Search

Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21 st century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.

Objective: Several mechanisms have been proposed for the biological effect of diacetyl. We tested the postulate that animal and cell exposures to diacetyl are associated with a disruption in iron homeostasis., Materials and Methods: Male, Sprague-Dawley rats were intratracheally-instilled with either distilled water or diacetyl. Seven days after treatment, animals were euthanized and the lungs removed, fixed, and embedded. Sections were cut and stained for iron, collagen, and ferritin. Human epithelial (BEAS-2B) and monocytic (THP-1) cells were exposed in vitro to ferric ammonium citrate (FAC), diacetyl, and both FAC and diacetyl. Cell non-heme iron concentrations and ferritin levels were quantified using inductively coupled plasma optical emission spectroscopy and an immunoassay respectively., Results: After exposure of animals to diacetyl, there were airway polypoid lesions which stained positively for both iron and the intracellular storage protein ferritin. Trichrome stain showed a deposition of collagen immediately adjacent to accumulated metal following diacetyl exposure. In in vitro cell exposures, FAC increased non-heme iron concentration but co-incubations of FAC and diacetyl elevated levels to significantly greater values. Levels of ferritin were increased with exposures of BEAS-2B and THP-1 cells to FAC but were similarly greater after co-exposure with FAC and diacetyl., Conclusions: Results of animal and cell studies support a disruption of iron homeostasis by diacetyl. It is proposed that, following internalization, diacetyl complexes intracellular sources of iron. The cell recognizes a loss of its requisite iron to diacetyl and imports greater concentrations of the metal.

Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.

Asbestos is well-recognized as the cause of a variety of disorders of the respiratory tract, including neoplastic as well as non-neoplastic conditions. Fiber dimensions and biopersistence are important determinants of the pathologic response, and analytical electron microscopy is a powerful technique for determining the fiber content of lung tissue samples. For decades our laboratory has examined lung tissue samples counting fibers measuring 5 µm or greater in length. More recent observations have indicated that fibers 10 µm or greater in length are pathogenic, and that a length of 10 µm and diameter less than 1.0 µm are useful features for distinguishing asbestiform fibers from cleavage fragments. We examined more than 570 fibers from more than 90 cases to determine the dimensions of fibers that might be classified as asbestos. The vast majority of fibers classified as amosite or crocidolite met the criteria for length greater than 10 µm and diameter less than 1.0 µm. However, a significant proportion of fibers classified as tremolite, actinolite, or anthophyllite did not meet these criteria. These findings have important implications for the identification and classification of elongated mineral particles, both in terms of pathogenicity as well as classification as asbestiform vs. cleavage fragments.

A variety of fibrotic lung diseases are caused by the inhalation of organic dusts. Many of these disorders have distinctive histopathology and can be readily diagnosed by routine histopathologic examination. However, in some instances, there is overlap in morphology between diseases caused by dust inhalation (mineral pneumoconiosis) and other lung diseases. In such cases, analytical scanning electron microscopy (SEM) can provide valuable information to assist the pathologist in making the correct diagnosis. We report herein our findings in 96 cases in which in situ particle analysis (ISPA) was performed with the SEM. This included 56 cases of pneumoconiosis as well as 40 cases of other types of interstitial lung disease. The most common diagnosis for which ISPA was performed in individuals with pneumoconiosis was mixed dust pneumoconiosis (14 cases). The most common diagnoses for which ISPA was performed in individuals with other diseases were sarcoidosis (13 cases) and hypersensitivity pneumonitis (10 cases). In addition to a detailed description of our methodology, we also report other circumstances in which ISPA assists in the diagnosis of pulmonary disease.

Exposure to hard metal (tungsten carbide) dust is a rare cause of interstitial lung disease. Although most cases have a distinctive morphology known as giant cell interstitial pneumonitis, other patterns have been described as well. In such cases, the true nature of the interstitial process may be difficult to recognize. We present a case with unusual morphological features in which analytical scanning electron microscopy (SEM) was used to detect the presence of tungsten as well as other metallic particles. A combination of careful exposure history and examination by analytical SEM is useful for arriving at the correct diagnosis in such difficult cases.

Pneumoconiosis is often considered a disease of the lung initiated by exposure to dust or other airborne particles, resulting in injury to the lungs. The term "endogenous pneumoconiosis" has been used in the literature to describe the deposition of compounds on the elastic fibers of the lung, usually in the setting of cardiac failure. In the case we present here, the patient aspirated a foreign body resulting in damage to the lung tissue and subsequent deposition of endogenous compounds on the elastic fibers of the pulmonary parenchyma and vasculature. We determined the composition of this mineral and mapped the distribution of elements using a combination of backscattered electron microscopy and energy dispersive spectrometry.

