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Abstract Objectives We aimed to test the hypothesis that in retroperitoneal dedifferentiated liposarcoma (DDLS) the presence of the dedifferentiated (DD) component at the resection margin is associated with adverse outcome. Methods We retrospectively searched the archive for primary resections of retroperitoneal DDLS performed at our institution between 1990 and 2017. Slides were rereviewed for diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer grade, myogenic differentiation, and the presence of the well-differentiated (WD) or DD component at the resection margin. The medical records were reviewed for patient age, sex, tumor size, tumor focality, adjuvant/neoadjuvant therapy, local recurrence, distant metastases, local recurrence-free survival (LRFS), overall survival (OS), and follow-up duration. Results The presence of the DD component at the resection margin was associated with worse LRFS compared with cases without the DD component at the margin (P = .002). However, OS was not significantly affected (P = .11). Conclusions LRFS is significantly shorter in cases with the DD component at the margin compared with cases without DD tumor at the margin, while there is no association with OS. We recommend reporting the presence or absence of DD tumor at the margin in retroperitoneal DDLS, as it adds meaningful prognostic information.

Introduction Dedifferentiated liposarcoma (DDLPS) is a fairly common subtype of soft tissue sarcoma, but relatively little is known about the clinical course and prognostic factors of this mesenchymal malignancy. Methods We performed a retrospective analysis of patients diagnosed with DDLPS at the University Hospital Leuven, Belgium between 1991 and 2022 based on an established clinical database and patient records. Results We identified 259 patients with DDLPS, with the retroperitoneum as most common location of the primary tumor (47.5%). 204/259 patients (78.8%) patients had primary surgery. Radiotherapy was administered in the pre- (46/259, 17.8%) or postoperative setting (51/259, 19.7%). At diagnosis 28/259 (10.8%) patients presented with locally inoperable disease and 26/259 (10.0%) with synchronous metastasis. In patients who had primary surgery, local relapses were seen in 114/259 (44.0%) patients and 80/259 (30.9%) patients developed metachronous metastasis. A total of 48/259 (18.5%) patients developed both local relapse and metastasis. Patients with inoperable or metastatic disease were often treated with systemic therapy. The most common first-line systemic therapies were doxorubicin (51/98, 52.0%), doxorubicin combined with ifosfamide (12/98, 12.2%) and different types of experimental treatments (18/98, 18.4%). The median overall survival from first diagnosis of DDLPS to death of all causes was 70.5 months (95% confidence interval [CI] 56.6–98.6) for all patients, 10.9 months (95% CI 3.6–29.2) in patients with inoperable disease, 28.4 months (95% CI 1.3-199.3) for patients with local relapse and only 9.4 months (95% CI 1.2–25.9) for patients with metastatic disease. We identified lower age, primary surgery, absence of synchronous metastasis, absence of local relapse and treatment with experimental therapy as statistically significant favorable prognostic factors. Conclusions DDLPS is a subtype of soft tissue sarcoma with an aggressive clinical course and very poor prognosis, especially in patients with inoperable or metastatic disease. The results with classic chemotherapy are poor, and experimental treatments may be a preferred choice for individual patients. Data from this retrospective series can inform the design of future prospective and ongoing trials in this setting.

Introduction Dedifferentiated liposarcoma (DDLPS) is a rare and aggressive subtype of soft tissue sarcoma, characterized by limited treatment options and poor prognosis. Despite surgical resection being the only potentially curative treatment for localized DDLPS, the recurrence rate remains high, and systemic chemotherapy, typically anthracycline-based, shows limited efficacy in advanced stages. While immune checkpoint inhibitors (ICIs) have shown promise in various sarcoma subtypes, including DDLPS, their role as a first-line treatment remains unclear. Methods We conducted a systematic meta-analysis to evaluate the efficacy of ICIs in treating patients with DDLPS. A total of 25 studies encompassing 245 patients were included. Data on overall response rate (ORR), progression-free survival, and grade III–V treatment-related adverse events were analyzed. We assessed treatment efficacy based on the line of therapy and treatment regimens, including ICI monotherapy, dual ICI therapy, and ICI combinations with other modalities. Results The pooled ORR for all ICI-based treatments was 7%. First-line ICI therapy yielded a significantly higher ORR of 22%, compared to 4% in later-line treatment. The combination of ICI with anthracyclines demonstrated the highest ORR of 52%. In contrast, ICI regimens combined with trabectedin or other agents showed limited efficacy. Sensitivity analysis confirmed the stability of results, and publication bias was not detected. Conclusion This meta-analysis supports the potential role of ICIs, particularly in combination with anthracyclines, as a first-line therapeutic strategy for DDLPS. These results provide a foundation for future prospective studies aimed at optimizing immunotherapy approaches for this rare and challenging malignancy.

Murine Double Minute Clone 2, located at 12q15, is an oncogene that codes for an oncoprotein of which the association with p53 was discovered 30 years ago. The most important function of MDM2 is to control p53 activity; it is in fact the best documented negative regulator of p53. Mutations of the tumor suppressor gene p53 represent the most frequent genetic change in human cancers. By overexpressing MDM2, cancer cells have another means to block p53. The sarcomas in which MDM2 amplification is a hallmark are well-differentiated liposarcoma/atypical lipomatous tumor, dedifferentiated liposarcoma, intimal sarcoma, and low-grade osteosarcoma. The purpose of this review is to summarize the typical clinical, histopathological, immunohistochemical, and genetic features of these tumors.

Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center. We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between 2018 and 2023. Patient demographics, disease characteristics, treatment history, and response to ICB were analyzed. Immunohistochemical analysis was performed on tumor samples to assess immune-related markers. ORR by RECIST 1.1 was 3.2% (n=1/31). Among all patients (n=31), 6% achieved partial radiographic response, while 39% had stable disease, and 55% showed progressive disease. Median progression-free survival (PFS) was 3.5 (95%CI:1.9, 4.7) months, and overall survival (OS) after ICB initiation was 19.7 (95%CI: 8.8, not reached) months. Patients without prior systemic therapy demonstrated better OS (p=0.004). Immunohistochemistry revealed no relationship between pre- or post-ICB expression of CD8, CD20, CD21 and PDL-1 and response. While the response to ICB in DDLPS remains limited, specific immune markers may influence treatment outcomes. CD20/21 post-ICB appear more important for prognosis. Further research is warranted to identify predictive factors for ICB efficacy in DDLPS.

Myxoid pleomorphic liposarcoma (MPLPS) is an exceedingly rare and recently recognized adipocytic neoplasm that primarily occurs in children and young adults and shows a strong predilection for the mediastinum. Clinically, MPLPS demonstrates aggressive behavior and exhibits a high propensity for systemic spread and a worse overall survival. Some cases have been associated with Li-Fraumeni syndrome. Histologically, MPLPS is composed of a variable mixture of myxoid and pleomorphic liposarcoma-like components. Immunohistochemically, the tumor cells show diffuse expression of CD34 and p16 and loss of nuclear RB expression. MPLPS lacks DNA damage inducible transcript 3 (DDIT3) rearrangements and MDM2 proto-oncogene (MDM2) amplifications but shows tumor protein p53 (TP53) mutations and RB transcriptional co-repressor 1 (RB1) deletions. Moreover, recent studies have demonstrated that the most consistent molecular feature of MPLPS is genome-wide loss of heterozygosity. Surgical excision with negative margins is the mainstay of treatment for localized MPLPS. The treatment of advanced/metastatic MPLPS still poses a huge therapeutic challenge. This review provides information about the clinicoradiological features, pathogenesis, histopathology, and management currently available for MPLPS. In addition, we discuss the differential diagnosis of this novel entity.

A recurrent intrachromosomal rearrangement on chromosome 12q in solitary fibrous tumor leads to the formation of a NAB2–STAT6 fusion oncogene. As a result, nuclear expression of the cytoplasmic transcription factor STAT6 is found in solitary fibrous tumor and serves as a useful diagnostic marker. STAT6 is located in 12q13, a region containing well-characterized oncogenes that are commonly amplified in dedifferentiated liposarcoma; we have previously reported that STAT6 is expressed in a subset of dedifferentiated liposarcoma. The aim of this study was to determine the frequency of STAT6 expression in dedifferentiated liposarcoma and the underlying genetic mechanism. STAT6 protein expression was analyzed by immunohistochemistry in a well-characterized series of 35 previously unpublished cases of dedifferentiated liposarcoma, all with nuclear MDM2 and/or CDK4 expression by immunohistochemistry and/or cytogenetic features of dedifferentiated liposarcoma. FISH for STAT6 was performed in all cases with STAT6 expression, and a subset of control cases without STAT6 expression. In total 4/35 cases (11%) showed STAT6 expression (three with multifocal staining of moderate to strong intensity and one with weak focal staining). FISH demonstrated amplification of STAT6 in all cases positive for STAT6 by immunohistochemistry; in contrast, FISH performed on four STAT6-negative dedifferentiated liposarcomas demonstrated no STAT6 amplification (P=0.0286). Of the four STAT6 amplified cases, three patients were male and one was female, ranging in age from 51 to 76 years. Tumors were located in the mediastinum (n=2), paratesticular soft tissue (n=1), and perirenal soft tissue (n=1). Three patients received pre-operative chemotherapy +/− radiation therapy. In conclusion, STAT6 is amplified in a subset of dedifferentiated liposarcoma, resulting in STAT6 protein expression that can be detected by immunohistochemistry and may be a potential pitfall in the differential diagnosis of dedifferentiated liposarcoma and solitary fibrous tumor. These findings suggest a role for STAT6-mediated transcriptional activity in some cases of dedifferentiated liposarcoma and highlight the genomic complexity and heterogeneity of dedifferentiated liposarcoma.

Introduction This research aimed to develop and validate a novel nomogram for predicting overall survival (OS) in Dedifferentiated liposarcoma (DDLPS) patients. Methods A retrospective cohort of 1,155 DDLPS cases diagnosed from 2004 to 2015 was identified through the Surveillance, Epidemiology, and End Results (SEER) registry. The prognostic model was subsequently developed by incorporating covariates independently associated with survival outcomes, as determined through multivariate analysis. To assess the model's predictive performance and clinical utility, we employed a suite of validation metrics. Results Cox regression revealed age, tumor size, laterality, AJCC stage, combined summary stage, radiation, chemotherapy, and surgery as independent predictive variables for DDLPS. The C-index of the nomogram in the training and validation cohorts was 0.708 and 0.704, which was higher than that of the AJCC system. All AUC values、NRI (> 50%), IDI (> 10%), calibration and DCA curves showed that the new model had an excellent ability to predict OS. Conclusions Our study represents the initial effort to develop a nomogram for predicting OS in DDLPS patients based on the SEER database. Significantly, the nomogram showed a greater potential for accurately predicting survival as opposed to the AJCC system.

Atypical lipomatous tumor or well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) share the same basic genetic abnormality characterized by a simple genomic profile with a 12q14–15 amplification involving MDM2 gene. These tumors are the most frequent LPS. This paper reviews the molecular pathology, general clinical and imaging features, histopathology, new diagnostic tools, and prognosis of ALT-WDLPS and DDLPS.