There exists a wide variation in the competence of the postgraduate residents trained in pathology in different institutions across India. This results in strong disparities in the clinical diagnostic skills, teaching skills, research capabilities and the managerial skills of the graduates. The end users of this training, namely the community, clinicians and health care institutions would benefit from a more uniform and better trained pathologist. The article reviews the reasons for the variation in the quality of the training programs. The main deficiencies include, lack of well-defined criteria for recruitment of residents, training facilities, faculty resources, curriculum with well-defined learning objectives and competencies, hands-on experiences in diagnostic and research activities, diagnostic specimens and medical autopsies, exposure to molecular pathology, pathology informatics, electron microscopy, research experiences, communication skills, professional behavior and bioethics, business practices in pathology and quality assurance. There is also a lack of defined career tracks in various disciplines in laboratory medicine, standard protocols for evaluation and regional and national oversight of the programs. The steps for rectification should include defining the competencies and learning objectives, development of the curriculum including teaching methods, facilities and evaluation strategies, communication skills, professional behavior skills, teaching skills, legal aspects of practicing pathology and the various career pathways to subspecialties in pathology. The training should include defined exposure to molecular pathology, electron microscopy, quality control and assurance, laboratory accreditation, business aspects of pathology practice, review of literature, evidence-based medicine, medical autopsy and medical informatics. Efforts should be made to share human and laboratory resources between regional cooperation. The oversight and accreditation policies should be evolved and well-documented. Web-based platforms need to be developed for easy interaction among residents, faculty and administrators on a national level.

Background: Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH). Materials and Methods: The frequency of CD4 ⁺ CD25 ⁺ Treg cells was evaluated from peripheral blood (PB) of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR. Results: Frequency of CD4 ⁺ CD25 ⁺ cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005) and CH patients (2.88 ± 1.92, P < 0.005). Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05). Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05) compared to CH group. Conclusions: We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC.

Background and Aims: Hepatic steatosis (HS) is highly prevalent in chronic hepatitis C and is an important variable predicting progression of histological injury, insulin resistance, and reduced response to antiviral therapy. There are limited data on HS in patients with chronic hepatitis B (CHB). This is relevant since response to current antiviral therapies for CHB is rather limited. We investigated the spectrum and predictors of HS in CHB patients. Materials and Methods: Liver biopsies of consecutive patients of chronic Hepatitis B Virus (HBV) infection were studied and were categorized as: Group I - hepatosteatosis (>5%) and Group II - no steatosis (£5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. Results: Of the 350 patients, 118 (33.7%) liver biopsies showed steatosis (Group I); 65 (55.1%) had mild (6 to <25%) and 53 (44.9%) had moderate to severe steatosis (³25%). Patients in group I, compared with group II, were older (35.5 ± 10.5 vs 27.9 ± 14.0 years, P < 0.01), predominantly male (M: F, 10.8: 1 vs 4.8: 1, P = 0.035), obese (75.0% vs 23.4%, P < 0.01), with higher body mass index (25.2 ± 4.8 vs 20.4 ± 3.5, P < 0.01), with higher triglycerides (138.8 ± 62.1 vs 88.0 ± 27.9, P = 0.02), with higher cholesterol (171.9 ± 43.5 vs 139.3 ± 37.6, P = 0.017), and with higher serum insulin (13.1 ± 9.1 vs 9.1 ± 6.0, P < .027) levels. HBV DNA level was significantly lower in group I than group II; however, HBV genotype did not influence HS. By multivariate regression analysis, only high serum triglyceride level was independent parameter associated with HS. Conclusions: Steatosis is seen in one-third cases with HBV-related chronic liver disease and is associated with host metabolic factors, especially serum triglyceride levels, whereas HBV DNA level negatively correlated with HS.

Background: The cytological diagnoses of serous effusions are usually made by routine cytomorphology with certainty. However, overlapping cases sometimes exist between reactive mesothelial and adenocarcinoma cells. We tried to evaluate the diagnostic utility of HBME-1 in distinguishing between reactive mesothelial cells and adenocarcinoma in serous effusions. Materials and Methods: Fifty-two cytologic specimens processed by cell-block technique were retrieved from the archive and were assigned to two groups: Group I: 26 effusions containing reactive/benign mesothelial cells; Group II: 26 effusions containing carcinoma cells. Immunostaining with HBME-1 was performed using an Envision technique. The staining intensity of cells, according to proportion of immunoreactive cells, was scored as: 0 (negative), 1+ (<10%), 2+ (10-50%), and 3+ (≥50%); and the predominant staining pattern of positive cells were determined. Statistical analysis and tests of significance were performed using SPSS software. Results: The calculated mean values (in percentile) for stained cells in adenocarcinoma and reactive mesothelial cells were 25.57 and 67.88, respectively ( P = 0.001). Thin membranous, thick membranous, thick and thin membranous, cytoplasmic and combined patterns of staining in adenocarcinoma cells were respectively 4 cases (21.1%), 0 case, 0 case, 8 cases (42.1%), and 7 cases (36.8%), and in reactive mesothelial cells, these were 7 cases (26.9%), 1 case (3.8%), 18 cases (69.2%), 0 case, and 0 case, respectively. The intensity of staining in majority (88.5%) of reactive mesothelial cells was scored 3+, but the distribution varied in the other group. Conclusions: The staining pattern and intensity for HBME-1 is a useful panel for differentiation of adenocarcinoma and mesothelial cells.

