Paucibacillary Pleural Tuberculosis Presenting as Subpleural Nodules: A Diagnostic Challenge With Negative PCR and Smear Tests.

Pleural tuberculosis is a common manifestation of extrapulmonary tuberculosis; however, its diagnosis remains challenging in paucibacillary disease, where clinical presentation may be atypical and microbiological tests frequently yield negative results. We report the case of a 27-year-old Syrian male who presented with a one-year history of left-sided pleuritic chest pain and unintentional weight loss. Imaging studies revealed left-sided pleural-based subpleural nodules with mild metabolic activity. Repeated sputum acid-fast bacilli smears, polymerase chain reaction testing for Mycobacterium tuberculosis, and bronchoscopy were all negative. Due to persistent clinical suspicion, thoracoscopic exploration was performed, revealing multiple subpleural nodules on both the parietal and visceral pleura. Histopathological examination demonstrated necrotizing granulomatous inflammation with caseous material, consistent with pleural tuberculosis. The patient was treated with a standard six-month antituberculous regimen and showed favorable clinical recovery. Pleural tuberculosis represents a diagnostic challenge due to its frequent paucibacillary nature and nonspecific clinical presentation, which often results in low sensitivity of conventional microbiological and molecular tests such as direct smears using Ziehl-Neelsen and Auramine staining. In this case, prolonged pleuritic chest pain with minimal systemic symptoms and repeatedly negative sputum smears and PCR delayed microbiological confirmation. Definitive diagnosis was achieved only through thoracoscopic pleural biopsy and histopathological examination. This highlights the limitations of noninvasive investigations in pleural TB and underscores the importance of early escalation to pleural biopsy when clinical suspicion persists despite inconclusive results. This case highlights pleural tuberculosis presenting as subpleural nodules as a diagnostic challenge in the setting of negative microbiological tests. Maintaining a high index of suspicion and early escalation to tissue diagnosis are essential to ensure timely treatment and prevent misdiagnosis.