Objective Vulvar squamous cell carcinoma and in situ lesions can be stratified by human papillomavirus (HPV) and TP53 status into prognostic risk groups using p16 and p53 immunohistochemistry. We assessed the significance of vulvar squamous cell carcinoma resection margin positivity for either differentiated vulvar intra-epithelial neoplasia (dVIN) or abnormal p53 immunohistochemistry, and other pathologic variables, in a cohort of patients with HPV-independent (HPV-I) p53 abnormal (p53abn) vulvar squamous cell carcinomas. Methods Patients with stage I–II HPV-I p53abn vulvar squamous cell carcinoma with negative invasive margins who did not receive adjuvant radiation from a single institution were included. Tumors underwent margin reassessment using p53 immunohistochemistry. Cases were segregated into (1) morphologic dVIN at margin; or (2) abnormal p53 immunohistochemistry staining at margin without morphologic dVIN (p53abn immunohistochemistry); or (3) margins negative by morphology and p53 immunohistochemistry. Clinicopathologic/outcome data were collected. Results A total of 51 patients were evaluated: (1) 12 with dVIN on margin; (2) 12 with p53abn immunohistochemistry on margin without morphologic dVIN; and (3) 27 with margins negative for morphologic dVIN and p53abn immunohistochemistry. The recurrence rate for patients with dVIN or p53abn immunohistochemistry on the margin was equally high at 75% each, compared with 33% with margins negative for morphologic dVIN and p53abn immunohistochemistry (p=0.009). On multivariate analysis, positive in situ margins maintained an association with disease recurrence (p=0.03) whereas invasive margin distance (radial and deep), lymphovascular invasion, and tumor size did not. Conclusions Patients with stage I–II HPV-I vulvar squamous cell carcinoma with margins positive for either dVIN or p53abn immunohistochemistry without morphologic dVIN showed increased disease recurrence, regardless of invasive margin distance. These findings show that p53 immunohistochemistry is a useful adjunct for evaluating margin status in HPV-I vulvar squamous cell carcinoma and may support repeat excision for positive in situ margins (dVIN or p53abn immunohistochemistry).

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia.A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed.We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (≤40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample.Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.

Human lungs are constantly exposed to a large number ofAspergillusspores which are present in ambient air. These spores are usually harmless to immunocompetent subjects but can produce a symptomatic disease in patients with impaired antifungal defense. In a small percentage of patients, the trachea and bronchi may be the main or even the sole site ofAspergillusinfection. The clinical entities that may develop in tracheobronchial location include saprophytic, allergic and invasive diseases. Although this review is focused on invasiveAspergillustracheobronchial infections, some aspects of allergic and saprophytic tracheobronchial diseases are also discussed in order to present the whole spectrum of tracheobronchial aspergillosis. To be consistent with clinical practice, an approach basing on specific conditions predisposing to invasiveAspergillustracheobronchial infections is used to present the differences in the clinical course and prognosis of these infections. Thus, invasive or potentially invasiveAspergillusairway diseases are discussed separately in three groups of patients: (1) lung transplant recipients, (2) highly immunocompromised patients with hematologic malignancies and/or patients undergoing hematopoietic stem cell transplantation, and (3) the remaining, less severely immunocompromised patients or even immunocompetent subjects.

This review aims to define the role of adenosine deaminase (ADA) and interferon gamma (IFN-γ) in the differential diagnosis of pleural effusion with special attention to their source, mechanism of release and methods of measurement in pleural fluid. The diagnostic performance of ADA and IFN-γ is analyzed, and the advantages and limitations of their use in differentiating between tuberculous and nontuberculous pleural effusion are disucussed. Several potential biomarkers of tuberculous pleurisy have been evaluated, but none have been found to be clearly superior to pleural fluid level of ADA or IFN-γ. The majority of recent studies confirm the high diagnostic utility of pleural fluid ADA and IFN-γ measurement; hence, these markers are included in different diagnostic algorithms for patients suspected of tuberculous pleurisy. Other relatively new tests show a high variability [nucleic acid amplification tests (NAATs)] or are technically demanding, costly and give equivocal results in patients with active tuberculosis [IFN-γ releasing assays (IGRAs)]. Pleural fluid ADA and IFN-γ are both sensitive and specific biomarkers of tuberculous pleurisy. Their diagnostic accuracy across the different studies shows a smaller variability than that of other tests, for example NAATs. There is also no convincing evidence that IGRAs are superior to pleural fluid ADA or IFN-γ measurement. Hence, the role of ADA and IFN-γ in the differential diagnosis of tuberculous pleurisy is pivotal.

