The mediastinum, made up by many organs and structures, comprises a wide range of affections, from simple cysts to low differentiated neoplasias and lymphomas. In their day-to-day activities, the diagnosis of these affections represent a real challenge to the pathologists. Furthermore, one of the main approaches to diagnosis includes mediastinoscopy. Therefore, the representation of the specimen for studies, as well as some artifacts to obtain the specimen, may pose some difficulty for a final diagnosis. This article will focus mainly on the problems faced to diagnose entities from the specimens obtained by mediatinoscopy in the surgical room, during the extraction of the material and at examination by freezing. The article will also update current criteria used to classify the tumors and the use of the immunohistochemistry to complement the diagnosis, criteria of invasion, and metastases. The purposes of this article are: recognize the main affections of the mediastinum, classify the main tumors, apply malignancy criteria, identify prognostic markers, and evaluate when there is need to establish a clinical, radiological and morphological correlation.

Keywords: Mediastinum. Mediastinum pathology. Prognostic markers.

The approach described below is an attempt to make order out of chaos for the pathologists dealing with diffuse lung disease and to provide radiologists some information about the histology of interstitial lung disease as it applies to HRCT. Obviously, the approach outlined is not applicable to all situations and many cases remain insoluble. Nevertheless, it does give the pathologist a framework within which interstitial lung disease can be assessed, and helps to develop a differential diagnosis histologically. The author thinks this approach also shows good correlation with many of the changes observed by the chest radiologist with HRCT of the lung. Recognizing an anatomic distribution may not necessarily be correlated with how a lesion is clinically viewed. For example, bronchiolocentricity is an important and prominent feature in hypersensitivity pneumonitis and respiratory bronchiolitis associated with interstitial lung disease, but neither is clinically considered an airway disease. The authors also make comments about transbronchial biopsy in opposition to open-lung biopsy in the pathologic assessment of difuse lung disease, although HRCT does provide information to the clinician to help select the most appropriate biopsy modality. Obviously, open-lung biopsy (and those retrieved by thoracoscopic techniques) offer more tissue and make it easier to observe anatomic distribution and reaction patterns. Nevertheless, transbronchial biopsies often include sufficient tissue (although fragmented) and the pathologist is able to mentally reconstruct the distribution and reaction pattern. Obviously, the changes assessed in transbronchial biopsy have to be individualized on a case-by-case basis, but it is surprising how often they are useful when carefully correlated with the clinical and radiological features in a given case.

Keywords: Pulmonary interstitial disorders. Pathology. Pulmonary fibrosis. Pulmonary biopsy.

Bronchiolitis or bronchiolitis obliterans are general terms used to describe a non-specific inflammatory injury that affects primarily the small airways, frequently not involving the pulmonary interstitium. Usually the terms utilized to categorize bronchiolitis are confused because they describe the clinical syndrome and also the histopathologic abnormalities. Unfortunately, most of the literature about bronchiolitis is based on isolated or small series. Additionally, there are many questions about epidemiology, pathophysiology, and treatment of bronchiolitis. The aim of this paper is to give a general view about the issue based on histopathologic features with the purpose of better understanding the clinical syndrome.

Biological markers are cellular, structural and biochemical components that can define cellular as well as molecular changes in both normal and neoplastic cells. There are two types of biological markers: 1) intermediate markers that evaluate cellular and molecular alterations before malignancy occurs; and 2) diagnostic markers, present in association with malignancy. The identification and validation of biological markers for clinical use are performed in stages: initial identification in cell cultures of the tumor;
testing of the marker in tissues obtained in biopsies of patients with an established diagnosis of the tumor;
testing of biopsies of normal tissues and tissues with an inflammatory process;
sputum, blood or urine tests for validation as a non-invasive test that can be used in high-risk populations. Sorologic and histopathologic biological markers are cellular, structural and biochemical components found in both normal and neoplastic cells that can be quantitatively assessed by biochemical, immunological and molecular methods in the body fluids or tissues, respectively, and may be associated with malignancies and, possibly, with the neoplastic organ. Biological markers are studied in diverse primary neoplasms. However, few of them proved to be clinically valuable. The role of biological markers in lung cancer patients remains unclear because only a small number of markers has been properly identifiassessed. The aim of this paper is to understand the role of sorologic and histologic biological markers in the prognosis and survival of lung cancer patients based on our previous works. Furthermore, we present a future perspective of the early detection of lung cancer on the basis of the role of intermediate biological markers.

