Pathology Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Matrix Metalloproteinases 2 and 9 Immunoexpression in Prostate Carcinoma at the Positive Margin of Radical Prostatectomy Specimens Sun, 06 Jul 2014 06:59:44 +0000 The aim of this study was to evaluate the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in prostate cancer in the main tumor mass and tumor cells at the positive margin as well as the influence of these biomarkers on the biochemical recurrence of the disease in prostatectomy patients. Tissue microarrays of 120 archival prostate carcinoma samples were immunohistochemically evaluated for MMP-2 and MMP-9 expression and compared with clinicopathological parameters. Tumors with positive surgical margins showed significantly higher overall expression of MMP-9 versus tumors with negative resection margins . MMP-9 expression was significantly elevated in tumors from patients who had biochemical recurrence . In the group of patients with negative margins, MMP-9 expression above the cut-off value was significantly associated with recurrence . Multivariate analysis indicated that MMP-9 is a good predictor of biochemical recurrence (odds ratio = 10.29; ). Expression of MMP-2 in tumor cells was significantly higher at the positive margins than in the main tumor mass . The present results highlight the potential value of MMP-2 and MMP-9 expression for predicting the behavior of prostate tumors after prostatectomy with both positive and negative surgical margins. Romano Oguić, Vladimir Mozetič, Eleonora Cini Tešar, Dora Fučkar Čupić, Elvira Mustać, and Gordana Đorđević Copyright © 2014 Romano Oguić et al. All rights reserved. A Prospective Study of Soft Tissue Tumors Histocytopathology Correlation Mon, 28 Apr 2014 07:38:02 +0000 Background. Soft tissue tumors are defined as nonepithelial extraskeletal tissue of the body exclusive of the reticuloendothelial system, glia, and supporting tissue of various parenchymal organs. The absence of recognizable tissue architectural patterns in cytological preparation makes diagnosis by FNAC more difficult. Aims. To assess the utility of FNAC in diagnosing soft tissue tumors and to determine their patterns compared with with the respective histopathology results. Materials and Methods. 150 cases of soft tissue tumors were included in this study for cytologic and histologic correlation. FNAC air dried smears were stained with Giemsa stain and 95% ethanol fixed smears were stained with Papanicolaou stain. The smears were studied for cytological diagnosis and were categorized as benign, suspicious of malignancy, and malignant along with specific subtyping of the lesion. All diagnostic FNAC results were compared for diagnostic concordance using histology results as the “gold standard.” Results. The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency were 70%, 100%, 97.90%, 100%, and 98%, respectively. value was 0.0001 which shows statistically extreme significant correlation. Conclusion. FNAC is a very important preliminary diagnostic tool in palpable soft tissue lumps with high degree of correlation with the final histopathology report. Priyanka Bhatia Soni, Anand Kumar Verma, Raj Kumar Chandoke, and Jitendra Singh Nigam Copyright © 2014 Priyanka Bhatia Soni et al. All rights reserved. Calretinin as a Diagnostic Adjunct for Ameloblastoma Tue, 15 Apr 2014 11:26:55 +0000 Background. Calretinin is a 29 kDa calcium-binding protein of the EF-hand family which is expressed in a variety of normal and tumorigenic tissues. Its expression in odontogenic epithelium during odontogenesis and in neoplastic odontogenic tissues has been demonstrated. Unicystic ameloblastoma poses a diagnostic challenge, as its histologic presentation can be sometimes mistaken for keratocystic odontogenic tumor (KCOT). This study was performed to assess the usefulness of calretinin as a confirmatory marker for ameloblastic tissue. Methodology. Total of 40 cases: 16 unicystic ameloblastoma, 4 multicystic ameloblastoma, and 20 KCOT, were evaluated immunohistochemically for the presence, localization, distribution, and intensity of calretinin expression. Statistical analysis was done using Chi-square test to intercompare the expression between ameloblastoma and KCOT. Results. Sixteen cases of ameloblastoma (12 unicystic, 4 multicystic) showed positive calretinin staining of ameloblastic epithelium and only one case of KCOT was positive for calretinin, with the positivity restricted to the stellate reticulum like epithelium. Intercomparison between two groups revealed statistically significant difference . Conclusion. Calretinin appears to be a specific immunohistochemical marker for neoplastic ameloblastic epithelium and may be an important diagnostic adjunct in the differential diagnosis of ameloblastoma and KCOT. Chitra Anandani, Rashmi Metgud, and Karanprakash Singh Copyright © 2014 Chitra Anandani et al. All rights reserved. Cervical Cytology and Human Papillomavirus Testing in Adolescent Women: Implications in Management of a Positive HPV Test Mon, 24 Mar 2014 00:00:00 +0000 Objectives. Consensus guidelines establish that HPV testing should not be used to manage adolescents with atypical squamous cells of undetermined significance (ASC-US). This study aimed to estimate the impact on follow-up of HPV testing after the first-time ASC-US diagnosis. Methods. From January 2009 to December 2010, all ASC-US diagnoses in adolescents were retrieved. Results. 