Pathology Research International The latest articles from Hindawi © 2018 , Hindawi Limited . All rights reserved. Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver Tue, 16 Jan 2018 08:43:43 +0000 Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs. Tamara C. M. Lopes, Débora F. Silva, Walyson C. Costa, Frédéric Frézard, José M. Barichello, Neila M. Silva-Barcellos, Wanderson G. de Lima, and Simone A. Rezende Copyright © 2018 Tamara C. M. Lopes et al. All rights reserved. Histopathologic and Cytologic Follow-Up in High Risk Male Patients with Unsatisfactory Anal Cytology Mon, 18 Sep 2017 07:55:28 +0000 Objective. Anal cytology is being increasingly used as part of anal cancer screening in patients at high risk for anal neoplasia. Most studies in anal cytology have focused on correlating the abnormal anal Pap smear with histopathologic outcomes. The aim of this study was to document histopathologic or repeat anal cytology outcomes in patients with unsatisfactory cytology. Materials and Methods. Unsatisfactory anal Pap tests in high risk male patients were correlated with follow-up histopathologic diagnoses or cytology. Results. 1205 anal tests were performed during the study period and 214 (17.8%) were unsatisfactory. Adequate follow-up cytology was available in 75 cases and revealed epithelial cell abnormality (ECA) in 40% [30/75] (atypical squamous cells of undetermined significance (ASCUS) [20%] and low-grade squamous intraepithelial lesions (LGSIL) [20%]) and was negative for intraepithelial lesion or malignancy (NILM) in 60% [45/75] of cases. 28.7% of unsatisfactory Pap smears had unsatisfactory repeat cytology. Histopathological follow-up on these unsatisfactory Pap smears revealed anal intraepithelial neoplasia (AIN) 1 and AIN 2/3 or 2/3+ in 39% and 18% of the total number of biopsy cases, respectively. Conclusions. High risk male patients with unsatisfactory Pap smears are at significant risk of epithelial cell abnormality and histopathologically verifiable anal intraepithelial lesions. Daniel J. Zaccarini and Kamal K. Khurana Copyright © 2017 Daniel J. Zaccarini and Kamal K. Khurana. All rights reserved. An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats Tue, 01 Aug 2017 00:00:00 +0000 It is already a proven fact that there exists a relationship between CLD (chronic liver disease) and kidney disease but still there is no available combined animal model of liver and kidney fibrosis on the same animal. An animal model is one of the important research tools in the field of medical science because it is important to build a model that can simulate the disease condition so that the particular disease can be studied. Therefore, the aim of this study is to build a less expensive, less time consuming, and reproducible model of hepatorenal fibrosis on rats. We administered combined intraperitoneal injection of CCl4 (Carbon Tetrachloride) and BSA (Bovine Serum Albumin) on a female Wistar rats. At the end, the liver and kidney tissues were examined under microscope to see whether we were successful in establishing the model or not. The results show that liver fibrosis was marked but the changes on the kidneys were mild. In this study, we were able to induce significant fibrosis in the liver and early stages of fibrosis in the kidneys. The result also demonstrated that the addition of BSA conferred a liver protective effect against CCl4 induced hepatotoxicity, whereas combination of CCl4 and BSA proved to be detrimental for kidneys. Manoj Hang Limbu, Liu Lei, Cheng Zhengyuan, Liu Jing, Zhang Xiaoyi, and Chen Pingsheng Copyright © 2017 Manoj Hang Limbu et al. All rights reserved. Development of Neurological Mouse Model for Toxoplasmosis Using Toxoplasma gondii Isolated from Chicken in Kenya Wed, 24 May 2017 09:16:13 +0000 Animal models for the toxoplasmosis are scarce and have limitations. In this study, a neurological mouse model was developed in BALB/c mice infected intraperitoneally with 15 cysts of a Toxoplasma gondii isolate. The mice were monitored for 42 days and euthanized at different time points. Another group of mice were orally treated with dexamethasone (DXM: 2.66 mg/kg daily, 5.32 mg/kg daily) at 42 days after infection and monitored for a further 42 days. A mortality rate of 15% and 28.6% was observed in mice given 2.66 mg/kg/day and 5.32 mg/kg/day of DXM, respectively. The mean cyst numbers in the brain of DXM treated mice increased up to twofold compared with chronically infected untreated mice. Infections up to 42 days were associated with an increase in both IgM and IgG levels but following dexamethasone treatment, IgM levels declined but IgG levels continued on rising. The brain of toxoplasmosis infected mice showed mononuclear cellular infiltrations, neuronal necrosis, and cuffing. The severity of pathology was higher in mice treated with dexamethasone compared to the positive control groups. The findings of this study demonstrate that DXM-induced reactivation of chronic toxoplasmosis may be a useful development of laboratory animal model in outbred mice used for in vivo studies. John Mokua Mose, David Muchina Kamau, John Maina Kagira, Naomi Maina, Maina Ngotho, Adele Njuguna, and Simon Muturi Karanja Copyright © 2017 John Mokua Mose et al. All rights reserved. High Expression of Galectin-3 in Patients with IgG4-Related Disease: A Proteomic Approach Tue, 16 May 2017 07:22:57 +0000 Objectives. Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan condition manifesting itself in different forms. This study aimed to investigate protein expression profiles and to find the possible biomarker for IgG4-RD by liquid chromatography mass spectrometry (LC-MS) using tissue sections in IgG4-RD patients. Methods. Protein expression profiles in five IgG4-related pancreatitis and three normal pancreatic samples were compared using LC-MS and were validated by quantitative real-time PCR (qRT-PCR), immunoblotting, and immunohistochemistry. ELISA was employed in the serum of 20 patients with systemic IgG4-RD before and during steroid treatment. Results. LC-MS indicated that the levels of 17 proteins were significantly higher and 12 others were significantly lower in IgG4-related pancreatitis patients compared to controls. Among these proteins, galectin-3 levels were 13-fold higher in IgG4-related pancreatitis (). These results were confirmed by immunoblotting and qRT-PCR. The average number of galectin-3 + cells in various organs of IgG4-RD patients, including salivary glands, lungs, and lymph nodes, was higher than in controls. Galectin-3 was detectable in macrophages, dendritic cells, and stromal myofibroblast-like cells, but not in lymphocytes by immunofluorescence staining. Serum galectin-3 levels were higher in patients with IgG4-RD compared with healthy donors and remained high during steroid therapy. Conclusion. Galectin-3 was overexpressed in IgG4-RD and the levels were indirectly related to clinical activity. Adeeb Salah, Hajime Yoshifuji, Shinji Ito, Koji Kitagori, Kaori Kiso, Norishige Yamada, Toshiki Nakajima, Hironori Haga, Tatsuaki Tsuruyama, and Aya Miyagawa-Hayashino Copyright © 2017 Adeeb Salah et al. All rights reserved. Utility of Immunohistochemistry and ETV6 (12p13) Gene Rearrangement in Identifying Secretory Carcinoma of Salivary Gland among Previously Diagnosed Cases of Acinic Cell Carcinoma Thu, 06 Apr 2017 00:00:00 +0000 Objective. Secretory carcinoma is a recently described entity with characteristic immunoprofile and ETV6 (12p13) rearrangement. Before its initial description, it was generally diagnosed as acinic cell carcinoma (ACCi). We evaluated immunoprofile and ETV6 rearrangement in cytological and surgical cases of previously diagnosed ACCi, in an attempt to identify any misclassified SC. Methods. Fifteen cytology and surgical cases of ACCi diagnosed over a 13-year period were retrieved and subjected to immunohistochemistry for S-100, mammaglobin, GATA-3 and DOG-1 as well as FISH for ETV6 (12p13). Results. Of the 8 cytology cases, only 1 was positive for S100, GATA-3, and mammaglobin, and negative for DOG-1. It also demonstrated ETV6 rearrangement and was reclassified as SC. The same immunoprofile was present in 2 of the 13 surgical cases. ETV6 rearrangement characterized by 3′ interstitial deletion was detected in one of these cases and was reclassified as SC. Immunohistochemistry and ETV6 rearrangement were useful in identifying 2 (13.3%) cases misclassified as ACCi. Conclusions. Characteristic immunoprofile and ETV6 gene rearrangement may prove useful in identifying cases of SC. The presence of ETV6 3′ interstitial deletion in one of our cases suggests that there may be additional ETV6 related genetic alterations contributing to the pathogenesis of SC. Rana Naous, Shengle Zhang, Alfredo Valente, Melissa Stemmer, and Kamal K. Khurana Copyright © 2017 Rana Naous et al. All rights reserved. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: An Evidence-Based Nomenclature Change Thu, 09 Feb 2017 06:42:05 +0000 A consensus panel recently used clinical evidence and pathologic parameters to rename noninvasive encapsulated follicular variant of papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to better reflect the indolent course of this tumor. NIFTP has stringent histopathologic diagnostic criteria established by the panel, including papillary-like nuclear features, and submission of the entire tumor capsule to exclude invasion. From a molecular standpoint, NIFTP is often characterized by RAS-type mutations, similar to other follicular-patterned lesions. While there has been prior evidence in the literature for the low malignant potential of these tumors, projects moving forward will help to independently reinforce the reliability of these criteria and nomenclature. With planned inclusion of NIFTP into the latest World Health Organization endocrine tumor classification scheme, this nomenclature shift provides a model for pathology efforts to refine diagnostic classifications to better guide treatment. In this review we discuss this nomenclature change and review the current literature. Rachel Jug and Xiaoyin Jiang Copyright © 2017 Rachel Jug and Xiaoyin Jiang. All rights reserved. Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review Wed, 08 Feb 2017 00:00:00 +0000 The presence of pulmonary parenchymal cysts on computed tomography (CT) imaging presents a significant diagnostic challenge. The diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the advent of high-resolution CT has facilitated making a diagnosis solely on analysis of CT image patterns, thus averting the need for a biopsy. While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological presentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes necessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the radiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration and description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the various disease entities are included and illustrative examples are provided for the common majority of them. In this article, we also classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate the characteristics of similar cystic appearances seen in various disease entities. Prajwal Boddu, Vamsi Parimi, Michale Taddonio, Joshua Robert Kane, and Anjana Yeldandi Copyright © 2017 Prajwal Boddu et al. All rights reserved. Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas Sun, 22 Jan 2017 00:00:00 +0000 Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs). Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections. The immunohistochemical results were correlated with clinicopathological parameters. Results. The overexpression of HER2 was found in 19.6% of the cases and it was associated with high grade tumors with a high mitotic index and phosphorylation of AKT and mTOR. Muscle-invasive tumors presented both cytoplasmic and nuclear losses of PTEN expression. There was no association between HER/AKT/mTOR pathway activation and CAM expression. Although cadherins were often coexpressed, only p-cadherin immunoreactivity was associated with tumor grade and high proliferative index. Conclusions. HER2 overexpression is found in a respective proportion of urothelial carcinomas. P-cadherin expression is associated with high grade UCs but it is not affected by HER2 overexpression or by activation of HER/AKT/mTOR pathway. Nikolaos Koletsas, Triantafyllia Koletsa, Spyros Choidas, Konstantinos Anagnostopoulos, Stavros Touloupidis, Thomas Zaramboukas, Georgia Raptou, Nikolaos Papadopoulos, and Maria Lambropoulou Copyright © 2017 Nikolaos Koletsas et al. All rights reserved. Retracted: Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review Tue, 28 Jun 2016 09:54:00 +0000 Pathology Research International Copyright © 2016 Pathology Research International. All rights reserved. Trypanosoma vivax Adhesion to Red Blood Cells in Experimentally Infected Sheep Mon, 16 May 2016 07:17:10 +0000 Trypanosomosis, a globally occurring parasitic disease, poses as a major obstacle to livestock production in tropical and subtropical regions resulting in tangible economic losses. In Latin America including Venezuela, trypanosomosis of ruminants is mainly caused by Trypanosoma vivax. Biologically active substances produced from trypanosomes, as well as host-trypanosome cellular interactions, contribute to the pathogenesis of anemia in an infection. The aim of this study was to examine with a scanning electron microscope the cellular interactions and alterations in ovine red blood cells (RBC) experimentally infected with T. vivax. Ovine infection resulted in changes of RBC shape as well as the formation of surface holes or vesicles. A frequent observation was the adhesion to the ovine RBC by the trypanosome’s free flagellum, cell body, or attached flagellum in a process mediated by the filopodia emission from the trypanosome surface. The observed RBC alterations are caused by mechanical and biochemical damage from host-parasite interactions occurring in the bloodstream. The altered erythrocytes are prone to mononuclear phagocytic removal contributing to the hematocrit decrease during infection. Alpidio A. Boada-Sucre, Marcello Salvatore Rossi Spadafora, Lucinda M. Tavares-Marques, Héctor J. Finol, and Armando Reyna-Bello Copyright © 2016 Alpidio A. Boada-Sucre et al. All rights reserved. Evaluation of Various Nuclear Cytological Changes in Normal Buccal Mucosa and Peritumoural Area in Patients with Oral Squamous Cell Carcinoma Receiving Concomitant Chemoradiotherapy Mon, 11 Apr 2016 16:02:54 +0000 Objectives. To evaluate the role of serial cytological assay in calculating the nuclear response of contralateral normal buccal mucosa and peritumoural area of squamous cell carcinoma of oral cavity in patients receiving fractionated radiotherapy (RT) and chemotherapy. Materials and Methods. This prospective, nonrandomized study was comprised of 76 histologically confirmed cases of oral squamous cell carcinoma on cyclical chemoradiation treatment. Chemoradiosensitivity was evaluated using serial scrape smears taken before and after immediate exposure to CCRT, at 17th day of CCRT (mid of treatment), and at the end of treatment. The nuclear changes, such as multinucleation, micronucleation, karyorrhexis, karyolysis, nuclear budding, prominent nucleoli, and binucleation occurring in both irradiated cancer cells and contralateral normal buccal mucosa, had a statistically significant dose related increase with concomitant chemoradiotherapy (). Conclusion. We recommend regular use of serial cytological assay during CCRT as it may prove to be a valuable tool for assessment of chemoradiosensitivity and persistence of tumour/dysplastic cells after radiotherapy. Sadia Minhas, Muhammad Kashif, and A. H. Nagi Copyright © 2016 Sadia Minhas et al. All rights reserved. A Histomorphological Pattern Analysis of Pulmonary Tuberculosis in Lung Autopsy and Surgically Resected Specimens Mon, 21 Mar 2016 11:51:09 +0000 Background. Tuberculosis (TB) is a major cause of morbidity and mortality globally. Many cases are diagnosed on autopsy and a subset of patients may require surgical intervention either due to the complication or sequelae of TB. Materials and Methods. 