Acta Radiologica http://acr.sagepub.com/
Chest CT findings of pleural tuberculosis: differential diagnosis of pleural tuberculosis and malignant pleural dissemination Jin Shil Kim, Sung Shine Shim, Yookyung Kim, Yon Ju Ryu and Jin Hwa Lee Acta Radiol published online 26 November 2013 DOI: 10.1177/0284185113513894 The online version of this article can be found at: http://acr.sagepub.com/content/early/2013/11/21/0284185113513894
Published by: http://www.sagepublications.com
On behalf of: Nordic Society of Medical Radiology
Additional services and information for Acta Radiologica can be found at: Email Alerts: http://acr.sagepub.com/cgi/alerts Subscriptions: http://acr.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Nov 26, 2013 What is This?
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
Acta Radiol OnlineFirst, published on November 26, 2013 as doi:10.1177/0284185113513894
Original Article
Chest CT findings of pleural tuberculosis: differential diagnosis of pleural tuberculosis and malignant pleural dissemination
Acta Radiologica 0(0) 1–6 ! The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185113513894 acr.sagepub.com
Jin Shil Kim1, Sung Shine Shim1, Yookyung Kim1, Yon Ju Ryu2 and Jin Hwa Lee2
Abstract Background: The imaging features of pleural tuberculosis (PTB) can be similar to those of malignant pleural dissemination (MPD) with several case reports of CT findings in atypical presentations of PTB. Purpose: To describe the computed tomography (CT) features of PTB by comparing these imaging findings with those of MPD and to use the results to differentiate between the two diseases. Material and Methods: The study included 135 patients with PTB and 69 with MPD. The CT images were assessed in terms of the presence, extent, and contour of pleural thickening. Pleural nodules were analyzed in terms of number, size, and location. The CT findings of PTB and MPD were compared. Results: The CT findings of PTB included circumferential pleural thickening (32.6%), mediastinal pleural involvement (31.9%), nodular thickening (8.9%), and pleural thickening >1 cm (2.2%). The CT features of MPD included nodular pleural thickening (56.5%), mediastinal pleural involvement (40.6%), circumferential thickening (23.2%), and pleural thickening >1 cm (7.2%). Comparing PTB and MPD, nodular pleural thickening was observed more frequently with MPD than PTB (P 10 mm.
Keywords Tuberculous pleuritis, pleural metastasis, pleural thickening Date received: 4 April 2013; accepted: 31 October 2013
Introduction Pleural tuberculosis (PTB) is one of the most common forms of extrapulmonary tuberculosis and lung parenchymal lesions are observed in 39–86% of patients with PTB (1,2). Differentiating between TB and malignant lung disease is a challenge for radiologists and clinicians, especially in areas with endemic granulomatous disease. Pulmonary TB frequently presents as a cavity or solid lung masses or nodules that mimic malignancies, and the central necrotic pattern of TB lymphadenopathy is not conducive to differentiation. Moreover, this becomes more challenging in patients with pleural lesions without lung or lymph node involvement and in rare presentations involving only pleural nodules without an associated effusion (1,3).
The characteristics of malignant pleural effusion that allow its differentiation in imaging studies are circumferential pleural thickening, pleural nodularity, pleural thickening >1 cm, and mediastinal pleural involvement (4–6). In addition, there are several reports of dry 1 Department of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
Corresponding author: Sung Shine Shim, Department of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, 911-1 Mok-6-dong Yangcheongu, Seoul 158-710, Republic of Korea. Email: [email protected]
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
2
Acta Radiologica 0(0)
disseminated pleural nodules, which are pleural metastases without pleural effusion (7,8). In comparison, the CT findings of PTB are pleural effusion, smooth pleural thickening with enhancement, and rarely involvement of the mediastinal pleura (9). Our clinical experience has shown that pleural nodules and pleural enhancement patterns are often misdiagnosed as malignant lesions, raising concern regarding the identification of the most helpful imaging finding to differentiate PTB from malignant pleural dissemination (MPD). Therefore, this study compared the CT features of PTB and MPD and used the results to differentiate between the two diseases.
Material and Methods
Table 1. Clinical characteristics of patients with pleural tuberculosis (n ¼ 135) and malignant pleural dissemination (n ¼ 69).
