Background: Asbestos is a naturally occurring fibrous silicate that was widely used in the past for commercial applications because of its heat-resistance properties. Asbestos exists in several forms. The 2 primary groups of asbestos comprise amphibole and serpentine fibers. Amphibole fibers, which are characteristically straight, rigid, and needlelike, can be subdivided into commercial amphiboles (crocidolite, blue asbestos, and amosite, or brown asbestos) and noncommercial amphiboles (actinolite, anthophyllite, and tremolite). Chrysotile (white asbestos) is the only form of serpentine asbestos that is used commercially, and it accounts for more than 90% of asbestos used in the United States.
For the most part, asbestos exposure has been industrial or occupational and primarily affects workers involved in mining or processing asbestos or those involved in the use of asbestos in the shipbuilding, construction, and textile- and insulation-manufacturing industries. Chrysotile is mined in Canada, and tremolite and anthophyllite are mined in Finland and North America. Crocidolite and amosite are mined in South Africa and Australia. About 2-6 million people in the United States are estimated to have had significant levels of exposure.
High exposures ceased in the United States in the late 1970s, and later in the United Kingdom, because of governmental legislation passed after the adverse effects became recognized. However, because the latency period between an initial exposure and the development of most asbestos-related disease is 20 years or longer, asbestos-related disease remains an important public health issue.
The spectrum of asbestos-related thoracic diseases includes benign pleural effusion, pleural plaques, diffuse pleural thickening, rounded atelectasis, asbestosis, mesothelioma, and lung cancer.
Asbestosis is defined as diffuse lung fibrosis due to the inhalation of asbestos fibers, and it is one of the major causes of occupationally related lung damage. Mesothelioma is a malignant pleural or peritoneal tumor that rarely occurs in patients who have not been exposed to asbestos.
The diagnostic approach to asbestos-related intrathoracic disease is different from that of other diffuse lung diseases because of the medicolegal implications. The likelihood of asbestos-related disease should be determined, and other possible causes should be eliminated. An assessment of the extent of disease is used to calculate compensation. Therefore, imaging plays a pivotal role in the diagnosis and management of asbestos-related disease.
Physical properties of asbestos fibers
Evidence regarding the relative importance of the different physical properties of the asbestos types in causing disease is conflicting. Certainly, fine fibers are more pathogenic than thick fibers. Fibers of 5 mm or more in diameter tend to become deposited in larger airways, in which they are effectively cleared through mucociliary action. In comparison, fibers that are more slender tend to be deposited in small airways or airspaces, from which only a proportion of them are cleared.
The effect of fiber length is less certain, but straight fibers that are approximately 5-20 mm long, such as crocidolite fibers, are not cleared as effectively as others are, and they can cause intense inflammation and fibrogenic changes within the interstitium. Conversely, chrysotile fibers are flexible, they usually do not fragment, and they are longer than 100 mm; therefore, they tend to be deposited in major airways, from which they are cleared to a large extent.
Despite differences in their physical properties, all types of asbestos fibers are fibrogenic. However, crocidolite is the most carcinogenic.
The pleura are more sensitive than pulmonary parenchyma to the effects of the fibers. Thus, pleural plaques develop after low, intermittent exposure, whereas asbestosis is associated with cumulative, high-level, long-term, continuous exposure in association with a definite dose-effect relationship. Nonmanual workers in industries involving asbestos, inhabitants of areas immediately surrounding asbestos mills, and families of asbestos workers have an increased incidence of mesothelioma. However, even with significant industrial exposure, asbestosis is unusual.
Pleural plaques are the most common manifestation of asbestos exposure, occurring after a latent period of approximately 20-40 years. A history of exposure can be elicited in more than 80% of patients. Histologically, pleural plaques consist of acellular collagen bundles that form a basket-weave pattern, which almost exclusively involves the parietal pleura. The plaques may contain chrysotile asbestos fibers.
The precise pathogenesis of pleural plaques remains undetermined. That they were caused by the mechanical effect of asbestos fibers piercing the visceral pleura (the scratching theory) was assumed. Currently, however, the fibers are believed to be transported to the parietal pleura via lymphatic channels, where they incite an inflammatory response. Plaques slowly grow over time, even after cessation of exposure, but they are not considered premalignant.
Calcification occurs later, often 30-40 years following exposure. Pleural plaques tend to occur in isolation without any other manifestations of asbestos-related disease; however, the converse is not true. Asbestosis is rarely seen in the absence of plaques.
