Dimitra Rontogianni

CXCL13 production in B cells via Toll-like receptor/lymphotoxin receptor signaling is involved in lymphoid neogenesis in chronic obstructive pulmonary disease.

RATIONALE Little is known about what drives the appearance of lymphoid follicles (LFs), which may function as lymphoid organs in chronic obstructive pulmonary disease (COPD). In animal infection models, pulmonary LF formation requires expression of homeostatic chemokines by stromal cells and dendritic cells, partly via lymphotoxin. OBJECTIVES To study the role of homeostatic chemokines in LF formation in COPD and to identify mechanism(s) responsible for their production. METHODS Peripheral lung homeostatic chemokine and lymphotoxin expression were visualized by immunostainings and quantified by ELISA/quantitative reverse transcriptase-polymerase chain reaction in patients with COPD with and without LFs. Expression of lymphotoxin and homeostatic chemokine receptors was investigated by flow cytometry. Primary lung cell cultures, followed by ELISA/quantitative reverse transcriptase-polymerase chain reaction/flow cytometry, were performed to identify mechanisms of chemokine expression. Polycarbonate membrane filters were used to assess primary lung cell migration toward lung homogenates. MEASUREMENTS AND MAIN RESULTS LFs expressed the homeostatic chemokine CXCL13. Total CXCL13 levels correlated with LF density. Lung B cells of patients with COPD were important sources of CXCL13 and lymphotoxin and also expressed their receptors. Cigarette smoke extract, H2O2, and LPS exposure up-regulated B cell-derived CXCL13. The LPS-induced increase in CXCL13 was partly mediated via lymphotoxin. Notably, CXCL13 was required for efficient lung B-cell migration toward COPD lung homogenates and induced lung B cells to up-regulate lymphotoxin, which further promoted CXCL13 production, establishing a positive feedback loop. CONCLUSIONS LF formation in COPD may be driven by lung B cells via a CXCL13-dependent mechanism that involves toll-like receptor and lymphotoxin receptor signaling.

Undifferentiated embryonal sarcoma of the liver mimicking acute appendicitis. Case report and review of the literature.

BackgroundUndifferentiated embryonal sarcoma (UES) of liver is a rare malignant neoplasm, which affects mostly the pediatric population accounting for 13% of pediatric hepatic malignancies, a few cases has been reported in adults.Case presentationWe report a case of undifferentiated embryonal sarcoma of the liver in a 20-year-old Caucasian male. The patient was referred to us for further investigation after a laparotomy in a district hospital for spontaneous abdominal hemorrhage, which was due to a liver mass. After a through evaluation with computed tomography scan and magnetic resonance imaging of the liver and taking into consideration the previous history of the patient, it was decided to surgically explore the patient. Resection of I–IV and VIII hepatic lobe. Patient developed disseminated intravascular coagulation one day after the surgery and died the next day.ConclusionIt is a rare, highly malignant hepatic neoplasm, affecting almost exclusively the pediatric population. The prognosis is poor but recent evidence has shown that long-term survival is possible after complete surgical resection with or without postoperative chemotherapy.

Teratoma occupying the left hemithorax

BackgroundTeratomas are manifested with a great variety of clinical and radiological features, while sometimes they simply represent incidental findings.Case presentationA rare case of benign teratoma of the dermoid cyst type, in an adult 40-year-old female patient, is reported. The patient had presented recurrent pulmonary infections for the previous 2 months, persistent cough, and progressively aggravating dyspnea. A chest X-ray showed total atelectasis of the left lung, and the thoracic CT-scan revealed a huge mass, containing multiple elements of heterogeneous density, probably originating from the mediastinum, occupying the whole left hemithorax. The mass compressed the vital structures of the mediastinum, great vessels and airways, and a chest MRI was performed to accurately detect the anatomical relations. The patient underwent left thoracotomy and the tumor was totally resected. The size of the tumor was extremely large although no invasion to the vessels or to the airway had occurred. Adherence to the adjacent left pulmonary artery and left main bronchus was present, but without erosion or fistulization. The postoperative course was uneventful, while the histological examination confirmed a teratoma.ConclusionA teratoma is a non-homogeneous pathological entity, clinically, radiologically or histologically. It is predominantly diagnosed between the second and fourth decade and the incidence is equal for both sexes. Symptoms are absent in one half of the patients. The case reported is noteworthy as the tumor appeared with total atelectasis of the left lung, and symptoms started 2 months prior to diagnosis. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.

Proliferation profile of classical Hodgkin's lymphomas. Increased expression of the protein cyclin D2 in Hodgkin's and Reed-Sternberg cells

There is accumulating evidence that Hodgkins and Reed–Sternberg cells of classical Hodgkins lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkins and Reed–Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkins and Reed–Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkins and Reed–Sternberg cells.

Elevated IgG4 Serum Levels Among Primary Sjögren's Syndrome Patients: Do They Unmask Underlying IgG4‐Related Disease?

To determine IgG4 levels in a cohort of consecutive patients with primary Sjögrens syndrome (SS) and other autoimmune diseases and explore whether they associate with distinct clinical, serologic, and histopathologic features.

