Dedifferentiated Liposarcoma Research Articles

SMALL BOWEL INTUSSUSCEPTION CAUSED BY METASTASIS FROM A LOWER LIMB LIPOSARCOMA

Abstract Introduction Liposarcoma represents one of the most frequent types of soft tissue sarcomas, constituting a heterogeneous group of lesions. There are four different subtypes: well-differentiated; dedifferentiated; myxoid and pleomorphic. Its main locations are the retroperitoneum, extremities, trunk and the cervical area. Clinical case A 90-year-old male with a pleomorphic liposarcoma in the left thigh in 2012, local recurrence from a dedifferentiated liposarcoma in 2018 and 2021, presented to our emergency department with abdominal pain and vomiting. CT scan revealed an image of intestinal intussusception in the distal jejunum due to a 5 cm intraluminal polyp. Emergency laparotomy revealed a change in the distal jejunum caliber caused by the intussusception finding a 5 cm polypoid mass. We made an intestinal resection with a L-L anastomosis. Histopathological examination showed evidence of metastasis from dedifferentiated liposarcoma. Discussion A sarcoma is a malignant tumor, an infrequent type of cancer from connective tissue. The liposarcoma is the most frequent subtype and the dedifferentiated type can occur as dedifferentiation from other subtypes. The most common sites of metastasis include the lung, liver, and bone. Metastasis to the small bowel is rare with few reported cases. Intestinal intussusception is an infrequent cause of mechanical intestinal obstruction in adults. Etiology is diverse and it is often caused by benign lesions in the small bowel and malignant lesions in the colon. The diagnostic technique of choice is the CT scan with contrast and treatment usually requires surgery. Intestinal reduction is controversial because of the risk of perforation or tumor spread.

DISGUISED INGUINAL HERNIA

Abstract Introduction Liposarcomas are malignant neoplasms that originate in fatty mesenchymal tissue and are the most common histological subtype of soft tissue sarcomas. They account for 1% of solid tumors in adults and are located mainly in the extremities, with the retroperitoneum being the second most frequent location. Given the rarity and aggressiveness of these tumors, it is advisable to establish a multidisciplinary approach towards them in order to improve the prognosis of patients. Clinical case Patient who was operated upon on a scheduled and outpatient basis for a left inguinal hernia. During surgery, a preperitoneal tumor was identified that was removed and revealed a high-grade dedifferentiated liposarcoma. In a second surgical act, a tumor mass of about 10 centimeters in length was found, lodged in the left pelvis and contacting sigma, which extended into the inguinal duct and scrotal pouch. Finally, compartment surgery and a left orchiectomy with end-to-end colo-sigmoid anastomosis were performed. Discussion Routine examination of the masses contained in the hernial sacs is recommended since, despite their infrequency (<0.1%), cases of liposarcomas that have their origin in the inguinal canal have been described. Surgery for retroperitoneal sarcomas must be compartmental, which requires the inclusion of viscera close to the tumor in the resection. Complete surgical resection R0 is the only potentially curative treatment. Compartment surgery should be performed by expert surgeons in referral centers with multidisciplinary teams to improve the prognosis of these patients.

The Characteristics of magnetic resonance imaging and immunohistochemical findings in de-differentiated liposarcoma.

Radiological imaging in Dedifferentiated liposarcoma (DDLPS) often shows the coexistence of fatty and non-fatty solid components; however, it has been shown that when fatty components were not identified on magnetic resonance imaging (MRI), the diagnosis of DDLPS would not have been diagnosed if immunohistochemical (IHC) staining had not been performed. The aim of this study was to investigate the pattern of MRI and relationship between MRI and IHC findings in DDLPS. We retrospectively reviewed the cases of 25 patients with DDLPS. To identify the MRI spectrum of DDLPS, tumors were classified into the following four categories based on MRI findings: I = a well-defined fatty mass and juxtaposed well-defined non-fatty mass, II = a non-fatty component within a predominantly fatty mass, III = a focal fatty component within a large non-fatty mass, and IV = a non-fatty mass with atypical MRI findings. IHC staining for CDK4, MDM2, and p16 were evaluated. Category IV tumor was the most common tumor in this population. Of the 22 patients who underwent IHC staining, MDM2, CDK4, and p16 were positive in 21, 20, and 19 patients, respectively. MDM2 was positive in all 11 patients with category IV tumors; CDK4 and p 16 were positive in 10 and eight patients, respectively. There was no difference of survival between the patients with category I, II and III and category IV. DDLPS without fatty components on MRI scans was mostly found. We recommend IHC staining to screen for DDLPS even if the tumors in STS cases have a non-fatty component.

