Coal miners or individuals exposed to asbestos often develop a chronic respiratory condition called:

Asbestosis

Asbestos is composed of strong, heat-resistant fibers of hydrated magnesium silicate classified morphologically as serpentine (chrysotile) or amphibole (crocidolite [riebeckite asbestos], amosite [cummingtonite-grunerite asbestos], anthophyllite asbestos, actinolite asbestos, and tremolite asbestos). In addition, certain asbestiform fibers (winchite, richterite, erionite) can cause adverse health effects identical to those of asbestos. Fiber dimensions and persistence in tissues are key determinants of toxicity. There is a dose–response effect between the quantity of asbestos inhaled and the severity of fibrotic lung disease. Asbestos is also a carcinogen, and increasing exposure is associated with increased risk for lung cancer, mesothelioma, ovarian cancer, and laryngeal cancer.

Although asbestos is no longer mined in the United States, importation of asbestos-containing products continues. Exposures also continue to occur, especially in construction and renovation (due to reservoirs of asbestos that are still present in many older buildings), the heating trades (where asbestos is often encountered), and with exposure to older or imported asbestos-containing automotive friction products such as brake linings and clutch facings. Workers exposed to asbestos can carry it home on their clothing, resulting in exposure of family members. Living near geological formations prone to asbestos formation in California has been implicated as a risk factor for mesothelioma.

The Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for asbestos is 0.1 fiber per cc air. This limit was based in part on the limits of the analytical methodology used in exposure assessment. Exposure to the PEL every day over a 45-year working lifetime has been estimated to be associated with an increased risk of cancer (lung, mesothelioma, and gastrointestinal) of 336 cases per 100,000 exposed persons and an increased risk of asbestosis of 250 cases per 100,000 exposed persons.

Asbestosis causes symptoms of dyspnea and cough. Latency between initial exposure and disease onset is related to exposure intensity. In the United States, this period is generally about two or more decades. The disease can lead to chronic respiratory failure. Effects of smoking add to the severity of the disease and can cause obstructive findings in addition to the expected decreased lung volume and diffusion capacity associated with fibrotic lung diseases. Bibasilar inspiratory crackles on auscultation, finger clubbing, and bibasilar small, irregular parenchymal opacities on chest x-ray with extension to mid- and upper-zones with advancing disease are characteristic.

The International Labour Organization (ILO) has established a system for classification (grading) of radiographs for the presence of radiographic abnormalities in lung parenchyma and pleura that are associated with pneumoconiosis, as well as their severity. The ILO classification system is widely used in epidemiology, surveillance, administrative, and legal settings. The small opacity profusion grades of 0/1 and 1/0 are often considered as defining the boundary between normal and abnormal lung parenchyma.

Overview and General Considerations

Pneumoconiosis literally means “dust in the lung,” and the term has come to refer to disease of the lung related to the inhalation of dusts. Pneumoconioses are for the most part due to the inhalation of inorganic dusts in the workplace, and the reaction of the lungs to these dusts is generally fibrosis. These diseases typically evolve over several decades, although there are some exceptions to this rule. The pathologic findings in these conditions can resemble those in other fibrotic and granulomatous disorders of the lung, so the pathologist must be familiar with their diagnostic features. Although no specific treatment is available for most of these disorders, proper diagnosis is crucial for accurate determination of prognosis and, when indicated, compensation.

The toxicity and corresponding fibrogenicity of inorganic particulates are related to both the nature of the dust and the nature of the host response.1 One important feature of particle toxicity is the aerodynamic diameter, with particles in the size range of 1 to 5 µm having the highest probability of deposition and retention within the respiratory tract. In addition, the total inhaled dose and intrinsic properties of the dust are important determinants of fibrosis. For example, crystalline silica is highly fibrogenic, whereas carbon is an innocuous nuisance dust. Host factors include the efficiency of clearance mechanisms and individual susceptibility. Many of the dusts have a characteristic reaction pattern or appearance in histologic sections, which permits an accurate diagnosis (Table 10.1). The silicotic nodule and the asbestos body are familiar examples. Others are associated with a reaction pattern that may suggest the diagnosis, but a careful occupational history or use of supplemental analytic techniques may be required to confirm the diagnosis, as with berylliosis, in which the histologic findings closely resemble those in sarcoidosis.

Analytic electron microscopy provides a powerful tool for identifying dusts in lung tissue samples, and these methods are emphasized when appropriate.2 An analytic electron microscope consists of a scanning or transmission electron microscope equipped with an energy-dispersive spectrometer. Electron microscopic techniques may permit the detection of particles too small to be observed by light microscopy. Furthermore, energy-dispersive x-ray analysis (EDXA) identifies the elemental composition of individual particulates, which can be critical to the identification and, in some cases, the source of the inhaled dust. It must be emphasized, however, that the identification of a particular xenobiotic in lung tissue is in and of itself not proof of disease and must be correlated with the pathologic response (if any) to the dust in routine histologic sections.

eFigure Image Gallery

eFigure 101.1. Silicosis: gross images.

