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BACKGROUND: Perls’ Prussian blue (PPB) stain recognizes Fe(3+) associated with hemosiderin. The employment of this stain in clinical medicine and research has been extensive and novel applications continue to evolve. SUMMARY: Ferruginous bodies are intracellular structures in lung tissue, bronchoalveolar lavage (BAL), and sputum which stain with PPB. Inhaled, insoluble, biopersistent particles and fibers are phagocytosed by lung macrophages and thought to be coated, either partially or completely, with an iron-containing protein at the interface forming a ferruginous body. These structures can be categorized as ferruginous bodies having either an inorganic or a carbonaceous core (e.g. asbestos and byssinotic bodies respectively). In lung tissue, BAL, and sputum, the only cells which stain with PPB are macrophages. These are described as iron- and hemosiderin-laden macrophages and called either siderophages or sideromacrophages. Siderophages can be observed in the lung tissue, bronchoalveolar lavage, and sputum after various exposures and can also be associated with many different pulmonary and extrapulmonary diseases. KEY MESSAGES: PPB staining by intracellular structures and cells in the lung is most consistent with an accumulation of iron after a disruption in the homeostasis of this metal in a macrophage. Such staining in the lung is not equivalent to an iron overload with a capacity to catalyze oxidant generation but frequently indicates a sequestration of the metal by an exposure (e.g. a particle or fiber) with a resultant functional cell iron deficiency.

To demonstrate the correlations between the concentrations of ferruginous body as well as uncoated fiber both of which can be observed with phase-contrast microscope and the concentration of various inorganic fibers including asbestos which requires the observation with TEM or SEM, we measured those indices among Japanese and Korean cases. Though the concentration of ferruginous body in lung tissue is an important index of asbestos exposure, uncoated fibers observed with phase-contrast microscope might be another index especially in such cases with relatively low exposure due to their history of living in a general environment. However, to establish the reliability of uncoated fibers as an index of asbestos exposure, analysis with more cases and from various backgrounds must be carried out.

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.

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients’ characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers.

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.

Exposures to fibers and particles can be associated with several different lung injuries including bronchitis, bronchiolitis, pneumonitis, pleuritis, pulmonary alveolar proteinosis, pneumoconiosis, mesotheliomas, and lung cancers. The mechanism of biological effect exerted by fibers and particles has not been exactly defined. Exposures to all fibers and particles introduce a solid-liquid interface into the lower respiratory tract. These surfaces all have some concentration of oxygen-containing functional groups that demonstrate a capacity to coordinate iron. Radical generation is catalyzed by this metal resulting in a cascade of cell signaling, transcription factor activation, and mediator release. We propose that the ferruginous body (i.e., a fiber or particle with a coating of both protein and iron) provides direct evidence of a participation of iron in the biological effect of both fibers and particles. It is recommended that an identification of ferruginous bodies in the lung be regarded as support for a metal-catalyzed oxidative stress in the mechanism of cell and tissue injury.

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.

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.

A 55-year-old male who had a remote history of occupational asbestos exposure consulted us because of chest pain. Chest X-ray revealed diffuse pleural thickening and pleural effusion on the right. A diagnosis of malignant mesothelioma, biphasic type was made by needle pleural biopsy. Fourteen months later, the patient died of brain metastasis. At autopsy, malignant mesothelioma of the pleura with metastasis to the brain and bilateral adrenal glands was observed. Brain metastases proven by autopsy are rare in cases of malignant mesothelioma. The ferruginous body count in the lung tissue was 16 per gram of wet weight.

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.

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.

Inorganic fibers form part of the complex mixture of environmental pollutants in Mexico City and in general locations. Upon entering the lungs, some of those fibers are transformed into ferruginous bodies (FB) that can be used as biological markers of exposure to fibers. Hence, the objectives of this study were, first, to describe the most frequent types of FB found in the lungs, and second, to determine the elemental composition of the cores of some of those FB. A total of 264 lung samples collected from autopsies performed at the National Institutes of Health in Mexico City were analyzed. The FB were obtained by digesting the samples in commercial bleach and all the FB were then collected in 0.45 µm Millipore membranes. All the FB obtained from each case were counted directly under bright field microscopy, and then classified by morphology. Results showed from 14.5 FB/g in Category 1 (housewives), to 50.2 FB/g for samples from Category 5 (construction workers), and 152 FB/g for Category 6 (miners). Significant differences were found upon comparing samples from Categories 5/6 to Category 1 (p < 0.05). Type 1 FB were the most frequent ones seen in the samples from Categories 1 to 5. Elemental analyses of the cores of several FB found aluminosilicates, fiberglass, tremolite and amosite asbestos among others. In conclusion, residents of Mexico show exposures to a variety of fibers that induce FB including asbestos.