1950 cervical cytologies were received from this population and 335 cases (17.1%) were reported as ASC-US. A total of 287 cases were included in the study. Cases were divided into control group (no HPV test; 46 cases) and case group (HPV test performed; 241 cases). On follow-up, in the control group, 43.4% patients had cytology, and 56.6% patients had no follow-up. The case group was divided into negative HPV (60 cases) and positive HPV (181 cases). In the negative-HPV group, 41.7% had cytology and 58.3% had no follow-up. In the positive-HPV group, 41% had cytology, 22% underwent colposcopy, and 37% had no follow-up. Patients with positive-HPV results were more likely to have follow-up than patients in the control and negative-HPV groups (63% versus 43.4% versus 41.7%, resp.). Conclusions. HPV infections are common in adolescents. A positive HPV test cannot predict which women will develop carcinoma. Adherence to current guidelines is recommended in this population. Marilin Rosa and Amir Mohammadi Copyright © 2014 Marilin Rosa and Amir Mohammadi. All rights reserved. Pathology of Experimental Encephalitozoon cuniculi Infection in Immunocompetent and Immunosuppressed Mice in Iraq Thu, 20 Mar 2014 00:00:00 +0000 This study was performed to evaluate pathology of experimental Encephalitozoon cuniculi (Iraqi isolate) infection in normal and immunosuppressed mice. Pathological changes were not seen in negative control mice while secondary bacterial infections were noted in the lungs, kidneys, and heart of mice given dexamethasone. Typical E. cuniculi infection lesions were found in brain, livers, lungs, and kidneys of mice given 107  E. cuniculi spores/mouse orally. These lesions were in the form of nonsuppurative meningoencephalitis with vasculitis in brain, interstitial inflammation with infiltration of both lymphocytes and plasma cells in lung tissue, and nonsuppurative interstitial (focal and diffuse) nephritis, presence of vacuole containing mature and immature spores in enterocytes within the tips of villi, and lymphoiod hyperplasia of the white pulp and vasculitis of the intratrabecular vessels. Mice that were given 107  E. cuniculi spores/mouse orally showed lesions similar to those observed in the previous group (vasculitis and granulomas) but the lesions were more severe and widespread. In conclusion, this is the first report of experimental E. cuniculi infection induced by E. cuniculi isolated from a naturally infected rabbit in Iraq and that infection became more severe and widespread upon the administration of dexaethasone. Hafidh I. Al-Sadi and Saevan S. Al-Mahmood Copyright © 2014 Hafidh I. Al-Sadi and Saevan S. Al-Mahmood. All rights reserved. A Cytological Study of Palpable Superficial Nodules of Parasitic Origin: A Study of 41 Cases Mon, 17 Mar 2014 07:06:33 +0000 Background. Few parasitic infestations present as only superficial palpable subcutaneous or intramuscular nodule. The current study highlights the role of FNAC in the diagnosis of superficial palpable parasitic lesions. Methods. This was a retrospective study in which we reviewed the FNAC record of all patients over a period of two years from September 2011 to August 2013. During this period, FNA was performed on 5954 cases which presented as superficial palpable lump at various sites of body. There were 41 cases diagnosed as parasitic lesion or suspicious of parasitic lesion on cytology which were included in the study. Results. In the present study, most of the patients were children and young adults. The lesions were located over trunk in 18 (43.9%) cases, extremities in 12 (29.3%) cases, and head and neck region in 11 (26.8%) cases. Out of 41 cases, 27 (65.8%) cases were confirmed on cytology and/or histopathology as parasitic lesions, including 21 (51.2%) cases of cysticercosis, 5 (12.2%) cases of filariasis, and one (2.4%) case of hydatid cyst. Cytological findings of remaining cases were suggestive of parasitic lesion. Conclusion. Careful assessment of cytological material is helpful to detect parasite or inflammatory response to parasite even in asymptomatic patients. Prashant Goyal, Shelly Sehgal, Soumyesh Ghosh, Deepti Mittal, Awanindra Kumar, and Sompal Singh Copyright © 2014 Prashant Goyal et al. All rights reserved. Study Assessing the Quality of Quantification of Estrogen Receptor Protein Expression by Immunohistochemistry and Gene Expression in Breast Cancer Thu, 06 Mar 2014 14:01:04 +0000 Although immunohistochemistry (IHC) is a widely used technique to classify tumors in ER-positive versus ER-negative ones, interlab variabilities can occur. This study aims to investigate the influences of preanalytical and analytical factors on IHC results. For this purpose, the different steps of the preparation of IHC sections and scoring procedures were compared between two participating laboratories and a central lab. There was a significant positive correlation between the IHC results of the participating laboratories and those of the central lab (correlation coefficient > 0.600; ). Nevertheless, some discordant cases for immunostaining (5.3% for ER and 5.6% for PR) and for scoring (10.5% for PR) occur at site 1. Comparing IHC results with ESR1 gene expression results revealed a significant positive correlation (correlation coefficients > 0.769; ). PCR results of ER target genes showed some heterogeneity in the ER-signalling pathway. These results suggest that differences in the IHC procedure between these laboratories did not have a big influence on the end result. Nevertheless, discordant cases caused by preanalytical and analytical lab-specific procedures have been identified. Sas Leen, Van Laere Steven, Dierick Anne Marie, Duwel Valérie, De Pauw Annemie, Van Den Eynden Gert, Van Dam Peter, Dirix Luc, Vermeulen Peter, and Lardon Filip Copyright © 2014 Sas Leen et al. All rights reserved. Mycobacterium genavense Infections in a Tertiary Hospital and Reviewed Cases in Non-HIV Patients Wed, 19 Feb 2014 12:57:44 +0000 Mycobacterium genavense is a relatively new species of nontuberculous mycobacterium reported to cause