ISRN Pathology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Do Foxp3+ Regulatory T Cells (Treg Cells) Play a Role in the Immunopathogenesis of Primary/Idiopathic Minimal Change Disease? Wed, 19 Feb 2014 00:00:00 +0000 Minimal change disease constitutes a major cause of nephrotic syndrome. It is regarded as a non-immune-complex mediated primary glomerulopathy and pathogenetically is characterised by podocyte injury and effacement of foot processes; therefore, it is also classified as a type of podocytopathy. T cell dysfunction with increased levels of a soluble glomerular permeability factor has been proposed to play a major role in the pathogenesis of minimal change disease. It has been therefore suggested that a dysfunction of regulatory T cells, the orchestrators of immune homeostasis, could be implicated in perpetuating T cell activation in this condition. However, the actual contribution of regulatory T cell dysfunction in the immunopathogenesis of primary minimal change disease is still largely unclear. We here propose a theoretical model based on the available evidence. Susan Swee-Shan Hue, Sufi Muhammad Suhail, Jason Chon Jun Choo, Nurhashikin Yusof, Alwin Hwai-Liang Loh, and Francisco Salcido-Ochoa Copyright © 2014 Susan Swee-Shan Hue et al. All rights reserved. A Comparative Histochemical Study of Mucous Cells in Odontogenic Cysts Tue, 29 Oct 2013 14:04:36 +0000 The diagnosis of a glandular odontogenic cyst (GOC) on an incisional biopsy continues to remain a diagnostic challenge for the histopathologist. A marker for distinguishing GOC from odontogenic cysts with mucous metaplasia is thus needed in routine pathology practice. This study aimed to determine the histochemical composition of the mucous cells in the GOC and to compare the findings with the mucous cells in odontogenic cysts that show overlapping histomorphological features with the GOC. GOCs (), dentigerous cysts (DCs) (), and radicular cysts (RCs) () with mucous metaplasia were stained using the combined alcian blue(pH 2.5)-PAS histochemical technique. The cysts were evaluated for the frequencies of acidic- (type I), neutral- (type II) and mixed- (acidic and neutral (type III)) mucin containing cells. Significant differences were found between the levels of type I, type II, and type III mucous cells within the 3 cyst types, GOC (), DC (), and RC (), which all showed a predominance of type III mucous cells. There were, however, no significant differences for each mucous cell type between the 3 cyst types. GOC thus appears to share the same histochemical mucin phenotype with the mucous cells in DC and RC. Ridwaana Carim and Farzana Mahomed Copyright © 2013 Ridwaana Carim and Farzana Mahomed. All rights reserved. Selenium Status in Patients Receiving Short-Term Parenteral Nutrition: Frequency of Deficiency and Response to a Standard Supplementation Regimen Mon, 23 Sep 2013 14:16:17 +0000 Background. This study aimed to determine the prevalence and correlates of Se deficiency in patients referred for parenteral nutrition (PN) and to assess the response to a standard supplementation regimen. Methods. Adult patients (53) were recruited prior to commencing a PN regimen delivering 32 µg (0.4 µmol) Se per 24–36 h. Serum Se concentrations were measured before and daily during PN. Results. At baseline 49 (92%) patients had serum Se concentrations below the reference range (0.9–1.65 μmol/L). Se concentrations climbed during PN from (mean ± SD) to  μmol/L (), but in 48 (91%) patients the concentrations remained low at post-PN. Taking a Se concentration below 0.6 μmol/L as indicative of depletion in the presence of an acute phase response (APR), 37 (70%) patients had Se depletion at baseline and in 27 (51%), levels remained low at post-PN. Baseline serum Se predicted the length of hospital stay (, ). Increased “malnutrition universal screening tool” score predicted low Se (, ). Conclusions. Patients referred for PN have a high prevalence of Se deficiency, even when the APR is taken into account. Se supplementation of 32 µg Se per 24–36 h is insufficient for most patients. Baseline serum Se may have prognostic value. Julia Walsh, Nariman D. Karanjia, Andrew Taylor, and Callum Livingstone Copyright © 2013 Julia Walsh et al. All rights reserved. Immunohistochemical Expression of Mast Cells Using c-Kit in Various Grades of Oral Submucous Fibrosis Thu, 29 Aug 2013 13:14:33 +0000 Oral submucous fibrosis (OSF) is a high risk precancerous condition characterized by changes in the connective tissue fibers of lamina propria and deeper parts of mucosa. Mast cells are local residents of connective tissue and have been identified to participate in fibrotic process. These cells produce pharmacologically active substances necessary for the physiological function of our body in response to various stimuli as and when required and also play a significant role in the pathogenesis of oral diseases. Ten healthy volunteers and 30 clinically diagnosed OSF cases with histopathological confirmation were included in the study. Immunohistochemical (c-kit) as well as acidified toluidine blue staining techniques were used to evaluate density and expression of mast cells. The mast cell density assessed using c-kit and toluidine blue showed significant difference in various stages of OSF. In general the mean number of mast cells obtained using c-kit was found to be more than