Diffuse pleural thickening is less specific for asbestos exposure than the presence of pleural plaques, since thickening also may be seen following TB pleuritis, hemothorax and empyema. Usually, the latent period is approximately 15 years. The pathogenesis is unclear, but it is believed to be due to inflammation and fibrosis of the visceral pleural lymphatics, and it has been considered to be an extension of parenchymal fibrosis. Histologically, the appearances are similar, although in diffuse pleural thickening, fusion of the visceral and parietal layers and asbestos bodies (which are absent in pleural plaques) is profuse. Development of diffuse pleural thickening has a similar time line as plaque formation.
Benign asbestos-related pleural effusions are often the earliest manifestation of asbestos-related disease, typically occurring within 10 years of exposure. The effusions are exudative. Occasionally, they are hemorrhagic, but otherwise, their features are nonspecific. Effusions tend to be self-limiting, with a duration of a few months, but they can be chronic or recurrent. Diffuse pleural thickening not uncommonly develops following resolution of the effusion.
Fibers not cleared by mucociliary action are believed to be transported into the interstitium, where they form aggregates, usually at the level of the respiratory bronchiole. Research results suggest that the fibers stimulate the release of a collagenase inhibitor–like protein that locally disturbs the balance of collagen turnover, resulting in fibrogenic changes within the interstitium.
Asbestosis is usually seen when levels reach 10 million asbestos fibers per gram of pulmonary tissue. Asbestosis characteristically occurs following a latent period of 15-20 years, with a progression of disease even after exposure has ceased. Fibrosis first arises in and around the respiratory bronchioles, predominating in the subpleural portions of the lung in the lower lobes. This progresses to involve the alveolar walls, eventually causing honeycombing in a minority of patients.
Folded lung (also termed round atelectasis, pulmonary pseudotumor, or Blesovsky syndrome) specifically refers to an area of atelectatic lung adjacent to pleural thickening, with characteristic in-drawing of bronchi and vessels. Blesovsky first reported folded lung in 1966. Although folded lung is strongly associated with asbestos exposure, it may also be seen as a consequence of any inflammatory or infective organizing pleural exudate.
The presence of the effusion has been postulated to cause passive atelectasis, with infolding of the lung resulting in invagination of the adjacent pleura. This process causes tethering, which prevents reexpansion of the lung upon resolution of the effusion and which causes round atelectasis. A more accepted alternative explanation is that an insult to the pleura leads to localized inflammation and fibrosis, which results in volume loss and buckling of the underlying lung. Interestingly, the changes have been shown to resolve after decortication. The lingula is the most common site, followed by the middle and then the lower lobes, although lesions may be multiple and bilateral.
Malignant pleural mesothelioma is a rare neoplasm, accounting for less than 5% of pleural malignancies. Malignant pleural mesothelioma is strongly associated with asbestos exposure, particularly crocidolite exposure, although the association does not appear to be dose-related because significant numbers of cases occur after trivial environmental or household exposure. No relevant history of any asbestos exposure is found in 20% of patients. The disease is frequently seen in the absence of any other manifestations of asbestos exposure and usually develops after a long latent period of 35-40 years.
Mesothelioma is 80% pleural and 20% peritoneal in origin. Pleural effusions are not a precursor of mesothelioma, but they often antedate development of malignancy. A confident diagnosis is often difficult to make and usually requires ultrastructural analysis and histochemical and immunohistochemical tests. Histologically, 3 forms of malignant mesothelioma are recognized: epithelial, mixed, and sarcomatous or mesenchymal. These must be differentiated from mesothelial hyperplasia and metastatic adenocarcinoma. The most common histologic subtype is epithelial, accounting for 50% of cases.
Bronchogenic carcinoma is estimated to develop in 20-25% of heavily exposed asbestos workers. Smoking has a cumulative effect, further increasing the risk of lung cancer to a factor of 90 versus a factor of 5 in exposed nonsmokers. Often, asbestos-related interstitial disease is associated; however, no correlation exists between the severity of asbestosis and the development of lung cancer. Furthermore, lung cancer has been reported in individuals without interstitial lung disease who are exposed to asbestos. A latency period of 25-35 years is usual. Histologically, the predominant subtype is bronchoalveolar cell carcinoma, but adenocarcinoma and squamous cell carcinoma also occur.
Associations between asbestos exposure and other cancers have been reported anecdotally. Carcinomas of the larynx, esophagus, stomach, colon, and a variety of lymphoid malignancies have been described.
Mortality/Morbidity: After the onset of symptoms, severe asbestosis may lead to respiratory failure and death over 12-24 years. Respiratory failure may be accelerated by the development of Caplan syndrome; pulmonary hypertension; or malignancy, including lung cancer or mesothelioma.