The drywall construction trade has in the past been associated with exposure to airborne asbestos fibres. This paper reports a drywall construction worker with 32 years of dust exposure who developed dyspnoea and diminished diffusing capacity, and showed diffuse irregular opacities on chest radiography. He did not respond to treatment with corticosteroids. Open lung biopsy examination showed desquamative interstitial pneumonia. Only a single ferruginous body was seen on frozen section, but tissue examination by electron microscopy showed an extraordinary pulmonary burden of mineral dust with especially high concentrations of chrysotile asbestos fibres. This report emphasises the need to consider asbestos fibre as an agent in the aetiology of desquamative interstitial pneumonia. The coexistent slight interstitial fibrosis present in this case is also considered to have resulted from exposure to mineral dust, particularly ultramicroscopic asbestos fibres.

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.

We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 microg/mL) was incubated with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H(2)O(2), and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.

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.

Background Occupational or environmental exposure to asbestos fibres is associated with pleural and parenchymal lung diseases. A histopathologic hallmark of exposure to asbestos is the presence in lung parenchyma of the so-called asbestos bodies. They are the final product of biomineralization processes resulting in deposition of endogenous iron and organic matter (mainly proteins) around the inhaled asbestos fibres. For shedding light on the formation mechanisms of asbestos bodies it is of fundamental importance to characterize at the same length scales not only their structural morphology and chemical composition but also to correlate them to the possible alterations in the local composition of the surrounding tissues. Here we report the first correlative morphological and chemical characterization of untreated paraffinated histological lung tissue samples with asbestos bodies by means of soft X-ray imaging and X-Ray Fluorescence (XRF) microscopy, which reveals new features in the elemental lateral distribution. Results The X-ray absorption and phase contrast images and the simultaneously monitored XRF maps of tissue samples have revealed the location, distribution and elemental composition of asbestos bodies and associated nanometric structures. The observed specific morphology and differences in the local Si, Fe, O and Mg content provide distinct fingerprints characteristic for the core asbestos fibre and the ferruginous body. The highest Si content is found in the asbestos fibre, while the shell and ferruginous bodies are characterized by strongly increased content of Mg, Fe and O compared to the adjacent tissue. The XRF and SEM-EDX analyses of the extracted asbestos bodies confirmed an enhanced Mg deposition in the organic asbestos coating. Conclusions The present report demonstrates the potential of the advanced synchrotron-based X-ray imaging and microspectroscopy techniques for studying the response of the lung tissue to the presence of asbestos fibres. The new results obtained by simultaneous structural and chemical analysis of tissue specimen have provided clear evidence that Mg, in addition to Fe, is also involved in the formation mechanisms of asbestos bodies. This is the first important step to further thorough investigations that will shed light on the physiopathological role of Mg in tissue response to the asbestos toxicity.

Previous work by our group among vermiculite miners exposed to fibrous tremolite demonstrated that asbestos body counts in sputum closely reflected intensity and duration of past exposure. In the present project sputum samples from nearly 600 volunteers from 11 cohorts of workers exposed to asbestos and other mineral fibres were found to contain much lower numbers of asbestos bodies than had been observed in vermiculite workers and these counts did not reliably reflect past levels of exposure. No evidence was found that occupational exposure to man-made mineral fibres led to any ferruginous body formation. Asbestos body counts appeared to differentiate between mesothelioma cases and controls and between levels of radiological asbestosis, but in both comparisons, based on small numbers, the power of discrimination was low. Substantial variation was found both in asbestos body and in macrophage counts in daily sampling of vermiculite workers but it was not sufficient to invalidate comparison between groups for epidemiological study. In individual subjects, however, little reliance can be put on results from a single sputum sample, particularly if negative.

Figure 1. A Ferruginous Body. The classic dumbbell-shaped, sometimes beaded appearance of an asbestos fiber, also known as a ferruginous body, is evident in an iron-mucopolysaccharide matrix on scanning electron microscopy (x1595). The fibers were obtained at the postmortem examination of a 58-year-old man with a history of smoking 100 packs of cigarettes per year and long-term exposure to asbestos who died of secondary interstitial pulmonary fibrosis and stage IV non-small-cell bronchogenic carcinoma.

