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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.

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.

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.

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.

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.

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.

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.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.Large numbers of chrysotile asbestos containing structures, the majority of respirable size, were present in each sample.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.

In 2011 this journal published a special issue with an emphasis on the “State of the Science and Mode of Action” as applicable to “Asbestos and Related Mineral Fibers.” Some issues discussed in the...

Background Asbestos inhalation is recognized as an exposure that increases the risk for the development of lung disease. It is unique among dusts in that it is both a carcinogen and capable of inducing extrapulmonary responses such as pleural thickening and fibrosis as well as malignancy. One feature of asbestos suggested as crucial in its pathological activity is its fibrous morphology. Long fibers that have been inhaled are cleared less readily and are thus more persistent in the body. Furthermore certain experimental models link fiber length to levels of risks for development of certain diseases. The present review will survey the data on this subject. Methods The review considers experimental models that have been used to assess the response to various lengths of fibers in animal models in addition to data obtained from studies of human materials. The review also emphasizes the importance in defining the method by which a sample is categorized. Results Data are offered which support the potential for longer fibers as well as shorter fibers to contribute to pathological responses. Conclusions The data presented argue that asbestos fibers of all lengths induce pathological responses and that caution should be exerted when attempting to exclude any population of inhaled fibers, based on their length, from being contributors to the potential for development of asbestos-related diseases. Am. J. Ind. Med. 44:291–297, 2003. © 2003 Wiley-Liss, Inc.

Background Lung tissue from 15 women who died from mesothelioma was evaluated for tissue burden of ferruginous bodies and uncoated asbestos fibers. The group contained individuals who had occupational exposure to asbestos and others had family members whose work history included vocations where contact with asbestos containing materials occurred. Methods Tissue samples from tumor free lung were digested and filtered and then investigated for ferruginous bodies by light microscopy and asbestos and non-asbestos fibers by analytical transmission electron microscopy (ATEM). Size and type of fibers were also analyzed. Results Asbestos bodies were found in 13 of the 15 samples and asbestos fibers were found in all cases. The most commonly found uncoated asbestos fiber in these individuals was amosite whereas tremolite was the second most commonly found form. The asbestos fiber burden in these females was often of mixed types. Conclusions The asbestos body and fiber burden in these cases show variation in tissue burden. Some cases in this study had appreciable burden, which was attributed to secondhand exposure from occupationally exposed family members. Mesothelioma can occur also in individuals with comparatively low tissue burdens of asbestos. Am. J. Ind. Med. 43: 188–195, 2003. © 2003 Wiley-Liss, Inc.

Lavage material was collected from 12 individuals whose work history included working in a cement manufacturing facility. The manufacturing processes of the facility included the use of crocidolite and chrysotile asbestos. Lavage material was prepared via digestion procedure and then analyzed for the presence of ferruginous bodies by light microscopy and for uncoated asbestos fibers by analytical transmission electron microscopy. A comparison was made as to the sensitivity between two analytical methods for linking a past exposure to a specific type of asbestos. The use of analytical transmission electron microscopy for identification of core material in the ferruginous bodies as well as for quantification of the uncoated asbestos fibers increased the sensitivity of the information obtained from lavage samples as necessary for confirming exposure in the past to specific types of asbestos.

Asbestos has been widely used in the past as a component in friction products. A unique setting of dust exposure to such products occurs when individuals are involved with refabrication of the worn components. It is of interest whether asbestos fibers are released from friction materials in the use phase and the postlife phase or if the mineral fibers are converted to a nonasbestos form. In the present study, an individual whose primary work activity had centered on clutch refabrication was evaluated for possible dust-related diseases. Tissue analysis revealed the presence of large numbers of asbestos fibers as well as ferruginous bodies. These particulates were characterized as to composition as well as dimensions. Clutches of the type typically used by this individual were obtained and material was rinsed from their surface for comparative purposes. Materials that were freed from the surface and reviewed by analytical transmission electron microscopy were clearly identifiable as chrysotile asbestos. The composition of the clutch material was compared with the components found in the patient's lung tissue. The conclusion from this comparison was that individuals exposed to friction materials under similar circumstances should use appropriate caution. Appreciable exposure to asbestos can occur and this exposure can be sufficiently high to result in disease.

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.