disseminated infections in patients with AIDS and later on in non-HIV immunosuppressed patients. We describe clinical and laboratory features and response to therapy in 7 patients, three of them with HIV infection and four non-HIV—three organ transplant recipients and one with hyper-IgE syndrome—in Valencia, Spain, in a ten years period. We then summarize the published cases of M. avium complex infection, with invasion of peripheral blood, liver, spleen, bone marrow, lymph nodes, and lungs. In clinical samples a large number of acid-fast bacilli were observed. M. genavense grew only from liquid media and after a prolonged incubation period. Its identification was accomplished through molecular methods. Patients were treated with prolonged combinations of antimicrobial agents. There was clinical favourable outcome in 4 patients. M. Santos, A. Gil-Brusola, A. Escandell, M. Blanes, and M. Gobernado Copyright © 2014 M. Santos et al. All rights reserved. Assessment of Tissue Eosinophilia as a Prognosticator in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma—An Image Analysis Study Wed, 19 Feb 2014 12:30:59 +0000 Association of tissue eosinophilia with oral squamous cell carcinoma has shown variable results ranging from favourable to unfavourable or even having no influence on prognosis. Also, very few studies have been done to know the role of eosinophils in premalignancy. So the present study investigated role of eosinophilic infiltration in oral precancer and cancer and its possible use as a prognosticator. 60 histopathologically proven cases (20 cases each of metastatic and nonmetastatic oral squamous cell carcinoma and oral leukoplakia with dysplasia of various grades) were included. Congo red is used as a special stain for eosinophils. Each specimen slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. As a result, a significant increase in eosinophil count was found in oral carcinomas compared to dysplasia. Nonmetastatic cases showed higher counts than metastatic carcinomas. So, it is concluded that eosinophilia is a favourable histopathological prognostic factor in oral cancer. Moreover, higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion thus suggesting that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for oral precancer and OSCC. Megha Jain, Sowmya Kasetty, U. S. Sudheendra, Manisha Tijare, Samar Khan, and Ami Desai Copyright © 2014 Megha Jain et al. All rights reserved. Trophoblastic Infiltration in Tubal Pregnancy Evaluated by Immunohistochemistry and Correlation with Variation of Beta-Human Chorionic Gonadotropin Thu, 09 Jan 2014 11:38:20 +0000 Objective. To evaluate trophoblastic cell proliferation and angiogenesis in tubal pregnancy assessed by immunohistochemical study and their correlation with an average variation of β-hCG in an interval of 48 hours before surgery. Methods. A prospective study was conducted on 18 patients with a diagnosis of tubal pregnancy. The patients were divided into two groups of ectopic pregnancy of which 11 showed rise of β-hCG levels and 7 patients showed declining β-hCG levels in an interval of 48 hours prior to surgery. Trophoblastic cell proliferation and angiogenesis were assessed by Ki-67 and VEGF, respectively. Trophoblastic cell proliferation was assessed by Ki-67 and was classified into three groups (grade I: less than 1/3 of stained nuclei, grade II: 1/3 to 2/3 of the stained nuclei, and grade III: more than 2/3 of the nuclei stained). The cases analyzed for VEGF were divided into three groups (grade I: less than 1/3 of the stained cytoplasm; grade II: 1/3 to 2/3 of the stained cytoplasm; grade III: more than 2/3 of the stained cytoplasm). Statistical analysis was performed using the chi-square, ANOVA, and Kruskal-Wallis tests. Results. The mean variation in the serum β-hCG levels in 48 hours in tubal pregnancy patients correlated with trophoblastic cell proliferation assessed by Ki-67 and showed a decline of 13.46% in grade I, a rise of 45.99% in grade II, and ascension of 36.68% in grade III (). The average variation in the serum β-hCG in 48 hours, where angiogenesis was evaluated by VEGF, showed a decline of 18.35% in grade I, a rise of 32.95% in grade II, and ascension of 37.55% in grade III (). Conclusions. Our observations showed a direct correlation of increased levels of serum β-hCG in 48h period prior to surgery with higher trophoblastic cell proliferation assessed by Ki-67 and angiogenesis assessed by VEGF in tubal pregnancy. Danyelle Farias Ferreira, Julio Elito Júnior, Edward Araujo Júnior, João Norberto Stavale, Luiz Camano, and Antonio Fernandes Moron Copyright © 2014 Danyelle Farias Ferreira et al. All rights reserved. Hospital-Based Study of Epithelial Malignancies of Endometrial Cancer Frequency in Lahore, Pakistan, and Common Diagnostic Pitfalls Mon, 06 Jan 2014 17:04:52 +0000 The current study was conducted to see the frequency of epithelial malignancies of endometrium with focus on the common diagnostic pitfalls and identify morphological and immunohistochemical markers helpful in the differential diagnosis between different subtypes. It is a retrospective descriptive study carried out on 52 specimens of endometrial tumors received in Fatima Memorial Hospital, Lahore, Pakistan, during three years (2010–2012). Patients were divided into 5 age groups: <40, 41–50, 51–60, 61–70, and >70 yrs. Tissues were fixed in 10% formalin and processed and stained with haematoxylin-eosin. Stained slides were examined to determine the histological types by WHO classification, and immunohistochemistry for WT1, p53, ER/PR, and MIB1 was done in cases where morphology alone was not helpful in making a confirmed diagnosis. 