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Clinical Investigations: LUNG CANCER |

Echogenic Swirling Pattern as a Predictor of Malignant Pleural Effusions in Patients With Malignancies* FREE TO VIEW

Chih-Feng Chian, MD; Wen-Lin Su, MD, MPH; Li-Hui Soh, MD; Horng-Chin Yan, MD, PhD; Wann-Cherng Perng, MD; Chin-Pyng Wu, MD, PhD
Author and Funding Information

*From the Division of Pulmonary Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Nei-Hu, Taipei, Taiwan, Republic of China.

Correspondence to: Chin-Pyng Wu, MD, PhD, Division of Pulmonary Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Rd, Nei-Hu, Taipei, Taiwan, ROC; e-mail: chest@mail.ndmctsgh.edu.tw



Chest. 2004;126(1):129-134. doi:10.1378/chest.126.1.129
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Objectives: Chest ultrasonography is a useful diagnostic tool for the detection of pleural effusions of different etiologies. Our purpose was to determine whether the echogenic swirling pattern identifiable on real-time chest ultrasonographic images is a predictor of malignant pleural effusions in patients with malignancies.

Design: Medical records of patients undergoing chest ultrasonography in the Tri-Service General Hospital (Taiwan) between January 2000 and December 2002 were reviewed retrospectively. Patients with an echogenic swirling pattern in the pleural effusion, or with malignant diseases associated with pleural effusions, whose pleural fluids had been examined cytologically or whose pleural tissues had been examined pathologically, were enrolled in this study (n = 140). Malignant pleural effusions were defined by the presence of malignant cells in the pleural fluid identified by thoracentesis or by pleural biopsy. The echogenic swirling pattern was defined as numerous echogenic floating particles within the pleural effusion, which swirled in response to respiratory movement or heartbeat. Correlation between malignant pleural effusions and the echogenic swirling pattern was compared in patients with an underlying malignant disease.

Results: In patients with underlying malignancies, malignant pleural effusions were diagnosed in 81.8% of patients with a positive echogenic swirling pattern and in 48% of those with no echogenic swirling pattern. The presence of echogenic swirling was significantly more predictive of malignant pleural effusions than was the absence of echogenic swirling (p < 0.01).

Conclusions: The echogenic swirling pattern is a useful predictor of possible malignant pleural effusions, and may be a good marker for malignant pleural effusions in patients with underlying malignancies.

Figures in this Article

Pleural effusions are a common manifestation of many diseases. Lung cancer and other malignancies are commonly associated with pleural effusions. Malignant pleural effusions are not symptoms of respiratory system disease only.1Autopsy studies in patients with malignant pleural effusions suggest that most effusions arise from tumor emboli to the visceral pleural surface, with secondary spreading to the parietal pleura.2Direct tumor invasion, distant hematogenous metastases, and lymphatic involvement may also lead to malignant pleural effusions. Paramalignant pleural effusions have been defined as effusions that are not the direct result of neoplastic involvement in the pleura, but are still related to the primary tumor, and include effusions due to tumor-related lymphatic obstruction, postobstructive pneumonia or atelectasis, chylothorax, and hypoalbuminemia.3

Real-time chest ultrasonography offers a more effective and convenient method than traditional radiography for the detection of pleural effusions.4 The role of real-time chest ultrasonography in identifying small-volume pleural effusions, pleural thickening, pleural metastases, pleural empyema, and pneumothorax is well documented.

In the course of our clinical practice, we have occasionally found an echogenic swirling pattern in pleural effusions. We ascertained that the majority of patients with this pattern have malignant disease with malignant pleural effusions, and that a minority have tuberculous pleural effusions. These findings prompted us to examine the etiology of the echogenic swirling pattern, the possible underlying mechanism, and finally the clinical significance of this pattern in patients with malignancies. To our knowledge, there have been no previous studies of ultrasonographic images from patients with malignant pleural effusions. The aims of this study were to determine the causes of the echogenic swirling pattern, to evaluate its clinical application as a predictor of malignant pleural effusions in patients with malignancies, and to propose the possible mechanism underlying the echogenic swirling pattern.

