PET/CT and Paraneoplastic Syndromes: A Comprehensive Review

Paraneoplastic syndromes (PNSs) are pathologic conditions produced by neoplasms not attributable to tumor invasion or metastasis. The clinical manifestations of PNSs can precede the diagnosis; these symptoms may serve as early indicators of underlying malignancy. Standard imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), have limited sensitivity in detecting small or early-stage PNS-associated tumors. FDG PET/CT identifies hypermetabolic lesions suggestive of malignancy and, therefore, facilitates early diagnosis, refined treatment planning, and potentially prolonged patient survival. This review evaluates the diagnostic accuracy, clinical utility, and emerging role of FDG PET/CT in detecting occult malignancies. Syndrome-targeted applications discussed include limbic encephalitis, cerebellar degeneration, Lambert-Eaton myasthenic syndrome, Cushing's syndrome, hypercalcemia of malignancy, dermatomyositis, and tumor-induced osteomalacia. In addition, the limitations of FDG PET/CT, including false-positive or false-negative findings, are reviewed, while newer PET tracers, like ⁶⁸Ga-DOTATATE, are also highlighted. Ultimately, FDG PET/CT has transformed clinical decision-making, enabling more timely interventions and improved patient management in the context of PNSs. Future directions in imaging, including PET/MRI and ongoing refinements in tracer design, promise to further enhance diagnostic precision, and therapeutic outcomes are also discussed.