Differentiation of Lung Malignancy from Benign Lesions in Patients with Nontuberculous Mycobacterial Infection: A Retrospective Analysis of Biopsy-Proven Cases

Background/Objectives: Nontuberculous mycobacterial (NTM) pulmonary infection may present with diverse radiologic manifestations that mimic lung malignancy. Furthermore, in patients with newly detected or progressively enlarging pulmonary lesions, distinguishing benign NTM-related lesions from coexisting malignancy is often challenging. When imaging findings are indeterminate, percutaneous core needle biopsy (PCNB) may be required for diagnostic clarification. This study aimed to evaluate the pathologic results, clinical characteristics, and CT features of pulmonary lesions in patients with NTM infection who underwent PCNB and to identify factors associated with malignancy. Methods: This retrospective study included 38 patients with NTM infection who underwent CT-guided PCNB for lung lesions between 2015 and 2025. Two blinded radiologists reviewed chest CT scans obtained within six weeks prior to the biopsies. Clinical variables and CT features were compared between malignant and benign lesions. Univariable and multivariable logistic regression analyses were performed to explore factors associated with malignancy. Results: Of the 38 patients, 9 (23.7%) were diagnosed with malignancy and 29 (76.3%) had benign lesions. Malignant lesions more frequently demonstrated a lobulated irregular morphology compared to benign lesions (88.9% vs. 37.9%). Emphysema was also more common in the malignancy group (88.9% vs. 24.1%, p < 0.001). In the multivariable logistic regression analysis, lobulated irregular morphology (odds ratio [OR], 19.856; 95% CI, 1.516–260.089; p = 0.023) and emphysema (OR, 35.531; 95% CI, 2.857–441.824; p = 0.005) were associated with malignancy. However, the wide confidence intervals indicate substantial uncertainty due to the limited number of malignant cases. Conclusions: In patients with NTM infection who underwent PCNB for suspicious lung lesions, a lobulated irregular morphology and the presence of emphysema were associated with malignancy in this exploratory cohort. These findings may provide useful information to support clinical decision-making regarding biopsy in patients with NTM infection and indeterminate pulmonary lesions.