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Pleural Disease in Silicosis: Pleural Thickening, Effusion, and Invagination¹

¹ From the Departments of Radiology (H.A., M.F.) and Pathology (K.H.), Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan; Departments of Respiratory Medicine (Y.S.) and Radiology (H.S., H.M.), Keihai Rosai Hospital for Silicosis, Nikko, Japan; and Department of Environmental Health, Fukui Medical School, Fukui, Japan (N.S.). Received August 4, 2004; revision requested October 8; revision received November 2; accepted November 12. Address correspondence to H.A. (e-mail: arakawa{at}dokkyomed.ac.jp).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To retrospectively evaluate pleural disease on images from patients with autopsy-proved silicosis.

MATERIALS AND METHODS: The study had institutional review board approval, and informed consent from relatives of diseased subjects was waived. Lung specimens were obtained at autopsy in 110 men (mean age, 72 years) who had been followed up radiologically for a mean of 14.8 years. Computed tomographic (CT) scans obtained within 2 years before death were examined for presence of pleural thickening; shape, composition, size, and subpleural location of progressive massive fibrosis (PMF); and pleural invagination (bandlike structure between lesion and pleura). Lung specimens were reviewed and compared with CT findings. Serial chest radiographs and CT scans were reviewed for presence of pleural effusion. Association between radiographic findings and pleural invagination was analyzed with ² and Student t tests. Multiple logistic regression analysis was used to find predictive variables for pleural invagination.

RESULTS: Pleural effusion was found in 12 (11%) patients at chest radiography and CT, and thickening was found in 64 (58%) patients at CT; the latter finding was significantly more frequent with complicated silicosis (P < .001). At CT, 128 PMF lesions were seen, 39 (30%) of which showed pleural invagination; CT scans showed pleural thickening in 36 (92%) of these 39 lesions. In 17 (44%) PMF lesions, CT scans depicted a bandlike structure that was pathologically confirmed to represent invaginated pleura in all cases. Pathologic presence of invagination was significantly associated with pleural thickening (P < .001), ipsilateral pleural effusion (P < .01), interstitial fibrosis (P < .05), and the nearness of PMF to the pleura (P < .005). Multiple logistic regression analysis showed that pleural thickening (odds ratio, 62.51; 95% confidence interval [CI]: 5.564, 70.2) and pleural effusion (odds ratio, 25.865; 95% CI: 1.992, 335.8) were significant CT variables associated with presence of pathologic pleural invagination (P = .001 and .013, respectively). Five PMF lesions had radiographic features of rounded atelectasis.

CONCLUSION: Various pleural abnormalities can occur in silicosis, especially in advanced disease.

© RSNA, 2005

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Pleural disease is a well-known entity found in asbestos-exposed patients and includes pleural plaque, pleural effusion, and diffuse pleural thickening (1). On the other hand, pleural disease in silicosis has not, to our knowledge, been extensively described in the literature (2–6). Thus, the purpose of our study was to retrospectively evaluate pleural disease on images obtained in patients with autopsy-proved silicosis.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Study Population
Our institutional review board approved this retrospective study, and informed consent from the relatives of the diseased subjects was waived.

Subjects were retrospectively identified from a pathology database at our hospital (Keihai Rosai Hospital for Silicosis) that is dedicated to records of patients with occupational lung disease, mainly those with silica-related pneumoconiosis. The database included records of 271 consecutive patients occupationally exposed to silica and nonasbestos silicate who died and in whom autopsy was performed between 1988 and 2001. The patients were medicolegally diagnosed with occupational lung disease before death and underwent chest radiography and computed tomography (CT) at our institution during follow-up between diagnosis and death. Clinical diagnosis of silicosis was made by an experienced occupational chest physician (Y.S.) on the basis of clinical and radiologic criteria (similar to the classification system of the International Labour Organization [ILO]), an unequivocal history of substantial silica and silicate exposure, and an appropriate interval of time after exposure. The physician made the official document for each patient and sent the document with a copy of the chest radiograph to the regional governmental committee by which the diagnosis was legally admitted.

