Lung cancer and interstitial lung diseases: the lack of prognostic impact of lung cancer in IPF.

Lung Cancer (LC) is the first cause of death worldwide. Recently increased interest in interstitial lung diseases (ILD) has highlighted an association with lung cancer, offering interesting insights into the pathogenesis of the latter. Describe the association between lung cancer and ILD and evaluate the impact of LC on survival in these populations. We collected clinical, radiological, histologic data of 53 cases of advanced pulmonary fibrosis with lung cancer: 17 with UIP pattern (usual interstitial pneumonia, UIP/IPF-LC) and 36 with non-UIP pattern (ILD-LC). Adenocarcinoma was the most frequent histological subtype of lung cancer in all three groups and in UIP/IPF-LC developed in the lung periphery and in an advanced fibrosis context. Patients with DLCO% < 38% showed survival < 10 months, irrespective of group and development of carcinoma in UIP/IPF does not necessarily affect survival, unlike in SR-ILD. Our results confirm that the oncogenic mechanism is closely linked to fibrotic and inflammatory processes and that the development of carcinoma affects survival in SR-ILD but not in IPF.

Serum Amyloid A in lung transplantation.

BACKGROUND: Serum Amyloid A (SAA) is an acute phase protein and we analyzed its concentrations in lung transplantated patients (LTX). METHODS: 26 LTX patients (58.6 ± 11 years) and 11 healthy controls (55 ± 11.3 years). Three groups of LTX patients: acute rejection (AR, 7) bronchiolitis obliterans syndrome (BOS, 3), acute infection (INF, 9) and stable patients (NEG, 7). RESULTS: In LTX patients SAA concentrations were significantly increased, particularly in AR and INF. In LTX-AR patients were observed a correlation between SAA levels and peripheral CD4+ lymphocyte percentage (r=0.9, p<0.01) and a reverse correlation with FVC percentages (r -0.94, p=0.01). CONCLUSIONS: SAA may represent a potential biomarker of LTX acute complications, with a prognostic value in AR. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 2-7).

A case of hypersensitivity pneumonitis in a worker exposed to terephthalic acid in the production of polyethylene terephthalate.

Occupational hypersensitivity pneumonitis (OHP) is an interstitial lung disease caused by sensitization to an inhaled antigen. Polyethylene terephthalate (PET) is mainly used for disposable beverage bottles. A clinical case of hypersensitivity pneumonitis (HP) in a 66-year-old patient in the follow-up as a worker formerly exposed to asbestos is presented. At the first visit in 2012 a diagnosis of asbestosis and pleural plaques was formulated. In 2017 the high resolution computed tomography was performed demonstrating a slight progression of the pulmonary fibrosis, while physical examinations revealed inspiratory crackles on auscultation, and lung function tests showed a decreased diffusing capacity for carbon monoxide. The radiological and histological pictures were compatible with HP. From 1992 to 2013 the patient worked in a chemical company that produced PET for disposable beverage bottles. A diagnosis of OHP was made, and the most likely causative agents were terephthalic acid and dimethyl terephthalate. To the best of the authors' knowledge, this is the first report of an OHP case in PET production. Int J Occup Med Environ Health. 2020;33(1):119-23.

Diagnosis of idiopathic pulmonary fibrosis by virtual means using "IPFdatabase"- a new software.