Keywords: Biologic markers. Lung cancer. Prognosis. Survival. Morphometric method.

Asbestos-induced diseases are still major health problems, as a remarkably large number of workers have been exposed to asbestos over the past 50 years. Personal injury lawsuits against asbestos manufacturers number hundreds of thousands, and new cases are still being filed. Asbestosis is a complex issue, and although the broad outlines of asbestos-related diseases are well set, many important areas, especially pathology, are poorly understood. In Brazil, since 1940, asbestos has been commercially explored, producing around 200,000 tons/year, exposing about 10,000 workers in the mining activity, and an unknown number of workers in asbestos-cement industry. A study, with scientific appropriate investigation, with the purpose to evaluate the effects of asbestos exposure over the health of the mine workers in this country, was done by interinstitution researchers, and untitled "Morbidity and mortality among workers exposed to asbestos in mining activities - 1940/1996". With the experience achieved in the course of this study, the objective of this report is to make an overview of asbestos-related diseases, mainly with respect to difficulties in establishing the histopathologic diagnosis.

Keywords: Asbestosis. Pathology. Neoplasms. Diagnosis.

The role of immunohistochemistry is to recognize antigens and, consequently, to identify and classify specific cells within a cell population whose morphology is heterogenous or apparently homogenous. The visualization of the antigen-antibody complex is made possible through the addition of either a fluorochrome conjugate or an enzyme to the antibody, which is then viewed under microscopy. Immunohistochemistry can be used in the routine diagnosis of lung cancer, in order to identify biological markers (diagnostic and prognostic). The essential immunohistochemistry panels will be discussed in this review.

Keywords: Immunohistochemistry; Tumor markers, biological; Lung neoplasms.

Objective: To present an alternative method of detecting micrometastases in lymph nodes previously testing negative for non-small cell lung cancer (NSCLC) by routine hematoxylin-eosin staining. Methods: A total of 77 hilar and mediastinal lymph nodes resected from 18 patients with NSCLC were investigated for the presence of micrometastases using a combination of microarray analysis and immunohistochemistry. Results: Micrometastases were detected by identifying cytokeratin- and chromogranin-positive cells in lymph node microarrays. Of the 18 patients initially staged as pN0 through routine hematoxylin-eosin staining, 9 (50%) were restaged as N1, and the prognoses were re-evaluated in terms of histological and clinical parameters. The comparison of the survival curves revealed that survival was higher in the patients without micrometastases than in those with micrometastases. In addition, in the multivariate analysis adjusted for age, gender, histological type, and restaging, the presence of micrometastases proved to be an independent predictor of survival. Among patients who had been previously staged as pN0, the risk of death was found to be 7-times greater for those later diagnosed with micrometastases than for those in whom no micrometastases were identified. Conclusion: The combination of microarray analysis and immunohistochemistry might represent a low-cost and less time-consuming alternative for identifying occult micrometastases and predicting prognoses in surgically resected patients with pN0 NSCLC. Larger randomized, prospective studies are needed in order to determine the accuracy of this method.

Keywords: Lung neoplasms; Microarray analysis; Chromogranin A; Survival analysis.

The lung is source to a large number of cytological and histologic specimens. Pathologists should diagnose these specimens and then participate in the clinical and pathologic staging of the tumor. The first priority of pathologists when evaluating a lung tumor with specific histologic diagnosis can usually be accomplished with routine cytological or histologic preparations. These may be supplemented as necessary with ancillary histochemical or immunohistochemical studies. If adequate diagnostic tissue is available, special studies such as electron microscopy, frozen section immunostaining, cytogenetics, and molecular studies can be performed. In the case of small specimens, all tissue should be routinely processed; if a diagnosis cannot be rendered, subsequent biopsies can be prospectively triaged for the necessary and appropriate special studies. This is typical in cases of malignant lymphoma, in which biopsy specimens may be too small for definitive diagnosis without the aid of immunophenotype studies. The pathologic staging of a primary lung tumor is contingent on appropriate gross and microscopic examination of resection specimens. Standardized and unified staging schemes are necessary for comparative and collaborative studies of lung tumors. The following approach can be applied to segmentectomy, lobectomy, pneumectomy, en bloc resections, and tracheal or bronchial sleeve resections.

