 U/L (Mean ± SD; 33.4 ± 25.45U/L). The donors seronegative for all disease markers were 24245 (96.6%). Of these, 21164 (87.2%) donors had their ALT within reference range while 2874 (11.8%) and 207 (0.8%) of donors had minimal and markedly elevated results. Thus, 621 blood bags (red cells, platelets and plasma) costing $ 39200.0 were discarded based on ALT results alone. Of 200 seronegative donors evaluated for hepatitis C nucleic acid, only one within markedly elevated ALT levels was found to be positive. The present work did not support a positive association between hepatitis C virus nucleic acid and elevated ALT in healthy serologically negative blood donors. Conclusion: We did not find serum ALT testing in donors as cost effective strategy for detection of hepatitis C virus ribonucleic acid. As the number of samples tested by us was small we suggest further work to evaluate the value of ALT levels in serologically negative donors in association with hepatitis C antigen and NAT testing to elucidate the true burden of disease in geographical regions where hepatitis C is endemic and voluntary blood donation is sparse.

Context: Von Willebrand disease is the most common inherited bleeding disorder with a prevalence of ≈ 1% in the general population. Studies available from India are limited, showing a prevalence of ≈ 10% of vWD amongst inherited bleeding disorders. Aims: This study aims to know the prevalence and subtypes of vWD in patients presenting with various bleeding manifestations to university hospital. Settings and Design: We investigated 840 patients presenting with bleeding manifestations in the period from August 2004 to August 2008 for bleeding disorders. Materials and Methods: Tests performed for the diagnosis of vWD included platelet count, bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT), Factor VIII:C assay, von Willebrand Factor Antigen assay and Ristocetin-induced platelet aggregation. Results: Amongst 840 patients, 230 (27.38%) had inherited bleeding disorder. Out of these, 40 (17.39%) patients were identified as vWD. Type 1 in 17 (42.5%), Type 2 in 11 (27.5%) and Type 3 vWD was present in 12 (30.0%) patients. Patients' age ranged from five months to 45 years, with 17 males and 23 females. Positive family history was seen in 12 patients (30%). Muco-cutaneous bleeding was the most common presentation. Menorrhagia was present in 100% women of reproductive age group, and hemarthrosis was seen in two male patients. Conclusions: We felt that Type I vWD with infrequent and mild bleeding episodes remain undiagnosed either because of unawareness of the disease in society or due to paucity of diagnostic facilities available in our country. Therefore, an awareness program along with enhancement of diagnostic facilities for vWD is required in our country to identify these patients for proper management thus avoiding hemorrhagic complications.

Waldenström's Macroglobulinemia (WM) is a B cell neoplasm characterized by infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM monoclonal gammopathy. We report a 15-year review of patients diagnosed with WM at our center. A total of 18 patients were diagnosed and treated at our center during the study period. Neurological symptoms were seen in almost 95% while B symptoms were present in almost 80% of patients. More than two-thirds of patients were anemic at the time of presentation and more than 90% showed bone marrow infiltration with lymphoplasmacytoid cells. Anemia, B symptoms, splenomegaly and neurological symptoms were the primary reasons in the majority of patients to initiate treatment. Chlorambucil was the primary treatment in more than half the patients followed by CVP. The median overall survival in all patients was 29 months (range 22-81 months). WM is a rare disorder and novel therapeutic modalities need to be identified to improve survival in these patients.

Objective: To study the association of tumor necrosis factor-a (TNF-a) and C - reactive protein (CRP) with microbiologically documented cases of sepsis versus clinically documented cases of sepsis. Materials and Methods: Seventy nine pediatric patients with sepsis were studied. Relevant specimens were processed for bacterial or fungal etiology. TNF-a was detected by enzyme immunoassay and CRP was detected by latex agglutination. Thirty healthy cases were included in the study to establish baseline TNF-α levels. Results: Forty two (53.2%) patients had a microbiologically documented sepsis. Among Gram negative bacilli Escherichia coli was the most common isolate followed by Klebsiella spp. Staphyloccus aureus and Streptococcus pneumoniae predominated among the Gram positive cocci. Patients with a positive culture had significantly higher TNF-α levels than patients with a negative culture (70pg/ml vs. 33 pg/ml P < 0.01). Further, pure gram negative infection correlated with significantly higher TNF-α levels than pure (P < 0.01) gram positive infection. The CRP values did not highlight these differences significantly. Conclusions: TNF-α level was significantly raised in patients with sepsis. TNF-a levels were raised significantly in culture positive cases in general and in Gram negative infections in particular. Serum TNF-α was a more sensitive marker for different categories of sepsis compared to CRP and microbiology culture.