Patients with silicosis entered into periodic follow-up if any of the following were noted: (a) the chest radiograph showed large opacities type "C" according to the ILO classification, (b) there was substantial respiratory impairment as measured by means of spirometry or arterial blood gas analyses, or (c) the case was complicated by either tuberculosis or chronic bronchitis. Inclusion criteria for this study were an autopsy report indicating the presence of silicosis, an absence of asbestos fibers in the lungs or pleura at autopsy, and chest radiographs and CT scans obtained within 2 years before death (mean, 286.5 days).

The study group comprised 110 men, the follow-up interval ranged from 0.6 to 33.7 years (mean, 14.8 years), and patient age at time of CT ranged from 44 to 91 years (mean, 72 years). All patients had the pathologic diagnosis of silicosis. Occupations were metal ore mining (n = 46), tunnel work (n = 35), stone masonry (n = 16), coal mining (n = 5), foundry (n = 3), or other occupations (n = 5). No patient had a known occupational exposure to asbestos.

Chart review was done by one of the authors (Y.S.), who was the referring pneumologist. Smoking habit and history of tuberculosis was assessed for each patient. Clinical history of tuberculosis was assessed as the detection of acid-fast bacilli in sputum, smear, or culture during life. In patients who had pleural effusion, the possible cause (eg, cardiac disease, renal disease, pneumonia, pleuritis, malnutrition, cirrhosis, malignancy) was sought. Final decision on the cause of pleural effusion was made on the basis of the combined clinical, radiologic, and pathologic information.

Serial Chest Radiographs
Chest radiographs were obtained at 120–130 kVp and a grid ratio of 14:1, with a variety of screen-film combinations. The review of the chest radiographs in each patient was performed by two experienced chest radiologists (H.S., H.A.); one chest radiologist was engaged in pneumoconiosis for more than 30 years, and the other was a chest radiologist with 13 years of experience. They were not certified B readers, but B-reader certification is not required in our country for official assessment of pneumoconiosis. A series of chest radiographs obtained every 3 years between the initial outpatient visit and death were available in all patients; these radiographs were reviewed to detect pleural effusion by consensus.

Chest radiographs obtained within 1 month of the last CT study were also reviewed independently at different sessions to categorize small opacities and to score the radiographic profusion of parenchymal opacities and the extent of pleural thickening according to the recently revised ILO classification system (7). The profusion of small opacities was graded on a 12-point scale of the ILO system (score of 1 for 0/– and score of 12 for 3/+). The sizes of large opacities and pleural thickening were scored by using a four-point scale of the ILO system. The mean values of the two ratings were used for analysis.

CT Scanning Protocol
In 82 patients, transverse CT (900S; Toshiba Medical, Tokyo, Japan) was performed with 10-mm collimation, 10-mm reconstruction intervals, 120 kV, and 200–280 mA. In the other 28 patients, spiral CT (Somatom Plus 4; Siemens Medical Systems, Forchheim, Germany) was performed with 10-mm collimation, a helical pitch of 1:1, 10-mm reconstruction intervals, 120 kV, and 280 mA. Lungs were scanned from apex to base, without contrast material, and all images were obtained with both lung and mediastinal window settings. For lung images, window width was 1500 HU and level was –650 HU; for mediastinal images, window width was 350–500 HU and level was 30–70 HU.

CT Image Analysis
The same two chest radiologists reviewed the CT images in consensus and were blinded to pathologic findings. The review session was held several months after that for the chest radiographs, and images were reviewed in random order. The radiologists assessed pleural thickening, pleural calcification, pleural effusion, interstitial fibrosis, and PMF lesions on the last CT images obtained in each patient. Pleural thickening was assessed as either segmented or diffuse on the basis of length: Segmented pleural thickening was defined as short thickening less than 5 cm in length, while diffuse pleural thickening was defined as that longer than 5 cm. The maximum length of pleural thickening at any scanned level observed in the entire circumference of each hemithorax was measured, and the summation of the length from each hemithorax was projected to the circumference of the right hemithorax at the level of tracheal carina. The summation of the length of pleural thickening was scored by using a five-point scale: score of 0, no pleural thickening; score of 1, length up to one-quarter of the circumference; score of 2, length exceeding one-quarter and up to one-half; score of 3, length exceeding one-half and up to three-quarters; and score of 4, length greater than three-quarters.