Subjects

We reviewed the records of patients undergoing chest ultrasonography between January 2000 and December 2002 at the Tri-Service General Hospital, a tertiary referral center in Taiwan. The inclusion criteria were that all patients showed the echogenic swirling pattern in pleural effusions detected by chest ultrasonography or had malignant diseases associated with pleural effusions, and all had undergone cytologic examination of their pleural effusions or pathologic examination of pleural tissues. Over the 3-year period, 140 patients were enrolled in the study. We classified the 140 patients into three groups. Group A (66 of 140 patients) contained those with underlying malignancies who were positive for the echogenic swirling pattern. Group B (50 of 140 patients) contained those patients with underlying malignancies with no echogenic swirling pattern. Group C (24 of 140 patients) were those with no history of underlying malignancies but were positive for the echogenic swirling pattern. The demographic characteristics of the patients are shown in Table 1 . Malignant effusions were defined as exudates with evidence of malignant cells on cytologic examination of pleural fluids or pathologic examination of pleural tissues. Paramalignant pleural effusions were defined as effusions that were not the direct result of neoplastic involvement of the pleura but were still related to the primary tumor. Tuberculous effusions were defined as exudates producing positive cultures of Mycobacterium tuberculosis, with no evidence of malignancy. Parapneumonic effusions were defined as exudative pleural effusions with pneumonia. Empyema was defined by pleural fluids positive for Gram stain. Hemothorax was defined by exudates with effusion hematocrits > 50% relative to blood. Systemic lupus erythematosus (SLE) effusion was defined as exudates associated with definite SLE and unrelated to other complications. Congestive heart failure (CHF) effusions were defined as transudates associated with an enlarged heart, neck vein distension, and cardiac gallop, which improved after CHF therapy. Liver cirrhosis effusions were defined as transudates associated with sonographic evidence indicating irregular liver surfaces, increased liver echogenicity, ascites, or splenomegaly. Nephrotic syndrome effusions were defined as transudates associated with daily protein loss > 3.5 g and hypoalbuminemia.

Ultrasonographic Criteria for Defining the Echogenic Swirling Pattern

Examinations were performed using a real-time ultrasound scanner (Toshiba SSA-340A; Toshiba; Tokyo, Japan) with 3.75-MHz sector transducers. All patients were examined in an upright sitting position or the lateral decubitus position. The chest ultrasonographic scanner was operated by well-trained chest physicians.

The echogenic swirling pattern was defined as numerous floating echogenic particles within the pleural effusion that moved in response to respiratory movement or heartbeat under real-time sonographic examination. Descriptions of this echogenic swirling pattern in pleural effusions have been recorded in previous chest ultrasonography reports.

Pleural Fluid Collection and Analysis

Pleural effusions were drawn by diagnostic thoracentesis and divided into different collecting tubes. All specimens were sent to laboratories for analysis of pH, specific gravity, bacterial cultures, Gram stain, tuberculosis, acid-fast stain, lactate dehydrogenase (LDH), total protein, differential total leukocyte counts, and cytologic parameters.

Statistical Analysis

The three groups of continuous variables were compared with one-way analysis of variance. χ2 analyses of contingency tables was used to compare the correlation of two categorical variables. Yates correction was used for 2 × 2 tables (1 degree of freedom). A Fisher exact test was used for 2 × 2 tables if the expected count of at least one cell was < 5. An α level of 0.05 was deemed significant for all statistical tests.

The demographic data of patients are shown in Table 1. There were 29 women and 37 men in group A, 19 women and 31 men in group B, and 6 women and 18 men in group C. The mean (± SD) ages were 66.3 ± 14.7 years in group A, 65.0 ± 15.9 years in group B, and 67.5 ± 18.2 years in group C. There was no significant difference between the mean ages of these three groups. The disease status of patients is shown in Table 1. In group A, 45 patients (68.2%) had lung cancer. In group B, 28 patients (56.0%) had lung cancer. In group C, nine patients (37.5%) had pneumonia and seven patients (29.2%) had tuberculosis of the lung, which were common etiologies of effusions.

Biochemical parameters (LDH, glucose, total protein) and differential cell counts of the pleural effusions were studied. Total protein levels in pleural effusions were significantly lower in group C than in either group A or group B (p = 0.002; Table 2 ).

