Utility of ¹⁸F FDG PET/CT in Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a fatal systemic inflammatory syndrome caused by a wide array of causes, which may be detected on ¹⁸F fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F FDG PET/CT). This study explores the utility of ¹⁸F FDG PET/CT in HLH.

Retrospective data of HLH patients referred for whole-body ¹⁸F FDG PET/CT were analyzed for abnormal findings, and quantitative analysis using standardized uptake value (SUV), spleen-to-liver ratio (SLR), and bone-to-liver ratio (BLR) was done and correlated with laboratory parameters, bone marrow (BM) findings, and final diagnosis.

Twenty-four patients (median age 22 years [interquartile range 13-34]) were included in the study. The most common cause of HLH was infection (33%), malignancy (29%), and autoimmune disorders (13%), and five patients had primary HLH. ¹⁸F FDG PET/CT was positive in 22/24 patients (92%). Hepatomegaly and splenomegaly were observed in 22 patients (92%) and 16 patients (67%), respectively, with six (25%) showing splenic lesions. Splenic uptake > liver was observed in 62.5% of patients and BM uptake > liver uptake in 50% of patients. There was no significant difference in median BM uptake (SUV_max 4.0 vs. 3.5, P = 0.6) and BLR (1.475 vs. 1.514, P = 0.4) in patients with and without HLH on marrow sampling, but a significant difference was observed in hypercellular vs. normocellular/hypocellular marrow (SUV_max 5.1 vs. 3.2, P = 0.019 and BLR 1.58 vs. 0.82, P = 0.043). A significant positive correlation was observed between splenic and BM uptake (r = 0.501, P = 0.013), BLR and SLR (r = 0.623, P = 0.001), C-reactive protein levels with BLR (r = 0.731, P = 0.001), and SLR (r = 0.594, P = 0.015), respectively. In 11 patients who underwent targeted sampling from most hypermetabolic sites, it helped reach the final diagnosis or eliminate malignant causes.

¹⁸F FDG PET/CT has a high diagnostic yield in HLH with the potential to detect its underlying causes and may be considered in the diagnostic algorithm of HLH.