Elongated particulate burden in an individual who died of mesothelioma and had an occupational history as a talc "mucker".

INTRODUCTION: Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual's work history including working as a "mucker" at a specific "industrial" talc mine. METHODS: Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed. DISCUSSIONS/CONCLUSIONS: The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a "non-commercial" type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.

A clinical evaluation and tissue fiber burden analysis of a lifetime resident of Libby, Montana with adenocarcinoma of the lung.

INTRODUCTION: Vermiculite mining operations near Libby, Montana were active from the 1920s to 1990. Rail facilities for shipment of the mined material as well as some vermiculite processing activities were ongoing within the community of Libby. A fibrous component within the mined material has been associated with asbestos-related diseases in vermiculite miners and in the local citizens of the community. CLINICAL HISTORY/METHODS: We present a clinical case history and tissue fiber burden analysis of an individual with a multifocal adenocarcinoma of the lung who was a lifelong resident of Libby and whose history of exposure was as a member of the general population there. RESULTS/DISCUSSION: To our knowledge this is the first time tissue from a member of the general population of Libby, Montana has been evaluated and shown to contain an appreciable presence of "Libby amphibole" fibers.

Tissue burden evaluation of elongated mineral particles in two individuals with mesothelioma and whose work history included manufacturing tile.

Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.

A clinical assessment and lung tissue burden from an individual who worked as a Libby vermiculite miner.

During its days of operation (1920s-1990), the world's largest source of vermiculite was extracted from a mine located near Libby, Montana. The material mined at this site was shipped for various commercial applications to numerous sites in the United States. There was a "fibrous" component with toxic potential within the vermiculite deposit that has resulted in "asbestos-like" diseases/deaths being reported in numerous studies involving miners as well as residents of the town of Libby. The present case involves the clinical assessments of an individual who worked at the mine from 1969 to 1990. He had no other known occupational exposures to fibrous materials. He developed a clinical picture that included "asbestos-like" pathological features and eventually an adenocarcinoma. The clinical assessment including radiographic features will be presented. The evaluation will also include the analytical evaluation of the fibrous/ferruginous body composition of the lung tissue. This is to our knowledge the first time such an extensive evaluation has been conducted in a vermiculite miner from Libby, Montana.

Analysis of asbestos concentration in 20 cases of pseudomesotheliomatous lung cancer.

Mesothelioma is a rare neoplasm caused by asbestos exposure. The majority of mesotheliomas arise from the pleural lining of the thoracic cavity, but also involve the peritoneal and pericardial cavities. Another type of neoplasm referred to as pseudomesotheliomatous adenocarcinoma is rare. Most "pseudomesotheliomas" arise in the pleural tissue of the chest cavity and resemble pleural mesotheliomas, macroscopically and histologically. While most arise in the pleura, there are some that metastasize to the pleura from another site. We evaluated asbestos fiber concentrations in 20 cases of pseudomesotheliomatous lung cancer and found a significant number to contain an elevated concentration of asbestos in their lung tissue, which is similar with our study of 55 mesothelioma cases published in 1997. This would provide evidence that some pseudomesotheliomatous lung cancers are caused by asbestos.

Biodurability/retention of Libby amphiboles in a case of mesothelioma.

Mesothelioma is considered a signal tumor for exposure to asbestos (fibrous materials) and can occur decades after first exposure. The present case study reports on tissue burden of fibrous dust in a person who used a vermiculite material (Zonolite) as an attic insulator some 50 years prior to her death. The exposure occurred in two construction/renovation projects in her private residencies. She potentially had exposures to wall board/joint compounds during renovations. She additionally was reported to occasionally be involved in occupational activity, including drilling holes in presumed asbestos-containing electrical boxes. The tissue burden analysis revealed the presence of noncommercial amphibole asbestos fibers and consistent presence in the lung and lymph samples of Libby amphibole fibers. The findings of Libby amphibole fibers in human tissue can be attributed to exposure to Libby vermiculite. This study illustrates that analytical transmission electron microscopy can distinguish these structures from "asbestos" fibers. Further, the findings indicate that a population of these structures is biodurable and retained in the tissue years after first/last exposure.

Malignant mesothelioma: facts, myths, and hypotheses.

Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. J. Cell. Physiol. 227: 44-58, 2012. © 2011 Wiley Periodicals, Inc.

Mesothelioma in an individual following exposure to crocidolite-containing gaskets as a teenager.

