MDM2 and DDIT3 coexpression in dedifferentiated liposarcoma with myxoid features: a retrospective cohort study

Dedifferentiated liposarcoma (DDLPS) can exhibit myxoid morphology that closely mimics myxoid liposarcoma (MLPS), creating significant diagnostic challenges. DDIT3 immunohistochemistry (IHC), a specific marker for MLPS, has been reported in a subset of DDLPS cases, but its frequency, staining pattern, and clinical significance remain poorly characterised. We retrospectively analysed 46 DDLPS cases with prominent myxoid features (≥ 10% myxoid component) confirmed by MDM2 IHC and fluorescence in situ hybridisation (FISH), treated at a single tertiary centre between January 2007 and January 2026. DDIT3 IHC was scored using a semiquantitative H-score system. DDIT3 positivity occurred in 11 of 46 cases (23.9%, 95% CI: 12.6-38.8%), predominantly as focal staining (9/11, 81.8%). All DDIT3-positive cases exhibited myxoid components comprising > 25% of tumour volume, versus variable myxoid extent in DDIT3-negative cases (p < 0.001). Mean H-score in DDIT3-positive cases was 48.6 ± 32.4 (range 15-120), significantly lower than in true MLPS controls (mean 278 ± 22, p < 0.001). Tumour size > 15 cm significantly increased the risk of local recurrence (risk ratio [RR] = 2.31, 95% CI: 1.02-5.24, p = 0.048). DDIT3 expression showed no significant association with local recurrence (p = 0.337), distant metastasis (p = 0.825), or mortality (p = 0.805). Kaplan-Meier analysis revealed no significant difference in overall survival (log-rank p = 0.782) or recurrence-free survival (log-rank p = 0.614) between DDIT3-positive and DDIT3-negative groups. DDIT3 positivity in DDLPS with myxoid features predominantly produces focal, low-intensity staining that distinguishes it from true MLPS. DDIT3 expression reflects chromosomal co-amplification within the 12q13-15 amplicon and lacks prognostic significance. Combined MDM2 and DDIT3 IHC with careful morphological assessment aids differential diagnosis, particularly when molecular testing is unavailable.