The transbonchial lung biopsy for diagnosis of diffuse parenchymal lung disease; Pro

The diagnosis of diffuse parenchymal lung disease (DPLD) may require invasive procedures after all noninvasive tools have failed. The clinical context in which these diseases develop and the radiological patterns are crucial for defining the timing and the methods to be used. After the introduction in clinical practice of HRCT scan, the evaluation of imaging patterns, along with the immunological status of the patient and the clinical course of the disease (acute vs. chronic) seem to be crucial to choose the best diagnostic procedure

Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations. Copyright (C) 2011 S. Karger AG, Base

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Measurement of neutron capture on 48^{48}Ca at thermal and thermonuclear energies

At the Karlsruhe pulsed 3.75\,MV Van de Graaff accelerator the thermonuclear $^{48}$Ca(n,$\gamma$)$^{49}$Ca(8.72\,min) cross section was measured by the fast cyclic activation technique via the 3084.5\,keV $\gamma$-ray line of the $^{49}$Ca-decay. Samples of CaCO$_3$ enriched in $^{48}$Ca by 77.87\,\% were irradiated between two gold foils which served as capture standards. The capture cross-section was measured at the neutron energies 25, 151, 176, and 218\,keV, respectively. Additionally, the thermal capture cross-section was measured at the reactor BR1 in Mol, Belgium, via the prompt and decay $\gamma$-ray lines using the same target material. The $^{48}$Ca(n,$\gamma$)$^{49}$Ca cross-section in the thermonuclear and thermal energy range has been calculated using the direct-capture model combined with folding potentials. The potential strengths are adjusted to the scattering length and the binding energies of the final states in $^{49}$Ca. The small coherent elastic cross section of $^{48}$Ca+n is explained through the nuclear Ramsauer effect. Spectroscopic factors of $^{49}$Ca have been extracted from the thermal capture cross-section with better accuracy than from a recent (d,p) experiment. Within the uncertainties both results are in agreement. The non-resonant thermal and thermonuclear experimental data for this reaction can be reproduced using the direct-capture model. A possible interference with a resonant contribution is discussed. The neutron spectroscopic factors of $^{49}$Ca determined from shell-model calculations are compared with the values extracted from the experimental cross sections for $^{48}$Ca(d,p)$^{49}$Ca and $^{48}$Ca(n,$\gamma$)$^{49}$Ca.Comment: 15 pages (uses Revtex), 7 postscript figures (uses psfig), accepted for publication in PRC, uuencoded tex-files and postscript-files also available at ftp://is1.kph.tuwien.ac.at/pub/ohu/Ca.u

Routine immunofluorescent and histochemical analysis of bone marrow involvement of lymphoma/leukaemia: the use of cryostat sections.

Enzyme histochemical and immunohistological (immuno-fluorescence and -peroxidase) techniques have been routinely used for investigating over 70 normal and pathological bone marrow samples. This recently standardized diagnostic procedure is very quick and can be performed in a few hours. In 6 cases the clinical diagnosis of leukaemia/lymphoma has become apparent only after the immunohistological analysis of the bone marrow. In 6 other cases the information about the staging of B cell malignancies was superior in the frozen biopsies to the paraffin embedded preparations. Amongst many other features the monoclonality of B CLL/lymphomas, the special features of B CLL infiltrates (RFA-1+, Leu-1+, HLA-DR+, SmIg+), follicular lymphoma deposits (containing follicular dendritic cells) and non-T, non-B acute lymphoblastic leukaemic blasts (terminal transferase+, HLA-DR+) as well as the sometimes conspicuous presence of infiltrating normal T cells could be clearly and reproducibly demonstrated

Unicentric mixed variant castleman disease associated with intrabronchial plasmacytoma.