Environmental factors affect the dissemination and distribution of intestinal parasites in human communities. To comprehend the prevalence of parasitic infestation and to examine whether geographical location and age also influence the prevalence of infection, fecal samples from 195 school children (rural = 95; male = 39; female = 56) (urban = 100; male = 60; female = 40) of five age groups ranging from 5 to 11 years in two different socio-economic zones (rural and urban) were screened for specific intestinal parasites using standard histological techniques. Percentage incidences of parasitic species found in fecal wet mounts and concentrates in rural children were Entamoeba coli (25.3%), Giardia lamblia (17.9%), Blastocystis hominis (14.7%), Entamoeba histolytica (4.2%), Iodamoeba butschlii (1.1%), Hymenolepis nana (1.1%) and Ascaris lumbricoides (1.1%). Whereas the percentage incidences among urban children were E. coli (26%), A. lumbricoides (21%), B. hominis (18%), G. lamblia (14%), T. trichiura (8%), I. butschlii (4%) and A. duodenale (1%). Such findings may be related to dietary differences, living conditions and the greater use of natural anti-helminthic medicinal plants in rural communities. These results are important for both epidemiological data collection and for correlating dietary differences to intestinal parasitic diseases. Aims: We chose to investigate whether geographical location and age affect the prevalence and distribution of intestinal parasites among school children from two separate regions (rural and urban) in areas surrounding, Chennai, Tamil Nadu, India. Settings and Design: A study of the prevalence of parasitic infestations was undertaken among primary school children, in rural and urban communities around Chennai, Tamil Nadu, India. Materials and Methods: Faecal sample collection, direct microscopic techniques, macroscopic examination and concentration techniques for identifying the parasites. Statistical analysis used: Percentage incidences of parasitic species found in faecal wet mounts and concentrates were done instead of statistical analyses. Results: Both macroscopic and microscopic examinations of faecal samples revealed that the overall percentage prevalence of parasite species encountered in rural children were Entamoeba coli (25.3%), G. lamblia (17.9%), B. hominis (14.7%), Entamoeba histolytica (4.2%), I. butschlii (1.1%), H. nana (1.1%), Ascaris lumbricoides (1.1%). The prevalence among urban children were E. coli (26%), A. lumbricoides (21%), B. hominis (18%), G. lamblia (14%), T. trichiura (8%), I. butschlii (4%) and A. duodenale (1%). Overall, comparative significant differences were noted between rural and urban children for E. histolytica (4.2 vs. 14%), G. lamblia (17.9 vs. 14%), A. lumbricoides (1.1 vs. 21%) and T. trichiura (0 vs. 8%), with the major difference being the much higher occurrence of A. lumbricoides and T. trichiura infections in urban children. Conclusions: One of the greatest challenges for healthcare professionals is the prevention and treatment of protozoal and helminthic parasitic infections. From our study we conclude that the prevalence of different pathogenic species of amoeba such as Entamoeba histolytica (4.2 vs. 0%) and G. lamblia (17.9 vs. 14%), (P value was equal to 1) was significantly higher among rural children compared to children from urban areas. In contrast, the prevalence of nematodes such as A. lumbricoides (21% vs. 1.1%), T. trichiura (8% vs. 0%) and A. duodenale (1%) was also significantly higher among rural children.