Mesothelioma is considered a signal tumor for asbestos exposure and typically occurs decades after first exposure to asbestos. Tissue analysis often indicates past exposure to mixed types of asbestos. This report describes the case of a 58-year-old man who developed mesothelioma after reported exposure to crocidolite from asbestos-containing gaskets beginning at age 16 during three summers during high school and for approximately four hours per day during the last semester of his senior year. He had no further known exposure to asbestos. Analytical transmission electron microscopy analysis of digested tissue samples revealed elevated levels of crocidolite asbestos fibers and the presence of crocidolite cored ferruginous bodies. This case is unique in that it establishes that relatively short and/or intense exposures to crocidolite asbestos traumatically released from a previously classified Category 1 nonfriable asbestos-containing material (NESHAP) was confirmed via tissue burden analysis years following the historically defined exposures.

Morphological and chemical mechanisms of elongated mineral particle toxicities.

Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos particle toxicity involve two facets for each particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable elongated mineral particles.

A technical comparison of evaluating asbestos concentration by phase-contrast microscopy (PCM), scanning electron microscopy (SEM), and analytical transmission electron microscopy (ATEM) as illustrated from data generated from a case report.

As reported in the literature, there are more than 30 different standard methods available for the analysis of asbestos in a variety of situations. The methods include those for determining asbestos concentration in air, water, bulk building materials, surface dust, soil, and lung tissue (Millette, 2006; Dodson, 2006). Knowledge of the various methodologies is essential in determining which methodology is appropriate for any given situation. To better understand the use of various techniques in evaluating asbestos, we use an example of an individual who was a machinist in an auto supply/parts business. His work activity during much of his professional career included grinding, arcing, and drilling brake components. Asbestos has been identified as an important component of friction products, particularly brakes, and exposure to asbestos brake dust is of concern, particularly in workers where grinding, arcing, sanding, and drilling of brake components are recognized as releasing appreciable dust. Various methods can be used to evaluate asbestos in tissue and air. The case reported herein was of an individual who died from a pleural mesothelioma. Paraffin-embedded lung tissue was examined by a laboratory using scanning electron microscopy (SEM) and was reported to contain elevated asbestos body concentrations and five fibers, of which two were asbestos (one chrysotile and one tremolite). Tissue from the same paraffin block was analyzed by the laboratory of one of us (RFD) using analytical transmission electron microscopy (ATEM). While one might think the number of asbestos bodies and fibers would be similar using SEM and ATEM, this was not the case. Slightly elevated numbers of ferruginous asbestos bodies were detected in the digestate by light microscopy. Large numbers of uncoated chrysotile fibers were found by ATEM, but not by SEM. The majority of the chrysotile structures were fibrils whose detection required resolution levels attainable only at higher magnification by ATEM. The findings in this case clearly indicate that analysis of lung tissue digestates by ATEM at a higher magnification (15,000x) identifies significant numbers of asbestos fibers that are not identified by SEM at 1000x. These results further indicate that if causation of an asbestos-induced disease such as mesothelioma is based on asbestos concentration of lung tissue, erroneous conclusions can be made by analyzing tissue only by SEM. Thus, the methodologies that are available to analyze asbestos in lung tissue are extensively discussed here with respect to the type of procedure that should be utilized in various situations.

Characteristics of asbestos concentration in lung as compared to asbestos concentration in various levels of lymph nodes that collect drainage from the lung.

Inhaled dust particulates are able to relocate to the extrapulmonary compartments, particularly the lymph nodes that drain the lung. There is little information about the concentration and type of asbestos in the lymphatics and lymph nodes. Quantitative analysis of asbestos lymph node burden conducted by light and analytical transmission electron microscopy has shown ferruginous bodies in lymph nodes that drain the lung and appreciable numbers of short asbestos fibers accumulate in lymph nodes in occupationally exposed individuals. The location of lymph nodes in the thoracic cavity was categorized according to the Naruke anatomical map. Tissue from eleven individuals with a history of asbestos exposure were selected for a comparative study of the asbestos content of lung with that found in the thoracic lymph nodes. The study used a digestion technique for tissue preparation and evaluated ferruginous body burden and concentration of asbestos fibers (> 0.5 microm in length). Comparison was made between sites and analysis was made as to the population of fibers detectable by light microscopy and defined as "Stanton fibers." The findings indicated the vast majority of all asbestos fiber types in all sites were shorter than 5 microm and would not have been counted in a light microscopy count scheme that included only those fibers > 5 microm. There were reproducible patterns of asbestos types of found in various lymph nodes, although there were variations in the amount of asbestos found in the sites sampled. In summary, asbestos fibers found in thoracic lymph nodes have predominately short fibers and, in this study group, consisted of a mixture of commercial and noncommercial amphiboles. When a long/thin fiber was found in the lung or lymph tissue, its detection required the use of analytical transmission electron microscopy for identification.