No treatment for asbestosis is effective. The primary strategy is prevention, with the worldwide elimination of asbestos use and with the replacement of asbestos by safe synthetic products.
Mesothelioma tends to appear late and is usually associated with an extremely poor prognosis. The median survival is 10 months or less, and most patients die within 2 years.
Race: No race predilection exists for asbestos-related disease.
Sex: Mesothelioma has a male-to-female ratio of approximately 4:1. Asbestos-related disease in women is uncommon and usually confined to spouses of industrial workers and secretarial and domestic staff working in asbestos industries.
Age: A minimum latency period of 8-10 years is required for an asbestos-related pleural effusion to develop; this is usually the earliest manifestation of asbestos-related disease. Similarly, a latency period of more than 20 years is required for the development of asbestosis. As a result, most patients with asbestos-related disease are older than 40 years.
Mesothelioma usually is seen after a longer latency period, with most patients in the sixth-to-eighth decades of life.
International staging system for malignant mesothelioma is as follows:
Preferred Examination: HRCT is playing an increasingly important role in the diagnosis of diffuse interstitial lung disease. However, chest radiography remains the initial modality for the detection and characterization of pleural and parenchymal disease. Ultrasonography has a role in characterizing pleural effusions and guiding pleural aspiration and biopsy. Nuclear medicine study has a limited role in the investigation of asbestos-related intrathoracic disease. Gallium-67 citrate testing has been used to differentiate benign from malignant asbestos-related pleural disease and to give a quantitative index of inflammatory activity.
Limitations of Techniques: The limitations of chest radiography in the diagnosis and evaluation of asbestos-related disease are well recognized. The quality of the radiograph and the size, shape, position, and degree of calcification determine whether the radiologist can detect pleural plaques on the image. While the identification of bilateral scattered calcified costal and diaphragmatic pleural plaques is virtually diagnostic of asbestos exposure, studies have shown an 11% false-positive rate with chest radiographs. In particular, extrapleural fat mimics pleural thickening and is a significant cause of false-positive readings. Conversely, a high false-negative rate has also been reported.
CT scans has long been known to be more sensitive and specific than chest radiographs for the diagnosis of asbestos-related pleural disease.
Radiographic-pathologic studies have shown that chest radiographic findings are normal in as many as 20% of patients with asbestosis. HRCT is more sensitive and specific than other studies, particularly when images are obtained with the patient in the prone position, which allows differentiation of mild parenchymal changes from dependent density (increased attenuation of the posterior, usually basal, lung, which is gravity induced and secondary to nonaeration of dependent alveoli).
Nuclear medicine studies have been used in small series, and their exact role remains unclear.
Causes of diffuse pleural thickening
Degree of Confidence: The presence of bilateral calcified pleural plaques can be considered diagnostic of asbestos exposure.
Unfortunately, the value of chest radiography is limited. Reviewing a series of 200 radiographs, Epstein et al have found that images in 18% of the patients showed small opacities. This finding was consistent with pneumoconiosis, according to the International Labour Office (ILO) classification. Of these patients, 61% had no known occupational exposure to asbestos. Furthermore, as many as 20% of patients with histologically proven asbestos-related lung disease have normal chest radiographic findings, and 80% of patients with radiographic findings of mild disease have histologic results of moderate or severe fibrosis.
The extent of malignant mesothelioma frequently is underestimated with chest radiography.
False Positives/Negatives: False-positive, false-negative, and interobserver variability rates are relatively high when chest radiographs are evaluated for pleural plaques. Prominent subpleural fat or normal rib companion shadows may mimic focal or diffuse pleural thickening, leading to false-positive diagnoses in as many as 20% of patients.
Plaques may be difficult to differentiate from diffuse pleural thickening radiographically. However, plaques usually spare the costophrenic angles and apices and rarely extend over more than 4 rib interspaces, while diffuse pleural thickening rarely calcifies and is usually more irregular and ill defined.
Extensive pleural calcification usually suggests other etiologies, such as talc exposure, hemothorax, empyema, and therapeutic pneumothorax. However, bilateral diaphragmatic calcification with costophrenic angle sparing is considered pathognomonic for asbestos-related disease.
The differential diagnosis of predominantly basal subpleural fibrosis includes idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis or usual interstitial pneumonitis), drug reactions, and connective tissue diseases.
The most important differential diagnosis of round atelectasis is bronchogenic carcinoma. Biopsy may be necessary. Round atelectasis is not specific for asbestos exposure and may be preceded by pulmonary infarction, Dressler syndrome, heart failure, and nonspecific pleural effusions.
