Zhonghua Bing Li Xue Za Zhi. 2026 May 08. 55(5):
419-425
Objective: To investigate the clinical application of DDIT3 gene rearrangement using fluorescence in situ hybridization (FISH) in myxoid liposarcoma (MLPS) and to analyze the cases with atypical signal pattern. Methods: A total of 386 cases were examined for DDIT3 gene rearrangement using FISH in the West China Hospital, Sichuan University, Chengdu, China from January 2018 to December 2024. The clinicopathologic data and molecular detection results were collected. Six MLPS with DDIT3 cryptic rearrangement (CR-MLPS) were identified and subject to FISH testing of FUS and EWSR1 break, EWSR1::DDIT3 and FUS::DDIT3 fusion, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction and Sanger sequencing. Results: Among the 386 successfully tested cases, 154 cases were histologically diagnosed as MLPS, of which 148 (148/156, 96.1%) were positive for DDIT3 gene rearrangements. In the positive cases, 57 cases were further subject to FUS and EWSR1 break-apart examination. Among them, 51 cases (51/57, 89.5%) showed FUS rearrangements, 5 cases (5/57, 8.8%) displayed EWSR1 rearrangements and 1 case was negative for FUS and EWSR1 rearrangement. DDIT3 gene rearrangements were negative in 238 cases (238/386, 59%). Six CR-MLPS were identified, including two females and four males, with an average age of 32 (14, 55) years, all located in the deep soft tissues of the extremities. All six cases of CR-MLPS presented typical MLPS morphology, with nodular distribution, abundant mucin, and visible branched capillaries. The cells were round and of medium size. Adipoblasts and cells with adipocyte-differentiation were also observed. The tumor cells in all six cases of CR-MLPS were negative or focally positive for S-100, and negative for p63 (4/4) and CDK4 (3/3). The Ki-67 index was 10% to 15%. Three of the six DDIT3 CR-MLPS showed small gap of DDIT3 break, one case revealed centromeric amplifications of DDIT3 gene, and two cases displayed 1 to 3 yellow/fusion signals. Subsequent FISH fusion test, reverse-transcriptase polymerase chain reaction and NGS confirmed that four cases had EWSR1::DDIT3 variants and two cases had FUS::DDIT3 variants. All six patients underwent surgical resection followed by radiotherapy. Among them, one patient had a recurrence 4 years after surgery, and another had recurrence and metastasis. Conclusions: FISH detection of DDIT3 gene rearrangements is important for the diagnosis of MLPS, whereas a small number of cases may still be missed due to cryptic rearrangement. The CR-MLPS cases present typical morphology, among which the EWSR1::DDIT3 variants are more commonly detected than the others.