Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713

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Pulmonary histopathological alterations in patients with acute respiratory failure: an autopsy study

Alterações histopatológicas pulmonares em pacientes com insuficiência respiratória aguda: um estudo em autopsias

Alexandre de Matos Soeiro, Edwin Roger Parra, Mauro Canzian, Cecília Farhat, Vera Luiza Capelozzi

J Bras Pneumol.2008;34(2):67-73

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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.

 


Detection of micrometastases in pN0 non-small cell lung cancer: an alternative method combining tissue microarray and immunohistochemistry

Detecção de micrometástases em câncer de pulmão não-pequenas células estádio pN0: um método alternativo combinando imunohistoquímica e análise em microsséries

Maíra Rovigatti Franco, Edwin Roger Parra, Teresa Yae Takagaki, Fernando Augusto Soares, Vera Luiza Capelozzi

J Bras Pneumol.2008;34(3):129-135

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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.

 


Using electron microscopy and multivariate cluster analysis to determine diagnosis and prognosis in cases of neuroendocrine lung carcinoma

Diagnóstico e prognóstico dos tumores pulmonares neuroendócrinos mediante microscopia eletrônica e análise multivariavel de agrupamento

Cecília Aparecida Vaiano Farhat, Edwin Roger Parra, Andrew V. Rogers, Silvia Nagib Elian, Mary N. Sheppard, Vera Luiza Capelozzi

J Bras Pneumol.2008;34(10):804-811

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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.

 


Esclerose sistêmica e pneumonia intersticial idiopática: diferenças histomorfométricas em biópsias pulmonares

Esclerose sistêmica e pneumonia intersticial idiopática: diferenças histomorfométricas em biópsias pulmonares

Edwin Roger Parra, Leandro Hideki Otani, Erika Franco de Carvalho, Alexandre Ab'Saber, Vera Luiza Capelozzi

J Bras Pneumol.2009;35(6):529-540

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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.

 


Immunophenotyping and gene rearrangement analysis in lymphoid/lymphoproliferative disorders of the lungs

Imunofenotipagem e rearranjo gênico em doenças pulmonares linfocíticas e linfoproliferativas

Camila Cristina Ishikawa, Alexandre Muxfeldt Ab'Saber, Edwin Roger Parra, Chin Jia Lin, Carmen Silvia Valente Barbas, Vera Luiza Capelozzi

J Bras Pneumol.2007;33(6):625-634

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Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis

Imunofenotipagem e remodelamento da matriz extracelular na sarcoidose pulmonar e extrapulmonar

Pedro Henrique Ramos Quintino da Silva, Edwin Roger Parra, William Sanches Zocolaro, Ivy Narde, Fabíola Rodrigues, Ronaldo Adib Kairalla, Carlos Roberto Ribeiro de Carvalho, Vera Luiza Capelozzi

J Bras Pneumol.2012;38(3):321-330

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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.

 


Morphological aspects as prognostic factors in malignant mesothelioma: a study of 58 cases

Marcadores morfológicos de prognóstico no mesotelioma maligno: um estudo de 58 casos

Alexandre Bottrel Motta, Germânia Pinheiro, Leila Antonângelo, Edwin Roger Parra, Maria Margarida Monteiro, José Carlos das Neves Pereira, Tereza Takagaki, Mario Terra Filho, Sandro Martins, Vera Luiza Capelozzi

J Bras Pneumol.2006;32(4):322-332

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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.

 


 

 


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