Simple SummaryMost fat-containing soft tissue tumors in children are benign, and liposarcomas are extremely rare in this age group. On the other hand, many benign fat-containing soft tissue tumors in children may demonstrate imaging features that can be reminiscent of adult liposarcoma. Although clinico-radiologic guidelines are available for adults, the diagnostic management of such tumors during childhood is still unclear. The aim of this study was to confirm the overall benignity of such tumors in a pediatric cohort and to highlight the clinical and imaging features that warrant a biopsy.AbstractPurpose: To confirm the overall benignity of fat-containing soft tissue tumors (STT) on a pediatric cohort and to define the clinical and imaging features that warrant a biopsy. Methods: A retrospective monocentric study was conducted on patients aged less than 25 years consecutively referred for fat-containing STT to our Comprehensive Cancer Center between 1998 and 2022. Tumor imaging characteristics at diagnosis (US, CT, or MRI) were correlated with pathology. Results: The database extraction identified 63 fat-containing tumors with clinical, histologic, and imaging data available for review. In total, 58 (92%) were benign tumors: 36 lipoblastomas and lipomas, 12 fibrous hamartomas of infancy (FHI), 5 lipofibromatosis, 2 lipomas arborescens, 2 lipomatosis and 1 spindle-cell lipoma. Five patients (8%) were diagnosed with liposarcoma. Factors significantly correlated with malignancy were age >10 years old (p< 0.001), having a cancer-predisposing condition (p< 0.001), a percentage of fat <25% (p= 0.002), and a presence of myxoid zones (p< 0.001) on imaging. Conclusion: Most fat-containing STT in children may be classified as benign tumors based on clinics and imaging. The indication for biopsy could be limited to patients aged 10 years or more with either a cancer-predisposing condition or imaging features demonstrating either a low-fat component (<25%) or the presence of myxoid zones.