Tuberculosis versus immune-related bronchiolitis under immune checkpoint inhibitor – a diagnostic challenge

INTRODUCTION: Immune checkpoint inhibitors (ICIs) improve survival in multiple malignancies but may induce immune-related adverse events (irAEs), including immune-related bronchiolitis (IRB). Radiologic patterns frequently overlap with infectious diseases, particularly tuberculosis (TB), whose reactivation risk may be increased by ICIs via disruption of granuloma integrity. Differentiation between IRB and TB is challenging, especially in patients from endemic areas. CASE PRESENTATION: We report the case of a 53-year-old Turkish man with metastatic clear-cell renal cell carcinoma, who underwent right nephrectomy followed by nivolumab plus ipilimumab. Four months after treatment, he developed fatigue, dyspnea, productive cough, and weight loss. Chest CT scan showed centrilobular nodules with a tree-in-bud pattern. QuantiFERON® testing was positive. Bronchoalveolar lavage showed lymphocyte predominance with no infectious or neoplastic cells. Transbronchial biopsy demonstrated non-caseating granulomas. PCR for Mycobacterium tuberculosis was negative, and cultures were pending. Given the overlap between IRB and TB, empirical quadruple anti-TB therapy and inhaled corticosteroids were initiated and immunotherapy was temporarily discontinued. After 2 months, given negative mycobacterial cultures and significant hepatotoxicity, isoniazid was discontinued, rifampicin was carefully reintroduced under close monitoring, and the total anti-TB treatment duration was shortened to 4 months. The patient subsequently showed gradual improvement in respiratory symptoms, biomarkers, and radiologic findings. CONCLUSION: This case illustrates the challenge of distinguishing IRB from TB in ICI-treated patients. Empirical anti-TB therapy may be warranted in high-risk settings despite absent microbiological confirmation but carries toxicity and complicates oncologic management. Pre-treatment latent TB screening and multidisciplinary decision-making are essential to balance infection control with cancer therapy.