One hundred and fourteen patients with asbestosis, 59% of whom were chronic cigarette smokers, were subjected to a cytological sputum examination which showed: 36 workers (31.6%) with squamous metaplasia, 20 (17.5%) with benigh columnar cell atypia, 5 (4.4%) with benign dysplasia, 2 with suspicious cells for carcinoma, and 1 with anaplastic (microcellular) carcinoma. Clinically and histologically five lung cancers were verified, two of which were cytologically false negatives. All asbestosis patients with lung cancer were chronic smokers. Of the 114 asbestosis patients, 49 (43.0%) had ferruginous bodies in their sputum. The workers from an asbestos quarry more frequently had ferruginous bodies in their specimens than the other patients. Radiographically moderate and severe asbestosis cases showed squamous metaplasia more frequently than those with radiographically slight asbestosis. Most of the detected cellular atypias represented reversible alterations of the respiratory epithelium. It is, however, important to screen the sputum of older (greater than 40 years of age) smoking asbestos workers with benign and suspicious cellular atypias regularly because these alterations may represent the first step int he pathway to bronchogenic cancer. The results of this study did not answer the question of whether bronchial cancer of patients with asbestosis is curable if detected early with cytological methods.

A comprehensive scheme is described for isolating amosite asbestos and ferruginous bodies from fixed and unfixed human lung tissue and sputum. This qualitative procedure avoids many of the problems associated with previous isolation techniques and illustrates the advantages of brief bleach digestions. The samples are digested in prefiltered Wright laundry bleach (9.2% sodium hypochlorite), collected on 0.2-microns Nucleopore filters by vacuum filtration, rinsed with distilled water and absolute ethanol, and examined visually for excessive residue. If organic residues are suspected or are known to occur, the sample is treated sequentially with 2% potassium permanganate, 8% oxalic acid, and 9.2% sodium hypochlorite, and rinsed with distilled water and absolute ethanol. The ethanol, potassium permanganate, and oxalic acid steps can be repeated as often as needed until the desired sample volume has been filtered. The entire procedure allows large volumes to be filtered and yields filters that have extremely clean backgrounds. Filtration can be completed in as little as 15 min, as opposed to the hours or days recommended for other procedures. The technique is applicable to specimens fixed in Saccomanno's fixative or glutaraldehyde, and to those in an unfixed state. The procedure does not appear to damage the gross morphology of the amosite fibers, and it does not produce a detectable change in their elemental composition when determined by energy-dispersive X-ray analysis.

Epidemiological studies have not revealed any significant health hazards from exposure to fibrous glass and animal experiments have been inconclusive. Baboons exposed to a fibrous-glass dust cloud with size features similar to those of crocidolite asbestos developed focal peribronchiolar fibrosis with scant ferruginous body formation. The lesions were similar to those produced by crocidolite but were less extensive. No neoplasms occurred.

The uncoated and coated fibre load in bronchoalveolar lavage (BAL) fluid was assessed using light microscopy, scanning electron microscopy, and x ray microanalysis in 15 subjects with previous, unprotected exposure to asbestos, including three with clinical and radiological evidence of asbestosis, and in 13 urban dwelling control subjects with no known occupational exposure to asbestos. The mean ferruginous body count per ml BAL fluid in asbestos exposed subjects as determined by light microscopy was 52 (range 0-333). No ferruginous bodies were detected in control subjects. The mean fibre count per ml BAL fluid in asbestos exposed subjects as determined by electron microscopy was 793 (133-3700), significantly greater than 239 (44-544) in controls (p less than 0.05). Electron microscopic counts correlated with duration of previous exposure to asbestos (r = 0.47, p less than 0.05) and with percentage neutrophil counts (r = 0.53, p less than 0.025). There was no relation between electron microscopic fibre counts and light microscopic ferruginous body counts. In 11 asbestos exposed cases x ray microanalysis confirmed the presence of asbestos and in six the asbestos fibre type was clearly identified. Of five subjects showing no asbestos bodies by light microscopy, all showed fibres by electron microscopy, and in three cases the presence of asbestos was confirmed by microanalysis. Among control subjects, fibres were either large organic fibres or smaller particles which microanalysis showed were not asbestos. In only one control case were a few fibres identified which were confirmed as asbestos fibres on microanalysis. Electron microscopic examination of BAL fluid may confirm past exposure to asbestos and probably gives a crude quantitative estimate of asbestos load.

The counts of ferruginous bodies (pulmonary-coated mineral fibers) in sputum samples from inhabitants in each of the two agricultural villages of Karain and Tuskoy (Cappadocia, central Turkey) increased with subjects' age, whereas 94% of samples collected in the neighboring villages were free of ferruginous body. These findings are consistent with the previous hypothesis that the very high frequency of mesothelioma in Karain and Tuskoy was related to exposure to airborne mineral fibers of natural origin.