80% of specimens were of endometrioid adenocarcinomas, 11% of serous tumors, 4% of clear cell carcinoma, and 4% of squamous cell carcinomas involving both cervix and endometrium. Most of the patients (28.84%) with endometrial carcinomas fall in the age range of 51–60 yrs. Endometrioid adenocarcinoma is the most common type of epithelial endometrial malignancies. Morphology is the keystone in the evaluation of these tumors, but immunohistochemistry can also be helpful in establishing the correct diagnosis. Imrana Tanvir, Sabiha Riaz, Afshan Hussain, Riffat Mehboob, M. Usman Shams, and Haseeb Ahmad Khan Copyright © 2014 Imrana Tanvir et al. All rights reserved. A Comparison of Hemoglobin Levels in Untreated and Treated Groups of HIV Patients on ART Including Zidovudine Thu, 26 Dec 2013 13:40:19 +0000 Objective. To assess the level of haemoglobin A2 in HIV patients on antiretroviral therapy (ART) including zidovudine with untreated HIV patients. Material and Methods. The study was a case control study. A total of 185 patients were included in the study; the case group included 125 HIV patients who were on antiretroviral therapy (ART) including zidovudine and 60 were in the control group who were not receiving ART. The high-performance liquid chromatography (HPLC) was done and hemoglobin A2 level was observed; value more than 3.5% was considered significant. The Hb A2 percentages of HIV patients were compared with those of control using an unpaired t-test. Results. The mean of Hb A2 in case group was 3.462% (SD 0.675) and in control group it was 2.815% (SD0.246). The higher Hb A2 value was seen in significant number of treated patients than control group (). Conclusion. The clinicians, pathologists, haematologists, and genetic counsellors should be aware of effects of nutritional anaemia and ART on Hb A2 to reduce the chances of misdiagnosis of β-thalassaemia especially in developing countries and for centres for antenatal screening. Jitendra Singh Nigam, Jyotsna Naresh Bharti, Dinker Kumar, and Ankit Sharma Copyright © 2013 Jitendra Singh Nigam et al. All rights reserved. Specimens from Biopsies of Colorectal Polyps Often Harbor Additional Diagnoses Tue, 24 Dec 2013 08:52:51 +0000 Objectives. The utility of examining specimens from colorectal biopsies of polyps for nonneoplastic diseases is currently unknown. Our objectives were to characterize such additional diagnoses that could be rendered. Methods. We retrospectively and prospectively reviewed specimens from endoscopic biopsies of colorectal polyps obtained during routine screening or surveillance. Results. 17 of 168 specimens (10.1%) contained additional diagnoses, including schistosomiasis, eosinophilic colitis, intestinal spirochetosis, melanosis coli, and other entities. These findings were easily overlooked because they often affected mucosa that was spared by the polyps or were often evident only at high magnification. Schistosomiasis, eosinophilic colitis, and intestinal spirochetosis were clinically occult. Conclusions. Specimens from biopsies of colorectal polyps often harbor other diagnoses, in addition to polyps, and can be simultaneously screened for polyps and examined for nonneoplastic diseases. Detection of other diagnoses in addition to polyps requires awareness, examination at high magnification, and examination of areas spared by the polyps. Shefali Chopra and Mark Li-cheng Wu Copyright © 2013 Shefali Chopra and Mark Li-cheng Wu. All rights reserved. Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma Thu, 19 Dec 2013 15:17:24 +0000 Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined. Kanupriya Gupta and Rashmi Metgud Copyright © 2013 Kanupriya Gupta and Rashmi Metgud. All rights reserved. Cytological and Pathological Correlation of FNAC in Assessing Breast Lumps and Axillary Lymph Node Swellings in a Public Sector Hospital in India Tue, 17 Dec 2013 10:38:50 +0000 Background. Breast lumps have varied pathology, and there are different techniques to prove the diagnosis. The aim of the present study is to analyze the role of fine needle aspiration cytology (FNAC) of the breast lesions at our center. Methods. We had retrospectively analysed 854 patients who underwent FNAC for primary breast lumps and 190 patients who underwent FNAC for an axillary lymph node in the year 2010. Results. Of 854 patients, histological correlation was available in 723 patients. The analysis was done for 812 patients as medical records were not available for 42 patients. FNAC was false negative in seven cases; 2 cases of phyllodes were reported as fibroadenoma, and 5 cases of carcinoma were diagnosed as atypical hyperplasia. The sensitivity, specificity, and false negative value of FNAC in diagnosing breast lumps were 99% (715/723), 100%, and 1%, respectively. Of 190 patients for whom FNAC was performed for axilla, 170 had proven to have axillary lymph node metastases, and the rest had reactive hyperplasia or inflammatory cells. Conclusions. FNAC is rapid, accurate, outpatient based, and less complicated procedure and helps in diagnosis of breast cancer, benign diseases, and axillary involvement in experienced hands with less chance of false results. Vasu Reddy Challa, Basavanna Goud Yale Guru, Poornima Rangappa, Vijayalakshmi Deshmane, and devi. M. Gayathri Copyright © 2013 Vasu Reddy Challa et al. All rights reserved. What We Have Learned about Autism Spectrum Disorder from Valproic Acid Sun, 08 Dec 2013 11:55:51 +0000 Two recent epidemiological investigations in children exposed to valproic acid (VPA) treatment in utero have reported a significant risk associated with neurodevelopmental disorders and autism spectrum disorder (ASD) in particular. Parallel to this work, there is a growing body of animal research literature using VPA as an animal model of ASD. In this focused review we first summarize the epidemiological