40 cases of resected lung specimens following surgery or autopsy in which a diagnosis of pulmonary tuberculosis was made were included. Histopathological pattern analysis of pulmonary tuberculosis along with associated nonneoplastic changes and identification of Mycobacterium tuberculosis bacilli was done. Results. The mean age of diagnosis was 41 years with male predominance (92.5%). Tuberculosis was suspected in only 12.1% of cases before death. Seven cases were operated upon due to associated complications or suspicion of malignancy. Tubercular consolidation was the most frequent pattern followed by miliary tuberculosis. The presence of necrotizing granulomas was seen in 33 cases (82.5%). Acid fast bacilli were seen in 57.5% cases on Ziehl-Neelsen stain. Conclusion. Histopathology remains one of the most important methods for diagnosing tuberculosis, especially in TB prevalent areas. It should be considered in the differential diagnosis of all respiratory diseases because of its varied clinical presentations and manifestations. Mamta Gupta, Flora D. Lobo, Deepa Sowkur Anandarama Adiga, and Abhishek Gupta Copyright © 2016 Mamta Gupta et al. All rights reserved. The Possible Role of Mast Cells in the Odontogenic Cyst’s Pathogenesis: A Comparative Study between Dentigerous Cyst and Keratocystic Odontogenic Tumor Wed, 24 Feb 2016 10:47:42 +0000 Background. Recently, mast cells were recognized in the pathogenesis of more aggressive pathologic lesions. This study was aimed to evaluate and compare the density of mast cells in Dentigerous cyst (DC) and Keratocystic odontogenic tumor (KCOT) regarding their different clinical behavior. Method. This study was conducted on 23 and 26 cases of DC and KCOT, respectively. Four-micron sections were prepared for Toluidine blue staining and mast cell densities in two desired cysts were studied. Final data was analyzed via -test and Mann-Whitney test method regarding the significant level lower than 0.05. Results. Mast cell densities were significantly higher in KCOTs for deep and superficial layers and both layers (). The density of degranulated mast cells in the deeper layers and both layers was significantly higher in KCOTs (). However, the density of degranulated mast cells in the superficial layer had no significant difference (). Conclusion. It seems that mast cells may be involved in the pathogenesis of KCOT, but, regarding wide range of mast cell’s biologic activities, further investigations are recommended to confirm the issue and prepare the details. Sareh Farhadi, Fatemeh Shahsavari, and MirMahdi Davardan Copyright © 2016 Sareh Farhadi et al. All rights reserved. Salivary and Urinary Total Antioxidant Capacity as Biomarkers of Oxidative Stress in Humans Sun, 07 Feb 2016 13:59:36 +0000 Total Antioxidant Capacity (TAC) is a biomarker often used in order to investigate oxidative stress in many pathological conditions. Saliva and urine can be collected noninvasively and represent attractive diagnostic fluids for detecting biomarkers of various pathological conditions. The reviewed case-control and intervention studies that measured salivary or urinary TAC revealed that diseases, antioxidant foods, or supplements and age, gender, and lifestyle factors influenced salivary or urinary TAC. Salivary and urinary TAC were particularly affected by oral or renal status, respectively, as well as by infection; therefore these factors must be taken into account in both case-control and intervention studies. Furthermore, some considerations on sample collection and normalization strategies could be made. In particular, unstimulated saliva could be the better approach to measure salivary TAC, whereas 24 h or spontaneous urine collection should be chosen on the basis of the study outcome and of the creatinine clearance. Finally, the uric acid-independent TAC could be the better approach to evaluate red-ox status of body, in particular after nutritional interventions and in diseases associated with hyperuricaemia. Ilaria Peluso and Anna Raguzzini Copyright © 2016 Ilaria Peluso and Anna Raguzzini. All rights reserved. Immunohistochemical Expression of Ki67 and p53 in Wilms Tumor and Its Relationship with Tumor Histology and Stage at Presentation Wed, 20 Jan 2016 13:12:30 +0000 Aim. Evaluate tumor proliferation marker (Ki67) and p53 tumor suppressor marker in Wilms tumor and correlate with histology, anaplasia, and staging. Design. Prospective, hospital based study conducted at a tertiary pediatric referral centre in south India. Setting. Wilms tumor is the most common childhood renal malignancy worldwide. Anaplasia on histology is associated with treatment resistance but not with aggressiveness clinical presentation. Chemotherapy for Wilms tumor is based on