Clinical Presentation

Patients demonstrate a range of clinical presentations, from asymptomatic with simple silicosis to markedly dyspneic with conglomerate silicosis. In conglomerate silicosis, hypoxemia and cor pulmonale may be fatal.

Pathologic Findings

Silicotic nodules are of firm consistency and typically slate gray in appearance, measuring from a few millimeters to approximately 1 cm in diameter (Figs. 9-1 and 9-2). As the disease progresses in severity, the nodules may become confluent (Figs. 9-3 and 9-4). Areas of confluent fibrosis greater than 2 cm in maximum dimension are the defining feature of conglomerate silicosis. Cavitation may occur within areas of confluent fibrosis and, when present, suggests the possibility of superimposed tuberculosis.

Figure 9-1 Silicosis. In this gross specimen, circumscribed areas of nodular fibrosis are slate gray and of firm consistency.

Figure 9-2 Silicosis. At low magnification, silicotic nodules are sharply circumscribed and densely collagenous (Masson trichrome stain).

Figure 9-3 Conglomerate silicosis. A Gough-Wentworth section of lung from a tobacco field worker demonstrates confluent fibrosis in the upper lobe (arrowhead).

Figure 9-4 Conglomerate silicosis. Multiple silicotic nodules have coalesced, forming an area of confluent fibrosis.

The histologic hallmark of silicosis is the silicotic nodule.^4,5 This lesion is a sharply circumscribed nodule consisting of dense, whorled hyalinized collagen (Fig. 9-5). More loosely arranged collagen bundles are typically found at the periphery of the nodule. In recently formed lesions, macrophages form a mantle around the fibrotic center. Longstanding lesions may be calcified or even ossified (Fig. 9-6). The nodules may be present anywhere within the lung parenchyma but typically are most numerous in the upper lung zones. Not uncommonly, they are concentrated beneath the pleura (Fig. 9-7). There may also be extensive pleural fibrosis⁶ (Fig. 9-8). Nodules are frequently also present within hilar lymph nodes (Fig. 9-9). In patients with extremely high exposures to very fine silica particles, the pattern of resultant lung injury may closely resemble that in pulmonary alveolar proteinosis, characterized by the presence of granular eosinophilic material filling the alveoli, alveolar ducts, and bronchioles (Fig. 9-10). Cholesterol clefts may be prominent within the intra-alveolar material. The granular proteinaceous exudate typically stains strongly positive with periodic acid/Schiff with diastase (D-PAS).

Figure 9-5 Silicosis. This silicotic nodule demonstrates the typical whorled appearance. Macrophages are present at the periphery of the nodule.

Figure 9-6 Silicosis. A mature silicotic nodule exhibits partial ossification.

Figure 9-7 Silicosis. The lung parenchyma underlying the pleura is a common location for silicotic nodules.

Figure 9-8 Pleural silicosis. A, Pleural involvement sometimes manifests as dense fibrosis. B, At higher magnification, a cellular area consisting of fibroblasts and histiocytes is evident. Polarizing microscopy showed numerous birefringent particulates.

Figure 9-9 Silicosis. Silicotic nodules within a lymph node characteristically contain centrally dense, hyalinized collagen surrounded by concentric whorls of more loosely arranged collagen bundles.

Figure 9-10 Acute silicosis. Granular eosinophilic material fills alveoli, imparting an appearance similar to that in pulmonary alveolar proteinosis. Note the presence of a silicotic nodule at left.

(From Sporn TA, Roggli VL. Pneumoconioses, mineral and vegetable. In: Tomashefski JF, ed. Dail and Hammar’s Pulmonary Pathology, vol 1, 3rd ed. New York: Springer-Verlag; 2008:911–949, with permission.)

Examination with polarizing microscopy shows faintly birefringent particulates within the fibrotic nodules (Fig. 9-11). Larger, brightly birefringent particles, which represent silicates, may also be seen, but these should not predominate (see later section on silicatosis).⁷ On scanning electron microscopy the particles appear angulated (Fig. 9-12). Analytic electron microscopy with EDXA reveals peaks for silicon only (Fig. 9-13).

Figure 9-11 Silicosis. Partial polarization of a silicotic nodule demonstrates faintly birefringent silica particles.

Figure 9-12 Silicosis. Scanning electron microscopy demonstrates angulated silica particles.

Figure 9-13 Energy-dispersive x-ray analysis (EDXA) spectrum shows a peak for silicon (Si).

