Deep Introspection Regarding Cumulative Prognostic Factors in Liposarcoma and Atypical Lipomatous Tumor

<i>Background and Objectives</i>: Prognostic evaluation for patients with liposarcoma and atypical lipomatous tumor is a complex process, considering the marked heterogeneity of this group of mesenchymal neoplasms. At the moment, guidelines recommend determining the tumor's histological grade by documenting proliferative activity and the presence of tumor necrosis. Proliferative intratumoral activity is an important tool for risk estimation; therefore, it has been studied using both conventional histopathological mitotic count and analysis of the Ki67 proliferation index. The histopathological subtype is of utmost importance for assessing disease progression and survival for liposarcoma, as pleomorphic and dedifferentiated subtypes often have an unfavorable evolution, while a well-differentiated liposarcoma/atypical lipomatous tumor clinically behaves like locally aggressive neoplasms. In a previous study that we published, we created an algorithm with prognostic-predictive significance for liposarcoma, the LEMON (Liposarcoma Evaluation Mitosis Origin Necrosis) two-tiered system, integrating histological subtype, mitotic activity, and tumor necrosis. The aims of the present study are to depict the overall survival of patients with liposarcoma stratified by Kaplan-Meier analysis categorized by tumor histological grade and to underscore the clinical utility of the LEMON score in risk stratification segregating indolent (low-risk) from aggressive (high-risk) liposarcomas across histological grades. <i>Materials and Methods</i>: We carried out a retrospective multicenter study on 99 patients diagnosed with primary liposarcoma between 2009 and 2023 who were followed up to assess the presence of metastases and their survival period. We performed Kaplan-Meier analysis for overall survival. Proliferative tumor activity was analyzed using conventional histopathological examination and Ki67 immunostaining, and the methods' sensitivity was compared using Bland-Altman analysis. <i>Results</i>: In this respect, tumors with a higher histological grade were associated with worse survival with statistically significant differences in survival between G1 and G3 liposarcomas. Ki67 immunostaining proved to be more sensitive in detecting cellular proliferation compared to histologically observed mitoses. Furthermore, the risk stratification of cases by tumor grade and LEMON score effectively segregates indolent lesions (low risk) from aggressive subtypes (high risk) and may have clinical utility. <i>Conclusions</i>: The histopathological examination for liposarcoma subtype, mitotic index, and tumor necrosis is crucial for assessing the risk of progressive disease and the overall survival of patients. This study focuses on describing the prognostic significance of tumor grade, emphasizing proliferative activity evaluation. The clinical utility of a two-tiered system classifying liposarcomas into "low-risk" and "high-risk" lesions can be evaluated by providing an overview of overall survival in relation to histological grade and LEMON risk score. Risk stratification is particularly important in identifying the patients with liposarcoma who may benefit from intensified surveillance or adjuvant therapies.