histology and staging. Most patients respond to current chemotherapy protocol. However, a small fraction relapses or metastasizes. Affordable prognostic markers are needed for histopathological evaluation of this tumor. Subjects. Cases of histologically confirmed Wilms tumor over five years. Cases after chemotherapy were excluded as the immunostaining was inconsistent in necrotic areas. Methods. The clinical and radiological findings of 31 cases of Wilms tumor were documented at a tertiary pediatric referral hospital over five years. In addition to Hematoxylin and Eosin staining, Ki67 proliferation index and p53 expression were correlated with tumor histology and staging. Results. Age incidence was 3–8 years with female preponderance. Significant correlation was noted between Ki67 proliferation index and tumor staging. p53 expression was not useful in stratification of Wilms tumor. Conclusion. Ki67 was cost-effective immunohistochemical marker for prognostication of pediatric Wilms tumor. O. H. Radhika Krishna, Geetha Kayla, Mohammed Abdul Aleem, Ramani Malleboyina, and Ramesh Reddy Kota Copyright © 2016 O. H. Radhika Krishna et al. All rights reserved. Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data Mon, 18 Jan 2016 10:56:35 +0000 Background. Neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery in locally advanced rectal cancer (LARC) improves pelvic disease control. Survival improvement is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. Potential predictive factors for Mandard response are analyzed. Materials and Methods. 167 patients with LARC were treated with nCRT and curative surgery. Tumor biopsies and surgical specimens were reviewed and analyzed regarding mitotic count, necrosis, desmoplastic reaction, and inflammatory infiltration grade. Surgical specimens were classified according to Mandard TRG. The patients were divided as “good responders” (Mandard TRG1-2) and “bad responders” (Mandard TRG3-5). According to results from our previous data, good responders have better prognosis than bad responders. We examined predictive factors for Mandard response and performed statistical analysis. Results. In univariate analysis, distance from anal verge and ten other postoperative variables related with nCRT tumor response had predictive value for Mandard response. In multivariable analysis only mitotic count, necrosis, and differentiation grade in surgical specimen had predictive value. Conclusions. There is a lack of clinical and pathological preoperative variables able to predict Mandard response. Only postoperative pathological parameters related with nCRT response have predictive value. Marisa D. Santos, Cristina Silva, Anabela Rocha, Carlos Nogueira, Eduarda Matos, and Carlos Lopes Copyright © 2016 Marisa D. Santos et al. All rights reserved. FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer Tue, 01 Dec 2015 07:29:49 +0000 Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP. Francesco Cetta Copyright © 2015 Francesco Cetta. All rights reserved. Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences Sun, 08 Nov 2015 15:06:18 +0000 The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction () and proliferation index (). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate () and multivariate () analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended. Rancés Blanco, Elizabeth Domínguez, Orlando Morales, Damián Blanco, Darel Martínez, Charles E. Rengifo, Carmen Viada, Mercedes Cedeño, Enrique Rengifo, and Adriana Carr Copyright © 2015 Rancés Blanco et al. All rights reserved. Comparison of Immunohistochemical Expression of Antiapoptotic Protein Survivin in Normal Oral Mucosa, Oral Leukoplakia, and Oral Squamous Cell Carcinoma Sun, 20 Sep 2015 09:54:43 +0000 Background. Oral squamous cell carcinoma is the sixth most frequent malignant tumor worldwide and the third most common cancers in developing countries. Oral leukoplakia is the best-known precursor lesion of oral squamous cell carcinoma. The aim of the present study was to compare immunohistochemical expression of antiapoptotic protein survivin in normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma. Method. Total 45 specimens of formalin fixed paraffin embedded tissue blocks, 15 in each of the following: normal oral mucosa, leukoplakia, and oral squamous cell carcinoma were used for the study. Immunohistochemical reaction for survivin protein was performed for the 4 µm thick histological sections taken on positively charged slides. Results. 