Malignancy Presenting As Recurrent Empyema: A Report of Two Cases and a Systematic Review

Lung malignancy presenting as empyema is a rare presentation, which is commonly associated with infection. We report two patients initially diagnosed with tuberculosis-associated pleural disease who were subsequently confirmed to have lung malignancy. The first case involved a woman in her 40s presenting with progressive dyspnea, hydropneumothorax, persistent exudative pleural drainage, and prolonged air leak despite anti-tuberculosis therapy. Repeated cytological and microbiological examinations were negative, while persistently low pleural adenosine deaminase (ADA) levels and lack of clinical improvement prompted thoracotomy biopsy, which confirmed adenocarcinoma. The second case involved a man in his 40s presenting with persistent empyema during tuberculosis treatment. Despite thoracotomy and decortication, the patient continued to develop progressive respiratory and systemic symptoms. Subsequent imaging demonstrated a chest wall mass and vertebral lytic lesions suggestive of metastatic disease, while histopathological examination confirmed squamous cell carcinoma. A systematic search of PubMed, Cochrane, ProQuest, and Wiley databases up to May 5, 2026, identified eight published cases of lung malignancy presenting as empyema. Clinical presentation was frequently non-specific, although several patients exhibited red flag features such as hemoptysis, weight loss, and anorexia. Laboratory findings were not sufficiently specific to distinguish malignancy-associated empyema from infectious etiologies. Computed tomography frequently revealed findings suggestive of underlying malignancy, including lung masses, mediastinal lymphadenopathy, bronchial obstruction, and invasion into adjacent structures. Initial investigations commonly supported an infectious diagnosis, while a definitive diagnosis was consistently established only after invasive tissue biopsy. Malignancy-associated empyema represents an important diagnostic pitfall, particularly in tuberculosis (TB)-endemic settings where infectious etiologies are strongly favored. Persistent or non-resolving empyema with atypical clinical, biochemical, or radiological findings should prompt early tissue biopsy to avoid delayed oncologic diagnosis and treatment.