that obtained using toluidine blue in various stages of OSF. The comparison of mast cell densities using immunohistochemistry (c-kit) and toluidine blue stain confirmed that c-kit is a more reliable technique to assess mast cell density in OSF. Musarrat J. Khatri, Rajiv S. Desai, G. S. Mamatha, Meena Kulkarni, and Jay Khatri Copyright © 2013 Musarrat J. Khatri et al. All rights reserved. Molecular Biology of Breast Cancer in the Horn of Africa: Case Series—A Pilot Study of Breast Cancer from Eritrea Mon, 03 Jun 2013 16:27:21 +0000 Background. Recently, gene expression profiling and its surrogate immunohistochemistry (IHC) markers classified breast cancer into four distinct molecular subtypes, which have different prognoses, targeted therapies, and/or clinical outcomes. Objective. To conduct a preliminary study, to correlate the clinical pathological profiles and taxonomy of molecular subtypes of breast cancer in Eritrea, in the Horn of Africa. Design. Review of pathology reports from Jan. 1 to Nov. 30, 2009, provided 22 cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Cytokeratin 5/6). Result. Twenty patients were female and most of them (68%) were under 50 years at presentation. 90% were invasive invasive carcinoma of no special type and were histological grade 3. The molecular subtypes were luminal A (55%), luminal B (5%), HER2 (5%), basal-like (10%), and unclassified (25%). Triple negative carcinoma (basal-like and unclassified combined) was 35%, mostly (71%) in women under 50 years with grade 3 tumours. Conclusion. Breast carcinoma in Eritrean women presents at a younger age and with a high histologic grade. The two predominant molecular subtypes are luminal A and triple negative. Determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Eritrean women with breast cancer. Asmerom Tesfamariam and Indrojit Roy Copyright © 2013 Asmerom Tesfamariam and Indrojit Roy. All rights reserved. Small Bowel Imaging: Clinical Applications of the Different Imaging Modalities—A Comprehensive Review Tue, 21 May 2013 11:08:28 +0000 In the last years, MR and CT techniques have been optimized for small bowel imaging and are playing an increasing role in the evaluation of small bowel disorders. In comparison to traditional barium fluoroscopic examinations, spatial and temporal resolution is now much more improved partially thanks to modern bowel distending agents. However, there is a global interest in implementing techniques that either reduce or eliminate radiation exposure. This is especially important in patients with chronic diseases such as inflammatory bowel disease who may require multiple studies over a lifetime. Owing to the excellent soft tissue contrast, direct multiplanar imaging capabilities, new ultrafast breath-holding pulse sequences, lack of ionizing radiation, and availability of a variety of oral contrast agents, MR is well suited to play a critical role in the imaging of small bowel disorders. Gabriele Masselli Copyright © 2013 Gabriele Masselli. All rights reserved. Role of HPV-16 in Pathogenesis of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma and Correlation of p16INK4A Expression in HPV-16 Positive Cases: An Immunohistochemical Study Thu, 21 Mar 2013 12:09:57 +0000 The objective of current study is to evaluate the role of HPV-16 in the pathogenesis of oral epithelial dysplasias (OED) and oral squamous cell carcinoma (OSCC) by immunohistochemistry (IHC) and to know whether HPV-16 participates in disruption of the regulation of p16 INK4A suppressor protein in OED and OSCC by IHC. Histopathologically diagnosed 20 cases of OED and 20 cases of OSCC were selected from amongst the patients attending the OPD of Vasantdada Patil Dental College and Hospital, Sangli. Biopsy tissue section were then tested for HPV-16 by IHC. HPV-16 positive tissue sections were then again tested by p16 by IHC. Overall 22.5% of cases in our study were found to be positive for HPV 16 which includes 10% of cases of OED and 35% cases of OSCC. Amongst the HPV 16 positive cases, more than 60% of cells were positive for p16INK4A IHC in OED (50%) and OSCC (85.71%). Thus, HPV 16 participates in disruption of the regulation of p16INK4A suppressor protein and can be used as surrogate biomarker for detection of HPV infection in OED and OSCC. Gaurav Pralhad Agrawal, Priya Shirish Joshi, and Anshita Agrawal Copyright © 2013 Gaurav Pralhad Agrawal et al. All rights reserved. Confocal Laser Endomicroscopy: Applications in Clinical and Translational Science—A Comprehensive Review Sat, 29 Dec 2012 14:24:45 +0000 Confocal laser endomicroscopy (CLE) is a novel tool in the endoscopist’s armamentarium. It allows on-site histological information. The ability of gastroenterologists to interpret such microscopic information has been demonstrated in multiple studies from the upper and lower gastrointestinal tract. Recently, the field of application has expanded to provide hepatobiliary and intra-abdominal CLE imaging. CLE allows “smart,” targeted biopsies and is able to guide endoscopic interventions. But CLE is also translational in its approach and permits functional imaging that significantly impacts on our understanding of gastrointestinal diseases. Molecular imaging with CLE allows detection and characterization of lesions and may even be used for prediction of response to targeted therapy. This paper provides a comprehensive review over