All diarrheagenic Escherichia coli carry at least one virulence-related property. Stool samples from 244 patients having acute or persistent diarrhea received after the exclusion of routine enteropathogens were investigated. Purely or predominantly isolated E. coli (n = 100) were subjected to serotyping, of which only 25 were typable. They belonged to 14 different O-serogroups comprising 5 O153, 4 O102, 3 O25, 2 each of O130 and O169, and 1 each of O1, O8, O15, O37, O86, O101, O127, O143, and O160. The typable E. coli isolates along with 5 other untypable isolates were investigated for molecular markers, such as intimin (eae), enterohemolysin (EhlyA), a-hemolysin, heat-labile enterotoxins (LT), heat-stable enterotoxins (STa), verotoxins (VT1 and VT2), invasivity (ial), enteroaggregative E. coli (EAEC) gene (EAGG), and enterotoxin (EAST). Two of the isolates (O153 and O86) were positive for enterohemolysin phenotypically and 5 for β-hemolysin both phenotypically and genotypically. Interestingly, 16.6% of the randomly isolated E. coli were O153, a serogroup common in cattle, and 10% belonged to EAEC pathotype of which two-thirds had the EAST gene, which is quite frequent in these strains. Additionally, there was one strain (O153) that was positive for EAST only. Between the two 0130:H6 strains isolated, one belonged to EAEC serogroup. None of the E. coli isolated were positive for verotoxins, eae, LT1, STa, and ial. Data obtained emphasize the need for additional research into the role of eae gene and other putative factors affecting the virulence of diarrheagenic E. coli in India.

Aim: Enteric fever is an ongoing problem in the developing nations. Resistance and reduced susceptibility to ciprofloxacin narrows the therapeutic options in enteric fever. The present study was carried out with the objective of determining molecular basis of resistance to fluoroquinolone among the clinical isolates of Salmonella enterica serovar Typhi from different parts of India. Materials and Methods: A total of 60 S.Typhi clinical isolates were subjected to antimicrobial susceptibility testing and determination of minimum inhibitory concentration (MIC) to ciprofloxacin and nalidixic acid. Polymerase chain reaction (PCR) for GyrA gene followed by restriction fragment length polymorphism (RFLP) with restriction enzyme (RE) SSiI was performed to detect mutation at position Ser83. Further confirmation of mutation was done by nucleotide sequencing of GyrA gene. Results: Isolates showed 100% sensitivity to first-line drugs ampicillin, chloramphenicol, and cotrimoxazole. Twelve of the 60 isolates (18%) were susceptible to nalidixic acid (NASST) and the remaining 48 (82%) were resistant to nalidixic acid (NARST). Of these 48 NARST strains, 46 (97.5%) had reduced susceptibility to ciprofloxacin (MIC 0.25-1.0 μg/mL), whereas 2 strains (2.75%) were resistant to ciprofloxacin (MIC 4.0 μg/mL). In RFLP analysis, all the NASST strains showed 3 fragments, whereas all the NARST strains showed 2 fragments due to the loss of 1 restriction site as a result of mutation. All the NARST strains with reduced susceptibility to ciprofloxacin (n = 46) had a single mutation in gyrA gene (Ser ⁸³→Tyr or Ser ⁸³→Phe), whereas double mutations (Ser ⁸³→Phe and Asp ⁸⁷→Asn) were found in each of the 2 ciprofloxacin-resistant strains. None of the NASST strains (n = 12) revealed any mutation. Conclusion: Our study exemplifies the correlation between nalidixic acid screening test, MIC values, and the detection of mutation in GyrA gene by PCR-RFLP with a novel RE SSiI.This was further confirmed by nucleotide sequencing.

Aim: Candida albicans occurs as a commensal of the gastrointestinal tract. Under predisposing conditions, candida can produce a broad array of infections. HIV seropositive individuals show increased oral colonization compared to the HIV seronegative healthy individuals. C. albicans shows a variety of pathogenic factors. We have studied one such factor here; the adherence property of C. albicans isolated from HIV seropositive individuals and HIV seronegative to Human Buccal Epithelial Cells (HBEC) of normal healthy individuals. Materials and Methods: Concentrated oral rinse specimen were collected from 50 healthy volunteers (control group) and 25 HIV positive individuals (test group) and used for isolation of C. albicans. Adherence assay was done using C. albicans isolates from both groups on HBEC collected from HIV sero-negative, normal individuals. The adherence assay method described by Kimura and Pearsall was used with minor modification. Statistical Analysis Used: The results of Adhesion assay were subjected to statistical analysis using student "t" test. Results: C. albicans isolated from both the groups were tested for their adherence property to normal HBEC. The isolates from test group showed more adherence to HBEC compared to those of the control group, with average rate of adherence being 56.6%. The control group showed average adherence rate of 29.1%. This was statistically significant with p value equal to 0.05. Conclusion: C. albicans from HIV infected individuals showed significant rise in degree of adhesion to the buccal epithelial cells than the isolates from healthy controls, suggesting the enhancement of virulence factors such as adherence in the presence of predisposing condition.

