Diagnostic Pitfalls of 18 F-FDG PET/CT in Presumed Malignant Pulmonary Nodules and Masses: A Retrospective Pathology-Based Study

Abstract Objective To characterize CT morphological and metabolic features of pulmonary nodules and masses initially considered suspicious for malignancy on 18 F-FDG PET/CT and to explore features associated with benign false-positive interpretations. Methods We retrospectively analyzed 31 patients with pulmonary nodules or masses considered suspicious for malignancy on 18 F-FDG PET/CT who subsequently underwent definitive pathological evaluation. Patients were categorized into malignant (n = 21) and benign false-positive (n = 10) groups. Firth penalized logistic regression was used to assess associations between CT morphological features, clinical characteristics, and false-positive outcomes. Results No significant difference in SUVmax was observed between the two groups. The prevalence of spiculation (80.0% vs. 33.3%, p = 0.023) and pleural indentation (60.0% vs. 14.3%, p = 0.015) was significantly higher in the benign false-positive group than in the malignant group. In multivariable Firth regression, spiculation was independently associated with false-positive outcomes (adjusted OR, 11.80; 95% CI, 1.97–106.87; p = 0.005), whereas serum tumor marker positivity was associated with lower odds of false-positive interpretation (adjusted OR, 0.09; 95% CI, 0.01–0.63; p = 0.013). Granulomatous inflammatory lesions and fungal infections accounted for 80% of benign false-positive lesions. Conclusion In pulmonary lesions presumed malignant on 18 F-FDG PET/CT, benign inflammatory and infectious diseases may reproduce both increased FDG uptake and malignant-like CT morphology. Spiculation and pleural indentation should therefore be interpreted cautiously, particularly when serum tumor markers are negative. Integration of clinical, imaging, pathological, and multidisciplinary information may help reduce unnecessary invasive management.