current applications of CLE in clinical applications and translational science. Martin Goetz Copyright © 2012 Martin Goetz. All rights reserved. Investigation of Tenascin Expression in Endometriosis Sun, 16 Dec 2012 14:59:47 +0000 Objective. To evaluate the serum and tissue levels and local expression pattern of tenascin, a high molecular weight extracellular matrix protein, in eutopic and ectopic endometrium from patients with and without endometriosis and to compare the proliferative and secretory phase differences. Materials and Methods. Thirty women with endometriosis and fifteen women without endometriosis undergoing surgery for benign indications were included in the study. Serum and tissue levels and proliferative and secretory phase expression patterns of tenascin in the ectopic and eutopic endometrium were analyzed with immunohistochemistry and immunoassays. The results were compared with Mann-Whitney U test. values <0.05 were considered as statistically significant. Results. Tenascin expression was detected in both of eutopic and ectopic endometrium of women with and without endometriosis. In immunohistochemical staining, intense staining of tenascin was observed in glandular cells of eutopic and ectopic endometrial tissue samples of both groups during secretory phase (). Eutopic and ectopic tissue levels of tenascin were higher than serum tenascin levels only secretory phase (). There was no significant difference between groups for tissue and serum levels of tenascin during cycle phases. Conclusion. Tenascin expression showed cyclic change on eutopic and ectopic endometrium. Zehra Sema Ozkan, Hasan Cilgin, Remzi Atilgan, Mehmet Simsek, Bengu Cobanoglu, Necip Ilhan, and Ekrem Sapmaz Copyright © 2012 Zehra Sema Ozkan et al. All rights reserved. Ki-67 Labeling Index in Primary Invasive Breast Cancer from Sudanese Patients: A Pilot Study Thu, 13 Dec 2012 15:11:22 +0000 Ki-67 labeling index has been linked to patient outcome in breast cancer patients. However, very few published reports have examined Ki-67 labeling index in African breast cancer patients. Sixty-two Sudanese breast cancer patients with primary invasive tumors were immunostained for Ki-67, ER, PR, Her-2/neu, CK5/6, and CK17. Ki-67 labeling index ranged from 0% to 50%, with a median of 5% (interquartile range 0–10). Low Ki-67 labeling index (immunostaining < 10%) was detected in 43/62 (69.4%) with a median of 0 (interquartile range 0–5), whereas high Ki-67 labeling index (immunostaining ≥ 10%) was revealed in 19/62 (30.6%) with a median of 20 (interquartile range 12–26). Ki-67 labeling index was significantly associated with tumor grade (, Mann-Whitney Test). There were no significant group differences between Ki-67 labeling index and ER (), PR (), Her-2/neu (), CK5/6 (), CK17 (), pathologic stage (), tumor histology (), breast cancer subtypes (), tumor size (), and age at diagnosis (). These results suggested that Ki-67 labeling index correlates with tumor differentiation and not with the tumor size or any other tested marker in Sudanese breast cancers. Thus, Ki-67 labeling index could be considered as a reliable measure of tumor proliferative fraction in Sudan. Khalid Dafaallah Awadelkarim, Renato Mariani-Costantini, Ihsan Osman, and Massimo Costanzo Barberis Copyright © 2012 Khalid Dafaallah Awadelkarim et al. All rights reserved. Mitochondrial Markers for Cancer: Relevance to Diagnosis, Therapy, and Prognosis and General Understanding of Malignant Disease Mechanisms Sun, 18 Nov 2012 16:52:03 +0000 Cancer cells display changes that aid them to escape from cell death, sustain their proliferative powers, and shift their metabolism toward glycolytic energy production. Mitochondria are key organelles in many metabolic and biosynthetic pathways, and the adaptation of mitochondrial function has been recognized as crucial to the changes that occur in cancer cells. This paper zooms in on the pathologic evaluation of mitochondrial markers for diagnosing and staging of human cancer and determining the patients’ prognoses. Boel De Paepe Copyright © 2012 Boel De Paepe. All rights reserved. Fine-Needle Aspiration in the Diagnosis of Thyroid Diseases: An Appraisal in Our Institution Mon, 03 Sep 2012 10:59:28 +0000 Objective and Aims. In the last two decades, fine-needle aspiration cytology (FNAC) of thyroid has been introduced as the most reliable and cost-effective method for diagnosing of clinically important thyroid disorders. The aim of our study was to determine the accuracy and reliability of FNAC in our center. Materials and Methods. Thyroid fine-needle aspiration cytology (FNAC) of 1639 patients from October 2007 to September 2011 was evaluated in our center. Only patients which had a solitary or multiple thyroid nodules were selected for FNA. The FNAC results are classified as benign, malignant, suspicious, and unsatisfactory. From above patients, 192 (11.7%) cases underwent surgery, and histopathologic examination was performed. By comparing the FNAC reports with the corresponding histopathologic results, the accuracy of thyroid FNAC was determined. Results. According to FNAC diagnostic criteria, there were 1054 (64.3%) benign cases, 128 (7.8%) malignant, 306 (18.66%) suspicious and 151 (9.2%) inadequate for diagnosis. In 192 cases, which underwent surgery, FNAC reports were compared with histopathologic results and statistical indices were