Variable Method of diagnosis Thoracentesis Pleural biopsy Surgical procedure Histopathological subtype Adenocarcinoma Non-small cell carcinoma Small cell carcinoma Squamous cell carcinoma Others
Pleural tuberculosis
Malignant pleural dissemination
124 (91.9%) 11 (8.1%) –
58 (84.1%) 9 (13.0%) 2 (2.9%)
– – – – –
38 17 6 5 3
(55.1%) (24.6%) (8.7%) (7.2%) (4.3%)
Patients The institutional review board approved this retrospective study. From 2007 to 2011, at our institution, 246 patients had histopathological diagnoses of PTB and 82 had histopathological diagnoses of MPD. PTB was confirmed by thoracentesis (n ¼ 225) or videoassisted thoracoscopic surgery (n ¼ 21). PTB was diagnosed if any of the following criteria were satisfied: (i) acid-fast bacilli identified in pleural fluid or tissue culture; (ii) caseating granulomas in pleural tissue; and (iii) positive TB PCR or adenosine deaminase (ADA) >40 U/L with no alternative explanation for the appearance of an effusion. Of these patients, we excluded those without a chest CT examination or with only nonenhanced chest CT (n ¼ 111). The diagnosis of MPD was confirmed with pleural fluid cytology (n ¼ 66), video-assisted thoracoscopic surgery (n ¼ 12), or surgical procedures (n ¼ 4). From these patients, we also excluded those without enhanced chest CT (n ¼ 13). Ultimately, 135 patients with PTB (mean age, 46.8 years; range, 9–94 years; 80 boys/men, 55 girls/ women) and 69 patients with MPD (mean age, 68.2 years; range, 34–89 years; 47 men, 22 women) with enhanced chest CT were included. Table 1 summarizes the diagnostic procedures in the patients with PTB and MPD with the histopathological types. Patients with a history of pleural diseases such as pleurodesis, environmental or occupational inorganic dust exposure, and other pleural diseases were excluded.
Image acquisition Chest CT was performed using 16- (n ¼ 166) and 64(n ¼ 38) channel multidetector (MD) CT scanners (Sensation; Siemens Medical Solutions, Erlangen, Germany). The parameters for 16-channel MDCT imaging were 120 kVp, 80–100 mA, 3–5-mm thickness, and 1.5-mm collimation. Contrast-enhanced chest CT was
obtained after injecting 30 g of iodinated contrast agent (100 mL iopromide, Ultravist 300, Berlex Laboratories, Montville/Wayne, NJ, USA) at a rate of 2.3 mL/s using a power injector (OP100; MEDRAD, Pittsburgh, PA, USA). The parameters for 64-channel MDCT imaging were 120 kVp, 100 mA, 3-mm thickness, and 1.2-mm collimation. Contrast-enhanced chest CT was obtained within 60 s after injecting 30 g of the iodinated contrast agent (100 mL iopromide, Ultravist 300) at a rate of 2.3 mL/s using a power injector (Stellant; MEDRAD, Pittsburgh, PA, USA). The scan data were displayed directly on two monitors (512 512 image matrices, 12-bit viewable grayscale) of a picture archiving and communication system (PACS) (Starpacs; Infinitt, Seoul, Korea).
Image interpretation The CT findings of 204 consecutive patients were analyzed by two radiologists (with 14 and 9 years of experience in chest CT interpretation) in random order without awareness of the pathology. Decisions on the findings were reached by consensus. The images were assessed in terms of the presence and nature of pleural thickening, as suggested by previous studies (4–6,10): focal smooth thickening; mediastinal pleural involvement; circumferential pleural thickening; pleural or fissural nodular thickening; and parietal pleural thickening >1 cm in diameter. The pleura was regarded as thickened when it was identifiable along the inner aspect of the ribs or when it was >2 mm thick in the intercostal space, paravertebral regions, or fissures. Focal smooth thickening was defined as areas of smooth, even pleural thickening with 1 cm Focal smooth thickening Pleural effusion Nodular or parietal thickening >1 cm*
12 43 44 3 76 135 3
39 28 16 5 19 67 16
1-cm thick pleura. Circumferential pleural thickening (Fig. 1) was present in 44 patients (32.6%), mediastinal pleural involvement in 43 patients (31.9%), and pleural or fissural nodular thickening (Figs. 2–4) in 12 patients (8.9%). Three patients (2.2%) with PTB had parietal pleural thickening >1 cm (Fig. 5).
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
4
Acta Radiologica 0(0)
Fig. 2. A 79-year-old man with pleural tuberculosis without lung parenchymal lesions. The transaxial CT (3.0-mm thickness) lung window shows nodular pleural and fissural thickenings (arrow) in the right costal and major and minor fissural areas with pleural effusion.
Fig. 3. A 51-year-old man with pleural and pulmonary tuberculosis. The transaxial CT (3.0-mm thickness) lung window shows multiple discrete nodules in the costal pleura, major and minor fissures, and both lungs. Pleural tuberculosis was diagnosed by pleural biopsy.