Asbestos is universally recognized as a carcinogen for the lower respiratory tract. However, asbestos is a contributory factor in a small fraction of lung cancers, the vast majority of which are related to cigarette smoking. The challenge for the pathologist is to determine when a lung cancer may be attributed to past asbestos exposure. The finding of asbestosis either clinically or pathologically is a useful marker for such a determination. However, in the absence of asbestosis, it has been suggested that a fiber burden as determined by analytical electron microscopy within the range of asbestosis is sufficient for determination of a causal contribution. We report here an example of a case of lung cancer in which fiber burden studies showed an asbestos concentration within the range of asbestosis as determined by scanning electron microscopy (SEM).

Epidemiological studies indicate that 80-90% of mesotheliomas are asbestos related. This suggests that 10-20% are not. Lung fiber burden analysis provides objective information about past exposures to asbestos. We have performed lung fiber burden analysis on a large cohort of mesothelioma cases and compared the findings with a reference population. Herein we report our findings along with demographic and exposure data.

There has been considerable interest in the exposure doses that contribute to the various asbestos-associated diseases. Epidemiological studies have shown important differences in the contributions of the various fiber types to asbestos-related diseases, with the amphiboles showing a greater degree of potency as compared to chrysotile. However, epidemiological studies have occasionally provided misleading results. Over the past several decades, there have been several examples where fiber analysis using electron microscopy produced unexpected results which were important to our understanding of disease-exposure relationships. It is the purpose of this article to summarize these fiber analysis vignettes.

Aluminum-induced lung injury is an uncommon, yet recognized pneumoconiosis capable of causing severe interstitial fibrosis. Important attention to the clinical history including occupational exposure is an essential component to making the correct diagnosis, despite which careful examination of the lung specimen is necessary to exclude other more common disease entities. We present a case of aluminum-induced pneumoconiosis in the setting of a bilateral lung transplant patient. Additionally, we review the literature on aluminum-induced pneumoconiosis and demonstrate the use of ancillary techniques including backscattered electron imaging and energy-dispersive spectrometry to aid in diagnosis.

Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 ± 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations.

As a result of the challenge of recent dust storms to public health, we tested the postulate that desert dust collected in the southwestern United States imparts a biological effect in respiratory epithelial cells and an animal model. Two samples of surface sediment were collected from separate dust sources in northeastern Arizona. Analysis of the PM20 fraction demonstrated that the majority of both dust samples were quartz and clay minerals (total SiO₂ of 52 and 57%). Using respiratory epithelial and monocytic cell lines, the two desert dusts increased oxidant generation, measured by Amplex Red fluorescence, along with carbon black (a control particle), silica, and NIST 1649 (an ambient air pollution particle). Cell oxidant generation was greatest following exposures to silica and the desert dusts. Similarly, changes in RNA for superoxide dismutase-1, heme oxygenase-1, and cyclooxygenase-2 were also greatest after silica and the desert dusts supporting an oxidative stress after cell exposure. Silica, desert dusts, and the ambient air pollution particle NIST 1649 demonstrated a capacity to activate the p38 and ERK1/2 pathways and release pro-inflammatory mediators. Mice, instilled with the same particles, showed the greatest lavage concentrations of pro-inflammatory mediators, neutrophils, and lung injury following silica and desert dusts. We conclude that, comparable to other particles, desert dusts have a capacity to (1) influence oxidative stress and release of pro-inflammatory mediators in respiratory epithelial cells and (2) provoke an inflammatory injury in the lower respiratory tract of an animal model. The biological effects of desert dusts approximated those of silica.

Context: A detailed evaluation of the correlation and linearity of industrial hygiene retrospective exposure assessment (REA) for cumulative asbestos exposure with asbestos lung burden analysis (LBA) has not been previously performed, but both methods are utilized for case-control and cohort studies and other applications such as setting occupational exposure limits., Objective: (a) To correlate REA with asbestos LBA for a large number of cases from varied industries and exposure scenarios; (b) to evaluate the linearity, precision, and applicability of both industrial hygiene exposure reconstruction and LBA; and (c) to demonstrate validation methods for REA., Methods: A panel of four experienced industrial hygiene raters independently estimated the cumulative asbestos exposure for 363 cases with limited exposure details in which asbestos LBA had been independently determined. LBA for asbestos bodies was performed by a pathologist by both light microscopy and scanning electron microscopy (SEM) and free asbestos fibers by SEM. Precision, reliability, correlation and linearity were evaluated via intraclass correlation, regression analysis and analysis of covariance. Plaintiff's answers to interrogatories, work history sheets, work summaries or plaintiff's discovery depositions that were obtained in court cases involving asbestos were utilized by the pathologist to provide a summarized brief asbestos exposure and work history for each of the 363 cases., Results: Linear relationships between REA and LBA were found when adjustment was made for asbestos fiber-type exposure differences. Significant correlation between REA and LBA was found with amphibole asbestos lung burden and mixed fiber-types, but not with chrysotile. The intraclass correlation coefficients (ICC) for the precision of the industrial hygiene rater cumulative asbestos exposure estimates and the precision of repeated laboratory analysis were found to be in the excellent range. The ICC estimates were performed independent of specific asbestos fiber-type., Conclusions: Both REA and pathology assessment are reliable and complementary predictive methods to characterize asbestos exposures. Correlation analysis between the two methods effectively validates both REA methodology and LBA procedures within the determined precision, particularly for cumulative amphibole asbestos exposures since chrysotile fibers, for the most part, are not retained in the lung for an extended period of time.