calculated. The sensitivity, specificity, and accuracy were 91.6%, 100%, and 97%, respectively. These findings strongly support that FNAC as a useful technic for preoperative diagnosis of thyroid lesions. Conclusion. This technique is easy to perform, cost effective, minimally invasive with few complications. FNAC has high sensitivity in diagnosis of thyroid malignancy and also has high diagnostic accuracy in the evaluation of thyroid disorders. Heydar Ali Esmaili and Hassan Taghipour Copyright © 2012 Heydar Ali Esmaili and Hassan Taghipour. All rights reserved. Assessment of Histopathological Response in Gastric and Gastro-Oesophageal Junction Adenocarcinoma following Neoadjuvant Chemotherapy: Which Scoring System to Use? Mon, 03 Sep 2012 08:22:27 +0000 Background. The standard of care for patients with operable gastric and gastro-oesophageal junction (GOJ) tumours involves neoadjuvant chemotherapy. This improves survival and reduces risk of tumour recurrence following surgery. The various grading criteria published to assess histological response to neoadjuvant treatments have never been compared in terms of their reproducibility and ability to predict survival. Methods. A study was carried out of 66 patients with gastric and GOJ (types II and III) adenocarcinoma treated with neoadjuvant chemotherapy according to the MAGIC protocol. Histology slides were reviewed independently by two histopathologists using three published grading systems (Mandard, Japanese, and Becker). Histological, demographic, and survival data were collected. The kappa statistic was used to assess interobserver reproducibility. Results. Three (5%) patients had a complete pathological response. There was reasonable interobserver agreement for the grading systems: κ-scores = 0.44 (Mandard), 0.28 (Japanese), and 0.51 (Becker). Only Mandard and Becker scores provided prognostic information: 5-year overall survival rates of 100% for complete or near complete responders versus 35% for nonresponders (𝑃<0.05) for both. Positive lymph nodes (𝑃=0.004) and resection margins (𝑃=0.004) were associated with poor survival. Conclusion. Becker’s score is most reproducible for the evaluation of histological response. Furthermore, lymph node and resection margins status provides prognostic information. A. Mirza, A. Naveed, S. Hayes, L. Formela, I. Welch, C. M. West, and S. Pritchard Copyright © 2012 A. Mirza et al. All rights reserved. Assessment of Lung Cytological Atypia among Shisha Smokers Sun, 02 Sep 2012 18:13:01 +0000 Objectives. The aim of this study was to assess frequency of lung epithelial atypia among Shisha users. Methods. Sputum samples were collected from 200 subjects (100 Shisha users (cases) and 100 nontobacco users (controls)). Cytological smears were prepared and demonstrated using Papanicolaou and silver nucleolar organizer region (AgNORs) methods. Results. Cytological atypia was identified among 2/100 (2%) of the cases, and no cytological atypia was found among controls. Respiratory squamous metaplasia was significantly higher among cases 42/100 (42%), compared to controls 7/100 (7%) (𝑃<0.001). Shisha users were found more susceptible for bacterial infections 34 (34%) compared to controls 3/100 (3%), (𝑃<0.0001). The mean AgNOR dots count was higher among cases (2.3Β±.23) than among controls (1Β±.2), 𝑃<0.001. Conclusion. In view of these findings, the consumption of Shisha is a risk factor for cellular proliferation activity in respiratory epithelium. The mean AgNORs count is a useful indicator for prediction of the risk of exposure to certain carcinogenic elements that may induce lung cancer. Ali Yousif Yahia Babiker, Isra Mohammed Khair Abas, Mohammad A. Alzohairy, and Hussain Ahmed Copyright © 2012 Ali Yousif Yahia Babiker et al. All rights reserved. Light Chain Proximal Tubulopathy: Expanding the Pathologic Spectrum with and without Deposition of Crystalline Inclusions Thu, 30 Aug 2012 15:56:38 +0000 Light chain proximal tubulopathy (LCPT) is an uncommon form of renal disease associated with dysproteinemias. It is characterized by intracytoplasmic deposition of crystallized mostly kappa monoclonal light chains in proximal tubules (PTs). Crystals are located within lysosomes by electron microscopy (EM). Rare lambda LCPT cases without crystals by EM were described. Retrospectively, we reviewed clinical, light microscopic (LM), immunofluorescence (IF), and EM findings in 9 cases) (8 males, 1 female; mean age 57 years (38–81)) with multiple myeloma. LM showed abundant cytoplasmic droplets in PT cells in all cases. Droplets were also present in the podocytes, endothelial and parietal cells in one case. IF revealed staining of crystals with kappa in 3 and lambda in 6. EM showed electron dense rectangular, rhomboid, or needle shaped crystals in PT cells in 3 cases (33%), one of which had crystals in podocytes and interstitial cells. Six lambda LCPT cases showed no crystals by EM (67%). This may reflect differences in the physicochemical properties of light chains. The mechanisms of crystal accumulation in these cells and the significance of this finding are unknown. Shree G. Sharma, Steven M. Bonsib, Didier Portilla, Ashutosh Shukla, Adam B. Woodruff, and Neriman Gokden Copyright © 2012 Shree G. Sharma et al. All rights reserved. Progressive Extracellular Matrix Disorganization in Chemically Induced Murine Oral Squamous Cell Carcinoma Wed, 29 Aug 2012 09:13:24 +0000 Introduction. Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting the human population. Tumor pathogenesis implies a multistep process in which cells acquire features that enable them to become tumorigenic and ultimately malignant. The process of OSCC carcinogenesis can be reproduced in animal models, the OSCC induction with 4-nitroquinoline-1-oxide (4NQO) in mice is a widely used tool for studying tumor pathogenesis. Objective. The aim of the present study was to determine the progressive changes in basal lamina and connective tissue remodeling during 4NQO-induced OSCC carcinogenesis. Material and Methods. Samples were classified according to “International Histological Classification of tumors” in mild, moderate, and severe dysplasia and invasive carcinoma. Five samples of each pathologic entity and control healthy tongues were used. Immunohistochemical analysis of collagen IV as well as histochemical analysis of glycosylated molecules (PAS) and collagen I (Picro Sirius red) were performed. Results. During experimental-induced carcinogenesis by 4NQO a progressive basal lamina destruction and collagen I disorganization in adjacent connective tissue can be observed. Conclusion. Our results confirm previous studies that show alterations in extracellular matrix (ECM) in malignant lesions, validating the experimental carcinogenesis induced by 4NQO. B. Fuentes, J. Duaso, D. Droguett, C. Castillo, W. Donoso, C. Rivera, B. Venegas, and U. Kemmerling Copyright © 2012 B. Fuentes et al. All rights reserved. Cyclin A2 Protein Overexpression Is Not Caused by Gene Amplification in Colon Cancer Wed, 29 Aug 2012 08:25:54 +0000 Increased expression of cyclin A2 protein has been detected in different types of cancers. However, its prognostic importance appears to differ between tumours. The significance and precise mechanisms behind cyclin A2 overexpression remain to be elucidated. We used real-time PCR to examine CCNA2 amplification in tumour cells isolated by laser microdissection and in total tumour tissue in colon cancer patients in which overexpression of cyclin A2 protein had been revealed by immunohistochemistry (𝑛=22 patients). The results were verified by FISH. CCNA2 amplification was not detected in either the isolated tumour cells or the total tumour tissue. We verified our methods by demonstrating amplification of CCNA2 by real-time PCR in three out of eight breast tumours that overexpressed cyclin A2 protein (this frequency is consistent with the findings of others). However, FISH did not reveal any CCNA2 amplification in the breast tumours, but it did reveal polysomy of chromosome 4 or segments of chromosome 4 in three tumour tissue samples, indicating the importance of verifying the real-time PCR results with another method. To conclude, the increased cyclin A2 protein expression in these patients could not be explained by CCNA2 amplification in isolated colonic tumour cells. Lise Aagaard Sørby, Kristin Jonsdottir, Klaus Beiske, Peter Blom, Ida Rashida Khan Bukholm, and Morten Bj. Jacobsen Copyright © 2012 Lise Aagaard Sørby et al. All rights reserved. Snail Protein Expression as a Hallmark of Gastric Carcinoma in Biopsy Samples Wed, 18 Jul 2012 16:08:37 +0000 Overexpression of the Snail gene transcriptional repressor promotes an epithelial-to-mesenchymal transition (EMT) in epithelial tumor cell lines. In this study, we aimed to determine the correlation between Snail protein expression and clinicopathological features and to test whether Snail can be used as a marker to distinguish gastric carcinomas from benign tissues in biopsy samples. The results of immunohistochemistry with an antibody against Snail showed that most adenocarcinomas had positive Snail expression, whereas weak Snail expression was detected in a small number of gastritis and gastric adenomas. Snail-positive cells were detected in the stroma as well as in the glandular epithelium in some adenocarcinomas. In addition to Snail immunostaining, immunostaining of the EMT-related molecules, E-cadherin and vimentin, was performed. E-cadherin was not detected in adenocarcinomas that expressed Snail, whereas gastritis and adenomas stained positively for E-cadherin. Vimentin expression was seen in adenocarcinomas with positive Snail expression, whereas gastritis and adenomas did not express vimentin. In conclusion, we propose that Snail is a useful biomarker to distinguish gastric adenocarcinomas from benign lesions in biopsy samples. Hiroyuki Tanishima, Ting Gui, Yujing Sun, Aiko Shimokado, Takashi Ozaki, and Yasuteru Muragaki Copyright © 2012 Hiroyuki Tanishima et al. All rights reserved. Analysis of the Distribution and Temporal Trends of Grade and Stage in Urothelial Bladder Cancer in Northern New England from 1994 to 2004 Thu, 12 Apr 2012 09:16:37 +0000 We investigate the distribution of bladder tumor category and stage in Northern New England by geographic region, smoking status, and over time. 1091 incident bladder cancer cases from the New England Bladder Cancer Study (NEBCS), a large population-based case-control study carried out in Maine, New Hampshire, and Vermont (2001–2004) and 680 bladder cancer cases from previous case-control studies in New Hampshire (1994–2000) were used in the analysis. Of 1091 incident bladder cancer cases from the NEBCS, 26.7% of tumors were papillary urothelial neoplasms of low malignant