20% normal mucosa cases, 53.33% cases of leukoplakia, and 80% of oral squamous cell carcinoma were found out to be survivin positive. One way ANOVA test indicated statistically significant difference of survivin expression between the three different groups . Conclusion. A high incidence of survivin protein expression in oral epithelial dysplasia and squamous cell carcinoma samples indicate that survivin protein expression may be an early event in initiation and progression of oral squamous cell carcinoma. Amita Negi, Abhiney Puri, Rakhi Gupta, Rajat Nangia, Alisha Sachdeva, and Megha Mittal Copyright © 2015 Amita Negi et al. All rights reserved. p40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations: A Comparative Immunohistochemical Study with 34betaE12 Sun, 08 Mar 2015 07:00:08 +0000 Immunohistochemistry is important for the accurate diagnosis of basal cells in atypical glandular proliferations of the prostate. p40, an isoform of p63, may be an adjunct to a marker panel in this setting. Biopsies of 68 patients were analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal cell staining was classified as negative, partial (<60%), or diffuse (≥60%); irregular staining was defined as discordant staining patterns. In acinar proliferations (), partial staining for both markers was seen in 42%, and diffuse staining in 46% of reactive cases. An irregular reactivity was noted in one case only (2%). Finally, these lesions were signed out as benign. Acinar proliferations negative for both markers and limited amount of glands (≤4) were termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two cases showed partial, three cases showed diffuse reactivity for both markers, and one case was stained irregular. All cases diagnosed as prostate carcinomas () had no evidence of basal cell staining for neither of the markers. p40 expression is closely correlated to 34betaE12 with respect to demonstration of basal cells of prostate glands and may provide further information on the dignity of glandular proliferations of the prostate. Hermann Brustmann Copyright © 2015 Hermann Brustmann. All rights reserved. Expression of Prostanoid EP3 Receptors in Oral Squamous Epithelium and Oral Squamous Cell Carcinoma Mon, 09 Feb 2015 08:25:50 +0000 Objectives. To carry out a descriptive analysis of the expression of the EP3 receptors of PGE2 in different histological grades of OSCC and adjacent normal epithelium. Material and Methods. A total of 46 patients presenting with various histological subtypes and grades of OSCC were recruited from Maxillofacial Surgery Department of Nishtar Institute of Dentistry Multan. Microscopically tumour subtyping and histological grading according to Anneroth’s grading system were carried out. Immunohistochemical staining with rabbit polyclonal EP3 receptor antibody was performed and sections were scored for intensity and proportion of positive adjacent squamous epithelial and tumour cells. Results. Out of 46 patients (60.9%) were well differentiated, (32.6%) were moderately differentiated, and only (6.5%) were poorly differentiated. All cases of OSCC were positive for EP3 receptor antibody, (30.4%) cases had strong intensity of anti EP3 antibody staining in tumour tissue, (37%) cases showed moderate intensity, and (32.6%) cases showed weak intensity. Conclusion. Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors. However, insignificant statistical relation to histological grades of OSCC has been observed. This might be due to small sample size of the study. Muhammad Kashif, Muhammad Ishfaq, and A. H. Nagi Copyright © 2015 Muhammad Kashif et al. All rights reserved. Leishmaniasis in Central Morocco: Seasonal Fluctuations of Phlebotomine Sand Fly in Aichoun Locality, from Sefrou Province Sun, 08 Feb 2015 08:50:17 +0000 Cutaneous leishmaniases (CL) are endemic in Morocco. They are common in the human population in different localities such as Aichoun in Sefrou province, Morocco. This study was carried out in Aichoun locality from April to October 2012 in order to study the spatiotemporal trends of the main Leishmania phlebotomine vectors in this focus. Overall, 1171 sand flies, belonging to four species, were collected by sticky traps. Phlebotomus sergenti was the predominant species (78.4%) followed by Ph. perniciosus (10.5%), Ph. papatasi (7.94%), and Ph. longicuspis (3.16%). Sandflies were active during 6 months (May–October). Ph. sergenti, Ph. perniciosus, and Ph. papatasi displayed a bimodal distribution with a first peak in July and a second peak in September, while Ph. longicuspis showed a monophasic trend with a peak in August. The high abundance and the lengthy period of activity of Ph. sergenti and Ph. perniciosus, vectors of L. tropica and L. infantum, respectively, are a cause for concern as they indicate the high potential risk of Leishmania transmission in the studied areas. Fatima Zahra Talbi, Abdelhakim El Ouali Lalami, Abdellatif Janati Idrissi, Faiza Sebti, and Chafika Faraj Copyright © 2015 Fatima Zahra Talbi et al. All rights reserved. Thyroid Cytopathology Reporting by the Bethesda System: A Two-Year Prospective Study in an Academic Institution Thu, 22 Jan 2015 11:36:05 +0000 Background. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has attempted to standardize reporting and cytological criteria in aspiration smears. Aims. The objective of this study was to analyze the thyroid cytology smears by TBSRTC, to determine the distribution of diagnostic categories and subcategories, to analyze cytological features, and to correlate the cytopathology with histopathology, wherever surgery was done. Materials and Methods. This was a prospective study of 225 fine needle aspirations (FNA) of thyroid nodules. All fine needle aspiration cytology (FNAC) diagnoses were classified according to the features given in the monograph of TBSRTC into nondiagnostic/unsatisfactory (ND/UNS), benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious of a follicular neoplasm (FN/SFN), suspicious for malignancy (SFM), and malignant. Cytohistological correlation was done, when surgical material was available. Results. The distribution of various categories from 225 evaluated thyroid nodules was as follows: 7.2% ND/UNS, 80.0% benign, 4.9% AUS/FLUS, 2.2% FN, 3.5% SFM, and 2.2% malignant. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Conclusions. TBSRTC is an excellent reporting system for thyroid FNA. It also provides clear management guidelines to clinicians to go for follow-up FNA or surgery and also the extent of surgery. Payal Mehra and Anand Kumar Verma Copyright © 2015 Payal Mehra and Anand Kumar Verma. All rights reserved. Morphological and Chemical Study of Pathological Deposits in Human Aortic and Mitral Valve Stenosis: A Biomineralogical Contribution Mon, 19 Jan 2015 09:20:43 +0000 Aim of this study was to investigate heart valve calcification process by different biomineralogical techniques to provide morphological and chemical features of the ectopic deposit extracted from patients with severe mitral and aortic valve stenosis, to better evaluate this pathological process. Polarized light microscopy and scanning electron microscopy analyses brought to light the presence of nodular and massive mineralization forms characterized by different levels of calcification, as well as the presence of submicrometric calcified globular cluster, micrometric cavities containing disorganized tissue structures, and submillimeter pockets formed by organic fibers very similar to amyloid formations. Electron microprobe analyses showed variable concentrations of Ca and P within each deposit and the highest content of Ca and P within calcified tricuspid aortic valves, while powder X-ray diffraction analyses indicated in the nanometer range the dimension of the pathological bioapatite crystals. These findings indicated the presence of highly heterogeneous deposits within heart valve tissues and suggested a progressive maturation process with continuous changes in the composition of the valvular tissue, similar to the multistep formation process of bone tissue. Moreover the micrometric cavities represent structural stages of the valve tissue that immediately precedes the formation of heavily mineralized deposits such as bone-like nodules. Valentina Cottignoli, Elena Cavarretta, Loris Salvador, Carlo Valfré, and Adriana Maras Copyright © 2015 Valentina Cottignoli et al. All rights reserved. Correlation of CK5 and EGFR with Clinicopathological Profile of Triple-Negative Breast Cancer Thu, 23 Oct 2014 08:23:11 +0000 Purpose. Triple-negative breast cancer (TNBC) is defined by the loss of expression of ER, PR, and Her2neu expressions. The aim of this study was to examine the expression of the EGFR, CK5, and Ki-67 among triple-negative breast cancer cases and to correlate the expression of the basal markers with the clinicopathological prognostic parameters. Materials and Methods. Thirty-six female patients with TNBC based on ER, PR, and the HER2neu negativities were studied by immunohistochemistry for EGFR, CK5, and Ki-67 expression. Statistical analysis was done using the SPSS software version 20. Results. The mean and median ages were 45.18 years and 46.70 years, respectively. Infiltrating ductal carcinoma NOS was the predominant histopathological type (29/36 [80.6%]). The commonest histological grade was grade 2 (17/36 [47.2%]). Tumour necrosis was seen in 16/36 (44.4%) patients. Infiltrative margins were shown in 69.44% (25/36) cases. Ki-67 was positive in 80.56% (29/36) cases, 61.11% (22/36) were CK5-positive, and 86.11% (31/36) were EGFR-positive. The only significant positive association observed was between the CK5 and histological grade (). Conclusion. CK5 shows a statistically significantly correlation with TNBC histological grade. The majority of the specimens show EGFR expression. Therefore TNBCs could potentially benefit from EGFR-targeted therapeutic strategies. Neelam Sood and Jitendra Singh Nigam Copyright © 2014 Neelam Sood and Jitendra Singh Nigam. All rights reserved. Histopathological Audit of 373 Nononcological Hysterectomies in a Teaching Hospital Tue, 09 Sep 2014 05:22:27 +0000 Hysterectomy, the most common gynecological surgery, provides a definitive cure to various diseases like DUB (dysfunctional uterine bleeding), leiomyoma, adenomyosis, chronic pelvic pain, prolapse, and malignancy. However, with advent of effective medical and conservative treatment modalities for nononcological causes it is now posing question mark on justification of hysterectomy. Therefore, an audit is required to assess the correlation between preoperative diagnosis and histopathological examination of specimen for justification of the procedure. In this study over period of one year (April 2013 to March 2014) 373 hysterectomies specimens were received in the department of pathology for nononcological causes. The age of patients ranged from 22 to 85 years with mean years. All cases were divided into five categories on the basis of age and audit was done. In this study the most common finding was leiomyoma (43.7%) followed by adenomyosis (19.3%). Almost 50% of hysterectomies causes were justified as preoperative diagnosis matched with histopathology. Cohen