Objective: To present the pulmonary histopathological alterations found in the autopsies of patients with acute respiratory failure (ARF) and determine whether underlying diseases and certain associated risk factors increase the incidence of these histopathological patterns. Methods: Final autopsy reports were reviewed, and 3030 autopsies of patients > 1 year of age with an underlying disease and associated risk factors were selected. All had developed diffuse infiltrates and died of ARF-related pulmonary alterations. Results: The principal pulmonary histopathological alterations resulting in immediate death were diffuse alveolar damage (DAD), pulmonary edema, lymphocytic interstitial pneumonia (LIP) and alveolar hemorrhage. The principal underlying diseases were AIDS, bronchopneumonia, sepsis, liver cirrhosis, pulmonary thromboembolism, acute myocardial infarction (AMI), cerebrovascular accident, tuberculosis, cancer, chronic kidney failure and leukemia. The principal associated risk factors were as follows: age ≥ 50 years; arterial hypertension; congestive heart failure; chronic obstructive pulmonary disease; and diabetes mellitus. These risk factors and AIDS correlated with a high risk of developing LIP; these same risk factors, if concomitant with sepsis or liver cirrhosis, correlated with a risk of developing DAD; thromboembolism and these risk factors correlated with a risk of developing alveolar hemorrhage; these risk factors and AMI correlated with a risk of developing pulmonary edema. Conclusion: Pulmonary findings in patients who died of ARF presented four histopathological patterns: DAD, pulmonary edema, LIP and alveolar hemorrhage. Underlying diseases and certain associated risk factors correlated positively with specific histopathological findings on autopsy.

Keywords: Respiratory insufficiency; Autopsy; Lung diseases, interstitial; Pulmonary edema; Hemorrhage.

A significant percentage of pleural effusions remains without a diagnostic explanation. In such circumstances, the anatomical-pathological result of nonspecific chronic pleuritis should be revised. This is an important issue, not only for the pathologist, but mainly for the pneumologist, who usually makes the clinical-pathological correlation during the routine practice. Although the existence of established criteria is accepted, they are certainly subjective and make the communication by means of a common language difficult, mainly among pathologists. The authors recently studied 311 pleural biopsies with histo-pathological diagnoses of chronic nonspecific pleuritis. All specimens were reviewed and the histo-pathological parameters quantified by stereology. The patients were stratified according to the final diagnosis of their disease, including cases of chronic renal failure, vasculitis, pancreatitis, tuberculosis, cancer, and congestive cardiac failure, in this case considering the pleura as normal. This procedure allowed us to obtain a discriminating model, whose morphological subcriteria classified almost 90% of the nonspecific chronic pleuritis biopsies, according to their final clinical diagnoses, which included true nonspecific chronic pleuritis or tuberculosis pleuritis, paraneoplastic pleuritis, or even normal pleura. By adding to this model the biochemistry or differential cytology of the pleural liquid, its classificatory power reaches 99% of correctness. This study represents the result of the experience acquired over several years in the histo-pathological interpretation of pleural biopsies, based on the correlation between morphology and biochemistry and cytology of the pleural fluid.

Keywords: Biopsy, needle. Pleura/pathology. Pleura/cytology. Pleural effusion.

Objective: The aim of this study was to examine the parenchymal and extracellular matrix remodeling process in two histologic patterns-nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP)-in cases of idiopathic and sclerosis/systemic sclerosis (SSc)-associated interstitial pneumonia. Methods: We examined 15 cases of idiopathic NSIP, 10 cases of idiopathic UIP, 5 cases of SSc-UIP and 9 cases of SSc-NSIP. In the lung parenchyma, epithelial cells, endothelial cells and myofibroblasts were evaluated by immunohistochemical staining, whereas histochemical staining was used in order to evaluate collagen/elastic fibers in the extracellular matrix. Results: The percentage of surfactant protein A-positive epithelial cells was significantly greater in idiopathic NSIP than in SSc-NSIP, as well as being greater in idiopathic UIP than in SSc-UIP. Idiopathic NSIP and idiopathic UIP presented significantly higher immunoexpression of alpha smooth muscle actin in myofibroblasts than did SSc-NSIP and SSc-UIP. The percentage of CD34 endothelial cells in the pulmonary microvasculature was significant lower in idiopathic UIP than in SSc-UIP. The density of collagen fibers was significantly greater in idiopathic NSIP and idiopathic UIP than in SSc-NSIP and UIP. In contrast, the elastic fiber density was significantly lower in idiopathic UIP than in SSc-UIP. Conclusions: Increased collagen synthesis, destruction of elastic fibers, high myofibroblast proliferation and poor microvascularization might represent a remodeling process found in idiopathic interstitial pneumonia, whereas the reverse might represent a repair process in SSc-associated interstitial pneumonia.