The presence of interstitial fibrosis was recorded if honeycombing, bilateral diffuse reticular opacities, or both were identified on the CT images in the lung bases. Attention was paid to the presence of diffuse interstitial fibrosis around PMF lesions. We defined PMF as the presence of pneumoconiotic nodules more than 2 cm in diameter on CT images, according to the criteria used by the College of American Pathologists (8). The shape (round, elongated, wedge, or other), location (the lobe that contained the center of the PMF lesion), and composition (consolidated, solid mass, coalescence of pneumoconiotic nodules) of PMF lesions were described. Those patients with PMF seen at CT were categorized as having complicated silicosis and those without PMF seen at CT were categorized as having simple silicosis. The PMF lesion was judged to be round if it had a circular shape on most CT images, as elongated if the diameter was longer in one direction than the other, and as wedge shaped if the lesion was fan shaped (usually extending from the pulmonary hilum). Composition of the PMF lesion was defined as consolidated if it contained an air bronchogram, as solid if it showed homogeneous soft-tissue attenuation, and as a coalescence of pneumoconiotic nodules if it formed a mass but each nodule forming the mass could still be identified in it. The two orthogonal diameters of each PMF lesion were recorded, and distance between a PMF lesion and the covering pleura was measured by one of the authors (H.A.). Observers also recorded, by consensus, the presence of any thickened band between the PMF lesion and pleura and any pleural thickening over the area of the lesion.

CT images other than the last one obtained were also reviewed, when available, for detection of pleural effusion. In 89 patients, images from two or more previous CT studies were available, and the interval between the oldest and the most recent CT studies ranged from 10 months to 15.8 years (mean, 6.2 years).

Autopsy Analysis
The lungs were sectioned at 10–15-mm thickness in the coronal plane and were photographed by one of the authors (K.H.), a pathologist with 22 years of experience in pneumoconiosis. Gough-Wentworth whole lung sections were prepared from the lung specimens containing the hilar area. The lungs were further sectioned for pathologic analysis, and the tissue specimens were prepared. Hematoxylin-eosin and elastic Goldner stains were usually used. The rest of the lungs were stored packed in the formalin. The attending pathologist examined the specimens and made the diagnosis of pneumoconiosis either as predominantly silicotic nodules or as mixed-dust fibrosis (9). The pathologic diagnosis of active or healed tuberculosis was made by identifying either tuberculous bacilli, encapsulated caseous foci, or caseating epithelioid granuloma in the lung or caseous necrosis compatible with tuberculosis in the silicotic nodules.

The autopsy materials were examined by two of the authors (H.A., K.H.); one was a chest radiologist, and the other was the pathologist who had prepared the autopsy materials. The material reviewed included gross images of the lungs, Gough-Wentworth whole lung sections, and histologic slides obtained in areas that included PMF lesions. Initially, we reviewed the gross images of the lungs to assess the pleural thickening (visceral or parietal) and invagination (enfolding). If there was any ambiguity about the relationship between the PMF lesion and the pleura, resected lung specimens were cut into thinner sections, and the presence or absence of pleural invagination was confirmed. When necessary, histologic slides were further examined.

Statistical Analysis
The interobserver agreement for radiographic category, size of large opacities (PMF), and pleural abnormalities was assessed by using weighted statistics. The interobserver agreement for radiographic profusion of small opacities was assessed by using Spearman rank correlation coefficient, and the difference of the two ratings was evaluated with a Bland-Altman plot (10). The differences in frequency of pleural diseases and extent of pleural thickening were analyzed by means of the ² test and the Student t test between simple and complicated silicosis, respectively. The difference in frequency of pleural thickening was also analyzed by using the ² test between patients with and those without history of tuberculosis. Differences in lesion size (defined as the product of the long and short diameters of the PMF lesion), distance from the pleura, profusion of small opacities on chest radiographs, and extent of pleural thickening were assessed by using the Student t test between PMF lesions with and those without pleural invagination. The ² test was used to analyze differences in the ratio of invaginated to noninvaginated PMF lesions between cases with and those without ipsilateral pleural effusion, pleural thickening, and interstitial fibrosis on CT images, as well as between the different shapes and compositions of PMF.

