Metagenomic next-generation sequencing unveils invasive aspergillosis masquerading as miliary tuberculosis in a neutropenic leukemia patient: a case report

Background Empirical anti-tuberculosis therapy is a common strategy when patients with acute leukemia chemotherapy-induced neutropenia develop diffuse pulmonary small nodular and subsolid lesions. However, the absence of pathogenetic verification may lead to catastrophic consequences. Methods Following negative conventional microbiological cultures (bronchoalveolar lavage bacterial culture, Gram/Gram-negative test) and ineffective anti-infective therapy, a second bronchoscopy revealed caseous obstructive lesions in the right upper lobe bronchus. Metagenomic Next-Generation Sequencing (mNGS) analysis of lavage fluid ultimately confirmed invasive pulmonary fungal disease. Results The mNGS analysis of the bronchoalveolar lavage fluid (BALF) reported 6,750 Aspergillus fumigatus sequences, 43 Aspergillus complex sequences, and 81 Candida albicans sequences (considered airway colonization with no pathogenic significance), confirming probable invasive pulmonary aspergillosis (IPA) in line with the 2023 revised EORTC/MSGERC consensus criteria for invasive fungal diseases. Following discontinuation of anti-tuberculosis therapy, targeted antifungal treatment with amphotericin B (40 mg daily) was initiated. Post-treatment, the patient’s temperature normalized. Follow-up CT demonstrated improved absorption of lesions in the left lung and right lower lobe, with stable cavitary nodules in the right upper lobe. Conclusion This case demonstrates that invasive pulmonary fungal infection can perfectly mimic the typical radiographic features of hematogenous disseminated pulmonary tuberculosis, including diffuse small nodular and subsolid lesions with a miliary distribution pattern predominantly in the upper lobes and extrapulmonary manifestations such as erythema nodosum. For unexplained pulmonary infections in immunocompromised hosts where conventional diagnosis and empirical treatment fail, the timely application of bronchoscopy combined with mNGS technology represents a critical breakthrough for achieving precise diagnosis.