Differential Diagnosis

Silicotic nodules must be distinguished from the fibrotic nodules of healed or “burned-out” sarcoidosis, as well as healed mycobacterial or fungal infections, a classic example being the so-called histoplasmoma. The presence of multinucleate giant cells and the absence of significant dust deposits favor sarcoidosis. Sarcoid granulomas may contain fine needle-like or large, platy birefringent particles, which represent endogenous calcium carbonate or oxalate, respectively (Fig. 9-14). These particles should not be confused with the foreign material of pneumoconiosis. The presence of necrosis in association with giant cells favors an infectious etiology. Patients with silicosis are at increased risk for acquiring tuberculosis.⁸ Both processes may be present simultaneously. Concurrent tuberculosis infection is most likely to occur with conglomerate silicosis.

Figure 9-14 Birefringent particles in sarcoidosis. In contrast to silicosis, this example of sarcoidosis contains large platy birefringent particles, typical for endogenous calcium oxalate.

Extrathoracic location does not rule out a silicotic origin of a fibrous nodule, because silicotic nodules have been found in the liver, spleen, bone marrow, and abdominal lymph nodes.⁹ Extrathoracic involvement, when present, usually occurs in the setting of advanced pulmonary silicosis. The diagnostic yield of transbronchial biopsy in silicosis is low, probably because the firm circumscribed nodules are pushed aside by the biopsy forceps.

Clinical Presentation

Patients exhibit a range of clinical presentations, from asymptomatic with simple CWP to markedly dyspneic with PMF. The latter is associated with hypoxemia and cor pulmonale and may be fatal.^10,11

Pathologic Findings

CWP is characterized by increased pigmentation in the lungs resulting from the deposition of coal dust (Figs. 9-15 to 9-17). Foci of accentuated pigmentation, superimposed on a background of diffusely increased pigment, are present on the pleura and within the lung parenchyma. In some cases, palpable nodules are present within the lung parenchyma and usually are most numerous in the upper lung zones. These nodules are grossly similar to silicotic nodules, except for being black rather than slate gray (Fig. 9-18). The most advanced cases of CWP feature greater than 2 cm in maximal dimension confluent areas of irregular fibrosis with the consistency of vulcanized rubber, typically in the upper to mid-lung zones (Fig. 9-19). These are the lesions of PMF. Cavitation may occur in areas of PMF and, when present, suggests superimposed tuberculosis.¹²

Figure 9-15 Normal lung. A Gough-Wentworth section of normal lung shows scattered minimal accumulations of anthracotic pigment and intact parenchyma.

(From Kleinerman J, Green FHY, Laquer W, et al. Pathology standards for coal workers pneumoconiosis. Arch Pathol Lab Med. 1979;103:375–432, with permission.)

Figure 9-16 Simple coal worker’s pneumoconiosis. This thin section of lung demonstrates multiple small, circumscribed black nodules, predominantly in the upper lobe.

(From Kleinerman J, Green FHY, Laquer W, et al. Pathology standards for coal workers pneumoconiosis. Arch Pathol Lab Med. 1979;103:375–432, with permission.)

Figure 9-17 Simple coal worker’s pneumoconiosis. In contrast to the normal lung, this thin section shows diffusely increased pigment resulting from the deposition of coal dust.

(From Kleinerman J, Green FHY, Laquer W, et al. Pathology standards for coal workers pneumoconiosis. Arch Pathol Lab Med. 1979;103:375–432, with permission.)

Figure 9-18 Simple coal worker’s pneumoconiosis. In addition to diffusely increased pigmentation, the lung parenchyma shows well-demarcated black nodules. Centrilobular emphysematous bullae are also present.

Figure 9-19 Complicated coal worker’s pneumoconiosis. The upper lobe contains a confluent irregular area of fibrosis with the consistency of vulcanized rubber. Central cavitation is present.

The histologic hallmark of CWP is the coal dust macule (Fig. 9-20). Coal dust macules consist of discrete collections of interstitial pigment deposition in the vicinity of respiratory bronchioles. Areas of emphysematous destruction, referred to as focal emphysema, are typically present at the periphery of macules. Pigment-laden macrophages may be present within alveolar spaces, and pigment deposits may occur anywhere along the lymphatic routes of the lung, including the secondary lobular septa, as well as in the pleura. Lymph nodes frequently contain numerous pigmented macrophages and may also demonstrate silicotic nodules. Silicotic nodules may also be present within the lung parenchyma, but unlike cases of pure silicosis, a collarette of pigmented macrophages often surrounds the nodules, imparting a “Medusa head” appearance (Fig. 9-21). Areas of massive fibrosis (Fig. 9-22) consist of collagen bundles that are arranged in a haphazard distribution and intermixed with abundant pigment (Figs. 9-23 and 9-24). Vascular obliteration is common within areas of PMF, and ischemia may be the cause of cavitation in some cases.

Figure 9-20 Simple coal worker’s pneumoconiosis. The coal dust macule is characterized by focal interstitial pigment deposition. In this example, destruction of the adjacent alveolar septa, termed focal emphysema, is also seen.

