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.

Pathophysiology:

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.

Pathogenesis

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.

Frequency:

• In the US: The number of individuals affected by asbestos-related disease is slowly increasing. However, whether this is secondary to a true increase in incidence or due to increased recognition is debated.

  The prevalence of benign pleural plaques in the non–asbestos-exposed general population is extremely low. The prevalence in environmentally exposed general populations in industrial societies is approximately 0.5-8%. Frequencies in exposed individuals are 3-58%, depending on occupation. The development of plaques depends on the length of exposure or the time from first exposure, as opposed to a threshold dose, which is the case for asbestosis. The prevalence of pleural plaques is 10% in exposed individuals 20 years after exposure, rising to 50% after 40 years.

  The prevalence of diffuse pleural thickening is not known, although it is reported to occur with frequency equal to that of pleural plaques. Thickening is a common concomitant finding to asbestosis, with a reported associated incidence of 10%.

  The frequency of benign asbestos-related pleural effusions in exposed individuals is reported to be 3-7%. However, this number may be an underestimate because most patients are asymptomatic; therefore, effusions are subclinical and undetected. The incidence rises with increasing levels of asbestos exposure.

  Asbestosis is reported to develop in 49-52% of adults with industrial asbestos exposure, after a latency period of 40-45 years.

  Approximately 2000-3000 cases of malignant mesothelioma are diagnosed annually in the United States, or 7-13 cases per million general population.

  Epidemiologic studies predict a decline in incidence in the United States after the year 2000, with a peak incidence in the United Kingdom in 2020. The prediction is probably applicable to benign pleural plaques also, because the latency period is similar. Lung cancer develops in as many as 25% of asbestos workers. In asbestos-exposed nonsmokers, the incidence of lung cancer is 5 times that of the general population. In exposed individuals, smoking further increases the risk of bronchogenic carcinoma by 80-90 fold.

• Internationally: The incidence of asbestos-related lung and pleural disease in the remainder of the industrialized world remains similar to that of the United States. In the United Kingdom, asbestos use was highest in the 1970s, later than in the United States; therefore, the peak incidence of disease lags as well. Legislation regarding asbestos varies from country to country, and although crocidolite is rarely used internationally, other forms of asbestos remain in use.

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.

Clinical Details:

• Pleural plaques are not reported to cause symptoms.

   

• Diffuse pleural thickening may be associated with symptoms and signs comparable to those arising from other causes of fibrothorax, such as dyspnea. The restriction of lung function rarely may be severe enough to warrant decortication of the lung.

   

• The clinical picture in benign asbestos-related pleural effusion varies from asymptomatic patients to patients with an acute episode of pleuritic chest pain and pyrexia.

   

• Asbestosis may cause an insidious onset of progressive dyspnea in addition to a dry cough. Clinical findings of basal inspiratory crackles associated with reduction in vital capacity and diffusion capacity are also seen.

   

• Asbestosis is usually diagnosed on the basis of certain clinical, functional, and radiographic findings outlined by the American Thoracic Society (ATS). However, these guidelines have not been updated since the routine clinical use of high-resolution CT (HRCT) scanning began in the early 1990s. Findings based on the ATS criteria include the following:

   

  • Reliable history of nontrivial asbestos exposure

     

  • Appropriate interval between exposure and detection (usually >10 y)

     

  • Abnormal chest radiographic findings

     

  • Restrictive lung disease as indicated by pulmonary function test results

     

  • Abnormal diffusing capacity

     

  • Bilateral crackles at the lung bases that are not cleared by coughing

   

• Clinical symptoms in malignant mesothelioma are frequently present 6-8 months prior to diagnosis. Symptoms include localized chest wall pain and weight loss. Cough and dyspnea may also be present.

International staging system for malignant mesothelioma is as follows:

• Tumor

   

  • T1a - Tumor limited to ipsilateral parietal pleura

     

  • T1b - Additional scattered foci of visceral pleural involvement

     

  • T2 - T1 plus involvement of diaphragmatic muscle and/or confluent visceral tumor (including fissures) or direct extension to the pulmonary parenchyma

     

  • T3 - Locally advanced but potentially resectable tumor encasing the lung with at least one of the following features:

     

    • Involvement of endothoracic fascia

       

    • Extension into mediastinal fat

       

    • Solitary focus of chest wall invasion

       

    • Nontransmural involvement of pericardium

     

  • T4 - Locally advanced unresectable tumor encasing the lung, with at least one of the following features:

     

    • Multifocal or diffuse chest wall involvement

       

    • Transdiaphragmatic peritoneal spread

       

    • Direct extension to contralateral pleura

       

    • Involvement of vital mediastinal structures

       

    • Direct extension to the spine

       

    • Transpericardial disease, with or without pericardial effusion or myocardial involvement

   

• Node

   

  • N0 - No regional nodal metastases

     

  • N1 - Ipsilateral bronchopulmonary or hilar nodal enlargement

     

  • N2 - Ipsilateral mediastinal (including internal mammary) or subcarinal nodal enlargement

     

  • N3 - Contralateral mediastinal, contralateral internal mammary, or supraclavicular nodal enlargement

   

• Metastasis

   

  • M0 - No distant metastases

     

  • M1 - Distant metastases present

   

• Staging

   

  • Stage Ia - T1a, N0, M0

     

  • Stage Ib - T1b, N0, M0

     

  • Stage II - T2, N0, M0

     

  • Stage III - Any T3, M0; any N1, M0, any N2, M0

     

  • Stage IV - Any T4, any N3, any M1

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.

