Introduction: Pleural effusion represents a frequent and diagnostically complex clinical challenge with more than 60 recognized etiologies. Establishing a definitive diagnosis remains a significant problem, as standard pleural fluid analysis and initial clinical evaluation frequently leave up to 25% of cases indeterminate.

Aim: Evaluation of the diagnostic yield of ultrasound guided closed pleural biopsy in patients with pleural effusion.

Methods: This retrospective study, analyses data from 50 patients hospitalized at the University Clinic for Pulmonology and Allergology, Skopje, with indeterminate pleural effusion over a six-year period, from 2020 to 2026. The cohort consisted of patients who underwent closed pleural biopsy for the diagnostic evaluation of pleural effusions which remained indeterminate, despite of initial biochemical and cytological fluid analysis. Variables included demographics, smoking, chest ultrasound (US), chest computed tomography (CT), pleural fluid biochemistry, cytology, histopathology and final clinical outcomes including Video-Assisted Thoracic Surgery (VATS). Statistical analysis included descriptive and comparative methods using Chi-square and Fisher’s exact tests, with diagnostic sensitivity calculated against the final clinical diagnosis.

Results: This study analyses 50 patients, (Mean age 67.52; range 30-81 years) predominantly male (38 patients, 76%). The majority of the patients 96% (48/50) had exudative effusion according to Light’s criteria. Chest CT identified distinct mass in 40% (20/50) of cases and irregular pleural thickening in 28% (14/50). Initial ultrasound guided closed pleural biopsy yielded a conclusive diagnosis in 62% (31/50) of the total cohort. Closed biopsy successfully identified malignancy in 56% of patients (28/50), demonstrating an overall diagnostic sensitivity for malignancy of 73.7% (28/38 confirmed malignancies), which reached 90% (18/20) in the presence of a CT defined mass, compared to 57,1% (8/14) for pleural thickening. The diagnostic yield for tuberculous pleuritis was 100% (3/3). Initial nonspecific inflammatory findings occurred in 36% (18/50) of biopsies, which upon diagnostic escalation revealed secondary malignancies in 7 cases and infectious etiologies in 11 cases. Secondary VATS was performed in 7 patients, providing a definitive diagnosis in 6 of the cases.

Conclusion: Ultrasound - guided closed pleural biopsy remains an essential, highly effective first line modality for undiagnosed exudative pleural effusions. It demonstrates strong diagnostic performance for malignancy 73.7% sensitivity overall (90% for CT defined mass) and 100% yield for tuberculosis. Non-conclusive cases should undergo secondary diagnostic escalation to video assisted thoracoscopic surgery (VATS).

Keywords: Pleural Effusions; Cytology; Pleural Punctate Biochemistry

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