evidence linking VPA to ASD and then comment on two important neurobiological findings linking VPA to ASD clinicopathology, namely, accelerated or early brain overgrowth and hyperexcitable networks. Improving our understanding of how the drug VPA can alter early development of neurological systems will ultimately improve our understanding of ASD. Taylor Chomiak, Nathanael Turner, and Bin Hu Copyright © 2013 Taylor Chomiak et al. All rights reserved. Immunoreactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Primary Lymphoid Tumors and Lymph Node Metastasis Thu, 28 Nov 2013 13:49:57 +0000 The reactivity of the 14F7 Mab, a highly specific IgG1 against N-glycolyl GM3 ganglioside (NeuGcGM3) in normal tissues, lymphomas, lymph node metastasis, and other metastatic sites was assessed by immunohistochemistry. In addition, the effect of chemical fixation on the 14F7 Mab staining using monolayers of P3X63Ag.653 cells was also evaluated. Moreover, the ability of 14F7 to bind NeuGcGM3 ganglioside inducing complement-independent cytotoxicity by a flow cytometry-based assay was measured. The 14F7 Mab was reactive in unfixed, 4% paraformaldehyde, 4% formaldehyde, and acetone fixed cells. Postfixation with acetone did not alter the localization of NeuGcGM3, while the staining with 14F7 Mab was significantly eliminated in both cells fixed and postfixed with methanol but only partially reduced with ethanol. The staining with 14F7 Mab was evidenced in the 89.2%, 89.4%, and 88.9% of lymphomas, lymph node metastasis, and other metastatic sites, respectively, but not in normal tissues. The treatment with 14F7 Mab affected both morphology and membrane integrity of P3X63Ag.653 cells. This cytotoxic activity was dose-dependent and ranged from 24.0 to 84.7% (10–1000 μg/mL) as compared to the negative control. Our data could support the possible use of NeuGcGM3 as target for both active and passive immunotherapy against malignancies expressing this molecule. Rancés Blanco, Damián Blanco, Yisel Quintana, Xiomara Escobar, Charles E. Rengifo, Marta Osorio, Zailí Gutiérrez, Janet Lamadrid, Mercedes Cedeño, Milagros Frómeta, Adriana Carr, and Enrique Rengifo Copyright © 2013 Rancés Blanco et al. All rights reserved. A Compendium of Urinary Biomarkers Indicative of Glomerular Podocytopathy Wed, 13 Nov 2013 11:50:10 +0000 It is well known that glomerular podocyte injury and loss are present in numerous nephropathies and that the pathophysiologic consecution of disease hinges upon the fate of the podocyte. While multiple factors play a hand in glomerulopathy progression, basic logic lends that if one monitors the podocyte’s status, that may reflect the status of disease. Recent investigations have focused on what one can elucidate from the noninvasive collection of urine, and have proven that certain, specific biomarkers of podocytes can be readily identified via varying techniques. This paper has brought together all described urinary biomarkers of podocyte injury and is made to provide a concise summary of their utility and testing in laboratory and clinical theatres. While promising in the potential that they hold as tools for clinicians and investigators, the described biomarkers require further comprehensive vetting in the form of larger clinical trials and studies that would give their value true weight. These urinary biomarkers are put forth as novel indicators of glomerular disease presence, disease progression, and therapeutic efficacy that in some cases may be more advantageous than the established parameters/measures currently used in practice. Miroslav Sekulic and Simona Pichler Sekulic Copyright © 2013 Miroslav Sekulic and Simona Pichler Sekulic. All rights reserved. Clinicopathological Study of 25 Cases of Diverticular Disease of the Appendix: Experience from Farwaniya Hospital Wed, 02 Oct 2013 15:39:55 +0000 Background. Diverticular disease of the appendix (DDA) is a rare disease and it has been shown to be associated with locoregional neoplasms. This study was conducted to characterize clinicopathological features and to investigate its association with appendiceal neoplasms. Methods. We searched the records of the Department of Pathology at Farwaniya Hospital for cases of diverticular disease of the appendix between 2003 and 2011. Histological slides and patient charts were reviewed for relevant information. Consecutive cases of acute appendicitis were selected as a control group. Results. We identified 25 cases of DDA, 24 of which occurred in men. Mean age of DDA patients was 35 ± 10.1 years and was significantly greater than that of appendicitis patients (). The mean temperature of cases (37.9°) was significantly higher () than that of the controls (37.3°). The cases had lower white blood cell (WBC) counts compared to controls (13.6 versus 16.7, ). Pathological diagnosis identified 4 cases of diverticulosis, 5 cases of diverticulitis, 6 cases of diverticulosis with acute appendicitis, and 10 cases of diverticulitis and appendicitis. None of the cases was associated with any type of neoplasm. Conclusions. DDA is a rare disease, and clinicians and radiologists should be aware of it. Male sex and adult age seem to be risk factors associated with DDA. The disease may not have any direct association with any neoplasm. Nabeel Al-Brahim, Ibrahim Al-Kandari, Musaad Munahai, and Prem Sharma Copyright © 2013 Nabeel Al-Brahim et al. All rights reserved. Comparative Study of Cytomorphological Robinson’s Grading for Breast Carcinoma with Modified Bloom-Richardson Histopathological Grading Wed, 25 Sep 2013 13:18:25 +0000 Objective. To study the correlation of cytomorphological Robinson’s grading for breast cancers with a modified Bloom-Richardson histopathological grading. Materials and Methods. One hundred