Figure 9-21 Simple coal worker’s pneumoconiosis. A collarette of pigmented macrophages gives a “Medusa head” appearance to this intraparenchymal silicotic nodule.

Figure 9-22 Complicated coal worker’s pneumoconiosis. A large black irregular fibrotic lesion has destroyed the perihilar lung parenchyma.

(From Kleinerman J, Green FHY, Laquer W, et al. Pathology standards for coal workers pneumoconiosis. Arch Pathol Lab Med. 1979;103:375–432, with permission.)

Figure 9-23 Complicated coal worker’s pneumoconiosis. In this example of progressive massive fibrosis, haphazardly arranged collagen bundles are interspersed with abundant pigment.

Figure 9-24 Complicated coal worker’s pneumoconiosis. A Masson trichrome stain highlights the collagenous composition of a heavily pigmented region of progressive massive fibrosis.

Examination with polarizing microscopy typically shows numerous faintly to brightly birefringent particulates within a background of black pigment (Fig. 9-25). This appearance reflects the mixed nature of coal dust, which is composed of amorphous carbon, silicates, and silica. The presence of silica in coal dust is responsible for the formation of silicotic nodules and is an important factor in the pathogenesis of PMF.¹³ Ferruginous bodies are sometimes seen in the lungs of coal workers, typically within the alveolar spaces (Fig. 9-26). These may be distinguished from true asbestos bodies by virtue of their black carbonaceous cores¹⁴ (Fig. 9-27). Tuberculosis may also complicate CWP (Fig. 9-28).

Figure 9-25 Coal worker’s pneumoconiosis. Partial polarization shows a mixture of faintly and brightly birefringent particles superimposed on black pigment.

Figure 9-26 Coal worker’s pneumoconiosis. Along with pigmented macrophages, this case demonstrates numerous intra-alveolar ferruginous bodies.

Figure 9-27 Coal worker’s pneumoconiosis. At higher magnification, the black carbonaceous core of this ferruginous body (pseudoasbestos body) is evident.

Figure 9-28 Coal worker’s pneumoconiosis. A caseous granuloma in this case of coal worker’s pneumoconiosis was found to contain acid-fast bacilli.

Differential Diagnosis

CWP must be distinguished from the anthracotic pigment deposition that occurs in urban dwellers and cigarette smokers, and from graphite worker’s pneumoconiosis. The extent of pigmentation in normal persons is a function of environmental exposure to carbon-containing dust and the natural ability of the lung to rid itself of particulates. Distinction from CWP is somewhat a matter of degree, but the presence of true coal dust macules, as described earlier, is indicative of CWP. The finding of anthracotic pigment-laden macrophages within alveoli is also a useful feature, but such macrophages may be absent in miners who have been retired for many years. Graphite worker’s pneumoconiosis appears similar to CWP, but graphite is crystalline, whereas the carbon present in coal is amorphous (Fig. 9-29). A giant cell reaction to the crystalline carbon of graphite assists in this distinction.³ Transbronchial biopsy may be useful in the diagnosis of CWP, showing the typical changes described earlier. However, areas of nodular fibrosis or PMF may be missed by such sampling. Therefore, transbronchial biopsy is not useful for assessing disease severity.

Figure 9-29 Graphite worker’s pneumoconiosis. Although somewhat similar in appearance to particulates in coal worker’s pneumoconiosis, graphite particles appear crystalline and elicit a giant cell reaction.

Clinical Presentation

In patients with asbestosis, the clinical presentation ranges from asymptomatic to severely dyspneic at rest. Hypoxemia and cor pulmonale may prove fatal in these patients. Pulmonary function testing typically shows restrictive changes, and the diffusion capacity is reduced. Patients with asbestosis who smoke cigarettes have a markedly increased risk for developing lung cancer. Pleural plaques in and of themselves are rarely symptomatic, and when present in isolation should not be referred to as “asbestosis.” Although the pleural and parenchymal changes caused by asbestos may be recognized on plain films, high-resolution computed tomography (HRCT) is considered to be a more sensitive and specific modality for the radiographic evaluation of asbestosis.

Pathologic Findings

The fibrosis in asbestosis demonstrates a fine, reticular pattern, and the macroscopic appearance of the lungs ranges from normal to severely scarred and shrunken (Fig. 9-30) with evidence of honeycombing.^17,18 Diffuse visceral pleural fibrosis is frequently present and is usually most severe over the lower lung zones. Parietal pleural plaques, which are frequently bilateral (Fig. 9-31), are present in the vast majority of cases and may be calcified. Although diffuse pleural fibrosis and plaques serve as a suggestive indicator of an asbestos etiology of pulmonary fibrosis, the term “asbestosis” should not be applied to these pleural abnormalities when they occur in the absence of parenchymal disease.