In the MPD group (n ¼ 69), 50 patients (72.5%) had nodular, circumferential, or mediastinal pleural involvement or >1-cm thick pleura. Of these, pleural or fissural nodular thickening was present in 39 patients (56.5%). Comparing PTB and MPD, focal smooth pleural thickening was observed more frequently on chest CT in the PTB group (56.3%) than in the MPD group (27.5%) (P 1 cm (PTB, 2.2%; MPD, 7.2%; P ¼ 089). The analysis of pleural or fissural nodules on chest CT is summarized in Table 3. At least 120 nodules were observed in 12 patients in the PTB group, and at least 301 nodules were observed in 39 patients in the MPD group. No significant difference was found regarding the total number and location of the nodules between the two groups (P ¼ 0.098 and 0.884, respectively). There was no significant difference in the size of the largest nodule in the two groups (P ¼ 0.114). However, nodules >10 mm in diameter were significantly more frequent in the MPD group than in the PTB group (P ¼ 0.038).
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
Kim et al.
5
Table 3. Analysis of pleural or fissural nodules at chest CT in pleural tuberculosis (n ¼ 12) and malignant pleural dissemination (n ¼ 39).
Number 10 Size (mm) 10 Location Costal pleura Mediastinal pleura Diaphragmatic pleura Major fissure Minor fissure
Pleural tuberculosis
Malignant pleural dissemination
0 2 10
11 3 25
7 5 0
17 11 11
9 3 3 4 6
34 12 10 16 11
P value 0.098 0.054 0.361 0.209 0.114 0.371 0.379 0.038 0.884 0.310 0.701 0.964 0.633 0.161
Discussion Although the absolute number of TB cases has been decreasing globally since 2006, TB remains a challenge because the incidence of this disseminated disease shows an upward tendency in some developing countries. TB is the most common cause of pleural effusion in some geographic areas (11). The diagnosis of PTB is difficult, even in the presence of concurrent pulmonary TB, because TB PCR testing, acid-fast bacillus (AFB) smears, and culture of pleural effusion specimens are not always available (12). In addition to early recognition and correct diagnosis, a major issue in the differential diagnosis of PTB is differentiation from MPD. Porcel and Vives found effective prediction models with which to differentiate TB from malignant pleural effusions based on readily available clinical (age, temperature, and history of malignancy) and pleural fluid (red blood cells [RBC], protein, adenosine deaminase [ADA], and pleural-to-serum lactate dehydrogenase ratio) data, although further validation is needed (13). Other non-invasive tests, such as measuring ADA activity or interferon (IFN)-g, have shown high sensitivity (68–100% and 78–100%, respectively) for the diagnosis of PTB in several reports (14–16). However, the diagnosis in most cases of this disease still depends on an invasive pleural biopsy, which has been the most sensitive diagnostic test since 1955 (12,17). Including the above-mentioned reports, many studies have attempted to differentiate between PTB and MPD in adults using clinical and laboratory
findings (13,15,16). To our knowledge, no specific attempts to differentiate between these two disease entities have focused on CT findings, other than several case reports of CT findings in atypical presentations of PTB (1,18). There is no doubt that chest CT is a very useful non-invasive diagnostic tool for evaluating active pleural responses and differentiating benign versus malignant causes. In the presence of pleural thickening on CT, the most useful diagnostic determinants for differentiating between malignant and benign pleural disease are the presence of circumferential pleural thickening, nodular thickening, thickening >1 cm, and mediastinal pleural involvement. The reported sensitivity of these CT findings for malignant pleural disease is as follows: circumferential pleural thickening 2241%; nodular pleural thickening 3751%; parietal pleural thickening >1 cm 3536%; and mediastinal pleural involvement 3156% (4,6). Leung et al. reported that 72% of malignant pleural disease had one or more of these features, compared to only 17% of benign pleural disease for a sensitivity of 72% (4). Our result is consistent with their study in that 72.5% of malignant pleural disease showed one or more of these findings. However, 43.7% PTB also had one or more of these findings, a much higher percentage than reported for benign pleural disease. Differentiating between PTB and MPD, even in the presence of lung parenchymal lesions, is sometimes difficult. This is because among benign pleural diseases, PTB shows a broad range of radiographic appearances, including extensive pleural disease or nodular thickening that might mimic MPD, especially in regions with a relatively high incidence of TB (3). Since the first case report of discrete multiple pleural masses