Aim: To evaluate the potential of p16INK4A and MIB-1 and to compare the expression and interrelationship of these markers in cervical preneoplasias and neoplasias. Materials and Methods: Immunohistochemical analysis of p16 and MIB-1 was performed in n = 63 tissue sections and by matching the corresponding Papanicolaou smears. Staining intensity for p16 was determined using the 0-3 grading system. For MIB-1, labelling indices (LI) were calculated and grading was performed using the I-III scoring system. Results: No positive staining of p16 was observed in the normal cervical epithelium. With increasing severity of cervical intraepithelial neoplasias (CIN), the p16 expression increased progressively. Significant up-regulation of p16 was observed in carcinoma cervix. MIB-1 LI was observed to increase with increasing grades of CIN, and significant overexpression of MIB-1 was observed in carcinoma cervix. Correlation between grades of p16 and that of MIB-1 among cervical neoplasias showed an increasing p16 expression with consistently increasing MIB-1 LI in the groups of increasing severity. Conclusion: This pattern of overexpression of p16 and MIB-1 demonstrate their use as a diagnostic marker for cervical neoplastic lesion. Therefore, p16 and MIB-1 markers in tissue sections can be used as an adjunct to definitively diagnose preneoplastic and neoplastic lesions in the cervix.

We hereby report the occurrence of mediastinal liposarcoma in a 11-year-old female child. Dyspnea and wheezing of long-standing duration were the presenting complaints and a preoperative biopsy failed to yield the diagnosis. Histologic examination revealed heterogeneous areas with well-differentiated liposarcoma-like areas, areas resembling myxoid liposarcoma, and areas of dedifferentiation. Osteosarcomatous foci and whorled areas reminiscent of meningioma were identified in the dedifferentiated areas. Liposarcomas in the mediastinum are extremely rare tumors of childhood and the present case showed unusual histologic features. Complete surgical excision with clear surgical margins remains the primary modality of treatment, although chemotherapy and radiotherapy have been tried.

Inflammatory myofibroblastic tumor is a diverse group of lesions first described in lung and later on reported in various sites like stomach, bowel, spleen, bone. We report a case of inflammatory myofibroblastic tumor in a 30-year-old male who presented with a slowly progressive scalp swelling of two-year duration. Magnetic resonance imaging showed an intradiploic well enhancing lesion in parietal and occipital bone, isointense on T1 weighted images and hypo intense on T2 weighted images with dural enhancement. On histopathological examination, the lesion was composed of variable admixture of spindle cells with eosinophilic cytoplasm and inflammatory cells comprising of plasma cells and lymphocytes. The lesion was infiltrating the underlying dura. The spindle cells showed strong positivity for smooth muscle actin on immunohistochemistry. A final histopathologic diagnosis of inflammatory myofibroblastic tumor was rendered.

Cardiac function has long been known to be altered in patients with thyrotoxicosis and atrial fibrillation occurs in patients with hyperthyroidism. In addition to its disabling symptoms, atrial fibrillation is a strong risk factor for systemic embolism, especially with regard to cerebral circulation. A right atrial appendage thrombus formation in atrial fibrillation is a rare phenomenon. In this report, we describe a case of a 30-year-old female, who suffered from hyperthyroidism and subsequently developed atrial fibrillation and a right atrial appendage thrombus with infarction of right atrial appendage.