(A) In this gross specimen, circumscribed areas of nodular fibrosis are slate gray and of firm consistency(arrows). (B) At low magnification, silicotic nodules are sharply circumscribed and densely collagenous (Masson trichrome stain).

eFigure 101.2. Silicosis on chest radiograph.

Frontal chest radiograph in a patient with silicosis shows a somewhat atypical distribution of small, round lung opacities. In this patient, opacities are best seen in the middle and lower lungs, rather than the more typically encountered upper and posterior lung location.

eFigure 101.3. Silicosis with eggshell calcification of hilar lymph nodes.

Detail of a frontal chest radiograph in a patient with silicosis shows the typical appearance of “eggshell” lymph node calcifications(arrow).

eFigure 101.4. Complicated silicosis: progressive massive fibrosis on chest radiograph and chest computed tomography.

(A) Frontal chest radiograph shows upper lobe masses with a background of small nodules and linear and reticular opacities. Axial chest computed tomography in soft tissue (B–C) and lung windows (D–E) shows the upper lobe masses and background of small, circumscribed nodules and lymph node calcifications(arrowheads). The associated videos (seeVideo 101.1, soft tissue windows, andVideo 101.2, lung windows) highlight the presence of calcification within the upper lobe masses as well as the upper lobe distribution of the lung opacities.

eFigure 101.5. Silicosis: progressive massive fibrosis on chest radiograph.

Frontal chest radiograph in a patient with silicosis and progressive massive fibrosis shows bilateral upper lobe opacities with areas of hyperlucency (between arrows) left in the “wake” of the migration of the opacities toward the hila.

Pneumoconiosis

Pneumoconiosis is defined as the non-neoplastic reaction of the lungs to inhaled mineral or organic dust, exclusive of asthma, bronchitis, and emphysema.

Anthracosis is often applied as a general and relatively nonspecific term to black pigment with minimal associated fibrosis in the lungs of heavy smokers and residents of heavily polluted urban environments. Pigmented dust macules also occur in coal workers, however, in whom the termanthracosis has a specific and more narrow interpretation, and therefore the term is probably best avoided.Coal worker's pneumoconiosis may present either as ‘coal nodules’ (of little functional significance) or as progressive massive fibrosis (which results in pulmonary function abnormalities).161–163

Silicosis results from the deposition in the lung of particles of free crystalline silica (quartz, silicon dioxide). The lesions are characterized by micronodular scars with a characteristic pattern of central lamellar fibrosis distributed in a bronchiolocentric pattern with a cellular periphery in which dust-laden macrophages predominate (Fig. 10.60). Complicated silicosis and progressive massive fibrosis result from fusion of nodules to form larger (≥1 cm) macroscopic nodules and masses. Larger nodules may undergo necrosis and cavitate as a result of ischemia, or more commonly superimposed mycobacterial infection; acid-fast stains should be performed when necrosis is identified. Silicotic nodules in patients with rheumatoid arthritis(Caplan syndrome) assume some of the morphologic changes characteristic of rheumatoid nodules, including central necrosis with palisaded histiocytes at the periphery.164

Silica particles are best demonstrated under polarized light. They appear as weakly birefringent spicules with pointed ends, 5 µm or less in length, and are usually accompanied by more brightly birefringent contaminants. They may be found intracellularly or extracellularly. It should be emphasized that the mere presence of silica particles in a lung specimen does not establish the diagnosis of silicosis. Such a diagnosis should be reserved for cases showing silica in association with characteristic silicotic nodules.165

Mixed dust fibrosis is the term used for pneumoconioses resulting from mixed dust exposure, including silica and quartz. It affects foundry workers, arc welders, hematite miners, and boiler scalers. Most cases show a combination of dust macules and fibrotic nodules that may or may not include a minor component of silicotic nodules.166

Asbestosis refers to diffuse lung fibrosis attributable to asbestos exposure. Aside from an incriminating occupational history, the clinical and radiological findings may be indistinguishable from other forms of diffuse fibrotic lung disease save for the presence of calcified pleural plaques on imaging studies. Histologic diagnosis requires a combination of diffuse interstitial fibrosis and asbestos bodies in ordinary 5-µm sections.167–169 The histologic features closely mimic UIP, although there tends to be less inflammation, fewer fibroblast foci, and more visceral pleural fibrosis (Fig. 10.61).169 The diagnosis of asbestosis in lung biopsy samples requires the identification of asbestos bodies, usually by conventional microscopy although special techniques can be helpful in a limited number of contexts.170 The typical asbestos body is a long, thin, symmetric, beaded structure with bulbous ends (Fig. 10.62). It is usually straight, but it may be bent or branched. Its core is translucent, a key feature in separating asbestos bodies from other types of non-asbestos ferruginous bodies.171

Prognosis

Simple CWP is not associated with premature death, but approximately 4% of deaths in coal miners are directly due to complicated pneumoconiosis. In workers with categories 1, 2, and 3 of simple CWP and category A of complicated CWP, life expectancy is the same as that for persons without pneumoconiosis in the general population.

