T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity

Background and Aims. Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation. Materials and Methods. We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni’s tests were used for statistical analysis. Results. Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes; p<0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm2; p<0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes, p<0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm2; p=0.009). Conclusions. The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS

Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations.

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs

A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies

Background: The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal inflammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by flow cytometry or frozen section immunohistochemistry (IHC), is a specific marker for CD. Aim: To establish a new IHC assay for γδ-IELs applicable to formalin-fixed paraffin-embedded (FFPE) duodenal biopsies. Methods: We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis. Results: Compared to those in non-celiac controls (n = 51), γδ-IEL density was significantly increased in newly diagnosed celiac disease patients (n = 22, p < 0.0001). In ROC-curve analysis, the cutoff of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specificity 95%). γδ-IEL density in CD patients on a gluten-free diet (n = 53) were also higher than in controls (p < 0.0001), but lower than those in newly diagnosed CD (p < 0.0001). The diagnostic value of γδ-IELs outperformed that of CD3 + IELs in both patient groups. γδ-IELs were better than CD3 + IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n = 12). Conclusions: Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specificity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease.publishedVersionPeer reviewe

Organotin compounds in touristic marinas of the northern Adriatic Sea: occurrence, speciation and potential recycling at the sediment-water interface

Butyltin compound (BTC) contamination was evaluated in two north Adriatic marinas, San Rocco (Italy) and Lucija (Slovenia). BTC sedimentary concentrations (121 \ub1 46 and 352 \ub1 30 ng Sn g 121 in San Rocco and Lucija, respectively) evidenced the past use of antifouling paints, confirmed by the reduced tributyltin content (~ 46%) with respect to the sumof BTC. Elemental and organic carbon isotopic (\u3b413C) analyses of bulk sediments and its lipid and humic substances were performed in order to evaluate their role in BTC partitioning and preservation. The \u3b413C of sedimentary bulk and refractory organic matter suggested that diagenetic processes could play a role in the preservation or release of pollutants. No contamination was found in water collected from the benthic chamber and thus, fluxes at the sediment-water interface were not assessed, except for MBT efflux at Lucija (28.9 ng Sn m 122 day 121). Nevertheless, BTC concentrations in porewaters (up to 75 ng Sn l 121) and rather low sediment-porewater partitioning coefficients (Kd) with respect to the data reported in the literature would suggest a potential risk of the reintroduction of BTC into the water column at both sites: at Lucija, sedimentary contamination is high despite the greater Log Kd, whilst at San Rocco, the low BTC concentration is associated with a reduced sediment affinity

O OR RI IG GI IN NA Macrophages and mast cells are involved in carotid plaque instability

Abstract The aim of this study was to evaluate the role of macrophages and mast cells and of microvascular density in atherosclerotic plaques collected from 63 consecutive symptomatic and asymptomatic patients undergoing carotid endarterectomy for carotid disease. Results have shown no statistically significant differences between the two groups as concerns: (i) the degree of stenosis; (ii) the extention of the lipidic core; (iii) the thickness of the fibrous cup; (iv) the inflammatory infiltrate; (v) the degree of calcification; (vi) the intraplaque hemorrhage. Otherwise, statistically significant difference was found in microvascular density, in the number of CD68-positive macrophages and tryptase-positive mast cells in plaques from symptomatic patients, as compared to asymptomatic patients. Overall, this study indicate that although advanced symptomatic and asymptomatic carotid plaques present similar histomorphological characteristics, the degree of macrophage and mast cell infiltration and differences in microvascular density could help to discriminate between symptomatic and asymptomatic patients

Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis

none10noAutoimmune cholestatic liver diseases are rare hepato-biliary disorders characterized by a progressive, inflammatory destruction of bile ducts. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. Both may evolve into secondary biliary cirrhosis and its complications. Therapeutic options are limited and liver transplantation remains the only definitive treatment for PBC and PSC.noneSarcognato, Samantha; Sacchi, Diana; Grillo, Federica; Cazzagon, Nora; Fabris, Luca; Cadamuro, Massimiliano; Cataldo, Ivana; Covelli, Claudia; Mangia, Alessandra; Guido, MariaSarcognato, Samantha; Sacchi, Diana; Grillo, Federica; Cazzagon, Nora; Fabris, Luca; Cadamuro, Massimiliano; Cataldo, Ivana; Covelli, Claudia; Mangia, Alessandra; Guido, Mari

Crosstalk between the Tumor Microenvironment and Immune System in Pancreatic Ductal Adenocarcinoma: Potential Targets for New Therapeutic Approaches

Pancreatic ductal adenocarcinoma is a lethal disease for which radical surgery and chemotherapy represent the only curative options for a small proportion of patients. Recently, FOLFIRINOX and nab-paclitaxel plus gemcitabine have improved the survival of metastatic patients but prognosis remains poor. A pancreatic tumor microenvironment is a dynamic milieu of cellular and acellular elements, and it represents one of the major limitations to chemotherapy efficacy. The continued crosstalk between cancer cells and the surrounding microenvironment causes immunosuppression within pancreatic immune infiltrate increasing tumor aggressiveness. Several potential targets have been identified among tumor microenvironment components, and different therapeutic approaches are under investigation. In this article, we provide a qualitative literature review about the crosstalk between the tumor microenvironment components and immune system in pancreatic cancer. Finally, we discuss potential therapeutic strategies targeting the tumor microenvironment and we show the ongoing trials

Benign biliary neoplasms and biliary tumor precursors

Benign biliary tumor are common lesions that are often an incidental finding in subjects who undergo medical imaging tests for other conditions. Most are true neoplasms while few result from reactive or malformative proliferation. Benign tumors have no clinical consequences, although the premalignant nature or potential for malignant transformation is of concern in some cases. The main practical problem for pathologists is the need to differentiate them from malignant biliary tumours, which is not always straightforward

Molecular changes of malignant mesothelioma in the testis and their impact on prognosis: Analyses of two cases

Malignant mesothelioma is a rare and aggressive tumour, generally asbestos-related. When the tumour arises in the pleura or peritoneum a non-occupational or environmental asbestos exposure has also been reported. The latency period from the initial asbestos exposure to the clinical diagnosis is variable but usually long, sometimes as long as 30-40 years. Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is extremely rare; in Italy, the standardized incidence rate for MMTVT is 0.2 cases per million inhabitants. Usually, in this site the tumour appears to be idiopathic in nature but exceptionally, an asbestos exposure has been documented. Here, we report two patients with locally advanced disease; an occupational history of asbestos exposure was ascertained in one case. Radical surgery was performed and adjuvant chemotherapy was administered only in one case