Logistic regression analysis was performed to calculate odds ratios for likely variables to be predictive of pleural invagination. Candidate predictive variables that were assessed with the logistic model included clinical information (age, smoking, history of tuberculosis), radiologic findings (extent of pleural thickening, pleural effusion, pleural calcification, reticular opacities, shape, location and composition of PMF lesion, lesion size, radiographic profusion and category of small opacities, distance between PMF and pleura), and pathologic diagnosis (predominantly silicotic nodule or mixed-dust fibrosis). Backward stepwise logistic regression analysis was performed to select predictive variables for pleural invagination by means of a log likelihood ratio test with an inclusion level of 0.05 and an exclusion level of 0.10. SPSS software (version 11.0 for Windows; SPSS, Chicago, Ill) was used for statistical analyses. A P value of less than .05 was regarded to indicate statistical significance.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Patients
Fifteen patients were nonsmokers, 57 were ex-smokers, and 29 were current smokers at the time of the last CT examination. In nine patients there was no information of smoking habits. No patient had known pulmonary disease other than silicosis. Sixty-eight patients had predominantly silicotic nodules, while 42 patients had predominantly mix-dust fibrotic lesions. Seventy-six patients had no history of tuberculosis; the other 34 patients, however, were either clinically or pathologically determined to have a history of pulmonary tuberculosis.

Interpretation of Chest Radiographs
Small rounded or irregular opacities on chest radiographs were identified in all but one patient, as shown in Table 1. The radiographic interpretations were in good agreement. The interobserver agreement for radiographic category, profusion, large opacities, and pleural abnormalities was 0.879, 0.866, 0.943, and 0.600, respectively. The Bland-Altman plot for profusion of small opacities is indicated in Figure 1. Pleural thickening on radiographs was seen more frequently in complicated silicosis than in simple silicosis (P < .001) and the extent of pleural thickening was significantly wider in complicated silicosis (mean extent, 1.4 vs 0.3; P < .001).

View larger version (16K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Bland-Altman plot for radiographic profusion of small opacities rated by two radiologists. Mean difference was –0.05, and the limits of agreement between two observers in each patient were small (range, –2 to 2). SD = standard deviation.

Pleural invagination and associated findings.—Diffuse reticular opacities or honeycombing were identified on CT scans in 19 (17%) patients in both lung bases. Seventeen (13%) of 128 PMF lesions were found in areas of diffuse interstitial fibrosis, which was confirmed at autopsy in all cases.

One hundred twenty-eight PMF lesions were found in 62 patients at CT. Lesions ranged in size from 10 to 60 mm at the smallest diameter and 20 to 92 mm at the largest diameter (mean, 28.9 and 45.4 mm, respectively). The distance between PMF lesion and pleura ranged from 0 to 60 mm (mean, 7.8 mm). PMF lesions were found in the upper (n = 100), lower (n = 26), and right middle (n = 2) lobes. Eighty-two PMF lesions were round, 25 were wedge shaped, 11 were elongated, and 10 were classified as other shapes. Ninety PMF lesions were solid, 28 were consolidated, and 10 were coalescent.

In 39 (30%) of 128 PMF lesions, fibrous thickening of the pleura was observed that invaginated through the lung to reach PMF lesions or invaginated directly into a subpleurally located PMF lesion as seen at autopsy. The presence of pleural invagination was exclusively associated with pathologically confirmed pleural thickening over the lesion (Table 3); pleural thickening was identified at CT in 36 (92%) invaginated lesions (segmented, n = 13; diffuse, n = 23). The association between the pleural invagination and CT evidence of pleural thickening was significant (P < .001). On CT scans, a thickened band extending from the PMF to the adjacent pleura was identified in 17 (44%) PMF lesions with pleural invagination. These thickened bands were pathologically confirmed to represent thickened pleural invagination into the lesions (Fig 2). In the other 22 PMF lesions, in which a thickened band was not identified on CT scans, all but one of the lesions involved were attached to the pleural surface on CT scans (Fig 3).