No definite evidence links benign asbestos-related pleural effusion to the development of malignant mesothelioma; however, malignant mesothelioma is an important differential diagnosis for benign asbestos-related effusion. Specific criteria for the diagnosis of a benign asbestos-related effusion include (1) a history of asbestos exposure, (2) the elimination of other etiologies of an effusion, and (3) the absence of malignancy for 3 years after the onset of the effusion. Although benign asbestos-related effusion and mesothelioma are both related to asbestos exposure, effusion tends to occur earlier than mesothelioma, with an onset approximately 10 years after exposure versus approximately 20-40 years.
Findings: CT has been established as the criterion standard in the evaluation of pleural disease. Recent developments in HRCT have made it an invaluable tool in the assessment of asbestosis. Scanning the patient in both the prone and supine positions increases sensitivity and specificity.
Degree of Confidence: Compared with radiographs, CT scans are more sensitive and specific for the detection of diffuse pleural thickening than chest radiographs. Furthermore, interobserver agreement in assessing pleural disease is greater with CT than with chest radiography.
The positive predictive value of chest radiographic findings for the diagnosis of pleural disease in asbestos-exposed individuals is reported to be 79% compared with 100% for HRCT findings.
HRCT scans can depict subtle parenchymal abnormalities in approximately 33% of patients with asbestos-related disease is cases with no chest radiographic evidence of interstitial disease and isolated borderline diminished lung capacity. However, no HRCT finding is specific for asbestosis. Thus, while HRCT is more sensitive than chest radiography for the diagnosis of asbestos-related disease, its specificity has been questioned.
The diagnosis is based on a combination of features, including bilateral pulmonary fibrosis and bilateral pleural plaques or diffuse pleural thickening in an individual with an appropriate history of exposure. The specificity of the diagnosis increases with the number of features identified; however, while asbestosis rarely occurs in the absence of plaques, plaques are not invariably present.
A small study correlating HRCT features and histopathologic findings revealed the presence of interstitial lines (84%), parenchymal bands (76%), architectural distortion (56%), subpleural lines (44%), and honeycombing (32%) in patients with proven asbestos-related lung disease. The specificity increased from 60% in patients in whom 1 feature was identified, to 80% with 2 features and 100% with 3 or more features.
In addition, HRCT is valuable in excluding disease in individuals with equivocal chest radiographic findings. CT is of value in differentiating benign disease from malignant pleural disease. The presence of a contiguous sheet or pleural rind, pleural nodularity, and thickening greater than 1 cm and the involvement of mediastinal pleura are regarded as suggestive of malignancy. However, case reports also report a variant of asbestos-related diffuse pleural thickening that appears nodular and that is radiologically indistinguishable from mesothelioma. In equivocal cases, biopsy is recommended.
False Positives/Negatives: Normal extrapleural fat can be seen on HRCT scans internal to the ribs, particularly posterolaterally from the fourth-to-eighth ribs extending into the costophrenic angles. Fat can be several millimeters thick. Fat may be difficult to distinguish from pleural plaques or thickening, particularly when extended window settings are used, but it is more easily recognizable on soft tissue window settings because of very low attenuation.
The transversus thoracis and subcostalis muscles, segments of intercostal veins, visceral pleural thickening, and confluent subpleural nodules (pseudoplaques) mimic pleural thickening. The transversus thoracis and subcostalis muscles usually are smooth, of uniform thickness, and are symmetric bilaterally. The subcostalis muscle is present only in a minority of individuals and is seen as 1- to 2-mm-thick lines internal to 1 or more lower ribs. The transversus thoracis muscle is almost always visible internal to the costochondral junctions anterior to the heart and adjacent to the sternum.
Intercostal vessels are seen commonly in the paravertebral regions and may cause spurious appearances of focal pleural thickening. Intercostal vessels can occasionally be traced to the azygos or hemiazygos veins; this observation allows the correct interpretation of the findings. Moreover, extrapleural fat should be visible between the vessel and the pleura, and when the images are read on the lung window setting, intercostal segments do not indent adjacent lung, while pleural plaques invariably indent. Furthermore, pleural plaques usually are visible over several contiguous intercostal segments and may contain calcification.
Bilateral calcified pleural plaques are usually considered asbestos related, although rare causes, such as radiation exposure, hyperparathyroidism, pulmonary infarction, and pancreatitis, have been reported. Unilateral pleural calcification rarely is related to asbestos exposure and should prompt consideration of old tuberculosis, empyema, or hemothorax. Unilateral noncalcified pleural plaques also are rare in asbestos-related disease.