without effusion as an unusual presentation of TB, several case reports have shown imaging findings similar to those of our cases (18–20). Circumferential pleural thickening, thickness >1 cm, or nodular thickening can occur in mesothelioma, lymphoma, and metastasis. TB should be considered in the differential diagnoses of these pleural findings, even when there is no associated effusion or parenchymal lung disease, particularly in TB-endemic areas. That the imaging features of PTB can be similar to those of MPD is not a novel observation. However, we believe that these results in a large group of PTB patients will help with the early detection of PTB using correlations with ADA or IFN-g and reduce needless further diagnostic procedures or invasive surgical procedures. Some limitations of this study should be mentioned, including its retrospective design and the use of a single center. The use of two different types of CT scanners is problematic, particularly regarding slice thickness. Our study might also have a selection bias, because we
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
6
Acta Radiologica 0(0)
excluded 111 PTB patients with non-enhanced CT or without CT examination. We also did not include patients in whom the diagnosis was suggested only by a positive tuberculin skin test reaction and who improved after anti-tuberculosis medication, or a lymphocytic exudate, and/or an increased level of ADA. In addition, not all nodules seen on CT were evaluated pathologically. Therefore, some nodules that we regarded as PTB or MPD could have been other benign nodules. Moreover, a full validation in a cohort was not presented. These limitations indicate the need for larger validation studies. In conclusion, the radiological manifestation of PTB can mimic those of MPD on chest CT. Despite overlapping CT findings, the most helpful CT feature in distinguishing MPD from PTB is nodular pleural or fissural thickening, especially with nodules >10 mm. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Ariyurek OM, Cil BE. Atypical presentation of pleural tuberculosis: CT findings. Br J Radiol 2000;73:209–210. 2. Kim HJ, Lee HJ, Kwon SY, et al. The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 2006;129:1253–1258. 3. Tang XN, Chu KA, Lu JY, et al. Multiple pleural nodules without effusion–a rare presentation of tuberculous pleurisy [in Chinese]. Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:187–190. 4. Leung AN, Muller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. Am J Roentgenol 1990; 154:487–492. 5. Traill ZC, Davies RJ, Gleeson FV. Thoracic computed tomography in patients with suspected malignant pleural effusions. Clin Radiol 2001;56:193–196. 6. Yilmaz U, Polat G, Sahin N, et al. CT in differential diagnosis of benign and malignant pleural disease. Monaldi Arch Chest Dis 2005;63:17–22. 7. Kim YK, Lee HY, Lee KS, et al. Dry pleural dissemination in non-small cell lung cancer: prognostic and diagnostic implications. Radiology 2011;260:568–574.
8. Shim SS, Lee KS, Kim BT, et al. Integrated PET/CT and the dry pleural dissemination of peripheral adenocarcinoma of the lung: diagnostic implications. J Comput Assist Tomogr 2006;30:70–76. 9. Yilmaz MU, Kumcuoglu Z, Utkaner G, et al. Computed tomography findings of tuberculous pleurisy. Int J Tuberc Lung Dis 1998;2:164–167. 10. Metintas M, Ucgun I, Elbek O, et al. Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases. Eur J Radiol 2002;41:1–9. 11. Valdes L, Alvarez D, Valle JM, et al. The etiology of pleural effusions in an area with high incidence of tuberculosis. Chest 1996;109:158–162. 12. Valdes L, Alvarez D, San Jose E, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998;158:2017–2021. 13. Porcel JM, Vives M. Differentiating tuberculous from malignant pleural effusions: a scoring model. Med Sci Monit 2003;9:CR175–CR180. 14. Greco S, Girardi E, Masciangelo R, et al. Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis. Int J Tuberc Lung Dis 2003;7:777–786. 15. Ogata Y, Aoe K, Hiraki A, et al. Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis? Acta Med Okayama 2011;65:259–263. 16. Zaric B, Kuruc V, Milovancev A, et al. Differential diagnosis of tuberculous and malignant pleural effusions: what is the role of adenosine deaminase? Lung 2008;186:233–240. 17. Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clinic Proc 1985;60:158–164. 18. Atasoy C, Kaya A, Fitoz S, et al. Discrete pleural nodules associated with a parasternal mass: an unusual manifestation of tuberculosis. J Thorac Imaging 2002;17:74–77. 19. Blunt SB, Harries MG. Discrete pleural masses without effusion in a young man: an unusual presentation of tuberculosis. Thorax 1989;44:436–437. 20. Moon WK, Kim WS, Kim IO, et al. Complicated pleural tuberculosis in children: CT evaluation. Pediatr Radiol 1999;29:153–157.