The rate of progression to PMF seems to be influenced chiefly by the age at which the miner begins to show radiographic changes of CWP: The earlier the diagnosis, the more likely there is to be progression reflecting individual susceptibility and the level of cumulative exposure.

Infections

CWP has also been linked with a number of specific infections, the most prominent of which historically has been tuberculosis. The association observed with coal mining (and hence CWP) in some countries appears to have been a consequence only of close contact during long hours of work in the confined mine environment. Nontuberculous mycobacteria, on the other hand, may infect lungs damaged by CWP with greater than usual frequency, and so CWP does appear to increase the risk for infection with opportunistic organisms. The development of mycobacterial infection in a patient with CWP may be symptomless, at least in its early course, and it may be difficult or impossible to distinguish it radiographically from PMF lesions since both characteristically begin in the apices. Similarly, it may be difficult to attribute changes in the radiographic appearances to advancing infection or progressive PMF. Other opportunistic infections have been reported in association with CWP, and Aspergillus species have been noted to colonize cavities in conglomerate lesions of complicated CWP.

Rheumatoid Pneumoconiosis

Rheumatoid pneumoconiosis (Caplan syndrome) was originally described as a variant of PMF in coal workers on the basis of its distinctive radiologic features. Active arthritis or circulating rheumatoid factor were commonly associated with rheumatoid pneumoconiosis.1 At present, most evidence suggests that the presence of rheumatoid arthritis, a predisposition to rheumatoid disease, or both is a host factor that modifies the response of an individual to coal mine dust exposure. Conversely, dust exposure does not appear to be a risk factor for rheumatoid arthritis.1 CWP does not appear to have an association with other connective tissue disorders.

4.4 Coal Workers' Pneumoconiosis

CWP is characterized by chronic inflammation that usually leads to fibrosis due to irritation caused by dust exposure. Although, the mechanisms of susceptibility to disease development and progression are not clear, several studies have proposed a genetic component (Borm and Schins, 2001). In a study investigating associations between TNFα gene polymorphisms and development of CWP, the frequency of the TNFα -308 variant was significantly increased in miners with CWP (50%), as compared with miners without lung disease (25%) or non-miners (29%) (Zhai et al., 1998). Similarly, the frequency of TNFα -308 variant was greater in Korean CWP patients (20.6%) and in patients with a large opacity (28.2%) in comparison with patients with simple CWP (13.4%) (Kim et al., 2002). The presence of the minor allele was significantly associated with increased relative risk of complicated CWP. In another study, the -308 A allele frequency was found to be higher in patients with CWP and nodular CWP compared to controls and subjects with PMF (Wang et al., 2005). The TNFα -308 and lymphotoxin-α (LTA) NcoI polymorphisms were also investigated in a prospective epidemiological study in miners differentially exposed to coal dust and cigarette smoke. While the LTA NcoI polymorphism found associated with CWP prevalence in miners with low blood catalase activity, the TNFα -308 SNP showed an interaction with erythrocyte GSH-Px activity in individuals with high occupational exposure (Nadif et al., 2003). The TNFα -238 and -308 polymorphisms were associated with CWP development and severity in Turkish coal miners, respectively (Ates et al., 2008). They also reported a protective effect of the IL-6 -174 variant in the development and severity of CWP. Genetic variants in IL-18, chemokines and chemokine receptors have also been studied in relation to CWP. The IL18 -137C allele was found to be associated with lower and slower progression of the computed tomography (CT) score and lower pneumoconiosis prevalence in a group of miners (Nadif et al., 2006a). The same group also reported an association between the CX3CR1 V249I and lower CWP prevalence, especially in miners with high dust exposure. In addition, the CX3CR1 I249 allele was significantly associated with lower and slower progression of the CT score in CCR5 Delta32 carriers (Nadif et al., 2006b). Recently, the IL-4 -590 CT/CC genotypes were reported to be associated with a significantly decreased risk of CWP in a Chinese population, particularly among subgroups of age <65 years and dust exposure years ≥26 years (Wang et al., 2011).

9 Discuss pneumoconioses and tumors that lead to nodular interstitial lung disease

Pneumoconioses that may produce a micronodular interstitial pattern are silicosis, coal workers’ pneumoconiosis, talcosis, and berylliosis. Pneumoconioses are diffuse interstitial lung diseases caused by inorganic dusts, most often related to occupational exposures. Mining, sandblasting, gravestone engraving, and pottery are some occupations in which workers may be exposed to silica dust with resultant silicosis; as identified in the name, coal workers’ pneumoconiosis is seen in coal miners. Berylliosis is an uncommon chronic pneumoconiosis that may be encountered in individuals who mine beryllium, who manufacture beryllium ceramics, or who previously manufactured beryllium lighting (these types of lights are no longer manufactured because of the high risk of acute and chronic berylliosis). Talcosis may occur as a result of the mining of talc or excessive inhalation of talcum powder and in intravenous drug abusers. Thyroid carcinoma is the prototypic tumor that produces thousands of tiny micronodular metastases and may appear as a nodular interstitial lung disease. Breast cancer may also produce this pattern of metastasis; other primary tumors rarely produce a micronodular pattern of lung metastasis.