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. CT scans and autopsy findings in a 74-year-old man with silicosis (former tunnel worker). (a, b) Transverse spiral CT scans obtained with 10-mm section thickness. (a) Lung window scan shows PMF (arrows) and pleural effusion in both lower lobes, surrounded by multiple small pneumoconiotic nodules. (b) Mediastinal window scan shows a thickened band (large arrow) between PMF and the thickened pleura on the left side. The PMF on the right side is adherent to the pleura, which shows smooth thickening at the site of attachment (small arrows). (c) Gross lung specimen from a coronal section confirms invagination of diffuse thick pleura into the black PMF on the left side (arrow, right side of image). The thickened band in b proved the continuation of thickened pleura. The right pleura also shows diffuse thickening and invagination (arrows, left side of image) into the PMF.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. CT scans and autopsy findings in a 74-year-old man with silicosis (former tunnel worker). (a, b) Transverse spiral CT scans obtained with 10-mm section thickness. (a) Lung window scan shows PMF (arrows) and pleural effusion in both lower lobes, surrounded by multiple small pneumoconiotic nodules. (b) Mediastinal window scan shows a thickened band (large arrow) between PMF and the thickened pleura on the left side. The PMF on the right side is adherent to the pleura, which shows smooth thickening at the site of attachment (small arrows). (c) Gross lung specimen from a coronal section confirms invagination of diffuse thick pleura into the black PMF on the left side (arrow, right side of image). The thickened band in b proved the continuation of thickened pleura. The right pleura also shows diffuse thickening and invagination (arrows, left side of image) into the PMF.

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. CT scans and autopsy findings in a 74-year-old man with silicosis (former tunnel worker). (a, b) Transverse spiral CT scans obtained with 10-mm section thickness. (a) Lung window scan shows PMF (arrows) and pleural effusion in both lower lobes, surrounded by multiple small pneumoconiotic nodules. (b) Mediastinal window scan shows a thickened band (large arrow) between PMF and the thickened pleura on the left side. The PMF on the right side is adherent to the pleura, which shows smooth thickening at the site of attachment (small arrows). (c) Gross lung specimen from a coronal section confirms invagination of diffuse thick pleura into the black PMF on the left side (arrow, right side of image). The thickened band in b proved the continuation of thickened pleura. The right pleura also shows diffuse thickening and invagination (arrows, left side of image) into the PMF.

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. CT scans and autopsy findings in a 61-year-old man with silicosis (former tunnel worker). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows rounded masses in both upper lobes (). The mass in the left lobe is attached to the pleura, and the mass in the right lobe is not. There are multiple silicotic nodules around the masses. (b) Mediastinal window scan shows thickened pleura (arrows) between the left mass and chest wall, as well as proliferation of the subpleural fat. Note the many eggshell calcifications in the mediastinal lymphadenopathy. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening and invagination (arrow) into PMF on the left side. Because the PMF is attached to the pleura, invagination was not identified as a thick band on the CT scans.

View larger version (92K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. CT scans and autopsy findings in a 61-year-old man with silicosis (former tunnel worker). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows rounded masses in both upper lobes (). The mass in the left lobe is attached to the pleura, and the mass in the right lobe is not. There are multiple silicotic nodules around the masses. (b) Mediastinal window scan shows thickened pleura (arrows) between the left mass and chest wall, as well as proliferation of the subpleural fat. Note the many eggshell calcifications in the mediastinal lymphadenopathy. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening and invagination (arrow) into PMF on the left side. Because the PMF is attached to the pleura, invagination was not identified as a thick band on the CT scans.

View larger version (164K): [in this window] [in a new window] [Download PPT slide]   Figure 3c. CT scans and autopsy findings in a 61-year-old man with silicosis (former tunnel worker). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows rounded masses in both upper lobes (). The mass in the left lobe is attached to the pleura, and the mass in the right lobe is not. There are multiple silicotic nodules around the masses. (b) Mediastinal window scan shows thickened pleura (arrows) between the left mass and chest wall, as well as proliferation of the subpleural fat. Note the many eggshell calcifications in the mediastinal lymphadenopathy. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening and invagination (arrow) into PMF on the left side. Because the PMF is attached to the pleura, invagination was not identified as a thick band on the CT scans.