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
Chest CT findings of pleural tuberculosis: differential diagnosis of pleural tuberculosis and malignant pleural dissemination Jin Shil Kim, Sung Shine Shim, Yookyung Kim, Yon Ju Ryu and Jin Hwa Lee Acta Radiol published online 26 November 2013 DOI: 10.1177/0284185113513894 The online version of this article can be found at: http://acr.sagepub.com/content/early/2013/11/21/0284185113513894
Published by: http://www.sagepublications.com
On behalf of: Nordic Society of Medical Radiology
Additional services and information for Acta Radiologica can be found at: Email Alerts: http://acr.sagepub.com/cgi/alerts Subscriptions: http://acr.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Nov 26, 2013 What is This?
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
Acta Radiol OnlineFirst, published on November 26, 2013 as doi:10.1177/0284185113513894
Original Article
Chest CT findings of pleural tuberculosis: differential diagnosis of pleural tuberculosis and malignant pleural dissemination
Acta Radiologica 0(0) 1–6 ! The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185113513894 acr.sagepub.com
Jin Shil Kim1, Sung Shine Shim1, Yookyung Kim1, Yon Ju Ryu2 and Jin Hwa Lee2
Abstract Background: The imaging features of pleural tuberculosis (PTB) can be similar to those of malignant pleural dissemination (MPD) with several case reports of CT findings in atypical presentations of PTB. Purpose: To describe the computed tomography (CT) features of PTB by comparing these imaging findings with those of MPD and to use the results to differentiate between the two diseases. Material and Methods: The study included 135 patients with PTB and 69 with MPD. The CT images were assessed in terms of the presence, extent, and contour of pleural thickening. Pleural nodules were analyzed in terms of number, size, and location. The CT findings of PTB and MPD were compared. Results: The CT findings of PTB included circumferential pleural thickening (32.6%), mediastinal pleural involvement (31.9%), nodular thickening (8.9%), and pleural thickening >1 cm (2.2%). The CT features of MPD included nodular pleural thickening (56.5%), mediastinal pleural involvement (40.6%), circumferential thickening (23.2%), and pleural thickening >1 cm (7.2%). Comparing PTB and MPD, nodular pleural thickening was observed more frequently with MPD than PTB (P 10 mm.
Keywords Tuberculous pleuritis, pleural metastasis, pleural thickening Date received: 4 April 2013; accepted: 31 October 2013
Introduction Pleural tuberculosis (PTB) is one of the most common forms of extrapulmonary tuberculosis and lung parenchymal lesions are observed in 39–86% of patients with PTB (1,2). Differentiating between TB and malignant lung disease is a challenge for radiologists and clinicians, especially in areas with endemic granulomatous disease. Pulmonary TB frequently presents as a cavity or solid lung masses or nodules that mimic malignancies, and the central necrotic pattern of TB lymphadenopathy is not conducive to differentiation. Moreover, this becomes more challenging in patients with pleural lesions without lung or lymph node involvement and in rare presentations involving only pleural nodules without an associated effusion (1,3).
The characteristics of malignant pleural effusion that allow its differentiation in imaging studies are circumferential pleural thickening, pleural nodularity, pleural thickening >1 cm, and mediastinal pleural involvement (4–6). In addition, there are several reports of dry 1 Department of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
Corresponding author: Sung Shine Shim, Department of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, 911-1 Mok-6-dong Yangcheongu, Seoul 158-710, Republic of Korea. Email: [email protected]
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
2
Acta Radiologica 0(0)
disseminated pleural nodules, which are pleural metastases without pleural effusion (7,8). In comparison, the CT findings of PTB are pleural effusion, smooth pleural thickening with enhancement, and rarely involvement of the mediastinal pleura (9). Our clinical experience has shown that pleural nodules and pleural enhancement patterns are often misdiagnosed as malignant lesions, raising concern regarding the identification of the most helpful imaging finding to differentiate PTB from malignant pleural dissemination (MPD). Therefore, this study compared the CT features of PTB and MPD and used the results to differentiate between the two diseases.
Material and Methods
Table 1. Clinical characteristics of patients with pleural tuberculosis (n ¼ 135) and malignant pleural dissemination (n ¼ 69).