BACKGROUND: The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) guidelines has some shortcomings. The aim of the present study was to develop a novel software, "IPFdatabase", that could readily apply the diagnostic criteria per IPF guidelines and make a 'virtual' diagnosis of IPF. METHODS: Software was developed as a step-by-step compilation of necessary information according to guidelines to enable a diagnosis of IPF. Software accuracy was validated primarily by comparing software diagnoses to those previously made at a Center for Interstitial Lung Diseases. RESULTS: Clinical validation on 98 patients (68 male, age 61.0 ±â€¯8.5 years), revealed high software accuracy for IPF diagnosis when compared to historical diagnoses (sensitivity 95.5%, specificity 96.2%; positive predictive value 95.5%, negative predictive value 96.2%). A general radiologist and a general pathologist reviewed relevant data with and without the new software: interobserver agreement increased when they used the IPFdatabase (kappa 0.18 to 0.64 for radiology, 0.13 to 0.59 for pathology). CONCLUSION: IPFdatabase is a useful diagnostic tool for typical cases of IPF, and potentially restricts the need for MDDs to atypical and complex cases. We propose this web-designed software for instant accurate diagnosis of IPF by virtual means and for educational purposes; the software is readily accessed with mobile apps, allows incorporation of updated version of guidelines, can be utilized for gathering data useful for future studies and give physicians rapid feedback in daily practice.

Airway-Centered Pleuroparenchymal Fibroelastosis Associated with Non-Necrotizing Granulomas: A Rare New Entity.

Pleuroparenchymal fibroelastosis is a rare form of upper-lobe-dominant progressive pulmonary fibrosis characterized histologically by visceral pleural thickening with collagenous fibrosis, subpleural elastosis, and intra-alveolar collagenous fibrosis. It was first described 25 years ago by Amitani et al. This report firstly describes a new variant or rare phenotype of PPFE with airway involvement, minimal pleuroparenchymal connections, and non-necrotizing granulomas.

A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated.IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity and attenuation. We provide a novel RSV vaccine concept based on a genome replication-deficient Sendai vector that has many favorable vaccine characteristics. The specific vaccine design guarantees genetic stability of the transgene; furthermore, it supports a favorable presentation of the antigen, activating the adaptive response, features that other vectored vaccine approaches have often had difficulties with. Wide immunological and pathological analyses in mice confirmed the validity and efficacy of this approach after both parenteral and mucosal administration. Above all, this concept is suitable for initiating clinical studies, and it could also be applied to other infectious diseases.

The prognostic significance of proliferative indices in surgically resected IIIA-N2 non-small cell lung cancer after induction chemotherapy.

BACKGROUND: The aim of this study was to assess the prognostic significance of Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after induction chemotherapy in surgically resected IIIA-N2 patients. METHODS: Between January 2002 and November 2008, we reviewed 50 consecutive patients (39 males) with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who underwent radical resection following induction chemotherapy. Five-year survival in the series was evaluated in relation to lymph node downstaging, histology, extent of resection, number of chemotherapy cycles, pT status, sex and age. It was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib 1 expression), dividing the patients into two groups according to whether they were above or below the 50th percentile for each parameter. The associations between mortality and the abovementioned prognostic factors were explored using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. RESULTS: The monovariate analysis confirmed the positive prognostic role of lymph node downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1 expression under the 50th percentile were also associated with better 5-yr survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither apoptosis nor the other prognostic factors showed any statistical impact on long-term survival. The multivariate analysis showed Mi to be an independent prognostic factor (P=0.005). CONCLUSIONS: Although lymph node downstaging has been considered the principal prognostic factor after induction chemotherapy and surgical resection, Mi and Mib1 expression in residual tumor can predict long-term survival more accurately.

Inflammatory lung disease in Rett syndrome.

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with "high" (39.8%) and "low" (34.8%) patterns dominating over "mixed" (19.6%) and "simple mismatch" (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease.

Diffuse panbronchiolitis in a patient with common variable immunodeficiency: a casual association or a pathogenetic correlation?

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease that seems to have an immunological pathogenesis and that causes a severe progressive suppurative and obstructive respiratory disorder. Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency and it is often associated with respiratory diseases. Herein, we describe a case of DPB in a 41-year-old man affected by CVID. We examined the patient's lungs, focusing on the characteristics of the inflammatory cells and of the foamy macrophagic nodules typical of DPB. Immunohistochemical typing of the lymphocytic infiltrate showed that B-cells were almost absent, matching the immunological profile of CVID. The case described is the first case reported in the literature of DPB in a patient affected by CVID. Moreover it seems to confirm the correlation between an immunodeficiency status and the development of DPB and provides more information on the accumulation of nodules of foamy macrophages in DPB. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5310709471138338.