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 4a. CT scans and autopsy findings in an 86-year-old man with silicosis (former metal ore miner). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows a rounded opacity (PMF) in the right lower lobe. Lung volume is reduced, and the major fissure is displaced (arrows). CT features were those of rounded atelectasis. Note multiple small nodules of silicosis in both lower lobes. (b) Mediastinal window scan at the same level as in a shows a thickened band (arrow) that connects PMF with the thickened pleura. There is a small amount of ipsilateral pleural effusion and multiple calcifications in the PMF. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening in the right lung base and invagination (arrow) into the mass. (d) Photomicrograph shows coalescence of calcified silicotic nodules forming the mass. Intervening lung tissue is black pigmented and shows various degrees of interstitial fibrosis and atelectasis. The pathologic features were compatible with PMF. Invagination of thickened pleura (arrows) into the mass is apparent. (Elastic-Goldner stain, original size.)

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 4b. CT scans and autopsy findings in an 86-year-old man with silicosis (former metal ore miner). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows a rounded opacity (PMF) in the right lower lobe. Lung volume is reduced, and the major fissure is displaced (arrows). CT features were those of rounded atelectasis. Note multiple small nodules of silicosis in both lower lobes. (b) Mediastinal window scan at the same level as in a shows a thickened band (arrow) that connects PMF with the thickened pleura. There is a small amount of ipsilateral pleural effusion and multiple calcifications in the PMF. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening in the right lung base and invagination (arrow) into the mass. (d) Photomicrograph shows coalescence of calcified silicotic nodules forming the mass. Intervening lung tissue is black pigmented and shows various degrees of interstitial fibrosis and atelectasis. The pathologic features were compatible with PMF. Invagination of thickened pleura (arrows) into the mass is apparent. (Elastic-Goldner stain, original size.)

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 4c. CT scans and autopsy findings in an 86-year-old man with silicosis (former metal ore miner). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows a rounded opacity (PMF) in the right lower lobe. Lung volume is reduced, and the major fissure is displaced (arrows). CT features were those of rounded atelectasis. Note multiple small nodules of silicosis in both lower lobes. (b) Mediastinal window scan at the same level as in a shows a thickened band (arrow) that connects PMF with the thickened pleura. There is a small amount of ipsilateral pleural effusion and multiple calcifications in the PMF. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening in the right lung base and invagination (arrow) into the mass. (d) Photomicrograph shows coalescence of calcified silicotic nodules forming the mass. Intervening lung tissue is black pigmented and shows various degrees of interstitial fibrosis and atelectasis. The pathologic features were compatible with PMF. Invagination of thickened pleura (arrows) into the mass is apparent. (Elastic-Goldner stain, original size.)

View larger version (158K): [in this window] [in a new window] [Download PPT slide]   Figure 4d. CT scans and autopsy findings in an 86-year-old man with silicosis (former metal ore miner). (a, b) Transverse CT scans obtained with 10-mm collimation. (a) Lung window scan shows a rounded opacity (PMF) in the right lower lobe. Lung volume is reduced, and the major fissure is displaced (arrows). CT features were those of rounded atelectasis. Note multiple small nodules of silicosis in both lower lobes. (b) Mediastinal window scan at the same level as in a shows a thickened band (arrow) that connects PMF with the thickened pleura. There is a small amount of ipsilateral pleural effusion and multiple calcifications in the PMF. (c) Gross lung specimen from a coronal section shows diffuse pleural thickening in the right lung base and invagination (arrow) into the mass. (d) Photomicrograph shows coalescence of calcified silicotic nodules forming the mass. Intervening lung tissue is black pigmented and shows various degrees of interstitial fibrosis and atelectasis. The pathologic features were compatible with PMF. Invagination of thickened pleura (arrows) into the mass is apparent. (Elastic-Goldner stain, original size.)