Kaposi's sarcoma is the malignant proliferation of the endothelial cell vessels. Its genesis is still unclear; however, it seems to be related to the herpes virus infection (HHV-8). This neoplasia usually affects the lower limbs and the affected persons are mostly from the Mediterranean region. The exclusive penile localization of the Kaposi's sarcoma in a patient with a negative HIV serologia is exceptional. Our case is of a 73-year old patient with a negative HIV serology presenting an exclusive penile localization of the Kaposi's sarcoma treated by radiotherapy.

Papillary lesions of the breast represent a heterogeneous group with differing biological behavior. Solid papillary carcinomas are uncommon tumors composed of circumscribed large cellular nodules separated by bands of fibrosis. Correct diagnosis is crucial but may be difficult, as many other benign and malignant lesions have similar histological appearances. Immunohistochemistry plays a useful role in their differentiation. We describe one such case of a solid variant of papillary carcinoma of the left nipple in a 75-year-old woman, who had no other palpable mass in rest of the breast tissue. The case is documented for the rarity of its occurrence and significance of recognition of this lesion.

Papillary renal cell carcinoma (PRCC) is the second most common carcinoma of the kidney, which is classified into two types. Type 1 displays single layer of cells with scanty pale cytoplasm and type 2 has pseudostratified high-grade nuclei with eosinophilic cytoplasm. Recently, apart from these two types, oncocytic PRCC and clear-cell PRCC have been described. To the best of our knowledge, lipocyte-like cells have not yet been reported to accompany any subtypes of renal cell carcinoma. Herein, we report a case of PRCC with lipocyte-like cells and sarcomatoid features. Lipocyte-like cells might represent a special type of PRCC or this feature may be an indication of poor prognosis regarding its association with sarcomatoid change.

A solitary fibrous tumor of the pleura (SFTP) is an uncommon tumor, in contrast to a relatively common mesothelioma in pleura. Its average size varies from 6 to 8 cm. We report herein a case of a giant SFTP in a 53-year-old man who presented with cough since five years along with chest pain on the left side and progressive dyspnea since two months. Radiological findings revealed a large pleural mass measuring 25 cm in its largest dimension, filling the pleural cavity with effusion. Biopsy showed a spindle cell tumor with areas of dense sclerosis. Subsequent excision unraveled a large multinodular, grey-white tumor, histologically, composed of spindle cells in a 'patternless' arrangement in dense collagenous stroma with areas of hyalinization. Focal areas showed hypercellularity with atypia and mitoses, but less than 4/10 High-Power Field, unassociated with necrosis. On immunohistochemistry, tumor cells showed diffuse positivity with vimentin, CD34 and BCL2 along with cytoplasmic positivity for MIC2 (CD99), whereas cytokeratin, EMA, calretinin and HBME-1 were negative. Diagnosis of an SFTP was substantiated over a close differential of a desmoplastic mesothelioma. In view of atypical features, a close follow-up of the case was recommended.

We report the simultaneous occurrence of the tall cell variant of papillary carcinoma and squamous cell carcinoma in the thyroid gland. Histology and immunohistochemical findings are discussed and it seems that the malignant squamous component was transformed from the tall cell variant of papillary carcinoma. Metastasis from the squamous cell carcinoma is diagnosed in the regional lymph node.

Although there have been a few reports of simultaneous infections and neoplasm in patients with acquired immune deficiency syndrome, no reports of coexistent lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis occurring in the same lymph node have been described. In this article, we describe coexistent lymphoma with tuberculosis in one case and Kaposi's sarcoma with tuberculosis in another case of human immune deficiency virus-infected individuals.

Acute respiratory distress syndrome (ARDS) caused by mycoplasmas is very rare. This report describes a severe case of atypical pneumonia due to M. pneumoniae in a formerly healthy young woman who developed high grade fever and cough leading to severe disseminated lung disease and finally to fatal ARDS. This case came into picture when killer atypical pneumonia, namely, SARS (severe acute respiratory syndrome), spread very fast from South-Asian countries to the rest of the world. Moreover, the clinical presentation and radiologic features of SARS bear resemblance to the syndrome of atypical pneumonia, which lead us to investigate this case into detail. We suggest that M. pneumoniae infections should be included in the differential diagnosis of pathogens causing ARDS, establishing an early diagnosis may have important therapeutic implications.