In group A, malignant pleural effusions were diagnosed in 54 patients: 45 patients by cytologic examination of the pleural fluid, 6 patients by pleural biopsy, and 3 patients by video-assisted thoracoscopic biopsy (VATS). Paramalignant pleural effusions were diagnosed in another 12 patients because no frank malignant cells were found in the pleural fluid. In group B, malignant pleural effusions were diagnosed in 24 patients: 21 patients by cytologic examination of the pleural fluid, 2 patients by pleural biopsy, and 1 patient VATS. Paramalignant pleural effusion was diagnosed in another 26 patients.

The etiologies of the echogenic swirling pattern were malignancy, pneumonia, tuberculosis, cirrhosis of the liver, SLE, hemothorax, empyema and, rarely, nephrotic syndrome or CHF. The overall rate of diagnosis of malignant pleural effusion was 67.2% in our study.

The correlation between the echogenic swirling pattern and malignant pleural effusions in patients with underlying malignancies was 81.8% (54 of 66 patients) in group A but only 48% (24 of 50 patients) in group B. In patients with underlying malignancies, the presence of the echogenic swirling pattern was more predictive of malignant pleural effusions than was the absence of swirling (p < 0.01; Table 3 ).

In those patients with malignant pleural effusions, we evaluated the correlation between the echogenic swirling pattern and the presence of adenocarcinoma in the pleural effusion (Table 4 ). In those groups with the echogenic swirling pattern, 88.9% had pleural effusions that were adenocarcinoma positive, whereas in the group with no swirling, only 79.2% were adenocarcinoma positive. Thus, we found no significant correlation between swirling and adenocarcinoma (p = 0.299).

Chest ultrasonography is well established as a useful imaging method in the differential diagnosis of pleural-based lesions,5peripheral pulmonary lesions,610 mediastinal masses,11pulmonary consolidations,12and chest-wall lesions.1314 Chest ultrasonography also is a very useful tool in assessing the nature of pleural opacities and effusions.1517 Malignant pleural effusions are one of the clinical manifestations of several malignancies, especially lung cancer.1,18Cytologic examination of pleural fluid is the simplest method of diagnosing malignant pleural effusions. According to one large study,19 the complication rate of thoracentesis is low (1%). The diagnostic rate by pleural fluid cytology is approximately 62 to 90%.3 In our study, excluding diagnoses made by pleural biopsy or VATS, the diagnostic rate by pleural fluid cytology was 57%.

The sonographic patterns of pleural effusions have been subclassified as anechoic, complex nonseptated, complex septated, or homogeneous.17 However, the sonographic pattern of malignant pleural effusions can present as any one of the patterns thus defined, and there has been no study of the capacity of ultrasonography to predict malignant pleural effusions. In our study, an echogenic swirling pattern was identified by real-time chest sonography examination in 90 patients, of whom 66 patients (73.3%) had underlying malignancies and 24 patients (26.7%) had underlying benign disease (Fig 1 ). The echogenic swirling pattern occurs with both malignant and benign disease. Therefore, there is no role for this pattern in differentiating benign from malignant pleural effusions.

Our results show that the echogenic swirling pattern did not correlate with pleural biochemical parameters (LDH, glucose, total protein), total leukocyte count, percentage of lymphocytes, or percentage of neutrophils. Although the mean protein level in group C was significantly lower than that in group A or group B (p < 0.05), this was due to four patients with transudates from underlying diseases, such as cirrhosis of the liver, nephritic syndrome, and CHF.

One study20 that examined the fibrinolytic and inflammatory processes in pleural effusions found that levels of plasminogen-activator inhibitor (PAI) levels (by measuring PAI activity, PAI-1 antigenicity, and PAI-2 antigenicity) and von Willebrand factor were significantly higher in patients with empyema or tuberculosis than in those with cancer or cardiac failure. This study also found elevated levels of tissue-type plasminogen activators (t-PA) in some malignant pleural effusions.20Another study, by Hua et al,21 reported significantly higher levels of t-PA in malignant pleural fluid than in tuberculous pleural fluid, and significantly higher levels of PAI-1 and tumor necrosis factor-α in tuberculous pleural fluid than in malignant pleural fluid. Both of these studies indicate that malignant pleural fluid has higher t-PA and lower PAI levels than empyema and tuberculosis fluid. Therefore, there is higher fibrinolytic activity and greater formation of fibrin in malignant pleural effusions. We also found that in some patients, the swirling pattern disappeared during the course of consecutive chest sonographic examinations. We suggest that the possible mechanism of the echogenic swirling pattern may be related to the fibrotic/fibrinolytic complex.