Our health center evaluated an individual for suspected pneumoconiosis, which had resulted from exposures in a foundry/metal reclamation facility. Appropriate consent forms were obtained for the procedures. Historically, individuals who work in foundries have been exposed to various types of dusts. The clinical findings in this case were consistent with silicosis with a suspicion of asbestos-induced changes as well. A sample from this individual, analyzed by electron microscopy, showed both classical and atypical ferruginous bodies. The uncoated fiber burden in this individual indicated an appreciable number of anthophyllite asbestos fibers. This finding, coupled with analysis of cores from ferruginous bodies and the presence of ferruginous bodies in areas of interstitial fibrosis, pathologically supported the diagnosis of asbestos-related disease. The unique factor associated with this case is that unlike in some settings in Finland where anthophyllite was mined and used commercially, this mineral fiber is not commonly found in commercially used asbestos products in the United States. Although the actual source of the asbestos exposure in this case is still being sought, it should be recognized that anthophyllite is a contaminant of many other minerals used in workplace environments, including foundries. The fiber burden indicates a unique type of exposure, differing from that usually construed as typical in occupational settings in the United States.

Study Objectives: Asbestos bodies (ABs) form as asbestos fibers become coated by a cellular iron- and protein-rich matrix. ABs have been reported in lymph nodes and a few extrapulmonary sites, but no data exist as to their formation outside of the lung. It is not clear whether the AB found in these extrapulmonary areas have been transported as mature structures from the lung or formed at the extrapulmonary site. This study was designed to determine if ABs are produced in extrapulmonary sites. The guinea pig efficiently forms ferruginous bodies in the lung and so it was chosen as a model to test the coating efficiency of amosite asbestos fibers in lung, liver and spleen. Design: Sized amosite asbestos (5 mg) was administered either endotracheally into lung (n=2) or directly into liver (n=4) and spleen (n=4) of healthy 10-week-old male guinea pigs. The lung, liver and splenic tissues were removed at 40 and 180 days post inoculation and were examined histologically for the presence of AB via light microscopy. Uncoated fibers isolated from the tissues were characterized by electron microscopy. The coating efficiency was calculated as a ratio of uncoated/coated fibers per organ. Results: The coating efficiency ratios of fibers that were collected at 40 days post-injection from the individual sites were: lung—350:1, liver—4200:1, and spleen—220,000:1. At 6 months post-injection the ratios for the individual sites consisted of: lung—176:1, liver—11,000:1, and spleen—1000:1. Conclusion: This study indicates that AB can be formed in extrapulmonary sites and that the coating efficiency in the lung is much greater than that within the liver or spleen.

Study objectives Asbestos fibers have not been reported in tissues from the peritoneal cavity. Therefore, omentum, mesentery, and lung tissues from 20 individuals in whom mesothelioma was diagnosed were analyzed for asbestos bodies and asbestos fibers. Design Tissue was digested and prepared filters were analyzed by light microscopy and analytical transmission electron microscopy. Results Asbestos bodies were found in the lungs of 18 individuals, mesentery samples from 5, and omentum samples from 2. Uncoated asbestos fibers were found in lungs of 19 patients, 17 of whom had fibers in at least one extrapulmonary site. The most common asbestos in the omentum and mesentery was amosite. Several features of asbestos found in lung influenced the likelihood of amphibole fibers being found in the omentum or mesentery. Lung features included total amphibole fiber burden, length, aspect ratio, and ferruginous body burden. An increased total ferruginous body burden was strongly associated with increased likelihood of detecting amphiboles in the omentum (p Conclusion Asbestos fibers reach areas in the peritoneal cavity where some mesotheliomas develop. This study suggests their presence can be predicted based on concentrations and characteristics of fiber burdens in lung tissue.

Background The thoracic lymph nodes are a part of the clearance system from lung tissue. Accumulation of dust in these nodes are known to occur following some types of exposure. However, no information exists as to asbestos content in lymph nodes from the general population. Methods The study cohort consisted of 21 individuals previously defined as nonoccupationally exposed to asbestos. Tissue burden of asbestos obtained from lung analysis by analytical electron microscopy was compared with burden in the lymph nodes. Results No asbestos fibers were detected in nodes from 8 cases. The majority of the fibers found in lymph nodes were short (

Background The potential for asbestos exposure among members of the general population is appreciable, considering its widespread use in many products. This study examined tissue burden of asbestos in such a population. Methods A group of 33 individuals who had no work history of occupational exposure to asbestos were included in the study. Tissue sections from areas adjacent to those sites sampled for digestion were found to be without ferruginous bodies (FB) or histopathology consistent with asbestos-induced changes. All individuals had 20 or less FBs per gram of digested wet lung, a number considered to reflect general population levels. Tissue analysis of uncoated fiber burden was carried out by analytical electron microscopy. There was a trend of a higher likelihood of FB and asbestos fiber content correlated with age. Results The data are not consistent with the findings that chrysotile is readily found in lung tissue from the general population, in that none was found in 19 of the cases. It was almost as likely that one would find anthophyllite (12 of 33 cases) in this study. The commercial amphiboles (amosite and crocidolite) were occasionally found in the tissue from the general population and, when observed, were few in numbers. Twenty-six of the patients had no FBs and ten had no uncoated asbestos fibers within the limits of detectability in this study. Conclusions The total tissue burden of asbestos in this study is much less than earlier reported observations from other general populations. Am. J. Ind. Med. 35:281–286, 1999. © 1999 Wiley-Liss, Inc.