sixteen cytologically malignant breast tumour cases were included in this study and correlated with paraffin embedded sections. Breast lumps were varied from less than 1 cm to 11 cm in greatest dimension. FNA was performed from different sites of the breast lump, and smears were stained with Giemsa and H&E stain and evaluated for cytological grading according to Robinson’s grading system. Paraffin embedded tissue sections were stained with hematoxylin and eosin stain and graded according to modified Bloom-Richardson grading system. Comparison between these two grading systems was done. Results. Cytologically grade I, grade II, and grade III cases were 13.8%, 64.65%, and 21.55%, respectively. Histologically 25%, 54.31%, and 20.69% cases were grade I, grade II, and grade III, respectively. Concordance rate between cytology and histology of grade I, grade II, and grade III tumors was 75%, 70.67%, and 60% respectively. The absolute concordance rate was 68.97%. Conclusion. In the era of multiple treatment modalities and neoadjuvant therapy, cytological grading can be used as a prognostic factor for better management of patients. Neelam Sood, Jitendra Singh Nigam, Poonam Yadav, Shivani Rewri, Ankit Sharma, Anita Omhare, and Jaya Malhotra Copyright © 2013 Neelam Sood et al. All rights reserved. Correlation of Various Techniques in Diagnosis of Tuberculous Lymphadenitis on Fine Needle Aspiration Cytology Thu, 19 Sep 2013 11:41:50 +0000 Objective. To study the correlation of cytomorphological features in fine needle aspiration smears from patients suspected of having tuberculous lymphadenitis with Ziehl-Neelsen staining (ZN), auramine-rhodamine staining (ARS), and autofluorescence (AF). Methods. A total of 145 lymph nodes were aspirated, 3 air-dried smears were stained with Giemsa, Ziehl-Neelsen, and auramine-rhodamine stains, and 1 smear was wet fixed for Papanicolaou staining. Needle washes were incubated in Lowenstein-Jensen medium for culture. Papanicolaou and auramine-rhodamine stained smears were examined under fluorescent microscope using a blue excitation filter (450–480 nm). Results. Ninety aspirates were reported on cytomorphology as suggestive of tuberculous lymphadenitis. Smear positivity for Mycobacteria by Ziehl-Neelsen method was 26.67% (24/90), while positivity increased to 34.44% (31/90) by auramine-rhodamine and 42.22% (38/90) on autofluorescence. Culture was positive in 27.78% (25/90) aspirates. Using culture as the reference method, the statistical values of ZN, ARS, and AF were as follows: sensitivity 80.0%, 88.0%, 96.0%; specificity 93.85%, 86.15%, 78.46%; positive predictive values 83.33%, 70.97%, 63.16%; and negative predictive values 92.42%, 94.92%, 98.08%, respectively. Conclusion. There is a definite advantage of autofluorescence over Ziehl-Neelsen and auramine-rhodamine which is to detect Mycobacteria, being more sensitive as well as an inexpensive technique. Autofluorescence can be a useful addition to routine cytology for early diagnosis and effective treatment. Brijesh Thakur, Ravi Mehrotra, and Jitendra Singh Nigam Copyright © 2013 Brijesh Thakur et al. All rights reserved. Diagnostic Modalities of Precancerous and Cancerous Cervical Lesions with Special Emphasis on CD31 Angiogenesis Factor as a Marker Tue, 17 Sep 2013 13:47:17 +0000 Objectives. To evaluate the role of angiogenesis tumor marker CD31 in the detection of precancerous and cancerous cervical lesions and to compare its efficacy with colposcopy and histopathology. Materials and Methods. 230 patients with a suspicious looking cervix and an abnormal Pap smear attending the Outpatient Department of Obstetrics and Gynaecology of GSVM Medical College were subjected to a colposcopic examination. 180 patients with suspected colposcopic findings were subjected to a colposcopic directed biopsy. Biopsy tissues were sent for histopathological examination out of which 50 biopsied samples were sent for immunostaining of CD-31. Statistical analysis was done. Results. Comparison of microvessel density (MVD) count by haematoxylin and eosin staining (HE) and immunostaining of CD31 in preinvasive group were and , respectively, and in invasive group were and , respectively, which showed that MVD was higher by CD31 both in preinvasive and invasive group, and it was statistically significant. Conclusion. Angiogenesis is a marker of tumor progression, and CD31 fixes up vessel better as compared to HE, so aggressiveness of the tumor can be better predicted by MVD-CD31 as compared to MVD-HE. Bandana Sharma, Neetu Singh, Neena Gupta, Pavika Lal, Shefali Pande, and Shashi Chauhan Copyright © 2013 Bandana Sharma et al. All rights reserved. Utility of Tissue Transglutaminase Immunohistochemistry in Pediatric Duodenal Biopsies: Patterns of Expression and Role in Celiac Disease—A Clinicopathologic Review Sun, 08 Sep 2013 12:00:11 +0000 Tissue transglutaminase (tTG) is a ubiquitous multifunctional protein. It has roles in various cellular processes. tTG is a major target of autoantibodies in celiac disease, and its expression by immunohistochemistry in pediatric celiac disease has not been fully examined. We studied tTG expression in 78 pediatric duodenal biopsies by utilizing an antibody to transglutaminase 2. Serum tTG was positive in all celiac cases evaluated. Serum antiserum endomysial antibody (EMA) and tTG were negative in all control subjects and in inflammatory bowel disease and eosinophilic gastroenteritis. There was a statistically significant difference between cases of celiac disease and normal controls in terms of tTG immunohistochemical staining in duodenal biopsies surface epithelium ( value = 0.0012). There was no significant statistical difference in terms of staining of the villous surface or crypt between