Thymoma and myasthenia gravis: clinical aspects and prognosis

Myasthenia gravis is present in a significant proportion of patients with thymoma. We investigated particular features of the clinical behavior of thymoma and its relationship to myasthenia in a retrospective study of 79 patients who underwent thymectomy for thymoma during the last 20 years. The presence of myasthenia gravis, Masaoka stage, World Health Organization histotype, myasthenia response, and survival were analyzed. The mean age of the patients was 56.1 ±12.4 years, and 39 had myasthenia gravis. A significantly higher proportion of patients with myasthenia was found in B2 and B3 histotypes compared to A, AB, and B1. Among myasthenic patients, 33.3% had no response, 50% had a partial response, and 16.7% achieved complete remission. During the follow-up period, 16 (21.1%) patients died. Mean survival was 4.8 ± 1.4 years for patients with no myasthenia response, whereas those with a partial or complete myasthenia response had significantly better survival.

The many faces of sarcoidosis: asymptomatic muscle mass mimicking giant-cell tumor

Sarcoidosis is a chronic, multisystem granulomatous disease of unknown etiology. Muscle involvement is frequent, but often asymptomatic. There are three forms of muscular sarcoidosis: only the nodular type can be recognized by imaging. MRI and 18F-FDG PET–CT are the best methods to attempt the diagnosis of nodular muscular sarcoidosis; nevertheless, the lesion can mimic a malignant tumor. In this case, biopsy is the only tool to identify the disease.

Bronchiolitis: adopting a unifying definition and a comprehensive etiological classification

Bronchiolitis is an inflammatory and potentially fibrosing condition affecting mainly the intralobular conducting and transitional small airways. Secondary bronchiolitis participates in disease process of the airways and/or the surrounding lobular structures in the setting of several already defined clinical entities, mostly of known etiology, and occurs commonly. Primary or idiopathic bronchiolitis dominates and characterizes distinct clinical entities, all of unknown etiology, and occurs rarely. Secondary bronchiolitis regards infections, hypersensitivity disorders, the whole spectrum of smoking-related disorders, toxic fumes and gas inhalation, chronic aspiration, particle inhalation, drug-induced bronchiolar toxicities, sarcoidosis and neoplasms. Idiopathic or primary bronchiolitis defines clinicopathologic entities sufficiently different to be designated as separate disease entities and include cryptogenic constrictive bronchiolitis, diffuse panbronchiolitis, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, neuroendocrine hyperplasia in infants, bronchiolitis obliterans syndrome in lung and allogeneic hematopoietic cell transplantation, connective tissue disorders, inflammatory bowel disease and bronchiolitis obliterans organizing pneumonia. Most of the above are pathological descriptions used as clinical diagnosis. Acute bronchiolitis, though potentially life threatening, usually regresses. Any etiology chronic bronchiolitis contributes to morbidity and/or mortality if it persists and/or progresses to diffuse airway narrowing and distortion or complete obliteration. Bronchiolitis in specific settings leads to bronchiolectasis, resulting in bronchiectasis.

In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution

Cellular senescence, an age-related process in response to damage and stress, also occurs during normal development and adult life. The thymus is a central lymphoepithelial organ of the immune system that exhibits age-related changes termed thymic involution. Since the mechanisms regulating thymic involution are still not well elucidated, we questioned whether cellular senescence is implicated in this process. We demonstrate, for the first time in situ, that cellular senescence occurs during human thymic involution using SenTraGor™, a novel chemical compound that is applicable in archival tissue material, providing thus further insights in thymus histophysiology.

Medical Research Council dyspnea scale does not relate to fibroblast foci profusion in IPF.

BackgroundIn Idiopathic pulmonary fibrosis (IPF) irreversibly progressive fibrosing parenchymal damage, leads to defects in mechanics and gas exchange, manifesting with disabling exertional dyspnea. Previous studies have shown a relationship between fibroblast foci (FF) profusion and severity and survival and a relationship between dyspnea grade and severity and outcome. We hypothesized a relationship between Medical Research Council (MRC) dyspnea scale with FF, and a relationship between FF and functional parameters and survival.MethodsWe retrospectively reviewed 24 histologically documented IPF patients. Profusion of FF was semiquantitatively evaluated by two scores, Brompton and Michigan. Survival analysis was performed by fitting Cox regression models to examine the relationship of the two scores with survival and the non-parametric Spearman correlation coefficient was calculated to describe the relationships of FF scores with dyspnea scores and functional parameters.ResultsNo statistically significant correlation between FF scores and the MRC scores was observed (p = 0.96 and p = 0.508 respectively). No significant correlation between FF scores and survival (p = 0.438 and p = 0.861 respectively) or any functional parameter was observed.ConclusionsThe lack of relationship between the MRC dyspnea scale and the FF might relate to the fact that dyspnea in IPF better reflects the overall of lung damage and its related consequences on mechanics and gas exchange whereas FF, one of its histological hallmarks, may not reflect its entire histology derangement also constrained by the geographically limited sampled tissue. This might be also valid for the observed lack of association between FF and survival or functional parameters.