Variable Method of diagnosis Thoracentesis Pleural biopsy Surgical procedure Histopathological subtype Adenocarcinoma Non-small cell carcinoma Small cell carcinoma Squamous cell carcinoma Others
Pleural tuberculosis
Malignant pleural dissemination
124 (91.9%) 11 (8.1%) –
58 (84.1%) 9 (13.0%) 2 (2.9%)
– – – – –
38 17 6 5 3
(55.1%) (24.6%) (8.7%) (7.2%) (4.3%)
Patients The institutional review board approved this retrospective study. From 2007 to 2011, at our institution, 246 patients had histopathological diagnoses of PTB and 82 had histopathological diagnoses of MPD. PTB was confirmed by thoracentesis (n ¼ 225) or videoassisted thoracoscopic surgery (n ¼ 21). PTB was diagnosed if any of the following criteria were satisfied: (i) acid-fast bacilli identified in pleural fluid or tissue culture; (ii) caseating granulomas in pleural tissue; and (iii) positive TB PCR or adenosine deaminase (ADA) >40 U/L with no alternative explanation for the appearance of an effusion. Of these patients, we excluded those without a chest CT examination or with only nonenhanced chest CT (n ¼ 111). The diagnosis of MPD was confirmed with pleural fluid cytology (n ¼ 66), video-assisted thoracoscopic surgery (n ¼ 12), or surgical procedures (n ¼ 4). From these patients, we also excluded those without enhanced chest CT (n ¼ 13). Ultimately, 135 patients with PTB (mean age, 46.8 years; range, 9–94 years; 80 boys/men, 55 girls/ women) and 69 patients with MPD (mean age, 68.2 years; range, 34–89 years; 47 men, 22 women) with enhanced chest CT were included. Table 1 summarizes the diagnostic procedures in the patients with PTB and MPD with the histopathological types. Patients with a history of pleural diseases such as pleurodesis, environmental or occupational inorganic dust exposure, and other pleural diseases were excluded.
Image acquisition Chest CT was performed using 16- (n ¼ 166) and 64(n ¼ 38) channel multidetector (MD) CT scanners (Sensation; Siemens Medical Solutions, Erlangen, Germany). The parameters for 16-channel MDCT imaging were 120 kVp, 80–100 mA, 3–5-mm thickness, and 1.5-mm collimation. Contrast-enhanced chest CT was
obtained after injecting 30 g of iodinated contrast agent (100 mL iopromide, Ultravist 300, Berlex Laboratories, Montville/Wayne, NJ, USA) at a rate of 2.3 mL/s using a power injector (OP100; MEDRAD, Pittsburgh, PA, USA). The parameters for 64-channel MDCT imaging were 120 kVp, 100 mA, 3-mm thickness, and 1.2-mm collimation. Contrast-enhanced chest CT was obtained within 60 s after injecting 30 g of the iodinated contrast agent (100 mL iopromide, Ultravist 300) at a rate of 2.3 mL/s using a power injector (Stellant; MEDRAD, Pittsburgh, PA, USA). The scan data were displayed directly on two monitors (512 512 image matrices, 12-bit viewable grayscale) of a picture archiving and communication system (PACS) (Starpacs; Infinitt, Seoul, Korea).
Image interpretation The CT findings of 204 consecutive patients were analyzed by two radiologists (with 14 and 9 years of experience in chest CT interpretation) in random order without awareness of the pathology. Decisions on the findings were reached by consensus. The images were assessed in terms of the presence and nature of pleural thickening, as suggested by previous studies (4–6,10): focal smooth thickening; mediastinal pleural involvement; circumferential pleural thickening; pleural or fissural nodular thickening; and parietal pleural thickening >1 cm in diameter. The pleura was regarded as thickened when it was identifiable along the inner aspect of the ribs or when it was >2 mm thick in the intercostal space, paravertebral regions, or fissures. Focal smooth thickening was defined as areas of smooth, even pleural thickening with 1 cm Focal smooth thickening Pleural effusion Nodular or parietal thickening >1 cm*
12 43 44 3 76 135 3
39 28 16 5 19 67 16
1-cm thick pleura. Circumferential pleural thickening (Fig. 1) was present in 44 patients (32.6%), mediastinal pleural involvement in 43 patients (31.9%), and pleural or fissural nodular thickening (Figs. 2–4) in 12 patients (8.9%). Three patients (2.2%) with PTB had parietal pleural thickening >1 cm (Fig. 5).
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
4
Acta Radiologica 0(0)
Fig. 2. A 79-year-old man with pleural tuberculosis without lung parenchymal lesions. The transaxial CT (3.0-mm thickness) lung window shows nodular pleural and fissural thickenings (arrow) in the right costal and major and minor fissural areas with pleural effusion.
Fig. 3. A 51-year-old man with pleural and pulmonary tuberculosis. The transaxial CT (3.0-mm thickness) lung window shows multiple discrete nodules in the costal pleura, major and minor fissures, and both lungs. Pleural tuberculosis was diagnosed by pleural biopsy.