Background: Intrathyroid lymphoid tissue is accrued in Hashimoto thyroiditis (HT). Histologically, this acquired lymphoid tissue bears a close resemblance to mucosa-associated lymphoid tissue (MALT) and can evolve to lymphoma. Aim: To demonstrate the morphological, and immunohistochemical profiles of Hashimoto thyroiditis and to ascertain the importance of light chain restriction in distinguishing HT with extensive lymphoplasmacytoid infiltrate from MALT lymphoma. Materials and Methods: We studied histopathologically and immunohistochemically (CD20, CD3, Igk, Igl and cytokeratin) 30 cases of HT for evaluation of the lymphoid infiltrate and the presence of lymphoepithelial lesions (LELs). Distinguishing between early thyroid lymphoma and HT was evaluated by light chain restriction. These findings were compared with two cases of primary thyroid lymphoma. Results: The histopathological findings were characteristic of HT. Immunohistochemistry confirmed inconspicuous, rare B-cell LELs as well as a prominent T-lymphocyte population. Testing for light chain restriction showed polyclonal population of plasma cells. The cases of MALT lymphoma had distinct destructive lymphoepithelial lesions, B-cell immunophenotyping and showed kappa light chain restriction in the plasmacytoid population. Conclusions: Hashimoto thyroiditis differs both histopathologically and immunohistochemically from thyroid lymphoma. In suspicious cases, immunohistochemistry could be helpful in reaching a definitive diagnosis.

Background: For management of thyroid nodules, distinction between benign and malignant tumors is essential. Present study was undertaken to differentiate between benign and malignant lesions by using Ki-67 and p53 immunostaining and radionuclide perfusion scan. Materials and Methods: Study comprised of 25 prospective and 25 retrospective cases of solitary thyroid nodules. Fine needle aspiration was done on 25 prospective cases, which was correlated with histopathological diagnosis in 24 surgically excised cases. Immunostaining for p53 and Ki-67 was put on histopathological sections of 25 retrospective and 24 prospective cases. Radionuclide perfusion scan was performed and vascularity patterns were compared with their pathological nature to differentiate between benign and malignant nodule. Results: Cytohistological correlation was present in 80% of cases. On immunostaining, significant difference in mean value of Ki67 positivity was found between benign and malignant nodules (P < 0.05). On p53 immunostaining significant difference was observed in counts of benign and malignant lesions (P = 0.037). On radionuclide perfusion scan mean of difference between maximum and minimum perfusion activity between benign and malignant nodules was found to be statistically significant (P = 0.04), however there was no correlation between perfusion patterns and antigenic characteristics. Conclusions: P53 and Ki-67 immunostaining along with radionuclide perfusion scan appears to be useful tools to differentiate between benign and malignant lesions in solitary thyroid nodule; however, more studies are needed to confirm this observation.

Background: Hepsin (HPN), a type II trans-membrane serine protease, has been reported to be one of the most up regulated genes in prostate cancer. The aim of the present study was to find out immuno-histochemistry based phenotypic expression of HPN in formalin fixed paraffin embedded sections of prostate cancer compared with that in benign prostatic hyperplasia, in a prospective clinical setting, to know the differential status of HPN expression in benign and malignant prostatic disease. Materials and Methods: Tissue biopsies of histologically proven cases of prostatic cancers (48), benign prostatic hyperplasia (42), benign prostatic hyperplasia with prostatic intraepithelial neoplasia (7) and 4 cases of benign prostatic hyperplasia with prostatitis, were subjected to immunohistochemical staining with HPN antibody by strepavidin biotin method. Results: Hepsin expression was 100% in prostate carcinoma, 11.9% (5/42) in benign prostatic hyperplasia, 57.14% (4/7) in benign prostatic hyperplasia with prostatic intraepithelial neoplasia (PIN), and none in benign prostatic hyperplasia with prostatitis. Hepsin staining showe higher expression in high grade tumor in comparison to low grade tumor. Conclusions: Positive immunohistochemical expression of hepsin in cent percent cases of prostate cancer cases is intriguing, underscoring the significance of hepsin gene expression in prostate cancer.

Background: Melanoma is quite a heterogeneous group of diseases of the skin. Prognostic markers of tumor behavior are important to precisely assign individual patients for appropriate treatment protocols. Aim: The aim of our first study was to investigate nucleophosmin expression in melanoma patients and to determine its relationship with the tumor characterictics and patient prognosis. Materials and Methods: We analyzed the immunohistochemical expression of nucleophosmin in 55 melanoma patients. The immunostaining pattern was classified into two groups: Diffuse nuclear and nucleolar relocalization. We also investigated the relationship between the expression of nucleophosmin and the clinicopathological parameters sucssh as Clark level, tumor thickness, stage, histological type, location, and survey. Results: In all cases the neoplastic cells were strongly positive for nucleophosmin (14 cases diffuse nuclear, 41 cases nucleolar relocalization). No correlation was demonstrated between the expression pattern of nucleophosmin and the clinicopathological parameters and survey. Conclusions: The implications of our results, nevertheless, are that the immunohistochemical detection of nucleophosmin is not a valuable tool for predicting the outcome of patients with melanoma or identifying subgroups of patients who may be at a higher risk.