In our study, patients were classified as having paramalignant pleural effusions when their pleural fluid or pleural cytologic results were negative for malignant cells. Because VATS was not used to assess these patients, the malignant status of their pleural effusions (whether positive or negative) could not be determined. Nor could the sensitivity, specificity, positive predictive value, or negative predictive value of the swirling be calculated in relation to malignant pleural effusions. The nature of the echogenic swirling pattern is still unknown, and how the swirling pattern develops has not been determined. Prospective studies should be conducted to resolve these issues.

Because these malignant pleural effusions were almost all adenocarcinomas, it might appear that adenocarcinomas are more likely to invade the pleural space. Nevertheless, among those patients with malignant pleural effusions, the correlation between swirling and adenocarcinoma was poor. Our results indicate a strong correlation between positive cytologic evidence of malignant cells and the echogenic swirling pattern in patients with pleural effusions and underling malignancies (81.8% vs 48%; p < 0.01)

In conclusion, the underlying diagnosis in patients showing swirling varies from benign disease (such as pneumonia) to malignancy. We found that swirling does not correlate with the presence of adenocarcinoma cells in malignant pleural effusions. However, swirling correlates strongly with malignant pleural effusions in patients with malignancies. This correlation suggests that swirling may be a useful and simple marker of malignant pleural effusions in such patients.

Abbreviations: CHF = congestive heart failure; LDH = lactate dehydrogenase; PAI = plasminogen-activator inhibitor; SLE = systemic lupus erythematosus; t-PA = tissue-type plasminogen activators; VATS = video-assisted thoracoscopic biopsy

This study was supported in part by the C. Y. Chai Foundation for the Advancement of Education, Science and Medicine.

Table Graphic Jump Location
Table 1. Demographics and Underlying Diseases in the Three Study Groups*
* 

Data are presented as mean ± SD (range) or No. (%), unless otherwise indicated.

 

χ2 for gender, p = 0.262.

Table Graphic Jump Location
Table 2. Characteristics of Pleural Effusions in the Three Study Groups*
* 

Data are presented as mean ± SD.

 

p < 0.05.

Table Graphic Jump Location
Table 3. Correlation Between Echogenic Swirling Pattern and Malignant Pleural Effusions in Patients With Underlying Malignancies*
* 

Yates correction, p < 0.01.

Table Graphic Jump Location
Table 4. Correlation Between Echogenic Swirling Pattern and Underlying Malignancies Stratified by Cytology Results*
* 

Fisher exact test, p = 0.299.

Figure Jump LinkFigure 1. Top: Ultrasonographic examination of the chest shows an echogenic swirling pattern (numerous floating hyperechoic particles within the pleural effusion in the pleural cavity) in a 58-year-old man with adenocarcinoma of the lung and malignant pleural effusion of the left thorax. Bottom: Ultrasonographic examination of the chest shows a pleural effusion of the left thorax in a 60-year-old man with CHF.Grahic Jump Location
Chernow, B, Sahn, SA (1977) Carcinomatous involvement of the pleura: an analysis of 96 patients.Am J Med63,695-702. [CrossRef] [PubMed]
 
Meyer, PC Metastatic carcinoma of the pleura.Thorax1966;21,437-443. [CrossRef] [PubMed]
 
American Thoracic Society. Management of malignant pleural effusions.Am J Respir Crit Care Med2000;162,1987-2001. [PubMed]
 
Hirsch, JH, Roger, JV, Mack, LA Real-time sonography of pleural opacities.AJR Am J Roentgenol1981;36,297-301
 
Yang, PC, Sheu, JC, Luh, KT, et al Clinical application of real-time ultrasonography in pleural and subpleural lesions.J Formos Med Assoc1984;83,646-657
 
