Abstract Cavitary pulmonary lesions present a diagnostic challenge, particularly in patients with structural lung disease and immunologic vulnerability. We report the case of a 74-year-old male with severe COPD and a remote history of treated tuberculosis who presented with acute on chronic hypoxic respiratory failure and was found to have a right upper lobe cavitary lesion. The differential diagnosis included reactivation tuberculosis, necrotizing bacterial pneumonia, and invasive fungal infection. Initial cultures were negative, and tuberculosis testing was indeterminate. Further serologic evaluation revealed positivity for Histoplasma capsulatum, Coccidioides immitis, and Aspergillus species, along with an elevated serum β-D-glucan level. The patient was treated with liposomal amphotericin B followed by itraconazole, in addition to supportive care and corticosteroids. This case emphasizes the importance of considering endemic mycoses in the differential diagnosis of cavitary lung lesions, even in the absence of classic immunosuppressive risk factors. Our patient presented with progressive dyspnea, productive cough, leukocytosis, anemia, and hypercapnic respiratory failure. Chest CT showed bilateral upper lobe opacities with a cavitary consolidation. Bacterial and mycobacterial studies were unrevealing, but fungal markers were repeatedly positive. Given clinical decline and diagnostic limitations, empiric antifungal therapy was initiated with subsequent improvement in oxygen requirements, inflammatory markers, and symptoms, supporting a fungal etiology. Serologic assays have limitations, including cross-reactivity between endemic fungi and false positives in non-neutropenic hosts, yet they remain essential when tissue sampling is impractical due to bleeding risk, respiratory instability, or comorbid conditions. In this case, bronchoscopy and endoscopy were deferred due to antiplatelet therapy and concern for respiratory compromise, reinforcing the need for alternative diagnostic pathways. Endemic mycoses, such as histoplasmosis, blastomycosis, coccidioidomycosis, and aspergillosis, may present as cavitary lesions, especially in patients with underlying structural lung disease. Although typically associated with overt immunosuppression, these infections are increasingly reported in elderly COPD patients with immunosenescence and prior lung injury. Cavitary and necrotizing pneumonias create substantial diagnostic uncertainty in regions where tuberculosis is also prevalent, as radiographic features of chronic pulmonary aspergillosis, histoplasmosis, and coccidioidomycosis overlap significantly with post-tuberculous cavities. This case highlights the diagnostic complexity of cavitary lung disease in COPD patients with prior tuberculosis, where fungal, bacterial, and mycobacterial etiologies converge. Early recognition of fungal infections is critical, as delayed therapy increases morbidity in structurally abnormal lungs. Clinicians should maintain a broad differential, understand the limitations of serologic testing, and consider empiric antifungal therapy when clinical suspicion is high and invasive sampling is unsafe. This abstract is funded by: None
Gonzalez et al. (Fri,) studied this question.