In the MPD group (n ¼ 69), 50 patients (72.5%) had nodular, circumferential, or mediastinal pleural involvement or >1-cm thick pleura. Of these, pleural or fissural nodular thickening was present in 39 patients (56.5%). Comparing PTB and MPD, focal smooth pleural thickening was observed more frequently on chest CT in the PTB group (56.3%) than in the MPD group (27.5%) (P 1 cm (PTB, 2.2%; MPD, 7.2%; P ¼ 089). The analysis of pleural or fissural nodules on chest CT is summarized in Table 3. At least 120 nodules were observed in 12 patients in the PTB group, and at least 301 nodules were observed in 39 patients in the MPD group. No significant difference was found regarding the total number and location of the nodules between the two groups (P ¼ 0.098 and 0.884, respectively). There was no significant difference in the size of the largest nodule in the two groups (P ¼ 0.114). However, nodules >10 mm in diameter were significantly more frequent in the MPD group than in the PTB group (P ¼ 0.038).
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
Kim et al.
5
Table 3. Analysis of pleural or fissural nodules at chest CT in pleural tuberculosis (n ¼ 12) and malignant pleural dissemination (n ¼ 39).
Number 10 Size (mm) 10 Location Costal pleura Mediastinal pleura Diaphragmatic pleura Major fissure Minor fissure
Pleural tuberculosis
Malignant pleural dissemination
0 2 10
11 3 25
7 5 0
17 11 11
9 3 3 4 6
34 12 10 16 11
P value 0.098 0.054 0.361 0.209 0.114 0.371 0.379 0.038 0.884 0.310 0.701 0.964 0.633 0.161
Discussion Although the absolute number of TB cases has been decreasing globally since 2006, TB remains a challenge because the incidence of this disseminated disease shows an upward tendency in some developing countries. TB is the most common cause of pleural effusion in some geographic areas (11). The diagnosis of PTB is difficult, even in the presence of concurrent pulmonary TB, because TB PCR testing, acid-fast bacillus (AFB) smears, and culture of pleural effusion specimens are not always available (12). In addition to early recognition and correct diagnosis, a major issue in the differential diagnosis of PTB is differentiation from MPD. Porcel and Vives found effective prediction models with which to differentiate TB from malignant pleural effusions based on readily available clinical (age, temperature, and history of malignancy) and pleural fluid (red blood cells [RBC], protein, adenosine deaminase [ADA], and pleural-to-serum lactate dehydrogenase ratio) data, although further validation is needed (13). Other non-invasive tests, such as measuring ADA activity or interferon (IFN)-g, have shown high sensitivity (68–100% and 78–100%, respectively) for the diagnosis of PTB in several reports (14–16). However, the diagnosis in most cases of this disease still depends on an invasive pleural biopsy, which has been the most sensitive diagnostic test since 1955 (12,17). Including the above-mentioned reports, many studies have attempted to differentiate between PTB and MPD in adults using clinical and laboratory
findings (13,15,16). To our knowledge, no specific attempts to differentiate between these two disease entities have focused on CT findings, other than several case reports of CT findings in atypical presentations of PTB (1,18). There is no doubt that chest CT is a very useful non-invasive diagnostic tool for evaluating active pleural responses and differentiating benign versus malignant causes. In the presence of pleural thickening on CT, the most useful diagnostic determinants for differentiating between malignant and benign pleural disease are the presence of circumferential pleural thickening, nodular thickening, thickening >1 cm, and mediastinal pleural involvement. The reported sensitivity of these CT findings for malignant pleural disease is as follows: circumferential pleural thickening 2241%; nodular pleural thickening 3751%; parietal pleural thickening >1 cm 3536%; and mediastinal pleural involvement 3156% (4,6). Leung et al. reported that 72% of malignant pleural disease had one or more of these features, compared to only 17% of benign pleural disease for a sensitivity of 72% (4). Our result is consistent with their study in that 72.5% of malignant pleural disease showed one or more of these findings. However, 43.7% PTB also had one or more of these findings, a much higher percentage than reported for benign pleural disease. Differentiating between PTB and MPD, even in the presence of lung parenchymal lesions, is sometimes difficult. This is because among benign pleural diseases, PTB shows a broad range of radiographic appearances, including extensive pleural disease or nodular thickening that might mimic MPD, especially in regions with a relatively high incidence of TB (3). Since the first case report of discrete multiple pleural masses without effusion as an unusual presentation of TB, several case reports have shown imaging findings similar