Keywords: Epithelial cells; Neovascularization, pathologic; Collagen; Elastin; Idiopathic interstitial pneumonias; Scleroderma, systemic.

Objetivo: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. Métodos: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL) e 7 casos de doenças linfoproliferativas pulmonares. Resultados: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vγ11/Jγ12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dβ1/Jβ2 e Vγ101/Jγ12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. Conclusões: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnósticObjetivo: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. Métodos: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL) e 7 casos de doenças linfoproliferativas pulmonares. Resultados: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vγ11/Jγ12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dβ1/Jβ2 e Vγ101/Jγ12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. Conclusões: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnóstica.

Keywords: Linfoma; Doenças pulmonares intersticiais; Biologia molecular; Reação em cadeia da polimerase.

Objective: To evaluate the pleurodesis and the lung damage caused by intrapleural silver nitrate or talc in an experimental model in rabbits to consider the use in human beings. Design: 112 rabbits were randomized to receive intrapleural 0.5% silver nitrate or 400 mg/kg talc slurry in 2 ml saline. Eight rabbits in each group were sacrificed 1, 2, 4, 6, 8, 10, or 12 months post injection. The degree of pleurodesis (gross pleural fibrosis and inflammation), lung damage (collapse and edema), and cellular infiltrates were graded on a 0 to 4 scale. Results: The intrapleural injection of silver nitrate produced a better pleurodesis than did the intrapleural injection of talc slurry. The lung damage was moderate 1 month after silver nitrate and greater than after talc. They were similar as from the second month. Conclusions: The better pleurodesis induced by silver nitrate persists for at least one year. The more evident lung damage after silver nitrate was mild with reversible changes which show a clear tendency to normalize with time. For these reasons, the efficacy of silver nitrate as a sclerosing agent in humans should be evaluated.

Keywords: Pleurodesis. Talc. Silver nitrate. Pleural effusion.

The authors report the case of a female patient who developed chronic eosinophilic pneumonia secondary to long-term use of nitrofurantoin for prophylaxis of recurrent urinary tract infections due to urethral stenosis. On high-resolution computed tomography scans, the pulmonary reaction to nitrofurantoin most commonly manifests as an interstitial-alveolar pattern in both lung bases. However, in this case, the alterations were most pronounced in the periphery of the upper lobes. In itself, this tomographic profile is strongly indicative of chronic eosinophilic pneumonia. The patient had previously been submitted to an open lung biopsy. The diagnosis of chronic eosinophilic pneumonia was confirmed through a review of the biopsy.

Keywords: Pneumonia; Pulmonary eosinophilia; Nitrofurantoin/adverse effects; Tomography, X-ray computed.

Objective: Wegener's granulomatosis (WG) can cause endothelial cell damage and thromboembolic events. Nevertheless, there have been few studies on the pulmonary microcirculation-small and medium-sized pulmonary arteries (SMSPA)-in patients with WG. The objective of this study was to quantify fibrin thrombi in the SMSPA of patients with WG. Methods: We analyzed 24 SMSPA samples collected from six patients with WG and 16 SMSPA samples collected from four patients without WG. In all samples, we used the endothelial cell marker CD34 and confocal laser scanning microscopy in order to detect intravascular fibrin thrombi. We calculated the total vessel area, the free lumen area, and the thrombotic area. Results: The mean total vessel area was similar in the WG and control groups (32,604 µm2 vs. 32,970 µm2, p = 0.8793). Thrombi were present in 22 (91.67%) of the 24 WG group samples and in none of the control group samples (p < 0.0001; OR = 297; 95% CI: 13.34-6,612). The mean thrombotic area was greater in the WG group samples than in the control group samples (10,068 µm2 vs. 0.000 µm2; p < 0.0001). In contrast, the mean free lumen area was smaller in the WG group samples than in the control group samples (6,116 µm2 vs. 24,707 µm2; p < 0.0001). Conclusions: Confocal laser scanning microscopy revealed a significant association between pulmonary microvascular thrombosis and WG. This suggests a possible role of microvascular thrombosis in the pathophysiology of pulmonary WG, evoking the potential benefits of anticoagulation therapy in pulmonary WG. However, further studies are needed in order to confirm our findings, and randomized clinical trials should be conducted in order to test the role of anticoagulation therapy in the treatment of patients with pulmonary WG.

Keywords: Vasculitis; Antibodies, antineutrophil cytoplasmic; Wegener granulomatosis; Thrombosis; Lung; Microscopy, confocal.

