Development and Validation of (18)F-FDG PET/CT-Based Multivariable Clinical Prediction Models for the Identification of Malignancy-Associated Hemophagocytic Lymphohistiocytosis

OBJECTIVE: (18)F-fluorodeoxyglucose (FDG) PET/CT is often used for detecting malignancy in patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), with acceptable sensitivity but relatively low specificity. The aim of this study was to improve the diagnostic ability of (18)F-FDG PET/CT in identifying malignancy in patients with HLH by combining (18)F-FDG PET/CT and clinical parameters. MATERIALS AND METHODS: Ninety-seven patients (age ≥ 14 years) with secondary HLH were retrospectively reviewed and divided into the derivation (n = 71) and validation (n = 26) cohorts according to admission time. In the derivation cohort, 22 patients had malignancy-associated HLH (M-HLH) and 49 patients had non-malignancy-associated HLH (NM-HLH). Data on pretreatment (18)F-FDG PET/CT and laboratory results were collected. The variables were analyzed using the Mann-Whitney U test or Pearson’s chi-square test, and a nomogram for predicting M-HLH was constructed using multivariable binary logistic regression. The predictors were also ranked using decision-tree analysis. The nomogram and decision tree were validated in the validation cohort (10 patients with M-HLH and 16 patients with NM-HLH). RESULTS: The ratio of the maximal standardized uptake value (SUVmax) of the lymph nodes to that of the mediastinum, the ratio of the SUVmax of bone lesions or bone marrow to that of the mediastinum, and age were selected for constructing the model. The nomogram showed good performance in predicting M-HLH in the validation cohort, with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.686–0.971). At an appropriate cutoff value, the sensitivity and specificity for identifying M-HLH were 90% (9/10) and 68.8% (11/16), respectively. The decision tree integrating the same variables showed 70% (7/10) sensitivity and 93.8% (15/16) specificity for identifying M-HLH. In comparison, visual analysis of (18)F-FDG PET/CT images demonstrated 100% (10/10) sensitivity and 12.5% (2/16) specificity. CONCLUSION: (18)F-FDG PET/CT may be a practical technique for identifying M-HLH. The model constructed using (18)F-FDG PET/CT features and age was able to detect malignancy with better accuracy than visual analysis of (18)F-FDG PET/CT images.