Using light and electron microscopy analysis, as well as electron diffraction, and energy-dispersive x-ray analysis, an aliquot of UICC chrysotile B was analyzed with special attention given to any tremolite contamination. Polarized light microscopy, with its limit of detection of approximately 1 micron when using dispersion staining, revealed chrysotile as the only fibrous asbestos component. Analytical electron microscopy at 333,000x of more than 20,000 consecutive fibers showed only the tubular morphology characteristic of chrysotile. These findings highlight that when this sample was used for exposure disease induced in animal models correlates with chrysotile-induced pathology, and does not support an explanation based on the "amphibole hypothesis." Thus, chrysotile should be considered as having the biologic ability to produce cancers, including mesotheliomas, based on the extensive use of this material as a standard reference material.

Objective This study sought to assess the fibrogenic and carcinogenic potential of erionite (a fibrous zeolite) on the pleural mesothelium of the Fischer 344 rat (n=24). Design The study was designed to examine rat pleural mesothelial changes by three independent observers at timed intervals, ranging from 1 to 480 days postinoculation using erionite from the Pine Valley, Nevada (USA) area. The mean length and width of the erionite fibers were 2.29 and 0.48 μm, respectively. Only microscopic observations made by majority (2/3) or unanimity (3/3) were accepted for final diagnosis. Results Pleural and lung tissue were available for examination in 21 of the 24 rats. Fibrosis, chronic inflammation, and foreign body reaction occurred in 6 of 21 rats. Mesothelial hyperplasia and dysplasia occurred in 9 and 3 of the 21 rats, respectively. A single mesothelioma was identified at 434 days in a rat that had gross nodular pleural lesions. Conclusions The findings reported herein confirm the strong fibrogenic potential of erionite but are at variance with previous studies reporting much higher yields of mesothelioma. The reasons for the low yield of mesothelioma in this study are not known, but may be related to the study design, the strict criteria used for histopathologic diagnosis, and/or possible differences in erionite physicochemical properties, associated with its geographic distribution, most previous animal studies having used erionite from the Rome, Oregon (USA) area.

Mesothelioma is a rare neoplasm that occurs most frequently in individuals with previous asbestos exposure. Differences for risk of development of asbestos-related mesothelioma and lung cancer have been attributed to the various types of asbestos, as well as to the dimension of the inhaled fibers. In the present study, 55 individuals with the pathological diagnosis of mesothelioma were evaluated as to ferruginous body and fiber content in lung tissue. The procedures used in the analysis included tissue digestion and analysis of the collected material for ferruginous bodies by light microscopy and for uncoated fibers by analytical transmission electron microscopy. Forty-six of the samples had ferruginous body concentrations of over 1000/per gram dry weight of lung tissue. The majority of the cores of these ferruginous bodies were amosite. Likewise, the most common uncoated asbestos fiber in the tissue was amosite. Only a small percentage of each type of asbestos would have been visible by light microscopy or even potentially by electron microscopy if the magnification was not sufficient to detect those with thin (< 0.2 micron) diameters. The consistent finding in most of the cases was a considerable presence of asbestos, often of mixed types.

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.

Tissue was obtained from two American groups. The tissue was defined by ferruginous body levels of eitheror = 1000 or1000 ferruginous bodies/g dry weight, and tissue was evaluated by light microscopy and analyzed by analytical transmission electron microscopy. Tissue was bleach digested, and uncoated asbestos fibers were classified with respect to type and size. In addition, some ferruginous body cores were analyzed. There was a wide range of uncoated fibers associated with each ferruginous body. A relationship was found between amosite fibers and ferruginous bodies. Other asbestos types were not associated significantly with the development of ferruginous bodies. Uncoated crocidolite fibers were not detected in these samples; this result further emphasizes the under-appreciated exposure of Americans to amosite. The levels of ferruginous bodies in both groups suggest exposures above those expected in the general population. Uncoated chrysotile levels were below the ranges reported previously for some general populations. The data suggest that there is a wide variation in the ratio of uncoated to coated fibers and that the amphibole in the United States is more likely to be amosite than crocidolite.