Exposure to asbestos is associated with chronic fibrosing processes, formation of ferruginous bodies, and an increased risk of carcinoma. It is possible to relate the various biological responses to asbestos exposure in terms of fundamental effects on the redox state of cells or tissues. Collagen synthesis is mediated by the level of α-ketoglutaric acid, and the rate of collagen formation is directly related to the rates of fibrosis, including elastin formation. The increase in oxidative reactions associated with collagen formation is thought to increase the amount of ferric iron bound to cellular protein, resulting in formation of a silicate-iron(III) bond on an asbestos fiber. The iron-containing protein bound to the asbestos fiber by the strong silicate ionic bond is a ferruginous body. The corresponding decrease in the ferrous-ferric redox couple inhibits electron transport, thus stabilizing exoper-oxides and free radicals thought to be involved in the initiation of carcinomas.

The Tyler Asbestos Workers Program is a continuing study of 1,105 former amosite asbestos workers. This report includes a study of six former workers, five of whom died and had autopsies, and one who underwent a lobectomy. Five of these men were exposed to asbestos for three months or less. Four had lung cancer, and one a rectal carcinoma. All were cigarette smokers. Ferruginous (asbestos) body content of the upper and lower lobes of the lungs was quantitated by a digestion technic. Tissue sections from upper and lower lobes were independently quantitated for fibrosis and ferruginous bodies, and chest roentgenograms were examined for interstitial fibrosis. (Control lung tissue was obtained from consecutive autopsies of 52 adults who did not have a known occupational exposure to asbestos.) Relatively low ferruginous body counts (less than 700/g lung tissue) were associated with mild degrees of fibrosis, and higher counts (greater than 10,000/g) with moderate to severe fibrosis. Mild to moderate pulmonary fibrosis could be identified on tissue sections before interstitial changes were detectable by chest roentgenograms.

(1982). Asbestos-Related Pleuropulmonary Diseases: Asbestosis, Mesothelioma and Lung Cancer. Pathology: Vol. 14, No. 3, pp. 239-243.

A method for extracting ferruginous bodies from sputum and fixed or unfixed lung is described. The principle is to digest the sputum or tissue completely in domestic laundry bleach (5.25% sodium hypochlorite) and to collect the solid residue on a membrane filter. This method allows one to extract from a specimen virtually every ferruginous body that is visible with the light microscope. With this method, ferruginous bodies were found in pulmonary tissue from each of 100 consecutive necropsies of patients 16 years old and over. In one case, ferruginous bodies were found in a concentration of about 750,000 per Gm. of wet fixed pulmonary tissue.

So-called “asbestos” bodies were produced in the lungs of hamsters injected intratracheally with respirable filamentous particles composed of aluminum silicate. The production of “asbestos” bodies by aluminum silicate challenges the concept that “asbestos” bodies are a pulmonary response specific to inhaled asbestos fibers. Instead of the term “asbestos” body, the designation of ferruginous body is suggested for the iron-containing structure that forms in response to the inhalation of filamentous dust of unknown composition, since the term “asbestos” body may be misleading and inappropriate.

Some pathologic and epidemiologic evidence suggests that benign fibrous plaques may form in the pleura as a reaction to inspired asbestos. The ferruginous bodies formed in reaction to asbestos and other respirable fibers have virtually never been demonstrated in these lesions by study of tissue sections. Using a tissue digestion and microfiltration technic the authors identified small numbers of typical ferruginous bodies in three of eight specimens studied. Also found was another type of iron-coated structure which was designated an “atypical ferruginous body.” These may be endogenous or exogenous in origin. Ferruginous bodies probably are of little significance in the genesis of fibrous pleural plaques.

Previous reports have indicated that a majority of the population has asbestos bodies within their lungs. These studies generally have been carried out using cohorts from urban environments. The present study compares the asbestos body levels from three unique cohorts: (1) a nonoccupationally exposed group from a large urban environment having a relatively low asbestos content, (2) patients with lung cancer from a nonurban setting, and (3) amosite asbestos workers, who worked and lived in a rural setting. The number of asbestos bodies in both the urban nonoccupationally exposed group and the patients with lung cancer was generally found to be low or below limits of detectability, with the exceptions being those persons in whom an occupational exposure was eventually found. The ferruginous body content of the occupationally exposed group varied considerably between individuals as well as between sites within the same individual. ( JAMA 1984;252:68-71)