Objectives: To investigate the impact of extreme data points in Finkelstein's 2009 findings of no association between lung levels of commercial and non-commercial amphiboles (principally tremolite as a marker for chrysotile asbestos) in brake repair workers with mesothelioma., Methods: We first identified potential outliers, high leverage points, and influential points among lung levels of commercial amphiboles and tremolite among 15 persons whose only known exposure to asbestos was through brake repair work. We used sensitivity analysis and quantile regression to account for extreme data points and model commercial amphibole levels as a predictor of tremolite levels. We also used quantile regression to evaluate whether case-reported duration of employment as a brake repair worker predicted lung levels of commercial amphiboles or tremolite., Results: We found lung levels of commercial amphiboles are a statistically significant predictor of tremolite levels via sensitivity analysis (r = 0.82, slope estimate P-value = 0.001, R² = 0.68) and quantile regression (slope estimate P-value <0.0001). Our data provide no evidence that duration of employment as a brake repair worker was a predictor of lung levels of tremolite or commercial amphiboles., Conclusions: Our findings suggest that elevated lung levels of tremolite in the lungs of brake repair workers with elevated levels of amphiboles arose from concurrent exposures to commercial amphibole and chrysotile asbestos in occupational settings other than brake repair work. These findings are supported by five new cases. The weight of the scientific evidence does not support a role for occupational exposure to brake dust and other friction products in the development of mesothelioma.

This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.

The causative relationship between asbestos exposure and mesothelioma is firmly established. Some information in this regard comes from analysis of the fiber content of lung tissue by means of analytical electron microscopy. The author has had the opportunity to study the lung asbestos content of 396 cases of mesothelioma, including 28 peritoneal cases, by means of analytical scanning electron microscopy. The highest fiber levels occurred in patients who also had asbestosis, which was found in 12% of pleural and 43% of peritoneal cases. Elevated tissue asbestos content was identified in 87% of pleural and 75% of peritoneal cases. Peritoneal cases that are asbestos related have on average a higher lung fiber burden than pleural cases. Mesotheliomas in women have elevated tissue asbestos content in about 60% of cases, and many of these had a history of exposure as a household contact of an asbestos worker. The main fiber type identified in our series was amphibole, predominantly amosite. These fibers have been demonstrated to reach the target tissue, the pleura.

Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.

Previous studies from this laboratory have demonstrated that in rats exposed briefly to aerosolized chrysotile asbestos, fibers initially deposited in the distal lung impact primarily at bifurcations of alveolar ducts. Subsequently, there is a progressive decrease in the numbers of fibers seen by scanning electron microscopy at the bifurcations with increasing time from initial exposure. The purpose of the present study was to assess the number and dimensions of fibers deposited in the lungs of these rats and to determine how these parameters changed at various intervals after the termination of exposure. This was accomplished using a sodium hypochlorite digestion-concentration technique to recover the fibers on a membrane filter. The numbers and dimensions of the fibers were then assessed using scanning electron microscopy. Utilizing these data, the mass of asbestos retained in the lung was calculated with a newly developed formula. Twenty-three percent of the respirable fraction was deposited in the lungs, and 19% of this amount was still present 31 days after exposure. Over the 31 days, there was a progressive increase (p less than 0.05) in mean fiber length and a significant decrease (p less than 0.05) in the diameter of the population of fibers retained in the lung. Such data should prove useful in attempting to understand the progressive pathogenesis of asbestos-induced interstitial lung disease, which seems to be related, at least in part, to the dimensions of the inhaled fibers.

We present a unique case of pulmonary blastoma and describe its histology and ultrastructure. The stromal component exhibited bizarre multinucleated giant cells containing previously undescribed granules. These membrane-limited granules were eosinophilic, periodic acid-Schiff positive, diastase resistant, acid phosphatase and nonspecific esterase negative, immunohistologically negative for lysozyme, albumin, and gamma globulin, and often homogeneously electron dense. A similar electron-dense material accumulated in the rough endoplasmic reticulum of these stromal giant cells, suggesting that the material in the granules is synthetic. The material appeared to be a glycoprotein but was not alpha1-antitrypsin, alpha-fetoprotein, or human chorionic gonadotropin by immunohistologic techniques. These stromal cell granules differ from granules described in epithelial cells of other pulmonary blastomas but resemble granules found in some sarcomas.