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Background and objective <p>The differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in patients with pleural effusion (PE) continues to pose significant clinical challenges. While conventional pleural fluid cytology has limited sensitivity, invasive diagnostic procedures are often costly or inaccessible, particularly in resource-limited settings. In this study, we investigated the diagnostic contribution of ratios derived from pleural fluid adenosine deaminase (ADA), total protein, serum lactate dehydrogenase (S-LDH), and pleural effusion lactate dehydrogenase (PE-LDH) levels in patients with histopathological confirmed pleural effusion etiology. Specifically, the diagnostic performance of biochemical and hematological parameters, particularly the ADA/serum protein, S-LDH/ADA and PE-LDH/ADA ratios were evaluated for their ability to discriminate between TPE and MPE.</p> Methods <p>This retrospective cross-sectional study was conducted among patients who underwent diagnostic evaluation and treatment for pleural effusion at a tertiary referral hospital between 1 November 2014 and 1 November 2024. A total of 1,003 patients with pleural effusion (397 TPE and 606 MPE: 409 primary, 133 metastatic, and 64 mesothelioma) were included, whose etiologies were determined using a composite reference standard based on clinical, radiological, microbiological, and histopathological findings, with multidisciplinary team (MDT) evaluation applied in selected cases where appropriate. Receiver operating characteristic (ROC) curve analyses were performed to determine diagnostic accuracy, sensitivity, specificity, and optimal cut-off values.</p> Results <p>Patients with TPE were significantly younger than those with MPE (median age: 32 vs. 65 years, <i>p</i> &lt; .001). Overall, 62.9% of the study population were male. ADA levels were significantly higher in the TPE group, whereas S-LDH levels were higher in the malignant effusion group. When ratio-based parameters were evaluated, the S-LDH/ADA ratio was markedly higher in patients with malignant pleural effusion and emerged as the most powerful discriminatory marker, with an area under the curve (AUC) of 0.938, sensitivity of 89.5%, and specificity of 91.3%. The ADA/serum protein ratio also demonstrated high diagnostic accuracy for differentiating TPE, with an AUC of 0.929, sensitivity of 89.9%, and specificity of 93.3%. In multivariate analysis, the S-LDH/ADA ratio, ADA/serum protein ratio, and PE-LDH/ADA ratio remained independently associated with diagnostic discrimination between TPE and MPE.</p> Conclusions <p>Biochemical ratios particularly the S-LDH/ADA and PE-ADA/serum protein ratios are reliable, minimally invasive diagnostic tools for distinguishing TPE from MPE. These ratios are especially useful in guiding clinical decision-making in settings where access to invasive diagnostic procedures is limited.</p>

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Diagnostic value of biochemical ratios in the differential diagnosis of tuberculous and malignant pleural effusions

  • 期刊论文

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  • 发表日期：

    2026年7月3日

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  • Umut İlhan,
  • Zeynep Güney,
  • Ayşe Özçelik,
  • Helin Su Kaya,
  • Erdogan Cetinkaya,
  • Mustafa Çörtük

摘要

Background and objective

The differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in patients with pleural effusion (PE) continues to pose significant clinical challenges. While conventional pleural fluid cytology has limited sensitivity, invasive diagnostic procedures are often costly or inaccessible, particularly in resource-limited settings. In this study, we investigated the diagnostic contribution of ratios derived from pleural fluid adenosine deaminase (ADA), total protein, serum lactate dehydrogenase (S-LDH), and pleural effusion lactate dehydrogenase (PE-LDH) levels in patients with histopathological confirmed pleural effusion etiology. Specifically, the diagnostic performance of biochemical and hematological parameters, particularly the ADA/serum protein, S-LDH/ADA and PE-LDH/ADA ratios were evaluated for their ability to discriminate between TPE and MPE.

Methods

This retrospective cross-sectional study was conducted among patients who underwent diagnostic evaluation and treatment for pleural effusion at a tertiary referral hospital between 1 November 2014 and 1 November 2024. A total of 1,003 patients with pleural effusion (397 TPE and 606 MPE: 409 primary, 133 metastatic, and 64 mesothelioma) were included, whose etiologies were determined using a composite reference standard based on clinical, radiological, microbiological, and histopathological findings, with multidisciplinary team (MDT) evaluation applied in selected cases where appropriate. Receiver operating characteristic (ROC) curve analyses were performed to determine diagnostic accuracy, sensitivity, specificity, and optimal cut-off values.

Results

Patients with TPE were significantly younger than those with MPE (median age: 32 vs. 65 years, p < .001). Overall, 62.9% of the study population were male. ADA levels were significantly higher in the TPE group, whereas S-LDH levels were higher in the malignant effusion group. When ratio-based parameters were evaluated, the S-LDH/ADA ratio was markedly higher in patients with malignant pleural effusion and emerged as the most powerful discriminatory marker, with an area under the curve (AUC) of 0.938, sensitivity of 89.5%, and specificity of 91.3%. The ADA/serum protein ratio also demonstrated high diagnostic accuracy for differentiating TPE, with an AUC of 0.929, sensitivity of 89.9%, and specificity of 93.3%. In multivariate analysis, the S-LDH/ADA ratio, ADA/serum protein ratio, and PE-LDH/ADA ratio remained independently associated with diagnostic discrimination between TPE and MPE.

Conclusions

Biochemical ratios particularly the S-LDH/ADA and PE-ADA/serum protein ratios are reliable, minimally invasive diagnostic tools for distinguishing TPE from MPE. These ratios are especially useful in guiding clinical decision-making in settings where access to invasive diagnostic procedures is limited.