Chandrasekhar, AJ, Reynes, CJ, Churchill, RJ Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses.Chest1976;70,627-630. [CrossRef] [PubMed]
 
Isumi, S, Tamaki, S, Natori, H, et al Ultrasonically guided aspiration needle biopsy in disease of chest.Am Rev Respir Dis1982;125,460-464. [PubMed]
 
Yang, PC, Luh, KT, Sheu, JC, et al Peripheral pulmonary lesions: ultrasonography and ultrasonically guided aspiration biopsy.Radiology1985;155,451-456. [PubMed]
 
Yuan, A, Yang, PC, Chang, DB, et al Ultrasound-guided aspiration biopsy of small peripheral pulmonary nodules.Chest1992;101,926-930. [CrossRef] [PubMed]
 
Yang, PC, Lee, YC, Yu, CJ, et al Ultrasonographically guided biopsy of thoracic tumors.Cancer1992;69,2553-2560. [CrossRef] [PubMed]
 
Yu, CJ, Yang, PC, Chang, DB, et al Evaluation of ultrasound-guided biopsies of mediastinal masses.Chest1991;100,399-405. [CrossRef] [PubMed]
 
Yang, PC, Luh, KT, Chang, DB, et al Ultrasonographic evaluation of pulmonary consolidation.Am Rev Respir Dis1992;146,757-762. [PubMed]
 
Suzuki, N, Saitoh, T, Kitamura, S Tumor invasion of the chest wall in lung cancer: diagnosis with US.Radiology1993;187,39-42. [PubMed]
 
Griffith, JF, Rainer, TH, Ching, AS, et al Sonography compared with radiography in revealing acute rib fracture.AJR Am J Roentgenol1999;173,1603-1609. [PubMed]
 
Rosenberg, ER Ultrasound in the assessment of pleural densities.Chest1983;84,283-285. [CrossRef] [PubMed]
 
Wu, RG, Yuan, A, Liaw, YS, et al Image comparison of real-time gray scale ultrasound and color Doppler ultrasounds for use in diagnosis of minimal pleural effusion.Am J Respir Crit Care Med1994;150,510-514. [PubMed]
 
Yang, PC, Luh, KT, Chang, DB, et al Value of sonography in determining the nature of pleural effusion: analysis of 320 cases.AJR Am J Roentgenol1992;159,29-33. [PubMed]
 
Sahn, SA Pleural diseases related to metastatic malignancies.Eur Respir J1997;10,1907-1913. [CrossRef] [PubMed]
 
Yang, PC, Kuo, SH, Luh, KT Ultrasonography and ultrasound-guided needle biopsy of chest diseases: indications, techniques, diagnostic yields and complications.J Med Ultrasound1993;2,53-63
 
Philip-Joet, F, Alessi, MC, Philip-Joet, C, et al Fibrinolytic and inflammatory processes in pleural effusions.Eur Respir J1995;8,1352-1356. [CrossRef] [PubMed]
 
Hua, CC, Chang, LC, Chen, YC, et al Proinflammatory cytokines and fibrinolytic enzymes in tuberculous and malignant pleural effusions.Chest1999;116,1292-1296. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Top: Ultrasonographic examination of the chest shows an echogenic swirling pattern (numerous floating hyperechoic particles within the pleural effusion in the pleural cavity) in a 58-year-old man with adenocarcinoma of the lung and malignant pleural effusion of the left thorax. Bottom: Ultrasonographic examination of the chest shows a pleural effusion of the left thorax in a 60-year-old man with CHF.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Demographics and Underlying Diseases in the Three Study Groups*
* 

Data are presented as mean ± SD (range) or No. (%), unless otherwise indicated.

 

χ2 for gender, p = 0.262.

Table Graphic Jump Location
Table 2. Characteristics of Pleural Effusions in the Three Study Groups*
* 

Data are presented as mean ± SD.

 

p < 0.05.

Table Graphic Jump Location
Table 3. Correlation Between Echogenic Swirling Pattern and Malignant Pleural Effusions in Patients With Underlying Malignancies*
* 

Yates correction, p < 0.01.