DIFFERENTIALS

Rib fractures

Other Problems to be Considered:

Causes of diffuse pleural thickening

Benign asbestos-related diffuse pleural thickening
Postexudative effusion, eg, parapneumonic effusion and connective tissue disease
Hemothorax
Mesothelioma

Causes of nodular pleural thickening

Malignant mesothelioma
Metastatic adenocarcinoma

Causes of basal subpleural fibrosis

Asbestosis
Usual interstitial pneumonia
Connective tissue disease
Drug-related fibrosis

Causes of a solitary pulmonary mass

Folded lung
Malignancy, eg, bronchogenic carcinoma, metastasis, and lymphoma
Benign neoplasm, eg, hamartoma and adenoma
Vascular, eg, arteriovenous malformation, pulmonary infarction, and hematoma
Infection, eg, tuberculosis, round pneumonia, and fungal infection

X-RAY

Findings:

• Benign pleural plaques

   

  • Benign pleural plaques may be seen in profile or en face. In profile, plaques appear as focal smooth opacities, usually less than 1 cm thick, paralleling the chest wall. Appearances en face are of a more ill-defined opacity with irregular margins.

     

  • Plaques may occur as isolated abnormalities or in association with lung parenchymal involvement.

     

  • Most pleural plaques are multiple, bilateral, and often symmetric and are located in the midportion of the chest wall between the seventh and 10th ribs, following rib contours, or adjacent to the aponeurotic portion of the diaphragm and vertebral column.

     

  • Visceral pleura, lung apices, and costophrenic angles are typically spared.

   

• Pleural calcification

   

  • On chest radiographs, the prevalence of calcification in pleural plaques is reported to be 10-15%.

     

  • In profile, calcified plaques appear as opaque lines that lie parallel to the chest wall, mediastinum, pericardium, and diaphragm.

     

  • Viewed en face, calcified plaques are seen as irregular heterogeneous densities, the so-called holly leaf.

     

  • The presence of bilateral, superior diaphragmatic surface calcifications with clear costophrenic angles is virtually pathognomonic for asbestos-related pleural disease.

   

• Diffuse pleural thickening

   

  • Asbestos-related diffuse pleural thickening is defined as a smooth, uninterrupted pleural opacity extending over at least one quarter of the chest wall, with or without obliteration of the costophrenic angles.

     

  • Pleural thickening may be difficult to diagnose using conventional chest radiographs, and differentiation between diffuse thickening and focal pleural plaques may be problematic. However, diffuse pleural thickening due to asbestos exposure rarely calcifies, it tends to involve the costophrenic angles (unlike plaques), it tends to be ill defined rather than sharply marginated, and it is more extensive than focal plaques.

     

  • Involvement of interlobar fissures is not uncommon.

     

  • Diffuse pleural thickening is associated more often with radiographically detectable asbestosis than are pleural plaques.

   

• Benign asbestos-related pleural effusions

   

  • Benign asbestos-related effusions have the same radiographic appearance as effusions due to other etiologies; the diagnosis usually is one of exclusion.

     

  • Effusions are usually small, they may be unilateral or bilateral, and they tend to resolve spontaneously over 3-4 months, although as many as 30% recur.

     

  • Some effusions are associated with pleural plaques.

     

  • Effusions tend to resolve over a period ranging from 1 month to 1 year, with residual blunting of the costophrenic angles due to pleural thickening in 50% of patients.

   

• Asbestosis

   

  • Asbestosis is defined as interstitial pulmonary fibrosis secondary to the presence of intrapulmonary asbestos bodies or asbestos fibers. The fibrosis is usually most severe in the subpleural lower zones.

     

  • Chest radiographic findings include fine reticular opacities and septal lines that progress towards a coarser linear pattern of honeycombing.

     

  • With advanced disease, the heart border and diaphragmatic contours become ill defined, the so-called shaggy heart.

   

• Round atelectasis

   

  • Round atelectasis appears as a well-defined, rounded, focal, subpleural, soft tissue mass of 2-7 cm in diameter that abuts an area of pleural thickening.

     

  • Most atelectases are located in the posterolateral or posteromedial parts of the lower lobes.

     

  • Occasionally, bilateral masses are seen.

     

  • Mild volume loss may be associated.

     

  • Appearances usually remain stable over time but, occasionally, masses may increase or decrease in size.

   

• Bronchogenic carcinoma associated with asbestos exposure

   

  • Appearances are those of non–asbestos-related lung cancer.

     

  • The most common radiographic finding is a pulmonary mass with associated mediastinal lymphadenopathy.

     

  • Lung cancer in asbestos-related disease tends to occur at the lung bases but can arise in any location if also associated with smoking.

   

• Malignant mesothelioma

   

  • Mesothelioma typically appears as irregular, nodular, diffuse pleural thickening, occasionally associated with a pleural effusion.

     

  • Less commonly, an isolated effusion or pleural mass is seen.

     

  • The tumor progresses to encase the entire hemithorax, encasing the lung.

     

  • The mediastinum usually is fixed or shifted toward the side of the tumor.

     

  • Evidence of other asbestos-related disease, such as plaques, is seen in only approximately 20-25% of patients.

     

  • Patients rarely may present with spontaneous pneumothorax.

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.