Background: There are few studies in the literature studying the yield of the diagnostic splenectomy in a suspicious lymphoma case. Moreover, their relevance is limited owing to low number of cases, the use of selection criteria, and the lack of modern ancillary studies. We present a histopathological review of splenectomy specimens referred as a case of lymphoma to our center. Materials and Methods: The medical charts and laboratory data on all patients of all splenectomy specimens between the years 2003 and 2008 were reviewed. Morphological and immunohistochemical features were analyzed and the lymphomas were sub-typed in accordance to 2008 WHO Classification of Hematolymphoid Neoplasms. Flow cytometry immunophenotyping available in few cases was correlated. Results: A total of 46 cases studied included splenic marginal zone lymphoma (SMZL) (19 cases), splenic diffuse large B-cell lymphoma (DLBCL) (14 cases), splenic diffuse red pulp B-cell lymphoma (DRP) (five cases), follicular lymphoma (three cases), hairy cell leukemia (HCL) (two cases), HCL variant (HCLv) (1 case), 1 case of hepatosplenic gamma delta T-cell lymphoma (TCL), and 1 cases of TCL (not otherwise specified). Conclusions: Predominantly splenic lymphoma is a biologically heterogeneous entity, ranging from low-grade SMZL to high-grade DLBCLs. TCLs constituted only 4% of all our cases. DRP, HCL, and HCLv have similar diffuse red pulp patterns of splenic involvement and are differentiated based on flow cytometric immunophenotyping. We had a large number of splenic DLBCL and none of these involved bone marrow (BM), while all other lymphoma subtypes had BM involvement (stage IV disease). Morphological and immunophenotypic (immunohistochemistry and flow cytometry) features of BM and splenectomy specimen need to be correlated to differentiate these rare though similar-looking entities with overlapping features.

Background: Crescentic glomerulonephritis (CrGN), defined as crescents involving more than 50% of the glomeruli, includes pauci-immune, immune complex-mediated and anti-glomerular basement membrane disease. Objectives: The present study was aimed at evaluating the various clinical, biochemical and histological parameters in CrGN with respect to these categories and clinical outcome. Materials and Methods: Renal biopsies diagnosed as CrGN between Jan 2008 and Feb 2010 were included. Clinical and laboratory parameters were retrieved along with the therapeutic approach and clinical outcome, wherever available. Renal biopsy slides were evaluated for various glomerular, tubulo-interstitial and arteriolar features. Appropriate statistical tests were applied for significance. Results: A total of 46 cases of CrGN were included; majority (71.7%) of cases were pauci-immune (PI) while 28.3% were immune complex-mediated (IC). Among clinical features, gender ratio was significantly different between PI and IC groups (P = 0.006). The various histological parameters, including proportion of cellular crescents, tuft necrosis and Bowman's capsule rupture, were similar in both the groups. Four unusual associations, including idiopathic membranoproliferative glomerulonephritis (MPGN), multibacillary leprosy, acute lymphoblastic leukemia and C1q nephropathy were detected. Adequate follow-up information was available in 21 (46%) of the patients. Of these, 11 (52.4%) were dialysis-dependent at the last follow-up. Adult patients required renal replacement therapy more frequently than pediatric cases (P = 0.05). Presence of arteriolar fibrinoid necrosis also showed association with poor clinical outcome (P = 0.05). Conclusions: Crescentic glomerulonephritis remains one of the main causes of acute renal failure with histological diagnosis. Immunohistologic examination is essential for accurate classification into one of the three categories. This condition should be considered in rare causal associations like leprosy or MPGN with renal failure, to allow for timely performed renal biopsy and appropriate aggressive therapy.

Background: Bone marrow transplantation is already an established therapy, which is now widely used in medicine to treat leukemia, lymphoma, and several inherited blood disorders. The culture of multilineage cells from easily available adipose tissue is another source of multipotent mesenchymal stem cells, and is referred to as adipose tissue-derived stem cells (ADSCs). While ADSCs are being used to treat various conditions, some lacuna exists regarding the specific proteins in these. It was therefore decided to analyze the specific proteins of embryonic cells in ADSCs. Aims: To analyze the specific protein of embryonic stem cells (ESCs) in ADSCs. Materials and Methods: Adult human adipose tissue-derived stem cells (ADSCs) were harvested from 13 patients after obtaining patients' consent. The specific markers of ESCs included surface proteins CD10, CD13, CD44, CD59, CD105, and CD166, and further nucleostemin,(NS) NANOG, peroxisome proliferator-activated receptor-gγ, collagen type 1 (Coll1), alkaline phosphate, (ALP) osteocalcin (OC), and core binding factor 1 (Cbfa1) were analyzed using by reverse transcription-polymerase chain reaction, (RT-PCR) immunofluorescence (IF), and western blot. Results: All the proteins were expressed distinctly, except CD13 and OC. CD13 was found individually with different expressions, and OC expression was discernable. Conclusions: Although the ESC with its proven self-renewal capacity and pluripotency seems appropriate for clinical use, the recent work on ADSCs suggests that these adult stem cells would be a valuable source for future biotechnology, especially since there is a relative ease of procurement.