Patients with thymomas have an increased risk of developing additional malignancies: lack of immunological surveillance?

AIMS: To assess the risk, for patients with thymoma, of developing an additional malignancy (AM). METHODS AND RESULTS: We studied 68 patients with thymomas. Based on the World Health Organization classification, the tumours were categorised as A, AB or B (B1, B2, B3) thymomas. Control populations comprised 114 patients with colorectal cancer, 108 patients with lymphoma and 123 patients with thyroid carcinoma. Patients with thymomas showed a higher risk of developing an AM (22 of 68 patients versus 11 of 114, eight of 108, and eight of 123 patients, respectively; P = 0.0002). The association between thymomas and AMs was related to the thymoma histotype, with B1, B2, B3 and AB tumours showing a higher risk of developing an AM than A thymomas (P = 0.0474). CONCLUSIONS: Patients affected by thymomas showed a significantly higher risk of developing additional malignancies than those in the control groups, and cases that exhibited a predominantly cortical component were more likely to develop other neoplasms. This may be related to the functions of cortical thymic epithelial cells in providing for T lymphocyte maturation through interaction with major histocompatibility complexes.

Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature.

An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.

Routine assessment of hormonal receptor and her-2/neu status underscores the need for more therapeutic targets in Kenyan women with breast cancer.

OBJECTIVE: To report the expression of estrogen receptors, progesterone receptors and human epidermal growth factor receptor (Her-2/neu) in 158 Kenyan women with breast cancer and correlation with other prognostic indicators in this high-risk group. This study stressed the importance of routine assessment of the steroid receptors and Her-2/neu as a mode of therapeutic selection of patients for antihormonal or targeting monoclonal antibody (Herceptin) therapy, directed at the juxtamembrane domain of Her-2/neu protein in the developing countries such as Kenya. STUDY DESIGN: The study population consisted of 158 female patients with histologically confirmed breast carcinoma seen at the pathology department of The Nairobi Hospital. An immunohistochemical (IHC) study of ER, PR and Her-2/neu was conducted, followed by fluorescent in situ hybridization (FISH) validation for Her-2/neu gene amplification in cases initially scored as positive 2+ with IHC. Mastectomy samples registered at the pathology department of The Nairobi Hospital were used for this study. The study was approved by the institution's ethical review committee and informed consent obtainedfrom the concerned patients. RESULTS: In the studied cohort, positivity for both hormonal receptors and Her-2/neu was noted in 10 (6.33%) cases and negativity in 44 (27.85%) cases. Conversely, Her-2/neu negativity was noted in 32 (20.25%) cases with both steroid receptors positive and Her-2/neu positivity with both steroid receptors negative in 20 (12.66%) cases. Overall, no predictive factor was found in the Her-2/neu amplified 31/153 (20.26%) cases completely assessed with IHC and FISH. Grade III invasive ductal carcinomas, however, had a high prevalence of Her-2/neu overexpression. Association of both menopausal status (p = 0.044) and progesterone receptor status (p = 0.004) with high grade tumors were found to be statistically significant at 95% CI (p < 0.5). Consistent with other studies, Her-2/neu overexpression in this cohort was 20.26%. CONCLUSION: Her-2/neu positivity may activate ER expression through signaling kinases, and the combined target of mitogenic estrogen plus the monoclonal antibody therapy against Her-2/neu-overexpressing tumors expand chances of survival for patients in developing countries such as Kenya. The cost factor for these tests, selection for appropriate combined therapies and lack of awareness were noted as limiting factors for access to basic health care service and resulted in advanced tumor grade at time of patient presentation.