Objective: To establish reproducible electron microscopic criteria for identifying the four major types of neuroendocrine tumors of the lung: carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; and small cell carcinoma. Methods: Measurements were made on electron micrographs using a digital image analyzer. Sixteen morphometric variables related to tumor cell differentiation were assessed in 27 tumors. The examination under electron microscopy revealed that all of the tumors could be classified as belonging to one of the four categories listed above. Cluster analysis of the morphometry variables was used to group the tumors into three clusters, and Kaplan-Meier survival function curves were employed in order to draw correlations between each cluster and survival. Results: All three clusters of neuroendocrine carcinomas were found to be associated with survival curves, demonstrating the prognostic significance of electron microscopic features. The tumors fell into three well-defined clusters, which represent the spectrum of neuroendocrine differentiation: typical carcinoid (cluster 1); atypical carcinoid and large cell neuroendocrine carcinoma (cluster 2); and small cell carcinoma (cluster 3). Cluster 2 represents an intermediate step in neuroendocrine carcinogenesis, between typical carcinoid tumors and small cell carcinomas. Conclusions: Our findings confirm that electron microscopy is useful in making the diagnosis and prognosis in cases of lung tumor.

Keywords: Neuroendocrine tumors/lung; Microscopy, electron; Cluster analysis; Survival analysis.

Objective: To study the clinical, radiological, and histopathological patterns of transbronchial biopsy (TBB) used in order to confirm the diagnosis in patients with clinical suspicion of interstitial lung disease (ILD) treated at a tertiary-care university hospital. Methods: We reviewed the medical records, radiology reports, and reports of transbronchial biopsies from all patients with suspected ILD who underwent TBB between January of 1999 and December of 2006 at the Hospital das Clínicas de Botucatu, located in the city of Botucatu, Brazil. Results: The study included 56 patients. Of those, 11 (19.6%) had a definitive diagnosis of idiopathic pulmonary fibrosis (IPF), the rate of which was significantly higher in the patients in which ILD was a possible diagnosis in comparison with those in which ILD was the prime suspect (p = 0.011), demonstrating the contribution of TBB to the diagnostic confirmation of these diseases. The histopathological examination of the biopsies revealed that 27.3% of the patients with IPF showed a pattern of organizing pneumonia, which suggests greater disease severity. The most common histological pattern was the indeterminate pattern, reflecting the peripheral characteristic of IPF. However, the fibrosis pattern showed high specificity and high negative predictive value. For CT scan patterns suggestive of IPF, the ROC curve showed that the best relationship between sensitivity and specificity occurred when five radiological alterations were present. Honeycombing was found to be strongly suggestive of IPF (p = 0.01). Conclusions: For ILDs, chest CT should always be performed, and TBB should be used in specific situations, according to the suspicion and distribution of lesions.

Keywords: Lung diseases, interstitial; Diagnosis, differential; Bronchoscopy.

Objective: The reproduction of an experimental emphysema model in rats by intratracheal instillation of papain was proposed for the evaluation of lung volume reduction surgeries. Method: The study used orotracheal instillation of papain (20 mg/kg) dissolved in 0.9% saline solution. Forty days after instillation, animals underwent mechanical ventilation. Elastance and resistance of the respiratory system were measured, and the rats were sacrificed by having their lungs removed. The pulmonary tissue of the animals was qualitatively analyzed with hematoxylineosin staining and submitted to morphometric analysis for the measurement of the mean alveolar diameter. The pulmonary tissue was also subjected to resorcin-fuchsin staining for the identification of elastic fibers, which were quantified in alveolar septa by digital imaging. Results: In the animals instilled with papain, the histological analysis of the lungs showed pan-acinar emphysema, with rupture of alveolar septa and hyperdistention. Morphometric analysis showed higher mean values for mean alveolar diameter in the lungs of the animals submitted to papain (149.08 μm and 100.56 μm) as compared to the group receiving saline solution (64.08 μm and 75.90 μm). The quantification of elastic fibers of alveolar septa of papain-treated animals was 70% lower than in the animals receiving saline solution. Mechanic ventilation did not show differences in respiratory system resistance of animals receiving papain or saline solution. Respiratory system elastance was lower in the group receiving papain than in the group receiving saline solution, showing a functional status compatible with pulmonary emphysema, with decreased elasticity of the pulmonary tissue. Conclusion: The reproduction of an experimental model of pan-acinar pulmonary emphysema in rats was achieved by papain instillation through the respiratory tree with functional and morphologic evidences.