the cases of celiac disease and cases with IBD ( value = 0.5970 and 0.5227, resp.). There was no detected correlation between serum tTG values and immunohistochemical positivity on duodenal biopsy in cases of celiac disease ( value = 1). There was no relationship between Marsh classification and positivity of villous surface for tTG ( value = 0.4955). We conclude that tTG has limited utility in diagnosis of celiac disease in pediatric duodenal biopsies. Saeeda Almarzooqi, Ronald H. Houston, and Vinay Prasad Copyright © 2013 Saeeda Almarzooqi et al. All rights reserved. Upregulation of Serum Vascular Endothelial Growth Factor in Patients with Salivary Gland Tumor Wed, 24 Jul 2013 13:51:06 +0000 Neoangiogenesis is essential for tumor development, invasion, and dissemination. The most potent of the cytokines associated with angiogenesis is vascular endothelial growth factor (VEGF). The aim of the present study was to determine VEGF serum level in patients with salivary gland tumor. Using an ELISA kit, the circulating levels of VEGF in sera from 58 patients with salivary gland tumor and 30 healthy controls were assessed. Mean VEGF levels in sera of patients with salivary gland tumors (574.9 ± 414.3) were significantly higher than those in controls (263.9 ± 310.0) (). Within the salivary gland tumor group, mean serum VEGF concentration in malignant tumors () was 727.3 ± 441.8 pg/mL, and that in benign tumors () was 442.2 ± 343.3 pg/mL. Mean serum VEGF concentration was significantly higher in malignant tumors than in benign tumors () and was higher in benign tumors than in controls (). The data in the present study clearly show that VEGF level was consistently upregulated in benign and malignant tumors in comparison to healthy controls. However, the role of VEGF as a prognostic factor in salivary gland tumor and its application in antiangiogenic therapy require further clinical research. Azadeh Andisheh Tadbir, Bijan Khademi, Mahyar Malekzadeh, Maryam Mardani, and Bahar Khademi Copyright © 2013 Azadeh Andisheh Tadbir et al. All rights reserved. A Naturally Occurring Feline Model of Head and Neck Squamous Cell Carcinoma Tue, 16 Jul 2013 11:45:48 +0000 Despite advances in understanding cancer at the molecular level, timely and effective translation to clinical application of novel therapeutics in human cancer patients is lacking. Cancer drug failure is often a result of toxicity or inefficacy not predicted by preclinical models, emphasizing the need for alternative animal tumor models with improved biologic relevancy. Companion animals (dogs and cats) provide an opportunity to capitalize on an underutilized and biologically relevant translational research model which allows spontaneous disease modeling of human cancer. Head and neck squamous cell carcinoma (HNSCC) is a common cancer with a poor prognosis and limited clinical advancements in recent years. One potential novel spontaneous animal tumor model is feline oral squamous cell carcinoma (FOSCC). FOSCC and HNSCC share similar etiopathogenesis (tobacco and papillomavirus exposure) and molecular markers (EGFR, VEGF, and p53). Both human and feline SCCs share similar tumor biology, clinical outcome, treatment, and prognosis. Future clinical trials utilizing FOSCC as a tumor model may facilitate translation of preclinical cancer research for human cancer patients. Jackie M. Wypij Copyright © 2013 Jackie M. Wypij. All rights reserved. Outcomes in Ovarian Cancer among Hispanic Women Living in the United States: A Population-Based Analysis Wed, 20 Feb 2013 08:52:02 +0000 Introduction. Ovarian cancer is the deadliest gynecologic cancer in the United States. There is limited data on presentation and outcomes among Hispanic women with ovarian cancer. Objective. To investigate how ovarian cancer presents among Hispanic women in the USA and to analyze differences in presentation, staging, and survival between Hispanic and non-Hispanic women with ovarian cancer. Methods. Data from January 1, 2000 to December 31, 2004 were extracted from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. Results. The study sample comprised 1215 Hispanics (10%), 10 652 non-Hispanic whites (83%), and 905 non-Hispanic blacks (7%). Hispanic women were diagnosed with ovarian cancer at a younger age and earlier stage when compared to non-Hispanic whites, non-Hispanic blacks; . Similar proportion of Hispanics (33%), non-Hispanic whites (32%), and non-Hispanic blacks (24%) underwent lymphadenectomy; . Hispanics with epithelial ovarian cancer histology had longer five-year survival of 30.6 months compared to non-Hispanic whites (22.8 months) and non-Hispanic blacks (23.3 months); . Conclusion. Hispanic women with ovarian cancer have a statistically significantly longer median survival compared to whites and blacks. This survival difference was most apparent in patients with epithelial cancers and patients with stage IV disease. Okechukwu A. Ibeanu and Teresa P. Díaz-Montes Copyright © 2013 Okechukwu A. Ibeanu and Teresa P. Díaz-Montes. All rights reserved. Plasmin Activation of Glial Cells through Protease-Activated Receptor 1 Mon, 28 Jan 2013 07:22:11 +0000 The objective of this study was to determine whether plasmin could induce morphological changes in human glial cells via PAR1. Human glioblastoma A172 cells were cultured in the presence of plasmin or the PAR1 specific activating hexapeptide, SFLLRN. Cells were monitored by flow cytometry to detect proteolytic activation of PAR1 receptor. Morphological changes were recorded by photomicroscopy and apoptosis was measured by annexinV staining. Plasmin cleaved the PAR1 receptor on glial cells at 5 minutes (). After 30 minutes, cellular processes had begun to retract from the basal substratum and by 4 hours glial cells had