Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim ...of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database.
Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified).
Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances).
This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.
•Systematic review of rare ovarian tumors identify minor and major histological discrepancies in all categories of ovarian tumors.•Systematic review of rare ovarian tumors has a direct implication in the management of patients.•Most of the major discrepancies relate to mucinous tumors, in evaluation of the degree of malignancy or in the distinction with a digestive metastasis.•The major discrepancies relating to sex cord tumors tumors mainly concern granulosa cell tumors in the distinction with fibroma or sertoli-leydig cell tumors.
Inflammatory bowel disease (IBD) is a chronic disorder whose etiology is linked to triggering events, including viral infections, that lead to immunoregulatory dysfunction in genetically susceptible ...people. Characteristic pathological changes include increased mononuclear leukocyte influx into the intestinal mucosa as well as mucosal smooth muscle cell (M-SMC) hyperplasia. Virus infection or viral mimic polyinosinic acid:polycytidylic acid (polyI:C) treatment of human colon M-SMCs in vitro increases cell surface hyaluronan (HA), and nonactivated mononuclear leukocytes bind to virus-induced HA structures by interactions that involve the HA-binding receptor CD44. In this study, confocal microscopy reveals increased HA on poly I:C-treated M-SMC surfaces within 3 hours, arrayed in coat-like structures. By 17 hours, novel, lengthy cable structures are evident, and these are primarily responsible for mediating leukocyte adhesion. Immunohistochemical staining demonstrates components of the inter-alpha-trypsin inhibitor (IalphaI) complex in both coat-like and cable structures. M-SMCs co-treated with polyI:C and a polyclonal antibody to IalphaI display HA in coats but with diminished cables, and they bind significantly fewer leukocytes than M-SMCs treated with polyI:C alone. Western blot data suggest that heavy chains of IalphaI are specifically associated with cable structures. Staining of tissue sections from patients with IBD demonstrates the presence of HA in inflamed colon tissue, and shows that HA-associated IalphaI staining increases in the mucosa of inflamed IBD specimens compared to noninflamed sections from the same patient, establishing a probable link between the observations in vitro and the progression of the inflammatory process in IBD.
Pathological changes in inflammatory bowel disease include an increase in intestinal mucosal mononuclear leukocytes and hyperplasia of the muscularis mucosae smooth muscle cells (M-SMCs). Because ...virus infections have correlated with disease flare, we tested the response of cultured M-SMCs to respiratory syncytial virus, measles virus, and the viral analogue, poly(I·C). Adhesion of U937 cells and peripheral blood mononuclear cells was used to measure the leukocyte-interactive potential of M-SMCs. Untreated M-SMCs, only minimally adhesive for leukocytes, bound U937 cells after treatment with respiratory syncytial virus or measles virus. Mononuclear leukocytes also bound to poly(I·C)-treated M-SMCs. Although both vascular cell adhesion molecule-1 mRNA and protein increased 3–4-fold in poly(I·C)-treated M-SMC cultures, U937 cell adhesion was not blocked by an anti-vascular cell adhesion molecule-1 monoclonal antibody. However, hyaluronidase digestion of poly(I·C)- or virus-treated M-SMCs dramatically reduced leukocyte adhesion (∼75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a ∼3-fold increase in surface-bound hyaluronan on poly(I·C)-treated M-SMCs compared with untreated controls. In addition, pretreatment of mononuclear cells with a blocking anti-CD44 antibody, greatly decreased adhesion to poly(I·C)-treated M-SMCs. Recognition of this virus-induced hyaluronan/CD44 mechanism of mesenchymal cell/leukocyte interaction introduces a new avenue in the research of gut inflammation.
In this study, we investigate whether human inflammatory bowel disease (IBD) (ulcerative colitis and Crohn's disease) is associated with altered lymphokine secretion profiles, as recently found in ...various animal models of chronic intestinal inflammation. In initial studies, we determined the proliferative responses of purified lamina propria (LP) CD4+ T cells from patients with IBD under defined conditions of T cell stimulation. We found that IBD LP CD4+ T cells in comparison with control LP CD4+ T cells have diminished TCR/CD3 pathway proliferative responses, whereas CD2/CD28 accessory pathway proliferative responses are relatively preserved. In further studies centering on lymphokine production, we showed that LP T cells from inflamed Crohn's disease mucosa manifest increased IFN-gamma secretion compared with control LP T cells, particularly when stimulated via the CD2/CD28 pathway. Subsequent ELISPOT analysis indicated that this was due to an increased number of IFN-gamma-secreting CD4+ T cells. In contrast, IL-4 and IL-5 production by Crohn's disease LP T cells was decreased compared with that of control LP T cells. Of interest, IL-2 production by Crohn's disease LP T cells was also reduced, as was IL-2 production by peripheral blood T cells. In parallel studies, LP T cells from inflamed ulcerative colitis mucosa stimulated via either the TCR/CD3/CD28 or CD2/CD28 produced increased amounts of IL-5, again when measured either as secreted IL-5 or by ELISPOT analysis. Such increased IL-5 production was not associated with increased IL-4 secretion and, in contrast to Crohn's disease, ulcerative colitis LP T cell production of IL-2 and IFN-gamma was normal. Taken together, these studies provide strong evidence that the immunopathologic process characteristic of the two major forms of IBD is associated with very different cytokine secretion patterns. These different patterns may determine the type of inflammatory process present.