The risk of human exposure from asbestos-containing material is directly related to the condition of the material, custodial/maintenance activities, and the methods used to reduce the potential exposure to workers, bystander employees, and occupants of the area containing the asbestos. Many consider floor tile to be nonfriable, which is in accordance with the National Emission Standards for Hazardous Air Pollutants regulations, although there is some documentation of fiber releases from deterioration of such asbestos-containing materials during polishing, removal, or routine walking, due to the friction generated by such activities. This study evaluates several commonly used procedures for removal of floor tile and quantifies the fibers released during those procedures using data obtained by analyses from phase contrast microscopy and analytical transmission electron microscopy. These data document that fibers are released when floor tile is broken and/or abraded during removal procedures. Fiber ...

A 62-year-old white male employed for 43 years in the polishing room of a cotton textile mill was admitted to a tertiary care center with progressive dyspnea and productive cough that had not responded to therapy for tuberculosis. In spite of aggressive antibiotic therapy and respiratory support, the patient died as a consequence of respiratory failure. Small rounded and irregular opacities had been noted on the chest radiograph. Review of job-site spirometry demonstrated a worsening restrictive pattern over a 4-year period prior to his death. Additional occupational history revealed long-term exposure to kaolin in the polishing room, and pathologic examination of lung tissue confirmed extensive fibrosis and substantial quantities of kaolin. Kaolinosis is a disease typically found among individuals involved in mining or processing this material rather than in user industries. This case illustrates the importance of obtaining a complete occupational history in reaching a diagnosis. The clinicopathologic aspects of kaolinosis are also reviewed.

A 59-y-old man was exposed to chrysotile asbestos while rebuilding clutches. Analytical electron microscopy showed a chrysotile core in 72% of the ferruginous bodies from lung tissue. Long, uncoated chrysotile fibers were also present. Sufficient exposure to long chrysotile in jobs such as this appears to allow the majority of ferruginous bodies to be formed on chrysotile, an exception to the rule that most ferruginous bodies form on amphibole cores.

Tissue from an individual with a history of exposure to asbestos and other dust was referred for particulate analysis. The digested material was reviewed by light microscopy to establish the numbers of ferruginous bodies per gram of tissue. Typical asbestos bodies were found at levels consistent with occupational exposure. A second type of elongated ferruginous body was formed on a thicker transparent core which suggested the minerals were sheet silicates. The number of ferruginous bodies with nonasbestos cores was over four times the number of asbestos cored ferruginous bodies. Electron microscopy was used to confirm the core composition of both populations and also to establish the levels of uncoated fibers. The nonasbestos ferruginous bodies were predominantly formed on talc.

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.

Classical ferruginous bodies in tissue samples are considered to be markers of past exposure to asbestos. Recent studies have shown that the presence of ferruginous bodies in bronchoalveolar lavage (BAL) fluid correlates with past exposure to asbestos and offers a more sensitive reference than occupational history. Lavage samples from five subjects who had worked in foundries were evaluated by light microscopy for the presence of ferruginous bodies and by transmission electron microscopy for both characterisation of the uncoated fibre burden and analysis of the cores of the ferruginous bodies. All samples at lower magnification (light microscopy (200 x)) contained ferruginous bodies that were externally consistent with asbestos bodies. At higher magnification (400 x), a separate population from this group could be identified by the presence of a thin black ribbon. Transmission electron microscopy of the core materials of ferruginous bodies and comparable uncoated particulates supported the reliability of higher magnification light microscopy for distinguishing most of those non-asbestos cores; however, a population of transparent non-asbestos cored ferruginous bodies were also shown to exist.

Digests of lungs, liver, and placenta from five stillborn infants of 22 to 38 weeks gestational age were examined for asbestos and other fibers using light and electron microscopy, energy dispersive X-ray analysis, and selected area diffraction analysis. Uncoated chrysotile asbestos fibers were found in the digests of at least one of the three tissues examined from each stillborn infant. The asbestos fiber burdens ranged from 71,000 to 357,000 fibers/g wet tissue. Most of the fibers were small, with the mean length ranging from 0.83 to 2.53 microns. While appreciable numbers of uncoated chrysotile fibers were present, no coated asbestos fibers were found in any of the stillborns. Both coated and uncoated nonasbestos fibers were found in at least one of the tissue digests of all five stillborns. The uncoated nonasbestos fibers were characterized as aluminum silicates, diatomaceous earth fragments, or other fibers. The coated nonasbestos fibers or ferruginous bodies were consistent with being formed on diatomaceous earth fragments, black carbon cores, or sheet silicate cores. Since the placenta is the only route of communication between the fetus and the outside environment, our findings strongly suggest a transplacental transfer of asbestos and other fibers in humans.