The results of logistic regression analyses are described in Tables 4 and 5. Dependent variables showing significant association with pleural invagination were pleural thickening at CT (odds ratio, 42.52; 95% CI: 5.59, 323.29), pleural effusion (odds ratio, 6.271; 95% CI: 1.527, 25.739), reticular opacities (odds ratio, 3.04; 95% CI: 1.07, 8.60), and distance between the PMF lesion and the pleura (odds ratio, 0.92; 95% CI: 0.87, 0.98). Other variables did not contribute significantly to the presence of pleural invagination. Backward stepwise logistic regression revealed the following parameters that best explained the association with the presence of pleural invagination with PMF: pleural thickening (odds ratio, 62.51; 95% CI: 5.564, 70.20), pleural effusion (odds ratio, 25.865; 95% CI: 1.992, 335.80), smoking habit (odds ratio, 22.147; 95% CI: 0.998, 496.601), distance between the PMF and the pleura (odds ratio, 0.082; 95% CI: 0.868, 1.009), and the shape of the PMF. Of these, pleural thickening and pleural effusion were the only statistically significant variables associated with the presence of pleural invagination (P = .001 and .013, respectively).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

In our study, pleural thickening was identified in 52 (47.3%) and 64 (58.2%) patients at chest radiography and CT, respectively. Pleural thickening was significantly more common and significantly more extensive in patients with PMF than in those without at both chest radiography (P < .01 for both) and CT (P < .001 and P < .01, respectively). The numbers are unexpectedly high in view of the data from studies performed in asbestos-exposed patients (17,18). In asbestos-exposed patients, pleural plaques and diffuse thickening have been seen on chest radiographs in 16.5% and 13.5% of patients, respectively (17). On CT scans, the numbers for pleural plaques and diffuse thickening were reported to be 31.2% and 13.9%, respectively (18). Because our study was limited to patients with pulmonary silicosis, direct comparison with those studies performed in patients with merely a history of asbestos exposure are not warranted.

Our study results confirmed that pleural thickening and fibrosis are common in silicosis, especially in advanced disease, and both the visceral and parietal pleura were thickened in most patients. It might be that pleural fibrosis occurs as a result of scarring and fibrosis in the pulmonary parenchyma. The fact that pleural fibrosis was less frequently identified in early silicosis than in advanced silicosis differs from studies performed in asbestos-exposed patients, in whom pleural effusion and plaque are the earliest manifestations. Our results were also different from those in asbestos plaques in that pleural thickening in silicosis involved both parietal and visceral pleura in many of our cases, whereas asbestos plaques typically involve the parietal pleura. Although we suppose that the pleural thickening and fibrosis is associated with silicosis as described in the literature (14,15), this high incidence of pleural thickening can, to some extent, be ascribed to pulmonary tuberculosis in silicosis. However, as we could not find a statistically significant association between pleural thickening and history of tuberculosis in our series, the contribution of tuberculosis in pleural thickening should not be overemphasized.

At pathologic evaluation, thickening and fibrosis occurred in both visceral and parietal pleurae in most of our cases and were adherent with each other. Results of clinical studies have shown that diffuse pleural thickening and fibrosis contribute to the restrictive pulmonary function in asbestos-exposed subjects independent of the presence of asbestosis (19,20). It is expected that the same may be true for silicosis, although we did not correlate the radiographic findings with pulmonary function tests.

In our series, pleural effusion was seen in 38 (35%) patients with silicosis; of these, pleural effusion was regarded as being associated with silicosis in only 12 (11%) patients. In the literature, to our knowledge, only one case report exists that described the association of pleural effusion and silicosis (2). The association between pleural effusion and silicosis is suggested by the analogy to asbestos exposure; in both diseases, release of chemical mediators induces inflammatory serum exudation in pleural space (21,22). However, the pathophysiologic mechanism of pleural effusion in silicosis is still to be determined. Because our review included only chest radiographs obtained every 3 years and occasional CT images, the incidence of pleural effusion can be expected to be higher than that observed in our study.

