Lipomas and atypical lipomatous tumors or well-differentiated liposarcomas (ALTs/WDLs), pose a diagnostic challenge due to their overlapping clinical and imaging features. Accurate differentiation is crucial as treatment strategies differ significantly between benign lipomas and malignant ALTs/WDLs. In recent years, medical imaging techniques have shown promise in distinguishing lipomas from ALTs/WDLs by providing enhanced visualization and assessment of various imaging parameters. This systematic review aimed to investigate the use of magnetic resonance (MR) imaging and computed tomography (CT) scan to differentiate lipomas from ALTs/WDLs. A systematic review was conducted by using MEDLINE, PubMed, PubMed Central, Cochrane Library, Google Scholar, and clinical trail.gov to identify imaging studies published between 2001 and 2022. Two independent reviewers reviewed 221 record to scrutinize the studies. The methodological quality of each included studies was assessed the using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Thirteen retrospective cohort studies included 1,390 of total patients. Among them, 11 studies used MR imaging, 2 studies used CT scan and MR imaging both to differentiate lipoma from ALTs/WDLs. The significant diagnostic variables identified in the included studies were age, size, texture, mean intensity, contrast enhancement, location, septation, and nodularity. The overall, sensitivity, specificity, and accuracy of the included studies for diagnosis of lesions range from 66% to 100%, 37% to 100%, and 76% to 95%, respectively. The positive and negative predictive values range from 46.9% to 90% and 86% to 100%, respectively. The most frequent diagnostic features of ALTs/ WDLs include tumors ⩾110 mm in size, often in patients over 60, predominantly in the lower extremities, with an irregular shape, incomplete fat suppression, contrast enhancement, nodularity, septation >2 mm, and predictive markers such as lactate dehydrogenase >220 and a short tau inversion recovery-signal intensity ratio >1.18.
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