Table Graphic Jump Location
Table 4. Correlation Between Echogenic Swirling Pattern and Underlying Malignancies Stratified by Cytology Results*
* 

Fisher exact test, p = 0.299.

References

Chernow, B, Sahn, SA (1977) Carcinomatous involvement of the pleura: an analysis of 96 patients.Am J Med63,695-702. [CrossRef] [PubMed]
 
Meyer, PC Metastatic carcinoma of the pleura.Thorax1966;21,437-443. [CrossRef] [PubMed]
 
American Thoracic Society. Management of malignant pleural effusions.Am J Respir Crit Care Med2000;162,1987-2001. [PubMed]
 
Hirsch, JH, Roger, JV, Mack, LA Real-time sonography of pleural opacities.AJR Am J Roentgenol1981;36,297-301
 
Yang, PC, Sheu, JC, Luh, KT, et al Clinical application of real-time ultrasonography in pleural and subpleural lesions.J Formos Med Assoc1984;83,646-657
 
Chandrasekhar, AJ, Reynes, CJ, Churchill, RJ Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses.Chest1976;70,627-630. [CrossRef] [PubMed]
 
Isumi, S, Tamaki, S, Natori, H, et al Ultrasonically guided aspiration needle biopsy in disease of chest.Am Rev Respir Dis1982;125,460-464. [PubMed]
 
Yang, PC, Luh, KT, Sheu, JC, et al Peripheral pulmonary lesions: ultrasonography and ultrasonically guided aspiration biopsy.Radiology1985;155,451-456. [PubMed]
 
Yuan, A, Yang, PC, Chang, DB, et al Ultrasound-guided aspiration biopsy of small peripheral pulmonary nodules.Chest1992;101,926-930. [CrossRef] [PubMed]
 
Yang, PC, Lee, YC, Yu, CJ, et al Ultrasonographically guided biopsy of thoracic tumors.Cancer1992;69,2553-2560. [CrossRef] [PubMed]
 
Yu, CJ, Yang, PC, Chang, DB, et al Evaluation of ultrasound-guided biopsies of mediastinal masses.Chest1991;100,399-405. [CrossRef] [PubMed]
 
Yang, PC, Luh, KT, Chang, DB, et al Ultrasonographic evaluation of pulmonary consolidation.Am Rev Respir Dis1992;146,757-762. [PubMed]
 
Suzuki, N, Saitoh, T, Kitamura, S Tumor invasion of the chest wall in lung cancer: diagnosis with US.Radiology1993;187,39-42. [PubMed]
 
Griffith, JF, Rainer, TH, Ching, AS, et al Sonography compared with radiography in revealing acute rib fracture.AJR Am J Roentgenol1999;173,1603-1609. [PubMed]
 
Rosenberg, ER Ultrasound in the assessment of pleural densities.Chest1983;84,283-285. [CrossRef] [PubMed]
 
Wu, RG, Yuan, A, Liaw, YS, et al Image comparison of real-time gray scale ultrasound and color Doppler ultrasounds for use in diagnosis of minimal pleural effusion.Am J Respir Crit Care Med1994;150,510-514. [PubMed]
 
Yang, PC, Luh, KT, Chang, DB, et al Value of sonography in determining the nature of pleural effusion: analysis of 320 cases.AJR Am J Roentgenol1992;159,29-33. [PubMed]
 
Sahn, SA Pleural diseases related to metastatic malignancies.Eur Respir J1997;10,1907-1913. [CrossRef] [PubMed]
 
Yang, PC, Kuo, SH, Luh, KT Ultrasonography and ultrasound-guided needle biopsy of chest diseases: indications, techniques, diagnostic yields and complications.J Med Ultrasound1993;2,53-63
 
Philip-Joet, F, Alessi, MC, Philip-Joet, C, et al Fibrinolytic and inflammatory processes in pleural effusions.Eur Respir J1995;8,1352-1356. [CrossRef] [PubMed]
 
Hua, CC, Chang, LC, Chen, YC, et al Proinflammatory cytokines and fibrinolytic enzymes in tuberculous and malignant pleural effusions.Chest1999;116,1292-1296. [CrossRef] [PubMed]
 
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