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&#x25;) were unsatisfactory. Adequate follow-up cytology was available in 75 cases and revealed epithelial cell abnormality (ECA) in 40&#x25; [30/75] (atypical squamous cells of undetermined significance (ASCUS) [20&#x25;] and low-grade squamous intraepithelial lesions (LGSIL) [20&#x25;]) and was negative for intraepithelial lesion or malignancy (NILM) in 60&#x25; [45/75] of cases. 28.7&#x25; 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&#x25; and 18&#x25; 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

Kamal K. Khurana

Histopathologic and Cytologic Follow-Up in High Risk Male Patients with Unsatisfactory Anal Cytology

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

Chen Pingsheng

An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats

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&#x2009;mg/kg daily, 5.32&#x2009;mg/kg daily) at 42 days after infection and monitored for a further 42 days. A mortality rate of 15&#x25; and 28.6&#x25; was observed in mice given 2.66&#x2009;mg/kg/day and 5.32&#x2009;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

Simon Muturi Karanja

Development of Neurological Mouse Model for Toxoplasmosis Using Toxoplasma gondii Isolated from Chicken in Kenya

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 (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6370001pt" id="M1" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>). 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

Aya Miyagawa-Hayashino

High Expression of Galectin-3 in Patients with IgG4-Related Disease: A Proteomic Approach

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&#x2032; 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&#x25;) cases misclassified as ACCi. Conclusions. Characteristic immunoprofile and ETV6 gene rearrangement may prove useful in identifying cases of SC. The presence of ETV6 3&#x2032; 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

Utility of Immunohistochemistry and ETV6 (12p13) Gene Rearrangement in Identifying Secretory Carcinoma of Salivary Gland among Previously Diagnosed Cases of Acinic Cell Carcinoma

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

Xiaoyin Jiang

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: An Evidence-Based Nomenclature Change

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

Anjana Yeldandi

Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review

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&#x25; 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

Maria Lambropoulou

Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas

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