We found 39 (30%) cases of pleural invagination in 21 (34%) patients, and 17 (44%) of these cases were identified at CT as having a thickened band between the thickened pleura and PMF lesion. We found only occasional reports describing the invagination of thickened pleura into a PMF lesion (6,23). There is no established explanation as to why the thickened pleura frequently invaginated into the PMF and did not invaginate into the lung in the absence of PMF, but a possible explanation can be drawn from our results. Because PMF apparently develops by means of a coalescence of small pneumoconiotic nodules that result from fibrosis and shrinkage of the surrounding lung tissue (9), there is usually a marked loss of volume and resultant emphysema around the lung that bears PMF. It is reasonable to suppose that the thickened pleura proliferates and enfolds toward the contracting PMF, especially when the intervening distance is small. The association between the presence of diffuse interstitial fibrosis and that of pleural invagination in our study further supports the idea that the process of invagination is associated with pulmonary fibrosis and shrinkage bearing the PMF lesion.

As noted earlier, five mass lesions that were diagnosed as PMF at pathologic evaluation showed radiographic features consistent with rounded atelectasis. Although it is not rare to observe PMF lesions in the lower lobes, we could observe volume loss of the affected lobe, and the appearances were unusual for ordinary PMF. The association between rounded atelectasis and asbestos exposure is well known (24,25). In asbestos-exposed patients, progressive pleural fibrosis occurs after development of pleural effusion (26), and this can cause rounded atelectasis with pleural enfolding (24). Regarding silica-exposed patients, there is a recently published report of rounded atelectasis in two patients with silicosis (3), and pathologic similarities between rounded atelectasis and PMF were found in those patients. In rounded atelectasis, fibrosis of the pleura is regarded as the initial event in its evolution; the adjacent lung then becomes entrapped and atelectatic, and the fibrotic pleura often invaginates into the area of atelectasis (27). Although it is only atelectasis initially, various degrees of interstitial fibrosis can occur over time. On the other hand, PMF develops by means of the conglomeration of nodular lesions, and the intervening lung tissue collapses with interstitial fibrosis, leading to the formation of a solid mass of fibrosis (28). Results in our five cases showed radiologic features of rounded atelectasis and showed some similarity to it even pathologically; however, our five cases were different from rounded atelectasis because they were fibrotic solid masses that occurred in silicosis.

This study had several limitations. First, chest radiographs obtained every 3 years were reviewed for the detection of pleural effusion and this might have caused underestimation in the frequency of pleural effusion in our series. Second, we reviewed CT scans obtained within 2 years before death and correlated the findings with those at autopsy. Although silicosis is a chronic disease that usually shows gradual progression over years, we could not exclude the possibility of progression of disease from the date of CT to that of autopsy. Third, we observed CT images that had reconstruction thicknesses of 10 mm, which is now considered rather thick for observation of the pulmonary parenchyma and pleura. This reconstruction thickness could also have caused underestimation of pleural thickening. In spite of these possible disadvantages, we had good agreement between CT observation of pleural thickening and that observed at autopsy. Fourth, we did not reveal the clinical effect of pleural thickening and invagination into PMF lesions. Although diffuse pleural thickening might cause restrictive functional deficit, the clinical importance of pleural invagination is not clear. However, we can say that the presence of invagination is the ancillary finding to diffuse pleural thickening with fibrosis in silicosis, and the presence of a thickened band on CT scans can help to diagnose it. Fifth, because our study group included only patients in whom autopsy was performed, there may be a selection bias. During life, these patients had substantial impairment of respiratory function, advanced silicosis at radiographic examination, or pulmonary complication due to silicosis, and these conditions required periodic follow-up.

In conclusion, various pleural diseases can occur with silicosis, including pleural thickening, pleural effusion, and PMF-associated pleural invagination. At CT, pleural thickening was visualized as one of the common findings in silicosis that was more prevalent in advanced disease. Pleural effusion was regarded as associated with the presence of silicosis in up to 11% of the cases. In complicated silicosis, the thickened pleura invaginated into the PMF lesions in 39 (30%) of the cases, and in five of these cases, radiographic similarities to rounded atelectasis were seen.

	FOOTNOTES

 

Abbreviations: CI = confidence interval • ILO = International Labour Organization • PMF = progressive massive fibrosis

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, H.A.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, H.A., K.H.; clinical studies, H.A., K.H., Y.S., H.S., H.M.; statistical analysis, H.A., N.S.; and manuscript editing, H.A., K.H., Y.S., H.S., H.M., M.F.

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 

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