The Blubbery Addle- Dedifferentiated Liposarcoma

The Blubbery Addle- Dedifferentiated Liposarcoma

Paratesticular Dedifferentiated Liposarcoma with Rhabdomyoblastic Differentiation: A Case Report and Review of the Literature

Liposarcomas of the paratesticular tissue is a rare pathological entity. The symptoms are similar to inguinal hernias or hydroceles. We present the case of an 84-year-old man with a rare paratesticular liposarcoma that manifested as painless right hemiscrotal swelling. Testicular tumour markers were negative. Imaging revealed a heterogeneous mass with a fat component. He underwent a radical orchiectomy on the left side to remove the associated mass. This revealed dedifferentiated liposarcoma (DDLS) with rhabdomyoblastic differentiation and MDM2 amplification. The surgical margins were negative, and the patient had a metastatic workup that included magnetic resonance imaging (MRI) of the abdomen and pelvis. Because of the disease’s rarity, there is no clear agreement on radiotherapy and chemotherapy roles.

Targeting Autophagy With the Synergistic Combination of Chloroquine and Rapamycin as a Novel Effective Treatment for Well-differentiated Liposarcoma.

Liposarcoma is a type of soft-tissue sarcoma arising from fat tissue. It is relatively common among soft-tissue sarcomas. Chloroquine (CQ), an antimalarial drug, can inhibit autophagy and induce apoptosis in cancer cells. Rapamycin (RAPA) is an inhibitor of mTOR. The combination of RAPA and CQ is a strong inhibitor of autophagy. Previously, we showed that the combination of RAPA and CQ was effective against a de-differentiated liposarcoma patient-derived orthotopic xenograft (PDOX) mouse model. In the present study, we investigated the mechanism of efficacy of the combination of RAPA and CQ to target autophagy in a well-differentiated liposarcoma (WDLS) cell line in vitro. The human WDLS cell line 93T449 was used. The WST-8 assay was used to test the cytotoxicity of RAPA and CQ. Western blotting was used to detect microtubule-associated protein light chain 3-II (LC3-II) which is a component of autophagosomes. Immunostaining of LC3-II was also performed for autophagosome analysis. Τhe TUNEL assay was used to detect apoptotic cells, and apoptosis-positive cells were counted in three randomly selected microscopic fields for statistical validation. RAPA alone and CQ alone inhibited the viability of 93T449 cells. The combination of RAPA and CQ inhibited 93T449 cell viability significantly more than either drug alone and increased the number of autophagosomes which led to extensive apoptosis. The combination of RAPA and CQ increased the number of autophagosomes which led to apoptosis in 93T449 WDLS cells, suggesting novel effective treatment for this recalcitrant cancer by targeting autophagy.

Complete Resection of a Cavoatrial Metastatic Liposarcoma under Hypothermic Circulatory Arrest.

A patient underwent surgical resection twice for primary and metastatic dedifferentiated liposarcomas. Computed tomography revealed a tumor mass at the cavoatrial junction. Prompt surgical resection of the tumor with thrombectomy was successfully performed using cardiopulmonary bypass with hypothermic circulatory arrest. Despite the poor prognosis of metastatic or recurrent liposarcoma, the patient has survived for 8 years since the first tumor resection.

Hypopharyngeal dedifferentiated liposarcoma treated by endoscopic submucosal dissection.

A 73-year-old woman visited our institution because of tumor regurgitation. Barium esophagography revealed the long pedunculated lesion in the esophagus (Fig. 1a). Esophagogastroduodenoscopy (EGD) showed the lesion covered with normal mucosa (Fig. 1b). The lesion arose from the hypopharynx, and was completely dissociated from the esophagus. Because she was symptomatic, endoscopic submucosal dissection (ESD) with the use of esophagogastroduodenoscope and the needle- and scissors-type knives was performed under general anesthesia and the insertion of a curved rigid laryngoscope.

A case of cellulitis due to extensive invasion of a huge dedifferentiated liposarcoma

A case of cellulitis due to extensive invasion of a huge dedifferentiated liposarcoma

Which modality is better to diagnose high-grade transformation in retroperitoneal liposarcoma? Comparison of computed tomography, positron emission tomography, and magnetic resonance imaging.

Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775-0.984; p < 0.001), maximum standardized uptake value (SUVmax) of 2.9 (AUC = 0.865 95% CI 0.792-0.980; p < 0.001), while MRI failed to differentiate DDLS. The cutoff values for distinguishing FNCLCC grades 1 and 2/3 were a mean CT value of 24 HU (AUC = 0.858, 95% CI 0.731-0.985; p < 0.001) and SUVmax of 2.9 (AUC = 0.885, 95% CI 0.792-0.978; p < 0.001). MRI had no sufficient power to separate these grades. Contrast-enhanced CT and PET were useful for predicting DDLS and FNCLCC grade 2/3, while MRI was inferior to these two modalities.