Keywords: Pulmonary emphysema. Experimental model. Papain. Rats. Drug instillations.

Microscopic Polyangiitis is a form of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated small-vessel vasculitis that preferentially involves venules, capillaries and arterioles and may also involve arteries and veins. It is one of the most common primary systemic small-vessel vasculitis. Its clinical presentation is not distinguishable from the Wegener's granulomatosis (WG) and the Churg-Strauss syndrome (CSS). These types of small-vessel vasculitis are histologically similar and can be differentiated by the presence of granulomatous inflammation in WG or asthma in CSS. The case of a 66-year-old man with microscopic polyangiitis presenting with alveolar hemorrhage is reported with a discussion of the differential diagnosis of other types of pulmonary small-vessel vasculitis.

Keywords: Microscopic polyangiitis. Alveolar hemorrhage. Pulmonary vasculitis

Objective: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. Methods: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. Results: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = −0.90; p = 0.04). Conclusions: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Keywords: Sarcoidosis; Granulomatous disease, chronic; Extracellular matrix; Immunophenotyping; Respiratory function tests.

Objective: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). Methods: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki-67), we evaluated post-diagnosis survival in 58 patients with MM. Results: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. Conclusion: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5% immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma.

Keywords: Pleural neoplasms; Mesothelioma; Tumor markers, Biological; Carcinoembryonic antigen; Prognosis.

Background: Structural alterations to the pulmonary circulation characterize the vascular remodeling process and are likely correlated with local variations in flow and ischemia. Objective: To define the histological alterations to the pulmonary circulation seen after experimentally-induced ischemia of the pulmonary artery and to correlate those alterations with known patterns of blood redistribution and vascular remodeling. Method: Wistar rats (n = 48) were randomized into two groups with ligation of the pulmonary artery and without (controls) and were sacrificed on post-ischemia days 1, 7, 30 and 60. Lungs were removed and inspected for signs of parenchymal injury. External diameters, as well as wall thicknesses in the pulmonary, alveolar and bronchial end arterioles, were measured. Internal diameter and wall thickness percentage were calculated. Results: Infarction, necrosis and hemorrhage occurred only in ischemic lungs. In nonischemic lungs, there was a sustained increase in the internal and external arteriolar diameters, with an initial reduction in wall thickness on day 1, and day-60 values were similar to those seen in controls. In ischemic lungs, there was a transitory reduction in the internal and external diameters of the pulmonary and bronchial end arterioles, together with an initial, equally transitory, increase in their wall thickness. The alveolar arterioles presented sustained and progressive increases in external diameter and wall thickness, with concomitant reductions in internal diameter. Conclusion: This model mimics distal arterial disease in patients with chronic pulmonary thromboembolism. The vascular response in nonischemic lungs was consistent with a pattern of flow remodeling, whereas that seen in ischemic lungs was more consistent with flow and ischemia. In the pulmonary and bronchial end arterioles, the response was transitory, in contrast to the sustained and progressive response seen in the alveolar arterioles, which was probably caused by delayed local flow.

Keywords: Key-words: Pulmonary embolism. Pulmonary circulation. Vascular remodelling. Pulmonary artery.

Objective: To determine the impact that open lung biopsy findings have on decisions regarding changes in the treatment strategies employed for critically ill patients presenting diffuse pulmonary infiltrates and suffering from refractory acute respiratory failure, as well as on their clinical improvement. Methods: This study involved 12 mechanically ventilated patients with acute respiratory failure who were subjected to open lung biopsy (by thoracotomy) after not presenting a clinical response to standard treatment. Results: The single most common cause of the acute respiratory failure was viral infection, which was identified in 5 patients (40%). The pre-operative evaluation of the cause of respiratory failure was modified in 11 patients (91.6%), and a specific diagnosis was made in 100% of the cases. Regardless of changes in treatment regimen, the mortality rate was 50%. Six patients (50%) survived to be discharged from the hospital. All of the discharged patients survived for at least one year after the open lung biopsy, for an overall one-year survival rate of 50% among the 12 patients studied. For the patients who died in the hospital, the time of survival after open lung biopsy was 14 + 10.8 days. Conclusion: We conclude that open lung biopsy is a useful tool in the management of acute respiratory failure when there is no clinical improvement after standard treatment, since it can lead to a specific diagnosis that requires distinct treatment, which probably lowers the mortality rate among such patients.

Keywords: Respiratory distress syndrome, adult; Lung/pathology; Biposy; Acute respiratory syndrome