Measurements of asbestos burden in tissues.

Asbestos inhaled into the lung is recognized as a potential causal agent for the development of diseases in man. The diseases induced by asbestos include lung cancer, fibrosis of the lung (asbestosis), and extrapulmonary tumors including mesothelioma (a tumor of the serosal membrane), as well as fibrosis and other changes in the pleura linings. The cause of these diseases can often be more specifically linked to asbestos exposure once tissue burden of asbestos is established. The asbestos burden in tissue can be defined as the number of asbestos bodies and/or the numbers and types of asbestos fibers found in the tissue. In either of these cases the quality of information is directly dependent on the preparative techniques and instrumentation used in the analysis. The present article will discuss the significance of findings of tissue burden based on both these variables.

Pleural mesothelioma in a woman whose documented past exposure to asbestos was from smoking asbestos-containing filtered cigarettes: the comparative value of analytical transmission electron microscopic analysis of lung and lymph-node tissue.

Asbestos has had many commercial applications, including its use as a major component in various types of filters. Between 1952 and 1956, crocidolite asbestos was used as a component of filters for cigarettes, reportedly greatly reducing tars and nicotine from mainstream smoke. This case report quantifies asbestos burden in lung and lymph node tissue in a 67-yr-old woman who succumbed to mesothelioma. Her only historically documented exposure to asbestos was from smoking crocidolite asbestos-containing filtered cigarettes between 1952 and 1956. Tissue digestion analysis by analytical transmission electron microscopy (ATEM) identified crocidolite fibers in lungs and thoracic lymph nodes. Combined ATEM data of lung and lymph node tissue clarified the patient's exposure to asbestos and particularly to crocidolite asbestos and thus to the presence of an entity recognized as the causal agent for mesothelioma.

Stability of ferruginous bodies in human lung tissue following death, embalmment, and burial.

The identification of asbestos bodies in tissue sections is an indicator of past exposure to longer asbestos fibers. These structures are formed in lung tissue as a consequence of interactions with pulmonary macrophages resulting in the deposition of a ferroprotein (ferruginous) coating on the fiber. While the process of ferruginous body formation is known to take months in animal tissue, there is no published information on the stability of ferruginous bodies in tissue following death. The material assessed in the present study was obtained from lung material collected from an exhumed body approximately 8(1/2) mo after death, embalmment, and burial. Tissue sections were reviewed for the presence of asbestos bodies. Additional pieces of lung tissue were digested, with the digestate being evaluated by light microscopy for ferruginous bodies and by electron microscopy for uncoated asbestos fibers and core analysis of asbestos bodies. Classical ferruginous (asbestos) bodies were found in abundance in the tissue sections including in areas with fibrosis. The levels of uncoated asbestos fibers and classical appearing ferruginous bodies (asbestos bodies) were consistent with occupational levels of tissue burden. The data from this study indicate that ferruginous bodies remain morphologically stable within the tissue for months following death, embalmment, and burial. Thus the lung tissue from this exhumed individual was usable not only to pathologically confirm asbestosis but also to provide quantitative data of occupational exposure to asbestos.

Asbestos burden in cases of mesothelioma from individuals from various regions of the United States.

Mesothelioma is a rare tumor that is considered an asbestos marker disease. It occurs in individuals following a longer latency period from first exposure than other asbestos-related diseases. The tumor also occurs in individuals with a wide range of exposures, including individuals with lower level or secondary exposures. In the present study lung tissue from 54 individuals with a pathological diagnosis of mesothelioma was evaluated for ferruginous body and uncoated asbestos fiber content. The data were compared with an earlier study of mesothelioma cases from the northwestern United States. Tissue was prepared via a digestion procedure, with the collected digestate reviewed by light microscopy for quantification of asbestos bodies and analytical transmission electron microscopy for determination of uncoated fiber burden. Twenty-seven cases in the present study had over 1000 ferruginous bodies per gram of dry tissue. The data suggest that amosite provides a more likely stimulus for ferruginous coating than the other forms of asbestos. All individuals were found to have asbestos fibers in their lung tissue. Amosite was the most commonly found fiber, with anthophyllite being the second most commonly found type of asbestos. The finding of tremolite in the tissue most often was associated with the finding of anthophyllite. A limited number of asbestos fibers of each type would have been seen in the light microscope, with the least detected being chrysotile. The majority of all fiber types were found as short fibers (< 8 mum), although some longer fibers were represented in each type of asbestos. The majority of the individuals were found to have mixed types of asbestos in their lungs.

Evaluation of the size and type of free particulates collected from unused asbestos-containing brake components as related to potential for respirability.