Fiberoptic bronchoscopy has permitted the development of lavage procedures for the collection of lung washes. In certain disease states this material may contain large numbers of phagocytic cells (macrophages and neutrophils). Since these phagocytes are the predominant "dust scavenger cells" in the lung, the assessment of their particulate burden as well as that of the overall lavage material has been suggested as a potentially important diagnostic tool. The studies to date have shown that the presence of ferruginous bodies is an indication of past occupational exposure. In the present study, a digestion procedure was carried out on bronchoalveolar lavage material collected from individuals who were occupationally exposed to asbestos and from samples obtained from the general population. The parameters used for distinguishing the source of these samples included both light microscopy assessment of the filters for the presence of ferruginous bodies and electron microscopic screening for the presence of uncoated fibers.

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.

Autopsy samples from eight former shipyard workers were collected from lung parenchyma, tracheal lymph nodes, and pleural plaques. The tissue from each respective area was prepared by a modified bleach digestion technique, and the residue was collected on a 0.2-micron pore polycarbonate or 0.22-micron mixed cellulose ester filter. Quantitation of ferruginous bodies and uncoated fibers was done by light and transmission electron microscopy, respectively. Differences in the asbestos burden were noted for each site. Ferruginous bodies were observed in both parenchyma and nodes but not in plaques. Three subjects were found to have more ferruginous bodies per gram dry weight in their lymph nodes than in their lung parenchyma. Likewise, all subjects were found to have more uncoated fibers per gram in the nodes than in the parenchyma. Amphibole and chrysotile fibers were noted in the lung and extrapulmonary sites, with chrysotile being the predominant asbestiform in plaques. The majority of the uncoated fibers in both the nodes and the plaques were less than or equal to 5 microns in length. However, some fibers with dimensions conforming to the "Stanton hypothesis" reached both areas. These residual patterns most likely reflect the impact of clearance on lung burden as opposed to the eventual accumulation and stasis in the extrapulmonary areas.

Background: We report a series of 196 cases of pseudomesotheliomatous neoplasms identified in one of our laboratories between 1983 and 2015. We also performed an extensive review of the literature. Most

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.

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.

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 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 (

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.

Asbestos fibers in occupationally exposed individuals relocate from the lung to extrapulmonary sites. A mechanism for relocation is via the lymphatic circulation. Indeed, asbestos fibers have been found in lymph nodes as well as pleural plaques. Our laboratory has recently shown that asbestos fibers also reach the mesentery and omentum in the peritoneal area where a small percentage of mesotheliomas occurs in exposed individuals. The present study uses light and analytical transmission electron microscopy for defining the asbestos burden in digested lung, omentum, and mesentery tissues from individuals considered as representing the general population in East Texas. The findings, when compared with previous data from occupationally exposed individuals, indicate extreme contrasts as to the level and types of fiber burden between individuals representing the groups.

Asbestos has been used in many applications, but possibly one of the more unique was in the manufacturing of filters for cigarettes. The type of asbestos used in this application was crocidolite. Data from several resources indicate that crocidolite was one of the least utilized types of commercial asbestos in the United States. The present study provides quantitative tissue burden analysis data for two mesothelioma cases where the work histories included manufacturing of cigarette filters that contained crocidolite. The data include the number of asbestos bodies and uncoated fibers per gram of tissue, as well as the dimensions of these structures. The conclusion of the findings indicates that the individuals had an appreciable homogeneous exposure to crocidolite asbestos.

OBJECTIVES: To present a case of asbestosis and small cell lung cancer caused by asbestos in a clutch refabricator. METHODS: Exposed surfaces of used clutches similar to those refabricated in the worker's workplace were rinsed, and the filtrate analysed by analytical transmission electron microscopy. Tissue samples were also analysed by this technique. RESULTS: Numerous chrysotile fibres of respirable dimensions and sufficient length to form ferruginous bodies (FBs) were detected from rinsed filtrates of the clutch. Bronchoalveolar lavage fluid contained many FBs, characteristic of asbestos bodies. Necropsy lung tissue showed grade 4 asbestosis and a small cell carcinoma in the right pulmonary hilum. Tissue analysis by light and analytical electron microscopy showed tissue burdens of coated and uncoated asbestos fibres greatly exceeding reported environmental concentrations (3810 FBs/g dry weight and 2,080,000 structures > or = 0.5 micron/g dry weight respectively). 72% Of the cores were identified as chrysotile. CONCLUSIONS: Clutch refabrication may lead to exposure to asbestos of sufficient magnitude to cause asbestosis and lung cancer.