potential (PUNLMP), 26.8% low-grade papillary urothelial carcinomas (PUC-LG), 31.3% high-grade papillary urothelial carcinomas (PUC-HG), 9.1% nonpapillary urothelial carcinomas (non-PUC), and 4.3% carcinoma in situ (CIS). Approximately 70% of cases were noninvasive (Tis/Ta), and all PUNLMP cases were of the Ta category. By contrast, half of all PUC-HG carcinomas were invasive. Short-term time trend analysis within the NEBCS (2001–2004) indicated an increase in the percentage of PUNLMP (𝑃-trend <0.0001) paralleled by a decrease in PUC-LG (𝑃-trend = 0.02) and for PUC-LG an increase in the percentage of non-invasive tumors (𝑃-trend 0.04). Our findings suggest possible short-term trends with an increase in the percentage of PUNLMP and a change in the percentage of PUC-LG towards non-invasive disease. Alan R. Schned, Petra Lenz, Lee E. Moore, Alison Johnson, Michael Jones, Masatoshi Kida, Debra T. Silverman, Molly Schwenn, Karl T. Kelsey, Angeline S. Andrew, Dalsu Baris, and Margaret R. Karagas Copyright Β© 2012 Alan R. Schned et al. All rights reserved. Clinical Usefulness of Cancer Markers in Primary Breast Cancer Thu, 29 Dec 2011 15:59:27 +0000 The aim of this study was to investigate the diagnostic power of CA 549, MSA and CA 15-3 in identifying breast cancer. The study included 232 patients of which 56 were healthy, 43 had benign breast cancer and 191 with other growths. The results were obtained using a specific immunoassay and using producers' cut offs. The following sensitivity and specificity of markers were found: CA 549 (sen.: 40%/spec.: 90%), MSA (sen.: 22%/spec.: 96%), and CA 15-3 (sen.: 33%/spec.: 86%). Ideal cut offs were defined with ROC curves. A significant correlation was found between CA 549, MSA, and CA 15-3. The combination of markers does not improve the clinical usefulness to identify only breast cancer. Serum tumor markers are abnormally elevated in patients with breast cancer. CA 549, MSA, CA 15-3 are useful clinical markers, good indicators of disease extent, and may have important prognostic value. This study demonstrates the role of the tumor markers in breast cancer. A. Verring, A. Clouth, P. Ziolkowski, and G. M. Oremek Copyright © 2011 A. Verring et al. All rights reserved. Investigation of Archived Formalin-Fixed Paraffin-Embedded Pancreatic Tissue with Whole-Genome Gene Expression Microarray Mon, 26 Dec 2011 08:20:08 +0000 The use of formalin-fixed, paraffin-embedded (FFPE) tissue overcomes the most prominent issues related to research on relatively rare diseases: limited sample size, availability of control tissue, and time frame. The use of FFPE pancreatic tissue in GEM may be especially challenging due to its very high amounts of ribonucleases compared to other tissues/organs. In choosing pancreatic tissue, we therefore indirectly address the applicability of other FFPE tissues to gene expression microarray (GEM). GEM was performed on archived, routinely fixed, FFPE pancreatic tissue from patients with congenital hyperinsulinism (CHI), insulinoma, and deceased age-appropriate neonates, using whole-genome arrays. Although ribonuclease-rich, we obtained biologically relevant and disease-specific, significant genes; cancer-related genes; genes involved in (a) the regulation of insulin secretion and synthesis, (b) amino acid metabolism, and (c) calcium ion homeostasis. These results should encourage future research and GEM studies on FFPE tissue from the invaluable biobanks available at the departments of pathology worldwide. Nete V. Michelsen, Klaus Brusgaard, Qihua Tan, Mads Thomassen, Khalid Hussain, and Henrik T. Christesen Copyright © 2011 Nete V. Michelsen et al. All rights reserved. Enzyme Histochemical Assessment of Mitochondrial Functions in Patients with Myopathic form of Limb-Girdle Syndrome Thu, 24 Nov 2011 12:57:01 +0000 Isolated mitochondrial myopathy is characterized by slowly progressive limb-girdle muscle weakness and resembles other muscle disorders like muscular dystrophy or inflammatory myopathy on clinical grounds. Identification of abnormal mitochondria in the muscle tissue is required for the diagnosis of isolated mitochondrial myopathy. Therefore, this study was done with aim to identify patients with isolated mitochondrial myopathy among those with limb-girdle muscle syndromes of undefined cause. Forty-eight consecutive patients with limb-girdle muscle disease from 2008 to 2010 were screened for Duchenne/Becker muscular dystrophy gene deletion, metabolic myopathy, and drug-induced and endocrine causes. Twenty patients without an identifiable cause were subjected to muscle biopsy for hematoxylin and eosin staining and enzyme histochemistry. Clinical, biochemical, and electrophysiological features in all these patients with limb-girdle muscle disease were nonspecific, and no conclusion regarding the underlying cause could be drawn from these investigations. On hematoxylin and eosin staining, 12 patients were diagnosed as muscular dystrophy, inflammatory myopathy with characteristic appearance of polymyositis was diagnosed in 4 patients, and 3 patients had normal muscle histology. After enzyme histochemistry, one patient was identified having mitochondrial myopathy. A brief case summary of the only patient diagnosed as isolated mitochondrial myopathy in our study is presented. Ritu Verma, Lily Pal, Rakesh Pandey, and Vimal Kumar Paliwal Copyright © 2011 Ritu Verma