Background: The multifunctional hepatocyte growth factor (HGF) is the ligand of c-Met receptor; it plays important role in mammary differentiation. HGF-Met signaling is a critical downstream function of c-Src-Stat3 pathway in mammalian tumorigenesis. Aim: Evaluation of tissue c-Met receptor hepatocyte growth factor receptor (HGFR) and serum level of HGF in female breast ductal carcinoma. Materials and Methods: Sixty-eight premenopausal females were divided as 30 control females subdivided into: [Group 1] 15 healthy volunteer females and [Group 2] five with fibrocystic disease and 10 having fibroadenoma of the breast and patients group [Group 3] consisted of 38 female patients with breast ductal carcinoma. Thorough clinical examination, preoperative fine needle aspiration cytology, estimation of fasting serum glucose, urea, creatinine, and uric acid levels, alanine aminotransferase activities, C-reactive protein, HGF level, before surgery and histopathological examination of the breast masses, and immunohistochemical detection of HGFR were done. Results and Conclusions: Significant increase in serum HGF levels were found in patients with breast cancer as compared with controls. Significant increase was also seen in patients with breast cancer with and without lymph node metastasis when each subgroup was compared with controls. Serum level of HGF is an independent prognostic indicator of breast cancer. Fibrocystic disease of the breast showed weak HGFR expression, while in normal tissue, HGFR was scanty; meanwhile, breast invasive ductal carcinoma showed homogenous strong reaction to HGFR. HGF is only one of a number of key factors involved in breast cancer and preoperative high serum HGF levels and malignancy occur usually together.

Background: Pediatric solid malignant neoplasms (PSMNs) are a significant cause of death among children. Our aim was to evaluate the pattern and frequency of PSMNs at our hospital in the United States and compare the results to data from other regions of the world. Materials and Methods: This is a retrospective review of 127 PSMNs in the Pathology database at Stony Brook University Medical Center (SBUMC) from 2000 to 2008. We compared our cases to a cohort of 101 cases from an academic hospital in India (1975-1982) (Christian Medical College and Hospital) and to reports from other parts of the world. Results: We report a male to female ratio of 1.16 : 1 and a mean age of 4.8 years for cases at SBUMC. Lymphomas and central nervous system (CNS) neoplasms were more common in the 5-12-year-old group while other major diagnostic groups were more common in the 0-4-year-old group. The top five most frequent tumor categories included CNS, sympathetic nervous system (SNS), soft tissue, lymphoid and renal tumors. Lymphomas were more common than soft tissue and SNS tumors in the United States' registries but all three occurred with equal frequency in our study. Tumors of the soft tissue and SNS were more frequent at SBUMC compared to registries around the world. At the academic hospital in India, the male to female ratio was 4 : 1 and the five most frequent tumor categories included lymphoid, SNS, CNS, renal and bone tumors. Lymphoid tumors made up a greater percentage and CNS tumors made up a lesser percentage of tumors at the hospital in India compared with SBUMC. The differences between CNS tumors, lymphomas and retinoblastomas between the two hospitals were statistically significant (P value <0.05 by Fisher's Exact test). Conclusions: Geographic differences in the incidence and histologic types of PSMNs exist. Despite advancements in diagnosis and treatment, PSMNs continue to be tragically lethal.

Background : The MIB-1 labeling index (LI) has proved to be useful in assigning grading and prognosis to astrocytomas. The purpose of our study was to analyze the utility of MIB-1 LI in differentiating astrocytomas of varying grades and the possible relationships of MIB-1 LI with clinical parameters like age and sex. We also wanted to study the prognostic role of MIB-1 index in predicting behavior of astrocytomas. Materials and Methods : Our study included 145 patients with astrocytic tumors of varying grades. Immunolabeling for all patients was done using MIB-1 antibody. Survival data could be obtained for 64 patients. A Mann-Whitney U test was used to test the difference in MIB-1 LI between different histological grades. The univariate analysis was done by the Kaplan-Meier method, and the multivariate analysis for survival was performed using the Cox proportional hazard model. Results : Significant differences were noted in mean MIB-1 LI of high-grade and low-grade diffuse astrocytomas. MIB-1 LI did not vary significantly with age and sex. Univariate analysis showed favorable prognostic factors for low histopathological grade, young patient age and low MIB-1 LI; however, multivariate analysis showed that only histopathological grade had independent prognostic significance. Conclusions : Our study proves that MIB-1 LI is not dependent on factors like age and sex and is solely dependent on histological grade. Though the average level of MIB-1 LI varies considerably in the different grades of astrocytomas, considerable overlap can be observed between them. MIB-1 LI is a very useful adjunct to the histopathological diagnosis and can be of great help in situations where the clinical and radiological findings do not correlate with histological diagnosis.

Introduction: Basal cell carcinoma (BCC) is the most frequent malignant skin tumor. BCC rarely metastasizes, but it is often locally aggressive. Cyclooxygenase-2 (COX-2) is critical for tumor formation, angiogenesis and metastasis. Matrix metalloproteinases (MMPs) are the members of the family of zinc (Zn)- and calcium-dependent endopeptidases that degrade the extracellular matrix. Materials and Methods: In our study, we used immunohistochemical methods for the evaluation of COX-2, MMP-2 and MMP-9 expression in tissue samples of 30 primary and 10 recurrent skin BCC cases. Results: Immunohistochemical COX-2 expression was significantly higher in the infiltrating pattern of BCC compared with the nodular (P = 0.005) and superficial (P = 0.041) subtypes in the primary BCC group. There was not a significant difference between nodular and superficial BCCs for COX-2 expression. In addition, COX-2 expression was significantly higher in the recurrent BCC group than in the primary BCC group (P = 0.030). There was no statistically significant difference between the histological subtypes of primary BCCs and between primary and recurrent BCCs for MMP-2 and MMP-9 expressions. Conclusions: Our data confirm previous findings that COX-2 and MMP-9 expressions are increased in BCC. Our results revealed an elevated COX-2 expression in recurrent BCCs. We suggest that COX-2 inhibition might have beneficial effects in BCCs, especially for the tumors with a higher level of COX-2 expression or aggressive phenotype.