become detached. Similar results were obtained by generating plasmin de novo from plasminogen. Morphological transformation was blocked by plasmin inhibitors aprotinin or epsilon-aminocaproic acid (). Cell viability was unimpaired during early morphological changes, but by 24 hours following plasmin treatment 22% of glial cells were apoptotic. PAR1 activating peptide SFLLRN (but not inactive isomer FSLLRN) promoted analogous glial cell detachment (), proving the role for PAR1 in this process. This study has identified a plasmin/PAR1 axis of glial cell activation, linked to changes in glial cell morophology. This adds to our understanding of pathophysiological disease mechanisms of plasmin and the plasminogen system in neuroinjury. André R. Greenidge, Kiana R. Hall, Ian R. Hambleton, Richelle Thomas, Dougald M. Monroe, and R. Clive Landis Copyright © 2013 André R. Greenidge et al. All rights reserved. MET/HGF Signaling Pathway in Ovarian Carcinoma: Clinical Implications and Future Direction Tue, 25 Dec 2012 18:20:06 +0000 The HGF/MET signaling pathway is abnormal in numerous cancers including ovarian cancer. MET is expressed in 70% of human cancer and it is overexpressed in 30% of ovarian cases and cancer cell lines. The HGF/MET pathway plays a role in the initiation and progression of ovarian cancer through the most distinctive biologic program known as “invasive growth” which is accomplished through a coordinated activation of cell motility, invasiveness, degradation of extracellular matrix, survival, and proliferation. Because of its ubiquitous role in cancer, the MET axis seems to be an attractive target for cancer therapy. Numerous HGF/MET pathway inhibitor compounds are already in use in clinical trials in various solid tumors. In this paper, we will discuss the HGF/MET pathway in ovarian cancer, its clinical significance, and its potential use as a target therapy in the future. Paulette Mhawech-Fauceglia, Michelle Afkhami, and Tanja Pejovic Copyright © 2012 Paulette Mhawech-Fauceglia et al. All rights reserved. Neuroinflammation as the Proximate Cause of Signature Pathogenic Pattern Progression in Amyotrophic Lateral Sclerosis, Aids, and Multiple Sclerosis Tue, 04 Dec 2012 14:15:13 +0000 The realization of injury to large motor neurons is embedded within contextual reference to the parallel pathways of apoptosis and necrosis of system-patterned evolution. A widespread loss of cell components occurs intracellularly and involves a reactive participation to a neuroinflammation that potentially is immunologically definable. In such terms, sporadic and hereditary forms of amyotrophic sclerosis are paralleled by the components of a reactive nature that involve the aggregation of proteins and conformational misfolding on the one hand and a powerful oxidative degradation that overwhelms the proteasome clearance mechanisms. In such terms, global participation is only one aspect of a disorder realization that induces the development of the defining systems of modulation and of injury that involves the systems of consequence as demonstrated by the overwhelming immaturity of the molecular variants of mutated superoxide dismutase. It is further to such processes of neuroinflammatory consequence that the immune system is integral to the reactive involvement of neurons as patterns of disease recognition and as the system biology of prevalent voluntarily motor character. It is highly significant to recognize various inflammatory states in the nervous system as prototype variability in phenotype expression and as incremental progression in pathogenesis. In fact a determining definition of amyotrophic lateral sclerosis is an incremental phenotype modulation within the pathways of the consequential loss and depletion of motor cell components in the first instance. Neuroinflammation proves a pattern of the contextual spread of such pathogenic progression in the realization of end-stage injury states involving neurons and neuronal networks. Lawrence M. Agius Copyright © 2012 Lawrence M. Agius. All rights reserved. False-Negative Results of Endoscopic Biopsy in the Diagnosis of Gastrointestinal Kaposi’s Sarcoma in HIV-Infected Patients Mon, 26 Nov 2012 09:01:08 +0000 Kaposi’s sarcoma (KS) is a rare endothelial neoplasm mainly involving the skin, but it is often associated with AIDS. Diagnosis of gastrointestinal (GI) tract KS, a common site of visceral involvement in AIDS, is important, but endoscopic biopsy carries a risk of false-negative results (FNRs) due to its submucosal appearance. This study sought to determine the rate and causes of FNR for endoscopic biopsy of GI-KS lesions. Endoscopic biopsy samples of 116 GI-KS lesions were reviewed retrospectively. All GI-KS lesions were confirmed to be resolved following KS therapy. FNRs were yielded for 41 of the lesions (35.3%). Among upper and lower GI sites, the esophagus was the only site significantly associated with FNRs (). Small size (<10 mm) and patches found on endoscopy were significantly associated with FNRs (). Findings of submucosal tumor (SMT) with ulceration were significantly associated with true-positive results (). In conclusion, FNRs were found in 35.3% of GI-KS lesions and were especially related to the site of the esophagus and endoscopic early stage (small size or patch appearance). An SMT with ulceration may be relatively easy to diagnose on endoscopic biopsy. Caution should be exercised when performing endoscopic biopsy of these lesions in AIDS patients and evaluating the histological features. Naoyoshi Nagata, Katsunori Sekine, Toru Igari, Yohei Hamada, Hirohisa Yazaki, Norio Ohmagari, Junichi Akiyama, Takuro Shimbo, Katsuji Teruya, Shinichi Oka, and Naomi Uemura Copyright © 2012 Naoyoshi Nagata et al. All rights reserved.