Chemical pleurodesis is a therapeutic procedure applied to create the symphysis between the parietal and visceral pleura by intrapleural administration of various chemical agents (e.g. talk, tetracycline, iodopovidone, etc.). The two major clinical conditions treated with chemical pleurodesis are recurrent pleural effusion (PE) and recurrent spontaneous pneumothorax. Although the history of chemical pleurodesis began over a century ago, detailed data on the mechanisms of action of sclerosing agents are highly incomplete. The following article aims to present the state of knowledge on this subject.It is believed that mesothelial cells are the main structural axis of pleurodesis. In response to sclerosing agents they secrete a variety of mediators including chemokines such as interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP-1), as well as growth factors - vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and transforming growth factor- β (TGF-β). Numerous data suggest that intact mesothelial cells and the above cytokines play a crucial role in the initiation and maintenance of different pathways of pleural inflammation and pleural space obliteration.It seems that the process of pleurodesis is largely nonspecific to the sclerosant and involves the same ultimate pathways including activation of pleural cells, coagulation cascade, fibrin chain formation, fibroblast proliferation and production of collagen and extracellular matrix components. Of these processes, the coagulation cascade with decreased fibrinolytic activity and increased fibrinogenesis probably plays a pivotal role, at least during the early response to sclerosant administration.A better understanding of various pathways involved in pleurodesis may be a prerequisite for more effective and safe use of various sclerosants and for the development of new, perhaps more personalized therapeutic approaches.

Although Meigs' syndrome is regarded as a well-defined entity, contradictory data on pleural fluid characteristics have been presented, with some papers classifying it as a transudate, whereas others stating that it is an exudate.The aims of the study were: (1) to evaluate pleural fluid characteristics in patients with Meigs' syndrome and (2) to analyze the prevalence of transudative and exudative pleural effusion in relation to the applied definition of the syndrome.We performed a search through medical databases (MEDLINE, EMBASE, SCOPUS, and GOOGLE SCHOLAR) to identify papers on Meigs' syndrome published between 1940 and 2013. Two authors independently reviewed each paper searching for prespecified data: (1) signs and symptoms, (2) tumor characteristics, (3) clinical and laboratory data on ascites, (4) clinical, radiological, and laboratory data on pleural fluid, (5) clinical course after tumor removal. All case reports were reclassified according to a new unequivocal classification of Meigs' syndrome-related entities.A total of 653 papers were initially identified, and 454 articles reporting 541 patients were included in the final analysis. After reclassification according to our case definitions, there were 196, 113, and 108 patients defined as classic Meigs' syndrome, nonclassic Meigs' syndrome, and pseudo-Meigs' syndrome, respectively. Significantly more patients presented with right-sided than left-sided and bilateral pleural effusions (P < 0.001). Median volume of withdrawn pleural fluid was 2950 (1500-6000) mL. The classification of pleural effusion with the use of Light's criteria was possible in only 7 patients. In 6 of these patients pleural effusion met the criteria for an exudate. When the protein concentration > 3.0 g/dL was applied as a criterion of pleural exudate, 88.8% (80/90) of effusions were classified as exudates. Increasing the cut-off level to 3.5 g/dL resulted in only a modest decrease in the percentage of exudative effusions (81%, 73/90).Surprisingly few reports on Meigs' syndrome present data reliably defining the character of pleural effusion. The available data indicate, however, that the majority of pleural effusions in patients with this entity are exudates. This finding may be a prerequisite for the verification of some earlier presented concepts.