Introduction: HER-2/neu status determines the eligibility for targeted therapy with trastuzumab in breast carcinoma. Evaluation for HER-2/neu protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH) has become the gold standard. Aims: Since data on HER-2/neu assessment by IHC and FISH and studies regarding concordance between the results of the two techniques are limited, especially from India, we sought to study HER-2 gene amplification status by FISH in equivocal (2+) cases by IHC and also study aberrant signal patterns. Settings and Design: Mastectomies and breast core biopsies, equivocal for HER-2/neu protein expression, were analyzed for HER-2 amplification by FISH. Materials and Methods: IHC (DAKO) and FISH (PathVysion dual-probe system) tests were performed on 68 of 112 (after exclusion) 10% neutral buffered formalin (NBF)-fixed paraffin-embedded tissues and evaluated according to American Society of Clinical Oncology ASCO guidelines. Statistical Analysis Used: Chi-square (χ² ) test and the two-tailed P value were applied using Graphpad Quickcels software, version 2006. Results: It was found that 73.5% of the IHC 2+ patients were negative for HER-2/neu amplification, 25% were positive (ratios ranging from 2.3 to 5.6) and 1 patient was equivocal (2.2). Retesting FISH HER-2 equivocal case on another tumor block by IHC demonstrated HER-2 overexpression of protein 3+, thus resolving the equivocal status. Polysomy and HER-2 genetic heterogeneity were seen frequently. Conclusions: The findings reiterate that IHC HER-2 equivocal cases are a heterogenous group and need FISH for further categorization. Low concurrence (25%) rate between both IHC and FISH results in the equivocal scenario can be attributed to tumors with polysomy 17 and HER-2/neu genetic heterogeneity.

Context: Thymectomy is an effective therapy for patients with myasthenia gravis, and the lesions usually identified are lymphoid hyperplasia and thymomas. Nodular epithelial proliferations, termed as microscopic thymoma, are rare. Aims: Our aim was to assess the incidence and clinicopathological features of microscopic thymomas. Setting and Design: Retrospective analyses. Materials and Methods: Thymectomies performed in 105 patients with myasthenia gravis were reviewed, and patients with microscopic thymomas were studied with respect to their clinicopathological features. These were compared with those in other reports in literature. Results: Four thymuses showed features of microscopic thymomas, an incidence of 3.8%. There were 2 males and 2 females, all myasthenic; the mean age was 31 years. The resected thymic tissues were seen as soft, capsulated adipose tissue. They showed variable degrees of involution or were atrophic. All had multifocal proliferation of ovoid-to-polygonal cells with tongue-like insinuations into the fat. After thymectomy, there was improvement in the symptoms. Eight patients reported in literature had similar clinicopathological features. Conclusions: Thorough examination of the thymectomies is required to increase the detection of these lesions for assessment of their incidence, causes, pathogenesis and functional significance.

Background: Bone marrow changes are common throughout the course of HIV infection. There is scanty data addressing this issue in Indian subcontinent. The present study was aimed at characterizing the bone marrow changes in the antiretroviral naive HIV-infected Indian patients with anemia. Materials and Methods: This was a nonrandomized cross-sectional observational study undertaken over a period of 2 years. Forty-six randomly selected patients with documented anemia served as the study population. None of them was on any antiretroviral therapy or suffering from any known causes of anemia. All the patients underwent thorough evaluation, including bone marrow examination. Results: Majority of the patients had normocytic-normochromic anemia (63%), in tune with the available data. In most of the cases bone marrow was hypercellular (63.04%), although in a significant proportion it was found to be hypocellular (19.57%). Erythropoiesis was suppressed in 36.96% of patients. Dysplastic changes involving isolated cell lines ranged from 13.04% to 45.65%, dysmegakaryopoiesis being the most common, followed by dyserythropoiesis. Marrow plasmacytosis was detected in 23.91% of patients. No statistically significant correlation was detected in between immunological status (CD4 count) and marrow cellularity, myelodysplastic changes or marrow plasmacytosis. In a fair number of cases bone marrow examination aided in the diagnosis of opportunistic infections. Conclusions: Bone marrow changes are common in Indian HIV-infected anemic population, particularly in the advanced stages of the disease. HIV infection should be considered in the differential diagnosis of patients with secondary myelodysplasia or unexplained bone marrow changes.

