Can Dedifferentiated Liposarcoma be Reliably Excluded Based on Mitotic Rate? Prognostic and Diagnostic Implications of Mitotic Activity in Liposarcoma.

Abstract

Distinguishing well-differentiated liposarcoma (WDLPS) from dedifferentiated liposarcoma (DDLPS) is challenging, particularly when the low-grade (LG) sarcoma component does not meet the histopathological criteria for typical DDLPS. Previous studies have suggested that the diagnosis of DDLPS requires at least five mitotic figures per 10 high-power fields (≥ 5/10 HPF). This study aimed to validate the prognostic and diagnostic significance of the mitotic rate in LPS. We retrospectively reviewed 238 cases of WDLPS and DDLPS from our institution and assessed the prognostic value of the mitotic rate, MDM2/CEP12 amplification ratio, and Ki-67 proliferation index. Digital pathology and automated image analysis were used to obtain precise mitotic counts and minimise inter-observer variability. Among 238 patients, 165 had WDLPS, 26 had LG DDLPS, and 47 had DDLPS. LG DDLPS was reclassified when intermediate histological features were observed along with a mitotic rate < 5/10 HPF. Recurrence-free survival (RFS) was significantly worse in LG DDLPS than in WDLPS (P = 0.012) but better than in DDLPS (P = 0.001). Notably, lung metastasis occurred in two (7.7%) of the 26 LG DDLPS cases. The MDM2 amplification ratio progressively increased from WDLPS to DDLPS, whereas the Ki-67 expression level was not significantly associated with prognosis. This study demonstrated that the mitotic rate is a crucial diagnostic and prognostic marker in LPS. LG DDLPS exhibits more aggressive behaviour than WDLPS. Our results suggest that LG DDLPS should not be underestimated or classified as WDLPS based solely on mitotic rate.