to those of our cases (18–20). Circumferential pleural thickening, thickness >1 cm, or nodular thickening can occur in mesothelioma, lymphoma, and metastasis. TB should be considered in the differential diagnoses of these pleural findings, even when there is no associated effusion or parenchymal lung disease, particularly in TB-endemic areas. That the imaging features of PTB can be similar to those of MPD is not a novel observation. However, we believe that these results in a large group of PTB patients will help with the early detection of PTB using correlations with ADA or IFN-g and reduce needless further diagnostic procedures or invasive surgical procedures. Some limitations of this study should be mentioned, including its retrospective design and the use of a single center. The use of two different types of CT scanners is problematic, particularly regarding slice thickness. Our study might also have a selection bias, because we
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
XML Template (2013) [19.11.2013–3:14pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/130166/APPFile/SG-ACRJ130166.3d
(ACR)
[1–6] [PREPRINTER stage]
6
Acta Radiologica 0(0)
excluded 111 PTB patients with non-enhanced CT or without CT examination. We also did not include patients in whom the diagnosis was suggested only by a positive tuberculin skin test reaction and who improved after anti-tuberculosis medication, or a lymphocytic exudate, and/or an increased level of ADA. In addition, not all nodules seen on CT were evaluated pathologically. Therefore, some nodules that we regarded as PTB or MPD could have been other benign nodules. Moreover, a full validation in a cohort was not presented. These limitations indicate the need for larger validation studies. In conclusion, the radiological manifestation of PTB can mimic those of MPD on chest CT. Despite overlapping CT findings, the most helpful CT feature in distinguishing MPD from PTB is nodular pleural or fissural thickening, especially with nodules >10 mm. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Ariyurek OM, Cil BE. Atypical presentation of pleural tuberculosis: CT findings. Br J Radiol 2000;73:209–210. 2. Kim HJ, Lee HJ, Kwon SY, et al. The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 2006;129:1253–1258. 3. Tang XN, Chu KA, Lu JY, et al. Multiple pleural nodules without effusion–a rare presentation of tuberculous pleurisy [in Chinese]. Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:187–190. 4. Leung AN, Muller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. Am J Roentgenol 1990; 154:487–492. 5. Traill ZC, Davies RJ, Gleeson FV. Thoracic computed tomography in patients with suspected malignant pleural effusions. Clin Radiol 2001;56:193–196. 6. Yilmaz U, Polat G, Sahin N, et al. CT in differential diagnosis of benign and malignant pleural disease. Monaldi Arch Chest Dis 2005;63:17–22. 7. Kim YK, Lee HY, Lee KS, et al. Dry pleural dissemination in non-small cell lung cancer: prognostic and diagnostic implications. Radiology 2011;260:568–574.
8. Shim SS, Lee KS, Kim BT, et al. Integrated PET/CT and the dry pleural dissemination of peripheral adenocarcinoma of the lung: diagnostic implications. J Comput Assist Tomogr 2006;30:70–76. 9. Yilmaz MU, Kumcuoglu Z, Utkaner G, et al. Computed tomography findings of tuberculous pleurisy. Int J Tuberc Lung Dis 1998;2:164–167. 10. Metintas M, Ucgun I, Elbek O, et al. Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases. Eur J Radiol 2002;41:1–9. 11. Valdes L, Alvarez D, Valle JM, et al. The etiology of pleural effusions in an area with high incidence of tuberculosis. Chest 1996;109:158–162. 12. Valdes L, Alvarez D, San Jose E, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998;158:2017–2021. 13. Porcel JM, Vives M. Differentiating tuberculous from malignant pleural effusions: a scoring model. Med Sci Monit 2003;9:CR175–CR180. 14. Greco S, Girardi E, Masciangelo R, et al. Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis. Int J Tuberc Lung Dis 2003;7:777–786. 15. Ogata Y, Aoe K, Hiraki A, et al. Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis? Acta Med Okayama 2011;65:259–263. 16. Zaric B, Kuruc V, Milovancev A, et al. Differential diagnosis of tuberculous and malignant pleural effusions: what is the role of adenosine deaminase? Lung 2008;186:233–240. 17. Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clinic Proc 1985;60:158–164. 18. Atasoy C, Kaya A, Fitoz S, et al. Discrete pleural nodules associated with a parasternal mass: an unusual manifestation of tuberculosis. J Thorac Imaging 2002;17:74–77. 19. Blunt SB, Harries MG. Discrete pleural masses without effusion in a young man: an unusual presentation of tuberculosis. Thorax 1989;44:436–437. 20. Moon WK, Kim WS, Kim IO, et al. Complicated pleural tuberculosis in children: CT evaluation. Pediatr Radiol 1999;29:153–157.
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