Introduction: Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by partial ocular and cutaneous albinism, increased susceptibility to pyogenic infections, the presence of large lysosomal-like organelles in most granule-containing cells and a bleeding tendency. The abnormal granules are most readily seen in blood and marrow leukocytes, especially granulocytes; and in melanocytes. Other clinical features include silvery hair, photophobia, horizontal and rotatory nystagmus and hepatosplenomegaly. Materials and Methods: The clinico-hematological profile of a series of 5 cases of CHS encountered at JIPMER Hospital with diagnostic work-up done in the Department of Pathology over the last 6 years is presented. The diagnostic work-up included complete hemogram with peripheral smear, bone marrow examination, skin and liver biopsies. Results: The age of the patients ranged from 5 months to 3 years. All patients had silvery hair and partial albinism and presented with fever and recurrent chest infection. Two patients were stable. Three patients were in accelerated phase; of them, 1 patient with associated hemophagocytic syndrome had a rapidly fulminant course. Peripheral blood smear showed anomalously large granules in the leukocytes. Skin biopsy showed sparse, coarse melanin pigment in the epidermis, and liver biopsy done in 2 patients with accelerated phase showed portal lymphohistiocytic aggregates. Conclusions: The diagnostic hallmark of CHS is the occurrence of giant inclusion bodies (granules) in the peripheral leukocyte and their bone marrow precursors. The case series is being presented because of the rarity of CHS and varied spectrum of clinical and hematological presentation.

Objectives: Urinary tract infection (UTI) as a result of Candida spp. is becoming increasingly common in hospitalized setting. Clinicians face dilemma in differentiating colonization from true infection and whether to treat candiduria or not. The objective of the present study was to look into the significance of candiduria in catheterized patients admitted in the ICUs and perform microbiological characterization of yeasts to guide treatment protocols. Materials and Methods: One hundred consecutive isolates of Candida spp. from the urine sample of 70 catheterized patients admitted in the ICU were collected and stocked for further characterization. A proforma was maintained containing demographic and clinical details. Blood cultures were obtained from all these 70 patients and processed. Species identification of yeasts was done on VITEK. Results: Candiduria was more common at extremes of age. The mean duration of catheter days was 11.1 ± 6 days. Other associated risk factors such as diabetes mellitus and antibiotic usage were seen in 38% and 100% of our study group. Concomitant candidemia was seen in 4.3% of cases. Non-albicans Candida spp. (71.4%) emerged as the predominant pathogen causing nosocomial UTI. Conclusion: The present study reiterates the presence of candiduria in catheterized patients, especially in the presence of diabetes and antibiotic usage. Non-albicans Candida spp. are replacing Candida albicans as the predominant pathogen for nosocomial UTI. Hence, we believe that surveillance for nosocomial candiduria should be carried out in hospitalized patients.

Background: Meropenem is empirically used as a last resort for the treatment of infections by non-fermenting gram-negative bacilli (NFGNB). Minimum inhibitory concentration (MIC) determined using agar or broth dilution methods is widely used for testing meropenem resistance. However, it is not possible in resource-poor settings. Aim: A prospective study was performed to evaluate the reliability of Kirby-Bauer disk diffusion (KBDD) method for detecting meropenem resistance among NFGNB. Materials and Methods: A total of 146 NFGNB consisting of 56 Acinetobacter baumannii, 24 Acinetobacter lwoffii, 48 Pseudomonas aeruginosa and 18 Pseudomonas spp. were included in the study. All the isolates were tested simultaneously by both KBDD method and agar dilution method. Results: Very major errors were not observed with A. baumannii, A. lwoffii and P. aeruginosa, while other Pseudomonas spp. showed a very major error rate of about 5.6%. The major error rates observed with A. baumannii, A. lwoffii, P. aeruginosa and Pseudomonas spp. were 1.8%, 0%, 2.1% and 28.6%, respectively. All the isolates showed a good correlation between zone diameters (KBDD method) and MICs (agar dilution method). The sensitivity and specificity of KBDD method for detecting meropenem resistance was above 90% for all the NFGNB except Pseudomonas spp. Conclusions: The KBDD method can be reliably used for routine testing of meropenem resistance in A. baumannii, A. lwoffii and P. aeruginosa. However, further studies are needed before employing this technique for detecting meropenem resistance in Pseudomonas spp.

Background: Biofilm formation is a developmental process with intercellular signals that regulate growth. Biofilms contaminate catheters, ventilators, and medical implants; they act as a source of disease for humans, animals, and plants. Aim: In this study we have done quantitative assessment of biofilm formation in device-associated clinical bacterial isolates in response to various concentrations of glucose in tryptic soya broth and with different incubation time. Materials and Methods: The study was carried out on 100 positive bacteriological cultures of medical devices, which were inserted in hospitalized patients. The bacterial isolates were processed as per microtitre plate method with tryptic soya broth alone and with varying concentrations of glucose and were observed in response to time. Results: Majority of catheter cultures were positive. Out of the total 100 bacterial isolates tested, 88 of them were biofilm formers. Incubation period of 16-20 h was found to be optimum for biofilm development. Conclusions: Availability of nutrition in the form of glucose enhances the biofilm formation by bacteria. Biofilm formation depends on adherence of bacteria to various surfaces. Time and availability of glucose are important factors for assessment of biofilm progress.

