J Korean Med Sci.  2025 Apr;40(13):e35. 10.3346/jkms.2025.40.e35.

Tuberculous and Malignant Pleural Effusions With Adenosine Deaminase Levels of 40–70 IU/L: Trends in New Cases Over Time and Differentiation Between Groups

• Lee J
• Park J
• Lim JK
• Park JE
• Lee YH
• Choi SH
• Seo H
• Yoo SS
• Lee SY
• Cha SI
• Park JY
• Kim CH

• KMID: 2566822
• DOI: http://doi.org/10.3346/jkms.2025.40.e35

Abstract

Background
The diagnosis of tuberculous pleural effusion (TPE) often relies on pleural fluid adenosine deaminase (ADA) levels. The diagnostic utility of ADA, however, is influenced by the prevalence of tuberculosis (TB) in local populations. Malignant pleural effusion (MPE) cases can exhibit moderately elevated ADA levels comparable to those seen in TPE. As population aging potentially impacts ADA levels, global TB incidence is decreasing whereas the burden of malignancy is on the rise. Consequently, epidemiological shifts and temporal changes in ADA distribution complicate the differential diagnosis between TPE and MPE when ADA levels are within the 40–70 IU/L range. Nonetheless, data specific to this subset are scarce.
Methods
This retrospective study included consecutive patients aged > 18 years with confirmed TPE and MPE, spanning from 2012 to 2023. ADA levels in pleural fluid were categorized into three groups: < 40 IU/L, 40–70 IU/L, and > 70 IU/L. The study examined annual trends in the frequency of new cases and ADA level distributions over time and identified discriminating factors between TPE and MPE in cases with ADA levels of 40–70 IU/L.
Results
In total, 297 TPE and 369 MPE cases were included in this study. Over the study period, the frequency of TPE progressively declined, while that of MPE increased. In the most recent four-year period, new TPE and MPE cases with ADA levels of 40–70 IU/L occurred at comparable numbers. Multivariable analysis identified pleural fluid carcinoembryonic antigen (CEA) levels and the number of focal pleural nodules as independent predictors for MPE. Specifically, the presence of either CEA levels > 15.7 ng/mL or more than eight pleural nodules yielded the highest diagnostic accuracy with a sensitivity of 88%, specificity of 100%, and an area under the curve of 0.95.
Conclusion
The differential diagnosis between TPE and MPE with pleural ADA levels of 40–70 IU/L has become increasingly critical due to evolving epidemiological patterns and ADA distribution changes over time. Pleural fluid CEA levels and the characteristics of pleural nodules may offer valuable guidance in distinguishing between TPE and MPE within this diagnostic gray zone.

Keyword

Trend Over Time; Tuberculous Pleural Effusion; Malignant Pleural Effusion; Adenosine Deaminase; Gray Zone

Figure

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  Fig. 1 Annual trends in (A) frequency, (B) median age, and the proportion of patients aged < 65 and ≥ 65 (C for TPE and D for MPE) over time in new cases of TPE and MPE.TPE = tuberculous pleural effusion, MPE = malignant pleural effusion.

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  Fig. 2 Annual trends in the distribution of pleural fluid ADA levels over time in new cases of (A) TPE and (B) MPE.ADA = adenosine deaminase, TPE = tuberculous pleural effusion, MPE = malignant pleural effusion.

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  Fig. 3 Changes in the proportion of TPE and MPE cases with adenosine deaminase levels of 40–70 IU/L across three timeframes.TPE = tuberculous pleural effusion, MPE = malignant pleural effusion.

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