et al. All rights reserved. Immunorecognition of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Some Normal and Malignant Tissues from Genitourinary System Wed, 05 Oct 2011 16:23:52 +0000 N-glycolyl neuraminic acid has been considered as a tumour-associated antigen forming both glycolipid and glycoprotein, expressed in some human malignant cells. In this work, we evaluate the 14F7 Mab (an IgG1 murine highly specific to N-glycolyl GM3 ganglioside) reactivity in a variety of genitourinary-system-derived tumors as well as in their normal counterparts. Immunohistochemical assays with 14F7 followed by anti-mouse biotinylated antibody and ABC/HRP system using formalin-fixed and paraffin-embedded tissues were carried out. In normal tissues, 14F7 was reactive only in renal tubules of kidney (2/6) and in the stromal component and blood vessels of ovary (3/5). Tumors of kidney (12/38), urinary bladder (8/9), breast (41/42), ovary (21/34), testis (4/5), prostate (17/20), and uterus (5/14) as well as prostatic nodular hyperplasia (5/8) were stained with 14F7. N-glycolyl GM3 recognized by 14F7 could be considered as one attractive target for both active and passive immunotherapy of genitourinary malignancies expressing this molecule. Rancés Blanco, Mercedes Cedeño, Xiomara Escobar, Damián Blanco, Charles E. Rengifo, Milagros Frómeta, Rosa Irene Alvarez, Enrique Rengifo, and Adriana Carr Copyright © 2011 Rancés Blanco et al. All rights reserved. Methodologic Approaches to Histologically Distinguishing Vaccine versus Nonvaccine-Associated Sarcomas Using Validated Time and Location Vaccination Histories in Cats Wed, 14 Sep 2011 13:45:05 +0000 Epidemiologic studies of feline vaccine-associated sarcoma (FVAS) require accurate sarcoma case definitions free from unverified assumptions for valid causal inference. This study developed methodologic approaches to improve reliable differentiation of vaccine versus nonvaccine-associated sarcomas on histologic characteristics using time windows of vaccine histories and body geographic information. Four case and five control definitions were used to classify 124 sarcomas. Results showed presence in the subcutis versus dermis, increased nuclear pleomorphism, more granulation tissue, and higher presence of inflammation in FVAS than presumptive non-FVAS. Correctly classifying sarcomas using stringent classification criteria as employed in this study will help reduce misclassification of FVAS in future epidemiologic studies of comparative risk. Anup Srivastav, Philip H. Kass, Lawrence D. McGill, Michael S. Kent, and Thomas B. Farver Copyright © 2011 Anup Srivastav et al. All rights reserved. Granules in Granular Cell Lesions of the Head and Neck: A Review Mon, 12 Sep 2011 08:06:53 +0000 Granular cell lesions of the oral mucosa, jaws, and salivary glands constitute a heterogeneous group of lesions which may be either odontogenic, salivary gland, or metastatic in origin. Granular cells in these proliferations most commonly are the result of lysosomal accumulation, aging, degenerative, metabolic alteration, increased apoptosis, cytoplasmic autophagocytosis, and many more. Many benign and malignant tumors that occur in the oral cavity contain granular cells as a characteristic component of their pathology. Sometimes dilemma exists in the proper diagnosis of these granular cell lesions and the cell of origin because they share similar light and electron microscopic features. Therefore, immunohistochemistry helps to confirm histologic impressions and differentiate other neoplastic entities with granular cytoplasmic features. Granularity in a normal histopathology is a rare but innocuous change and does not influence the biologic behaviour of smooth muscle tumors except few lesions such as cutaneous granular cell angiosarcoma and granular cell ameloblastoma which have shown poor prognosis. This paper aims to review the clinical and pathologic features, different immunohistochemical profiles of granules in granular cell lesions of head and neck with an attempted working classification. T. Lakkashetty Yogesh and S. V. Sowmya Copyright © 2011 T. Lakkashetty Yogesh and S. V. Sowmya. All rights reserved. Glycogen as a Putative Target for Diagnosis and Therapy in Brain Pathologies Sun, 04 Sep 2011 09:14:08 +0000 Brain glycogen, a glucose polymer, is now considered as a functional energy store to the brain. Indeed, when neurons outpace their own possibilities to provide themselves with energy, astrocytic metabolism is in charge of feeding neurons, since brain glycogen synthesis is mainly due to astrocyte. Therefore, malfunctions or perturbations of astrocytic glycogen content, synthesis, or mobilization may be involved in processes of brain pathologies. This is the case, for example, in epilepsies and gliomas, two different situations in which, brain needs high level of energy during acute or chronic conditions. The purpose of the present paper is to demonstrate how brain glycogen might be relevant in these two pathologies and to pinpoint the possibilities of considering glycogen as a tool for diagnostic and therapeutic approaches in brain pathologies. Jean-François Cloix and Tobias Hévor Copyright © 2011 Jean-François Cloix and Tobias Hévor. All rights reserved. Evaluation of the In Situ Hybridization Signal Patterns of Liquid-Based Cytological Human Papillomavirus Specimens for Diagnosing Squamous Intraepithelial Lesion Wed, 10 Aug 2011 08:55:38 +0000 To examine the diagnostic utility for squamous intraepithelial lesion (SIL) by cytological in situ hybridization (c-ISH) for the human papillomavirus using liquid-based cytology specimens, we investigated c-ISH signal patterns in the cases of low-grade SIL (LSIL), atypical squamous cells of undetermined significance (ASC-US), and high-grade SIL (HSIL). Episomal (E) and/or integrated (I) signals were observed. Two signal patterns (𝐸≧𝐼 or 𝐼>𝐸) were obtained by counting the number of 𝐸+ or 𝐼+ cells. 