Background: Microsporidia are intracellular parasites responsible for human infections. Recently, there has been an increase in the incidence of microsporidial keratoconjunctivitis (MKC) affecting normal individuals worldwide. Aim: To determine the characteristics of MKC in an Indian cohort. Materials and Methods: This is a retrospective, noncomparative, observational case series, involving patients with MKC between June and September 2009. Of the 24 patients identified, microbiological confirmation in direct smear was obtained in 22 cases and selected. Standard microbiological workup was performed in all the cases. We studied the demographics, predisposing conditions, antecedent treatment received before presentation, clinical characteristics, treatment offered, and resolution time with sequel. The management consisted of simple debridement and application of chloramphenicol ointment (1%) two times a day. Results: Mean age of onset was 18.7 years (95% CI, 15.7-21.7; range, 11-36s years). All patients gave history of prior outdoor activity and exposure to rain water/mud. Antecedent treatment comprised of Acyclovir eye ointment (45.4%) and antibiotic eye drop (27.3%) most commonly. Microsporidia were identified in Gram stain (81.8%), 10% potassium hydroxide mount (72.7%), modified Ziehl-Neelsen staining (36.4%), and Giemsa (18.2%). Majority presented as unilateral superficial keratoconjunctivitis with punctate epithelial keratitis. Mean resolution time was 9 days (95%CI, 7.9-10.2). Conclusions: MKC can occur in normal patients with exposure to rain and mud, related to outdoor activity often misdiagnosed as viral ocular infections. Strong clinical suspicion with proper microbiological evaluation helps to diagnose this commonly misdiagnosed condition.

Background: Microorganisms develop biofilm on various medical devices. The process is particularly relevant in public health since biofilm associated organisms are much more resistant to antibiotics and have a potential to cause infections in patients with indwelling medical devices. Materials and Methods: To determine the efficiency of an antibiotic against the biofilm it is inappropriate to use traditional technique of determining Minimum Inhibitory Concentration (MIC) on the free floating laboratory phenotype. Thus we have induced formation of biofilm in two strains (Pseudomonas aeruginosa and Staphylococcus aureus, which showed heavy growth of biofilm in screening by Tube method) in a flow cell system and determined their antibiotic susceptibility against ciprofloxacin by agar dilution method in the range (0.25 mg/ml to 8 mg/ml). The MIC value of ciprofloxacin for the biofilm produced organism was compared with its free form and a standard strain as control on the same plates. Observations: Both the biofilm produced strains showed a higher resistance (MIC > 8 mg/ml) than its free form, which were 2 μg/ml for Pseudomonas aeruginosa and 4 mg/ml for Staphylococcus aureus. Thus biofilm can pose a threat in the patient treatment.

We report a case of a 47-year-old female (posthysterectomy) with bleeding per vaginam. Imaging studies showed a large abdomino-pelvic mass diagnosed as extrauterine adenomyoma with uterus-like features. This pathological entity is extremely uncommon with only few case reports available in the reported literature. This case is being highlighted for its rarity and to discuss the possible theories for origin of this uncommon condition.

Warthin tumor is a well-recognized benign salivary gland neoplasm consisting of an epithelial as well as a lymphoid component. Malignant transformation in Warthin tumor is rare and its reported incidence is up to 1%. The more common types of carcinomas described in Warthin tumor are the squamous and mucoepidermoid types, with high-grade adenocarcinoma being extremely rare. A high-grade adenocarcinoma (ductal type) arising in the Warthin tumor in a 72-year-old man is presented for its rarity and diagnostic difficulties.

Struma ovarii are specialized form of mature ovarian teratoma comprised predominantly of thyroid tissue (>50%). Most of the struma ovarii are benign; rarely can they undergo malignant transformation. Elevated CA-125 levels with benign struma ovarii have been seen in only 5 cases in literature. The association of malignant struma ovarii and high CA-125 levels with pseudo-Meig syndrome has been reported in only 2 cases in English literature. We describe a case of a 46-year-old multigravida who presented with an abdominal mass and raised CA-125 levels. Radiological investigations revealed bilateral cystic adnexal masses with ossified elements on left side suggesting a teratoma. Intraoperative frozen section and final pathology revealed bilateral teratoma with follicular variant of papillary thyroid carcinoma arising in the left ovary. To the best of our knowledge, this is the first case of malignant struma ovarii in combination with bilateral teratoma. The dilemmas related to preoperative diagnoses with elevated CA-125 levels, mimicking an epithelial ovarian neoplasm; intraoperative frozen section consultation; management and follow-up issues in this rare malignancy are discussed.

Alveolar soft-part sarcoma is a clinically and morphologically distinct soft-tissue sarcoma of adolescent and young adult patients. Though immunohistochemical stains implicate a myogenic origin, the histogenesis of this tumor has not yet been established. Its high vascular nature leads to dissemination of the tumor cells into the bloodstream and metastasis. It comprises less than 1% of all soft-tissue sarcomas and less than 0.1% of sarcomas of the head and neck, preferably involving the orbit (48%) and tongue (25%). Lingual involvement is very rare and only about 31 cases have been reported in English literature. Their deceivingly indolent clinical courses often lead to misdiagnosis and delayed treatment. The reported case indicates its asymptomatic nature and microscopic similarity to granular cell tumor, which is the common benign tumor of the tongue.

Glomus tumor is a rare neoplasm of the distal extremities. It occurs very rarely in the deep visceral organs such as stomach, lung, pancreas, ovary, and liver. Herein, we report a very rare case of glomus tumor of the liver in a 50-year-old woman presenting with abdominal mass which was diagnosed after surgery. The tumor was large and cystic; however, the morphology was similar to the ordinary soft-tissue glomus tumor. Tumor cells were reactive with CD34 and SMA. The patient's follow up failed to show any evidence of malignant behavior or tumor recurrence. This report is the third primary glomus tumor of the liver in the English literature.

