Incremental value of whole-body 18F-fluorodeoxyglucose PET/computed tomography in cavernous sinus syndrome: guiding biopsy and improving diagnostic outcome

OBJECTIVE: Cavernous sinus syndrome (CSS) has diverse causes and correctly identifying the underlying pathology is difficult. The study aimed to determine the incremental value of whole-body 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in detecting extra-cranial involvement in CSS, to guide biopsy sites; and characterizing cavernous sinus pathologies based on metabolic activity. METHODS: Participants with treatment-naive CSS after clinical assessment and MRI brain were recruited prospectively from July 2022 to December 2023. All the participants underwent whole-body 18F-FDG-PET/CT, and images were analyzed for the presence, site, extent, and standardized uptake value (SUVmax) and feasibility of biopsy from cavernous sinus and extracranial lesions. Reference standards were histopathology, definite MRI findings, or established diagnostic criteria for immunoglobulin G4-related disease, neurosarcoidosis and Tolosa-Hunt syndrome. RESULTS: Data of 54 patients (mean age: 44.8 years) was analyzed. Cavernous sinus lesion was detected in all 54 patients, and 26 (48.1%) patients had extra-cranial lesions. PET-directed biopsies were done from the local extension of FDG-avid cavernous sinus lesions in 20 (37%) and extra-cranial lesions in 12 (22.2%) patients. The final etiological diagnoses were infection in 18 (33.3%), inflammatory disorders in 18 (33.3%), benign neoplasms in 11 (20.5%), and malignancy in seven (12.9%) cases. PET/CT demonstrated significantly lower FDG-avidity in benign cavernous sinus neoplasms (median SUVmax: 5.5, IQR: 4.5-8.0) as compared to the infective, inflammatory, and malignant conditions involving the cavernous sinus (median: 15.0, IQR: 10.7-22.4; P < 0.001). Bony erosions and contiguous paranasal involvement were more frequently associated with infective CSS (P < 0.001). CONCLUSION: Whole-body 18F-FDG-PET/CT effectively identifies extracranial disease in CSS, enables less invasive biopsy site selection, and enhances diagnostic yield while minimizing high-risk intracranial biopsies. 18F-FDG-PET/CT should be considered in imaging of CSS, especially when definite diagnosis is not established with conventional workup.