Diagnostic Value of 18F-FDG PET/CT in Guiding Biopsy Decisions and Differentiating Infectious, Inflammatory and Malignant Lesions

<b>Background/Objectives:</b> 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is used in oncology but has limited specificity due to uptake in infectious and inflammatory conditions. This study evaluated the diagnostic value of 18F-FDG PET/CT in patients with infectious, inflammatory, and malignant lesions and its role in guiding histopathological biopsy decisions in an infectious disease setting. <b>Methods:</b> A retrospective cohort study included 186 adult patients who underwent 18F-FDG PET/CT between 2018 and 2023 for diagnostic evaluation at a tertiary care hospital. Clinical indications were fever of unknown origin (FUO), inflammation of unknown origin (IUO), lymphadenopathy of unknown origin, and suspected solid mass. Diagnostic yield, biopsy decisions, and factors associated with biopsy were analyzed. <b>Results:</b> The diagnostic yield of 18F-FDG PET/CT was 58.6%, with higher in malignant conditions (hematologic malignancy 85.7%, solid organ malignancy 88.9%) and lower in autoimmune/inflammatory diseases (20.8%) and mycobacterial infections. PET/CT showed moderate sensitivity (59.8%) and high specificity (98.7%) for infection detection, improving to 67.8% sensitivity after excluding mycobacterial infections. Biopsy was performed more in patients with lymphadenopathy, higher SUVmax (>7.4), and PET/CT findings not suggestive of infection. Analysis identified lymphadenopathy (aOR = 2.77), PET/CT not suggestive of infection (aOR = 4.73), and SUVmax > 7.4 (aOR = 4.98) as predictors of biopsy. <b>Conclusions:</b> 18F-FDG PET/CT provides moderate diagnostic value across infectious, inflammatory, and malignant diseases and guides biopsies effectively, particularly in patients with lymphadenopathy, elevated SUVmax, and non-infectious findings. Its limited performance in mycobacterial and autoimmune diseases requires cautious interpretation. Overall, 18F-FDG PET/CT supports clinical decisions in complex diagnostic scenarios.