Primary lymphomas of the spermatic cord are extremely rare. To date, only 15 cases have been reported in the international literature. Herein, we report a new case of a primary lymphoma of the spermatic cord. A 73-year-old patient presented at the Urology Department, complaining of bilateral painful masses at the inguino-scrotal region. A computed tomography scan revealed spermatic cord tumor. A right inguinal orchidectomy was performed in order to establish a definitive diagnosis. Macroscopically, the tumor was restricted to the spermatic cord area, leaving unaffected the testis and the epididymis. The histopathological and immune-histological evaluation has indicated a diffuse large B-cell lymphoma. Postoperatively, the patient was investigated thoroughly but no further signs of the disease were found.

Primary cardiac lymphoma (PCL) is a rare and fatal disorder. It may often mimic other common cardiac tumors like cardiac myxoma because of similarities in the clinical presentation. We report a case of PCL of diffuse large B-cell type, in a 38-year-old, immunocompetent male who presented with superior vena cava syndrome that was excised as a myxoma. Histology revealed a large cell population diffusely and strongly expressing CD45, CD20, MUM1/IRF4 and FOXP1 hinting at an activated B-cell (ABC)-like phenotype. After four cycles of Rituximab with CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) the tumor regressed completely but the patient had a relapse and subsequently succumbed to the disease confirming the aggressive nature. The aggressive behavior of PCL may be possibly linked to its ABC-like origin.

Hemophagocytic syndrome (HPS) has been associated with infections, hematological malignancies and autoimmune conditions. Malaria is rarely reported to cause HPS. We report a case of an 11-month-old infant with fever, hepatosplenomegaly, pancytopenia, high serum ferritin, hypertriglyceridemia, and bone marrow hemophagocytosis, consistent with hemophagocytic syndrome. Gametocytes of plasmodium falciparum were identified on bone marrow aspiration. Rapid recovery was observed after treatment with antimalarials.

Sickle cell/beta ⁰ -thalassemia (S/β⁰ -thal) is a compound heterozygous state for βS and β⁰ thalassemia. There are rare reported cases of patients with sickle cell disease who developed hematological neoplasms including myeloid and lymphoid conditions; however, to the best of our knowledge, chronic myelogenous leukemia (CML) occurring in S/β⁰ -thal has been reported in one case and this is the second such report.

Anaplastic large cell lymphoma (ALCL) is a distinct type of CD30+ T/null-cell non-Hodgkin's lymphoma that frequently involves nodal and extranodal sites. The presence of leukemic phase in ALCL is extremely rare and occurs exclusively with ALK1-positive ALCL. We describe two patients with ALK1-positive ALCL who developed a leukemic phase with rapid progression of the disease. Immunophenotypic pattern assessed on peripheral blood by flow cytometry revealed CD45, CD30, and CD25 positivity in both cases but NPM-ALK1 was expressed in only one case. Both patients developed leukemic phase as a terminal event of the disease and we share the immunophenotypic features of both cases.

Manifestations of parvovirus B19 vary even in the normal host from asymptomatic or subclinical infection to a spectrum of illness with symptoms during viremic and immune complex mediated stage of disease. We report the morphological findings of parvovirus B19 infection (confirmed on serology) in a patient of T-acute lymphoblastic lymphoma (T-ALL) who underwent induction phase of chemotherapy (MCP 842 protocol). Persistent pancytopenia in the bone marrow aspirate with mild increase in blasts was thought to be due to failure to achieve marrow remission. However, giant pronormoblasts with prominent intranuclear inclusions confirmed on trephine biopsy led to the suspicion of parvovirus B19 infection which was later confirmed on serology. This case is presented to report the rarely seen classical morphological feature of parvovirus infection on bone marrow examination which was incidentally the first investigation to diagnose the viremic phase of the infection, indicating that a high index of suspicion needs to be kept in mind while examining bone marrows of susceptible patients.

Granulocytic sarcoma (GS) usually presents concomitantly with or after the onset of acute myeloid leukemia, blastic phase of chronic myeloid leukemia (CML), or myelodysplastic syndromes. Rarely, it may present even before the onset of overt leukemia and when so, it is often misdiagnosed. We are reporting a case of GS of kidney presenting as an isolated renal mass with normal laboratory investigations including a normal peripheral blood smear. It was initially misdiagnosed as lymphoma as the blasts, in addition to the morphological similarity with lymphoma cells, also showed positive immunohistochemistry for B cell markers. Based on further investigations including immunophenotyping and cytogenetic studies, a final diagnosis of CML-blast crisis (mixed phenotype) presenting initially as GS was made. To the best of our knowledge, this is the first antemortem report of nonleukemic GS presenting as kidney mass that later on progressed to CML-blast crisis with mixed phenotype blasts.

Apparent hemoglobinopathy acquired after blood transfusion is an uncommon cause of diagnostic dilemma resulting in repeated testing and delay in the diagnosis. Out of the 1530 hemoglobin (Hb)- high-performance liquid chromatography (HPLC) performed at our hospital (May 2009 to April 2010), 3 pediatric cases of thalassemia major were detected having posttransfusion hemoglobinopathy with HbS ranging from 9.9% to 18.5%. In all three cases, there was no variant hemoglobin in earlier documented Hb-HPLC. It is important to be aware of and consider apparent transfusion-induced hemoglobinopathy in patients with unusual percentage of variant hemoglobin to avoid unnecessary treatment and counseling.