Coal miner’s pneumoconiosis, silicoses, and sarcoidosis occasionally can give rise to confluent subpleural nodules (pseudoplaques) that may mimic pleural plaques; however, these are associated with pulmonary nodules rather than pulmonary fibrosis. Interstitial fibrosis seen in asbestosis is indistinguishable from idiopathic pulmonary fibrosis at radiographic, HRCT, and pathologic examination; the only distinguishing feature is the presence of asbestos bodies.
In most patients, CT appearances of round atelectasis are sufficiently characteristic to obviate intervention; however, differentiating benign fibrotic masses from bronchial carcinoma is essential, and some patients require close follow-up monitoring or biopsy. Although bronchial neoplasms can opacify to some degree after the intravenous administration of contrast material, uniform enhancement has not been reported as a feature of lung cancer. On radiographs, malignant mesothelioma cannot be reliably distinguished from pleural metastases resulting from an adenocarcinoma. Focal mesothelioma may be mistaken for a benign fibrous tumor.
Findings: The role of MRI in the diagnosis of interstitial lung disease has not been established, and no consistent pattern of signal intensity has been described for round atelectasis. However, MRI has a complementary role in the evaluation of pleural effusions and mesothelioma.
Mesothelioma typically shows high signal intensity on T1-weighted images and moderately high signal intensity on T2-weighted images.
Degree of Confidence: MRI and CT scanning have been shown to be similar in terms of their accuracy in the diagnosis of malignant mesothelioma, although MRI is superior to CT in depicting isolated foci of chest wall and diaphragmatic invasion. However, this difference has not been shown to confer any benefit in terms of overall staging.
MRI provides a certain advantage because the thorax can be directly imaged in various planes. The normal pleural space cannot be depicted by using current MRI techniques. T2-weighted sequences may offer tissue-specific information concerning pleural effusions and chest wall invasion by malignant processes because of increased tumor-to-muscle contrast.
Findings: Ultrasonography is useful in characterizing pleural effusions and evaluating pleural thickening or masses. Ultrasonography also facilitates image-guided pleural intervention.
Sonography has also been used to help evaluate round atelectasis. It has been shown to reliably demonstrate both the mass and adjacent pleural thickening. The presence of a highly echogenic line within the mass, which represents invaginated fibrotic pleura, is described as a useful ancillary finding, one seen in 86% of patients.
Findings: Lung uptake of 67Ga has been used to create a quantitative index of inflammatory activity in patients with asbestosis. Combined with evidence of serum markers indicating inflammation-associated pulmonary collagen formation, these findings may provide a clinically useful algorithmic approach permitting an early diagnosis of asbestosis. Single photon-emission computed tomography (SPECT) improves the sensitivity for detecting the presence and extent of interstitial occupational lung disease.
67Ga study has also been used to differentiate malignant from asbestos-related pleural disease. Although studies in 86% of patients with asbestos-related mesothelioma show radionuclide uptake, only 19% of patients with benign asbestos effusions have positive findings.
Positron emission tomography with [fluorine 18]-fluoro-2-deoxy-D-glucose has been suggested to aid in the differentiation of round atelectasis from bronchogenic carcinoma. To date, limited studies have shown round atelectasis to be metabolically inactive.
Degree of Confidence: Although experience is limited, the combination of HRCT, 67Ga scanning, and inflammatory serum marker testing may allow for an earlier diagnosis of asbestosis.
False Positives/Negatives: Mesothelioma unrelated to asbestos exposure is also known to give rise to positive findings on 67Ga scans.
Intervention: No treatment for asbestosis is effective. The primary strategy is prevention, with the worldwide elimination of asbestos use and with the replacement of asbestos by safe synthetic products.
Image-guided pleural thoracentesis or pleural biopsy is occasionally required for the further evaluation of pleural effusions and masses.
Symptomatic patients with malignant pleural effusions may initially be treated by means of therapeutic aspiration or drainage; however, effusions tend to recur and often require pleurodesis. Pleurectomy is considered only if the prognosis is otherwise good. Percutaneous biopsy is occasionally required to differentiate round atelectasis from bronchogenic carcinoma. Asbestos bodies have been identified in fine-needle aspirates from round atelectasis.
A theoretical risk exists of seeding tumor cells along the needle track after biopsy of suggested malignant mesothelioma. Some centers advocate prophylactic radiation therapy at the biopsy site, which should be marked with India ink immediately after the procedure.