Cytological diagnostic features of late breast implant seromas. From reactive to anaplastic large cell lymphoma

Late breast implant seroma may be the presentation of a breast implant-associated anaplastic large cell lymphoma (BI-ALCL), which claims for a prompt recognition. However, BI-ALCL diagnosis on fine-needle aspiration (FNA) might be challenging for pathologists lacking experience with peri-implant breast effusions. Sixty-seven late breast implant seromas collected by FNA from 50 patients were evaluated by Papanicolaou smear stain and immunocytochemistry on cell blocks. A diagnostic algorithm based on the cellular composition, cell morphology and percentage of CD30+ cells was developed. Histological evaluation of the corresponding peri-prosthetic capsules was also performed. Most of the effusions (91% of the samples) were classified as reactive and 9% as BI-ALCL. In the BI-ALCL cases, medium-to-large atypical cells expressing CD30 represented more than 70% of the cellularity, whereas in in the reactive effusions CD30+ elements were extremely rare (<5%) and consisted of non-atypical elements. The reactive effusions were categorized into three patterns: i) acute infiltrate with prominent neutrophilic component (33% of the samples); ii) mixed infiltrate characterized by a variable number of neutrophils, lymphocytes and macrophages (30% of the samples); iii) chronic infiltrate composed predominantly of T lymphocytes or macrophages with only sporadic granulocytes (37% of the samples). The inflammatory cytological patterns were consistent with the histology of the corresponding capsules. Our results indicate that cytological analysis of late breast implant effusions, supported by the knowledge of the heterogeneous cytomorphological spectrum of late seromas, is a valuable approach for the early recognition of BI-ALCL

Pheromone Recognition and Selectivity by ComR Proteins among Streptococcus Species.

International audienceNatural transformation, or competence, is an ability inherent to bacteria for the uptake of extracellular DNA. This process is central to bacterial evolution and allows for the rapid acquirement of new traits, such as antibiotic resistance in pathogenic microorganisms. For the Gram-positive bacteria genus Streptococcus, genes required for competence are under the regulation of quorum sensing (QS) mediated by peptide pheromones. One such system, ComRS, consists of a peptide (ComS) that is processed (XIP), secreted, and later imported into the cytoplasm, where it binds and activates the transcription factor ComR. ComR then engages in a positive feedback loop for the expression of ComS and the alternative sigma-factor SigX. Although ComRS are present in the majority of Streptococcus species, the sequence of both ComS/XIP and ComR diverge significantly, suggesting a mechanism for species-specific communication. To study possible cross-talk between streptococcal species in the regulation of competence, and to explore in detail the molecular interaction between ComR and XIP we undertook an interdisciplinary approach. We developed a 'test-bed' assay to measure the activity of different ComR proteins in response to cognate and heterologous XIP peptides in vivo, revealing distinct ComR classes of strict, intermediate, and promiscuous specificity among species. We then solved an X-ray crystal structure of ComR from S. suis to further understand the interaction with XIP and to search for structural features in ComR proteins that may explain XIP recognition. Using the structure as a guide, we probed the apo conformation of the XIP-binding pocket by site-directed mutagenesis, both in test-bed cultures and biochemically in vitro. In alignments with ComR proteins from other species, we find that the pocket is lined by a variable and a conserved face, where residues of the conserved face contribute to ligand binding and the variable face discriminate among XIP peptides. Together, our results not only provide a model for XIP recognition and specificity, but also allow for the prediction of novel XIP peptides that induce ComR activity

Remodelage de la signalisation calcique dans la tumeur prostatique : signature moléculaire de la récidive du cancer de prostate après chirurgie ?

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A silent-growing and fast-killing melanoma in a teenager [Un mélanome de progression insidieuse et rapidement fatale chez une adolescente]

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The molecular surface properties of apo-ComR <i>S</i>. <i>suis</i>.

<p>(A) Solvent accessible surface representation colored by amino-acid conservation using the Consurf server and the bacterial strains used in this study. Darker red indicates increased conservation with dark red showing completely conserved positions. Unconserved residues are shown in grey, with dark grey as least conserved. The XIP binding site consists of a conserved surface and a variable surface. Residues of interest are indicated by position and labeled. The inset shows the DBD and TPR domain interface that consists of highly conserved residues, with hydrogen bonds indicated by a dashed green line. (B) The solvent accessible hydrophobic residues of the ComR <i>S</i>. <i>suis</i> surface are highlighted in orange (C) Electrostatic surface potential as calculated by APBS with a contour of -10 kT/e to 10 kT/e. (D) Alignment of ComR <i>S</i>. <i>suis</i> with all species studied in this work. Secondary structure is annotated as <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005979#ppat.1005979.g004" target="_blank">Fig 4</a>. Conserved and homologous residues are highlighted in red with the XIP variable face residues in a gray box. The alignment was generated by Clustal Omega and Espript3</p

X-ray crystallographic data collection and refinement statistics

<p>X-ray crystallographic data collection and refinement statistics</p

Structural comparison of the XIP binding pocket between different peptide recognition types.

<p>(A) Residues from strict and promiscuous ComR proteins are compared and labeled by color. <i>S</i>. <i>suis</i> in purple, <i>S</i>. <i>mutans</i> in pink, <i>MGAS5005</i> in green, and <i>S</i>. <i>bovis</i> 83 in orange. (B) Crystal packing artifact of the N-terminus (yellow) may mimic initial ComR peptide recognition. Residues making van der Waals contacts and/or hydrogen bond with the peptide are shown in purple, hydrogen bonds are represented by a dashed green line.</p

Distribution and conservation of competence pathways in <i>Streptococcus spp</i>.

<p>(Top) The Type-I ComRS pathway is found in the Salivarius group (yellow shading) and the ComCDE pathway in the Anginosus and Mitis groups (blue shading). The Type-II ComRS pathway is present in Bovis, Mutans, and Pyogenic groups of <i>Streptococcus</i> (red shading). The Suis group, or Type-III ComRS pathway (violet), contains attributes distinguishable from Type-I and Type-II. Underlined species indicate the demonstration of natural competence under laboratory conditions. (Bottom) The putative XIP sequences from the Type-II ComRS pathway demonstrate a conserved double tryptophan motif. Represented sequences were derived from small ORFs directly downstream of ComR and include the C-terminal 7 or 8 amino acids predicted to encode the mature pheromone. ^<i>a</i>The ComR derived from <i>S</i>. <i>agalactiae</i> NEM316 was not investigated, however this species does encode a putative Type-II XIP. ^<i>b</i>The <i>S</i>. <i>suis</i> 05ZYH33 XIP represents a Type-III XIP encoding two tryptophan residues (in green) interrupted by glycine and threonine. ^<i>c</i>The <i>S</i>. <i>thermophilus</i> LMD-9 Type-I XIP, lacking a WW-motif, is included for reference.</p

Designed XIP agonists of ComR <i>S</i>. <i>agalactiae</i> 2603.

<p>XIP peptides found to be ineffective signals for ComR <i>S</i>. <i>agalactiae</i> 2603 were redesigned to satisfy hypothetical ComR-activating criteria. Designed synthetic peptides were titrated to strain ES1 carrying ComR <i>S</i>. <i>agalactie 2603</i> reporter and maximum relative luciferase activities were recorded.</p