kappa statistics were used to measure agreement between preoperative and postoperative histopathological diagnosis which was found to be fair with κ value being 0.36. This study highlights that regular audit of surgeries can help improve quality of health care services and provide safe conservative option to patients. Kanwardeep Kaur Tiwana, Sarita Nibhoria, Tanvi Monga, and Richa Phutela Copyright © 2014 Kanwardeep Kaur Tiwana et al. All rights reserved. In Vitro Studies on the Antioxidant Property and Inhibition of α-Amylase, α-Glucosidase, and Angiotensin I-Converting Enzyme by Polyphenol-Rich Extracts from Cocoa (Theobroma cacao) Bean Mon, 08 Sep 2014 11:01:07 +0000 Background. This study sought to investigate the antidiabetic and antihypertensive mechanisms of cocoa (Theobroma cacao) bean through inhibition of α-amylase, α-glucosidase, angiotensin-1 converting enzyme, and oxidative stress. Methodology. The total phenol and flavonoid contents of the water extractable phytochemicals from the powdered cocoa bean were determined and the effects of the extract on α-amylase, α-glucosidase, and angiotensin-1 converting enzyme activities were investigated in vitro. Furthermore, the radicals [1,1-diphenyl-2 picrylhydrazyl (DPPH), 2,2..-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl (OH), and nitric oxide (NO)] scavenging ability and ferric reducing antioxidant property of the extract were assessed. Results. The results revealed that the extract inhibited α-amylase (1.81 ± 0.22 mg/mL), α-glucosidase (1.84 ± 0.17 mg/mL), and angiotensin-1 converting enzyme (0.674 ± 0.06 mg/mL [lungs], 1.006 ± 0.08 mg/mL [heart]) activities in a dose-dependent manner and also showed dose-dependent radicals [DPPH (16.94 ± 1.34 mg/mL), NO (6.98 ± 0.886 mg/mL), OH (3.72 ± 0.26 mg/mL), and ABTS (15.7 ± 1.06 mmol/TEAC·g] scavenging ability. Conclusion. The inhibition of α-amylase, α-glucosidase, and angiotensin-1 converting enzyme activities by the cocoa bean extract could be part of the possible mechanism by which the extract could manage and/or prevent type-2 diabetes and hypertension. Ganiyu Oboh, Ayokunle O. Ademosun, Adedayo O. Ademiluyi, Olasunkanmi S. Omojokun, Esther E. Nwanna, and Kuburat O. Longe Copyright © 2014 Ganiyu Oboh et al. All rights reserved. Bone Marrow Mesenchymal Stem Cells Ameliorates Seawater-Exposure-Induced Acute Lung Injury by Inhibiting Autophagy in Lung Tissue Tue, 19 Aug 2014 05:48:07 +0000 Seawater drowning can lead to acute lung injury (ALI). Several studies have shown that bone marrow mesenchymal stem cells (BMSC) treatment could attenuate ALI. However, the mechanisms underlying this phenomenon still remain elusive. Therefore, this study aimed to investigate whether BMSC treatment can ameliorate seawater-induced ALI and its underlying mechanisms in a rat model. In this study, arterial blood gas, lung weight coefficient, and TNF-α, and IL-8 in bronchoalveolar lavage fluid (BALF), as well as histopathology examination, were used to detect the lung injury of seawater exposure. Moreover, western blot and RT-PCR were used to explore autophagy in lung tissues. The results demonstrated that seawater exposure induced ALI including impaired arterial blood gas, pulmonary edema, histopathologic changes, and inflammatory response in lung tissues. What is more, these changes were partly ameliorated by BMSC treatment through inhibition of autophagy in lung tissues. The application of BMSC may be a potential effective treatment for seawater-induced ALI. Qiu-ping Liu, Dang-xia Zhou, Li Sun, Luo Ling, Chang-gui Wu, Pu Lin, and Shui-ping Han Copyright © 2014 Qiu-ping Liu et al. All rights reserved. Cytohistopathological Study of Salivary Gland Lesions in Bundelkhand Region, Uttar Pradesh, India Mon, 18 Aug 2014 11:24:21 +0000 Background. FNAC is a useful method for evaluating suspicious salivary glands lesions due to its low cost, minimum morbidity, rapid turnaround time, high specificity, and sensitivity. Aim. To know the frequency of the salivary gland lesions and cytohistological correlation in the Jhansi region, Uttar Pradesh, India. Material and Methods. In present study 124 cases were included and cytohistological correlation was made in 86 cases only. FNA was performed by using a 23/24-gauge needle without local anaesthesia. Air dried and 95% ethyl alcohol fixed wet smears were stained with Giemsa stain and Papanicolaou stain, respectively. Paraffin embedded tissue sections were stained with Haematoxylin and Eosin. Results. Parotid gland was the most commonly involved salivary gland. The commonest age group was 20 to 29 years, 30 to 39 years, and 60 to 69 years for nonneoplastic lesions, benign tumours, and malignant tumours, respectively. The overall male to female ratio was 1.17 : 1. The diagnostic accuracy of FNAC was 100%, 93.3%, and 88.2% for nonneoplastic lesions, benign tumours, and malignant tumours, respectively. Conclusion. The high accuracy, sensitivity, and specificity of FNAC confirm that preoperative cytology is a useful, quick, reliable diagnostic technique for rapid diagnosis and suitable for developing countries. Anita Omhare, Sanjeev Kumar Singh, Jitendra Singh Nigam, and Ankit Sharma Copyright © 2014 Anita Omhare et al. All rights reserved.