𝐸≧𝐼 was specific to LSIL and ASC-US (10/12); 𝐼>𝐸, to HSIL (9/11) (𝑃<0.01, χ2 test), suggesting significant utility of c-ISH in diagnosing SIL. In the cell fraction, 𝐸≧𝐼 in large cells was dominant in LSIL. Two cases of 𝐼>𝐸 in large cells of LSIL showed HPV persistence and/or progression during follow-up. Thus, c-ISH is useful in routine testing for diagnosing cervical dysplastic lesions, especially for detecting LSIL suspected for progression. Katsunari Ishida, Makoto Nagasaki, Masayuki Kobayashi, Tatsushi Nakagawa, Toru Nabika, and Kiyomi Taniyama Copyright © 2011 Katsunari Ishida et al. All rights reserved. Triple Negative Breast Carcinoma: A Comparative Study between Breast Lesion and Lymph Node Metastases: A Preliminary Study Thu, 28 Jul 2011 17:33:07 +0000 Aims and Background. Triple negative breast carcinoma is a genetic and molecular subtype of breast carcinoma with poor prognosis. Some immunohistochemistry studies have been proposed to identify BLBC. Most studies consider primary breast carcinoma but not metastases. Methods. Immunohistochemical characteristics in 11 triple negative breast carcinomas were studied in both primary lesions and lymph node metastases. All cases were reevaluated to estrogen and progesterone receptors and HER2-Neu. An FISH probe for HER2/neu was also performed. Immunohistochemical studies were performed with cytokeratin 5/6, 17, Cam 5.2, p63, EGFR, and Ki-67 in breast carcinoma and lymph node metastases. Results. The age of the patients ranged between 42 and 73 years (mean 53), and the mean followup was 68.25 months. A total of 54.55% of the patients were disease-free, and 45.45% died of carcinoma. Axillary lymph nodes maintained triple negative phenotype (11/11). Metastatic tumors showed CAM 5.2 (81.83%) and EGFR (72.73%) expression. Basal marker expression was variable in primary carcinoma and lymph node metastases (63.64%). Conclusions. Triple negative breast carcinomas maintained this immunoprofile at lymph node metastases. Triple negative carcinomas showed variable expression of basal cell markers. David Parada, Karla Peña, Francesc Riu, and Pilar Hernandez Copyright © 2011 David Parada et al. All rights reserved. Fine-Needle Aspiration Cytology Is an Alternative Source of High Quality Archival Samples in Biobanking Tue, 26 Jul 2011 16:09:07 +0000 Advances in fine-needle aspiration cytology (FNAC) techniques allows for a whole range of procedures on these limited sources of tissue. Where fresh aspirates are not readily available, archival FNAC samples had also been used for clinical diagnoses, molecular profiling, and disease monitoring with impressive results. Nonetheless, legitimate concerns exist regarding the reliability of these banked specimens. Increased demands on human tissues in response to the rapid acceleration on emerging scientific platforms will probably make tissue bank creation derived from archival FNAC a priority. To highlight its future prospects as a resource for tissue banking, this paper provides an overview of the use of archival FNAC in clinical situations and ancillary studies. It is concluded that tissue banks of archival FNAC specimens might have great promise in optimizing patient care and translational research. Sani Abubakar Malami Copyright © 2011 Sani Abubakar Malami. All rights reserved. Hydralazine Reverses Stress-Induced Elevations in Blood Pressure, Angiotensin II, Testosterone, and Coronary Pathology in a Social Colony Model Wed, 20 Jul 2011 10:41:27 +0000 Background. The vasodilator hydralazine (HYZ) has been used successfully to lower blood pressure (BP) in hypertension. Recently proposed novel mechanisms suggest it may be an important drug in reducing cardiovascular pathology. Methods. The hypothesis was that social stress would increase BP and endocrine factors that lead to increased coronary artery collagen deposition, and that HYZ treatment would reverse these changes. SHR males were compared: controls, colony stress and colony stress with HYZ treatment. Results. BP was significantly elevated in the stress group compared to controls and HYZ reduced the BP compared to controls. Plasma Ang II and T were significantly increased by colony stress compared to controls and HYZ restored both to control values. Collagen deposition in the coronary artery was increased in the colony stress group compared to controls but HYZ treatment restored the collagen to that of control values. Conclusions. HYZ reduced not only BP, but also reduced coronary adventitial collagen. The mechanism of the BP effect is most likely through vasodilation and the collagen reduction may be due to both a direct action of HYZ on collagen synthetic enzymes and indirectly through an effect of testosterone and angiotensin II. Changying Li, Ron Salisbury, and Daniel Ely Copyright Β© 2011 Changying Li et al. All rights reserved.