Castleman disease (CD), described as a heterogeneous lymphoproliferative disorder, can be divided into different subtypes according to clinical appearance (unicentric and multicentric form) and histopathological features (hyaline vascular, plasma cell, mixed type, human herpesvirus 8-associated and multicentric not otherwise specified). Unicentric CD is known to be usually of the hyaline vascular variant, plasma cell and mixed type of this form are quite uncommon. Malignancies are mainly associated with the multicentric form. We report a rare case of unicentric mixed variant CD evolving into intrabronchial, extramedullary plasmacytoma.Intrabronchial mass with consequential obstruction of the left main bronchus, left lung atelectasis and mediastinal lymphadenomegaly was detected by chest CT in our patient suffering from cough and hemoptysis. Pulmonectomy was performed, histopathological and immunhistochemical analysis of lymph nodes revealed mixed type of CD with interfollicular monotypic plasma cell proliferation. The intrabronchial mass consisted of monotypic plasma cells confirming plasmacytoma. Systemic involvement was not confirmed by further tests.Although malignancies more often present in multicentric CD that usually belongs to the plasma cell subtype, this case confirms the neoplastic potential of the rarest, unicentric mixed variant of CD.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2872096831190851

Ectopic primary type A thymoma located in two thoracic vertebras: a case report

<p>Abstract</p> <p>Background</p> <p>The thymus arises in the ventral portion of the third and fourth pharyngeal pouch. It descends into the anterior mediastinum at 6^thweek of gestation. Any errors occurring during this process can cause dissemination of aberrant nodules that are responsible for most atypical thymomas.</p> <p>Case Presentation</p> <p>The authors report a unusual case of type-A thymoma located in D10 and D11 vertebral bodies.</p> <p>The histology showed a uniform growth of short, spindle shaped, mitotically inactive cells. A few small, normal lymphocytes were seen scattered or in small groups. The immunohistochemical investigation for neuroectodermal, neuroendocrine, vascular and muscular markers were negative. It also confirmed the presence of CD3+, CD5+ T lymphocytes and the absence of immature T-lymphocyte markers.</p> <p>Conclusions</p> <p>The case described shows a thymic hystogenesis for spindle cell tumours. To our knowledge no other cases of vertebral thymomas have been described in international literature.</p

Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis

BACKGROUND: Fibroblast foci (FF) are considered a relevant morphologic marker of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), and are recognised as sites where fibrotic responses are initiated and/or perpetuated in this severe disease. Despite their relevance, the cellular and molecular mechanisms responsible for the formation of FF and their role in tissue remodelling are poorly defined. In previous studies we have provided evidence of abnormal activation of the wnt-signaling-pathway in IPF/UIP that is centred on FF and the overlying epithelium. This important morphogenetic pathway is able to trigger epithelial-mesenchymal-transition (EMT), a mechanism involved in developmental and metastatic processes, which is also potentially involved in pulmonary fibrosis. METHODS: Since EMT is characterised by enhancement of migratory potential of cells, we investigated the molecular profile of FF in 30 biopsies of IPF/UIP and a variety of control samples, focussing on the immunohistochemical expression of three molecules involved in cell motility and invasiveness, namely laminin-5-γ2-chain, fascin, and heat-shock-protein-27. RESULTS: We provide evidence that in UIP these three molecules are abnormally expressed in discrete clusters of bronchiolar basal cells precisely localised in FF. These cellular clusters expressed laminin-5-γ2-chain and heat-shock-protein-27 at very high levels, forming characteristic three-layered lesions defined as "sandwich-foci" (SW-FF). Upon quantitative analysis SW-FF were present in 28/30 UIP samples, representing more than 50% of recognisable FF in 21/30, but were exceedingly rare in a wide variety of lung pathologies examined as controls. In UIP, SW-FF were often observed in areas of microscopic honeycombing, and were also found at the interface between normal lung tissue and areas of dense scarring. CONCLUSION: These molecular abnormalities strongly suggest that SW-FF represent the leading edge of pulmonary remodelling, where abnormal migration and re-epithelialisation take place, and that abnormal proliferation and migration of bronchiolar basal cells have a major role in the remodelling process characterising IPF/UIP. Further investigations will assess their possible use as reliable markers for better defining the UIP-pattern in difficult cases

The multifaceted roles of perlecan in fibrosis

Perlecan, or heparan sulfate proteoglycan 2 (HSPG2), is a ubiquitous heparan sulfate proteoglycan that has major roles in tissue and organ development and wound healing by orchestrating the binding and signaling of mitogens and morphogens to cells in a temporal and dynamic fashion. In this review, its roles in fibrosis are reviewed by drawing upon evidence from tissue and organ systems that undergo fibrosis as a result of an uncontrolled response to either inflammation or traumatic cellular injury leading to an over production of a collagen-rich extracellular matrix. This review focuses on examples of fibrosis that occurs in lung, liver, kidney, skin, kidney, neural tissues and blood vessels and its link to the expression of perlecan in that particular organ system