Figure 9-30 Asbestosis. The lower lobe parenchyma shows patchy fibrosis. Visceral pleural thickening also is evident (arrowhead).

(From Roggli VL, Oury TD, Sporn TA, eds. Pathology of Asbestos-Associated Diseases, 2nd ed. New York: Springer; 2004, with permission.)

Figure 9-31 Pleural plaque. The gross appearance has been likened to that of candle wax drippings.

Histologically, asbestosis is characterized by discrete foci of fibrosis in the walls of respiratory bronchioles accompanied by asbestos bodies¹⁷ (Box 9-3 and Fig. 9-32). As the fibrotic process progresses, it extends distally to the alveolar ducts and proximally to the membranous (terminal) bronchioles. The fibrosis also extends radially to involve alveolar septa distant from the respiratory bronchiole (Fig. 9-33). In the most advanced cases, honeycomb fibrosis is present (Fig. 9-34), characterized by 0.5- to 1-cm–diameter fibrotic-walled cysts that are lined by bronchiolar epithelium and often contain pools of mucus. Alveolar macrophages are sometimes so prominent as to suggest a diagnosis of desquamative interstitial pneumonia (DIP). In some cases, multinucleate giant cells may be identified, within either the interstitium or the alveolar spaces (Fig. 9-35). Rarely, hyperplastic alveolar type II pneumocytes may contain cytoplasmic hyaline (Fig. 9-36) reminiscent of that found in the cytoplasm of hepatocytes in alcoholic liver disease.

Figure 9-32 Asbestosis. A, The histologic hallmarks of asbestosis are peribronchiolar fibrosis accompanied by asbestos bodies. B, Numerous asbestos bodies are present within a fibrotic alveolar septum in this case with heavy asbestos exposure. Note the variable beaded, rod-like, and dumbbell shapes.

Figure 9-33 Asbestosis. Peribronchiolar fibrosis extends into adjacent alveolar septa. Centrilobular emphysema and visceral pleural fibrosis (top) are also seen.

Figure 9-34 Asbestosis. In a more advanced case, honeycombing (arrowhead) is seen, in addition to lower lobe fibrosis.

Figure 9-35 Asbestosis. Within an interstitial giant cell lies a curvilinear asbestos body in this transbronchial biopsy specimen.

Figure 9-36 Asbestosis. Type II pneumocytes demonstrate cytoplasmic hyaline.

The hallmark of asbestos exposure is the asbestos body, a rod-like, beaded, or dumbbell-shaped structure with golden brown coating and a thin, translucent core.¹⁹ Asbestos bodies are typically found in the peribronchiolar interstitium (Fig. 9-37), but, with heavy exposure, may be seen in the alveolar spaces (Fig. 9-38). Detection of asbestos bodies may be facilitated by the use of iron stains, which impart a deep blue color (Fig. 9-39). Asbestos bodies may also be seen in sputum (Fig. 9-40) and in thoracic lymph nodes (Fig. 9-41) of patients with heavy exposure to asbestos. Pleural plaques consist of layers of acellular hyalinized collagen, arranged in a “basketweave” pattern (Fig. 9-42). Visceral pleural fibrosis may show this basketweave pattern or appear as compact layers of collagen. A mild lymphocytic infiltrate sometimes accompanies the fibrosis.

Figure 9-37 Asbestosis. In a transbronchial biopsy, interstitial fibrosis and an asbestos body (upper left) can be seen.

Figure 9-38 Asbestosis. Asbestos bodies are present within an alveolar space in this case of severe asbestosis.

Figure 9-39 Asbestosis. In this iron-stained section of lung, an asbestos body has a characteristic beaded morphology and deep blue color.

Figure 9-40 Asbestosis. Asbestos bodies in a sputum cytology specimen.

Figure 9-41 Asbestosis. A section from a thoracic lymph node from a heavily exposed individual contains numerous asbestos bodies.

Figure 9-42 Pleural plaque. Pleural plaque showing the typical composition of layers of acellular hyalinized collagen arranged in a “basket-weave” pattern.

Digestion procedures have been developed for quantifying the content of asbestos in lung tissue (Fig. 9-43). Any of the commercial forms of asbestos (chrysotile and amphiboles) may be identified in lung tissue from patients with asbestosis by means of analytic electron microscopy²⁰ (Figs. 9-44 and 9-45). In cases in which asbestos bodies are not identified in histologic sections, the fiber burden is typically always more than 2 standard deviations below the mean value in cases with bona fide (histologically confirmed) asbestosis.²¹ Polarizing microscopy is not useful for the detection of asbestos in histologic sections.

Figure 9-43

Buy Membership for Pulmolory and Respiratory Category to continue reading. Learn more here