A variety of obstacles have hindered the ultrastructural localization of hyaluronan (HA). These include a lack of adequate fixation techniques to prevent the loss of HA, the lack of highly sensitive ...and specific probes, and a lack of accessibility due to the masking of HA by HA-binding macromolecules such as proteoglycans and glycoproteins. Despite these problems, a number of studies, both biochemical and histochemical, have been published indicating that HA is not restricted to the extracellular milieu, but is also present intracellularly. This review focuses on the possible functions of intracellular HA, its potential relationships to extracellular HA structures, and implications for inflammatory processes.
There is mounting evidence that perturbations in endoplasmic reticulum (ER) function play a key role in the pathogenesis of a broad range of diseases. We have examined the ability of ER stress to ...modulate leukocyte binding to colonic and aortic smooth muscle cells. In vitro, control smooth muscle cells bind few leukocytes, but treatment with compounds that induce ER stress, including tunicamycin, A23187, and thapsigargin, promotes leukocyte binding. Likewise, dextran sulfate, another agent capable of inducing ER stress and promoting inflammation in vivo, strongly induces leukocyte adhesion. The bound leukocytes are released by hyaluronidase treatment, indicating a critical role for hyaluronan-containing structures in mediating leukocyte binding. Affinity histochemistry demonstrated that hyaluronan accumulates and is present in cable-like structures in the treated, but not the untreated, cultures and that these structures serve as attachment sites for leukocytes. Hyaluronan-rich regions of both murine and human inflamed colon contain numerous cells that stain intensely for ER-resident chaperones containing the KDEL sequence, demonstrating a relationship between ER stress and hyaluronan deposition in vivo. These results indicate that ER stress may contribute to chronic inflammation by forming a hyaluronan-rich extracellular matrix that is conducive to leukocyte binding.
We report the first search for a non-standard-model resonance decaying into $\tau$ pairs in $e^{+}e^{-}\rightarrow \mu^{+}\mu^{-} \tau^+\tau^-$ events in the 3.6-10 GeV/$c^{2}$ mass range. We use a ...62.8 fb$^{-1}$ sample of $e^+e^-$ collisions collected at a center-of-mass energy of 10.58 GeV by the Belle II experiment at the SuperKEKB collider. The analysis probes three different models predicting a spin-1 particle coupling only to the heavier lepton families, a Higgs-like spin-0 particle that couples preferentially to charged leptons (leptophilic scalar), and an axion-like particle, respectively. We observe no evidence for a signal and set exclusion limits at 90% confidence level on the product of cross section and branching fraction into $\tau$ pairs, ranging from 0.7 fb to 24 fb, and on the couplings of these processes. We obtain world-leading constraints on the couplings for the leptophilic scalar model for masses above 6.5 GeV/$c^2$ and for the axion-like particle model over the entire mass range.
We present the first measurement of the ratio of branching fractions of inclusive semileptonic $B$-meson decays, $R(X_{e/\mu}) = \mathcal{B}(B\to X \, e \, \nu) / \mathcal{B}(B\to X \, \mu \, \nu)$, ...a precision test of electron-muon universality, using data corresponding to $189\,\mathrm{fb}^{-1}$ from electron-positron collisions collected with the Belle II detector. In events where the partner $B$ meson is fully reconstructed, we use fits to the lepton momentum spectra above $1.3\,\mathrm{GeV}/c$ to obtain $R(X_{e/\mu}) = 1.007 \pm 0.009~(\mathrm{stat}) \pm 0.019~(\mathrm{syst})$, which is the most precise lepton-universality test of its kind and agrees with the standard-model expectation.
The L_{μ}-L_{τ} extension of the standard model predicts the existence of a lepton-flavor-universality-violating Z^{'} boson that couples only to the heavier lepton families. We search for such a ...Z^{'} through its invisible decay in the process e^{+}e^{-}→μ^{+}μ^{-}Z^{'}. We use a sample of electron-positron collisions at a center-of-mass energy of 10.58 GeV collected by the Belle II experiment in 2019-2020, corresponding to an integrated luminosity of 79.7 fb^{-1}. We find no excess over the expected standard-model background. We set 90%-confidence-level upper limits on the cross section for this process as well as on the coupling of the model, which ranges from 3×10^{-3} at low Z^{'} masses to 1 at Z^{'} masses of 8 GeV/c^{2}.
BACKGROUND Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to ...maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn's disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms. AIMS To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. PATIENTS AND METHODS Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-xL, and Bax, and mean fluorescence intensity measured by flow cytometry. RESULTS Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-xL, was significantly greater in LPT, resulting in lower Bcl-xL/Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-xL, but correlation with Bcl-2 was absent in LPT. Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-xL/Bax ratio. The significant correlation of Bcl-xL to Bax was preserved in CD, but not UC, LPT. CONCLUSIONS Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-xL/Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.
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