BACKGROUND: Chrysotile asbestos has found multiple applications in the production of friction products. At one point it comprised 40-50% of the composition of brake linings thus generating the potential for the development of asbestos related diseases in millions of workers involved in vehicle repairs. While some attention has been given to the health status of workers involved in the handling of worn components, little has been given to the potential for exposure during the handling and fitting of new (unused) components as replacement parts. METHODS: Unused brake linings or brake shoes with attached linings from four different sources were gently rinsed with prefiltered water that was then collected on filters for analysis by Analytical Transmission Electron Microscope. RESULTS: Large numbers of chrysotile asbestos containing structures, the majority of respirable size, were present in each sample. CONCLUSIONS: We conclude that any manipulation of new asbestos containing brake components would be expected to yield free dust containing chrysotile asbestos of respirable size. That the vast majority of these fibers and particulates would not be counted as regulated fibers rendering assessment of potential exposures in the work place, based on data of Permissible Exposure Limits or Regulated Fibers, questionable.

Quality control analysis of the potential for asbestos contamination during tissue processing in pathology laboratories.

CONTEXT: Various quality assurance procedures are applied in pathology and analytical microscopy laboratories to ensure accurate results. OBJECTIVE: To assess the potential of cross-contamination of tissue with asbestos fibers and asbestos bodies during the fixation and washing process. DESIGN: Lung tissue from 10 patients with potential asbestos-related disease was evaluated. Samples of fixative, water, and lung tissue from each case were evaluated by light and analytical transmission electron microscopy for asbestos bodies and uncoated asbestos fibers. RESULTS: The lung samples tested contained a range of asbestos bodies and uncoated asbestos fibers. One wash water sample contained one asbestos body. No asbestos bodies or uncoated asbestos fibers were found in any other water or fixative samples. CONCLUSIONS: The absence of uncoated asbestos fibers in wash water or fixative samples argues that the fixation process stabilizes asbestos fibers within tissue and the protocol used in this pathology laboratory protects against cross-contamination of tissue. The finding of one asbestos body in one water sample further supports the efficiency of the protective controls used in the testing methods, since this asbestos body was in the external solution that was being discarded before tissue sampling occurred.

Quantitative analysis of asbestos burden in a series of individuals with lung cancer and a history of exposure to asbestos.

Asbestos is recognized as a lung carcinogen. In the present study, tissue from 20 individuals who died from lung cancer and who had a history of exposure to asbestos was evaluated for the presence of asbestos bodies and uncoated asbestos fibers. A digestion procedure was used to isolate the particulates from the tissue. The samples were evaluated by light microcopy to quantify the numbers of ferruginous bodies in the tissue. The uncoated fibers (which included all fibers equal to or greater than 0.5 microm) were analyzed by analytical transmission electron microscopy. Seventeen of the 20 cases were positive for ferruginous bodies (which were morphologically consistent with asbestos bodies). Five of these were found to have concentrations within the range used in our laboratory for the general population (<20 ferruginous bodies/g wet tissue). Nineteen of the 20 cases were found to have asbestos fibers in the higher magnification scan (either 16 K or 20 K). Some of the asbestos fibers identified were specific for the types of exposures that were reported. Most individuals in this study were found to have mixed populations of asbestos fibers in the lung tissue. This suggests that when there are exposures to products containing commercial asbestos there are likely exposures to dust containing noncommercial asbestos. A contrast exists in the dust burden within the lung of these individuals as compared to samples from the general population in that occupational or "occupational-like" exposures such as in these cases are often reflected by the presence of longer fibers of asbestos in the tissue.

Pulmonary granulomatous vasculitis induced by insoluble particulates: a case report.

The authors report a case of a 39-year-old woman who sustained an injury to her left knee requiring arthroscopic surgical medial menisectomy and ganglionic block for reflex sympathetic dystrophy syndrome. Approximately 1 year after injury, the patient presented with an elevated white blood cell count and fever and was diagnosed to have a psoas muscle abscess, which was treated with antibiotics. She was also taking 4 different oral medications that contained microcrystalline cellulose as a filter. Approximately 1 month after being diagnosed with the psoas muscle abscess, the patient developed shortness of breath, marked weakness, diaphoresis, and intermittent emesis. She became hypotensive and tachyneic and expired. Postmortem examination showed granulomatous vasculitis with extensive occlusions of pulmonary arteries by birefringent crystalline material identified to be cellulose histochemically and by analytical electron microscopy evaluation. This case report describes the ultrastructural and chemical features of various medicinal tablet fillers and compares them to pure samples. This report also demonstrates the usefulness of analytical electron microscopy in accurately identifying birefringent material in lung tissue.