Retroperitoneal liposarcoma with pancreatic metastasis and gastric cancer: a case report.

On computed tomography scanning, a 63-year-old man with vomiting and anorexia was discovered to have a mass in the pancreatic body and a retroperitoneal mass extending to the right lobe of the liver. An esophagogastroduodenoscopy revealed an advanced gastric carcinoma in the middle gastric body, and a biopsy specimen revealed a poorly differentiated adenocarcinoma. The pancreatic and retroperitoneal masses were considered metastatic lesions of gastric cancer, and a biopsy was taken from the pancreatic lesion using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The histology of the EUS-FNA pancreatic specimen revealed atypical spindle-shaped cells and increased stromal collagen fibrosis, and liposarcoma was considered. Conversely, a percutaneous ultrasound-guided biopsy was taken for the retroperitoneal lesion, and the histology revealed that it was a dedifferentiated liposarcoma. On the basis of histopathological and imaging findings, the retroperitoneal liposarcoma was identified as the primary lesion, the pancreatic lesion as a metastasis of the primary liposarcoma, and the gastric carcinoma as an independent tumor. As far as we know, there have only been three reports of metastatic pancreatic liposarcoma diagnosed via EUS-FNA. In this case, the patient also had gastric cancer, and EUS-FNA was helpful in differentiating metastatic pancreatic tumors from gastric cancer.

Lipidomics and Transcriptomics Differ Liposarcoma Differentiation Characteristics That Can Be Altered by Pentose Phosphate Pathway Intervention.

Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor's metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.

INSM1 Expression in Mesenchymal Tumors and Its Clinicopathological Significance.

Insulinoma-associated protein 1 (INSM1) has been identified as a nuclear marker of neuroendocrine tumors. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumor, its expression and clinicopathological significance in mesenchymal tumors remain unclear. We analyzed INSM1 mRNA level in GEO database and conducted immunohistological staining to detect the expression of INSM1 on 576 mesenchymal tumors from pathology department of Tongji Hospital. At transcription level, INSM1 expression in AITL (angioimmunoblastic T-cell lymphoma) was higher than their adjacent normal tissues as well as Hodgkin's lymphoma. Moreover, INSM1 expression in well-differentiated liposarcoma (WDLPS) was significantly higher than normal fat (P = 0.014) and dedifferentiated liposarcoma (DDLPS) (P = 0.0248). At protein level, the positive rate of INSM1 in AITL was 18/48 (47.4%), while in DDLPS was 9/20 (45%). INSM1 expression in AITL was significantly higher than Hodgkin's lymphoma (P = 0.008). And INSM1 expression in WDLPS was significantly lower than DDLPS (P = 0.015). The combination of GEO data and immunohistochemistry data indicated that the expression level of INSM1 was higher in AITL compared with normal control, suggesting that INSM1 may be involved in pathogenesis of AITL. The abnormal expression of INSM1 was found in WDLPS, and the positive rate of INSM1 was higher in DDLPS than in WDLPS. INSM1 may be involved in the regulation of liposarcoma development. There were significant differences in the expression of INSM1 between AITL and Hodgkin's lymphoma and WDLPS and DDLPS. These findings may assist in the differential diagnosis of these tumors when common markers are difficult to identify, enriching the diagnostic index system of mesenchymal tumors.

Genomic alterations and clinical outcomes in patients with dedifferentiated liposarcoma.

Patients with unresectable dedifferentiated liposarcoma (DDLPS) have poor overall outcomes. Few genomic alterations have been identified with limited therapeutic options. Patients treated at Levine Cancer Institute with DDLPS were identified. Next generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) testing were performed on tumor tissue collected at diagnosis or recurrence/progression. Confirmation of genomic alterations was performed by orthologous methods and correlated with clinical outcomes. Univariate Cox regression was used to identify genomic alterations associated with clinical outcomes. Thirty-eight DDLPS patients with adequate tissue for genomic profiling and clinical data were identified. Patient characteristics included: median age at diagnosis (66 years), race (84.2% Caucasian), and median follow-up time for the entire cohort was 12.1 years with a range from approximately 3.5months to 14.1 years. Genes involved in cell cycle regulation, including MDM2 (74%) CDK4 (65%), and CDKN2A (23%), were amplified along with WNT/Notch pathway markers: HMGA2, LGR5, MCL1, and CALR (19%-29%). While common gene mutations were identified, PDE4DIP and FOXO3 were also mutated in 47% and 34% of patients, respectively, neither of which have been previously reported. FOXO3 was associated with improved overall survival (OS) (HR 0.37; p=0.043) along with MAML2 (HR 0.30; p=0.040). Mutations that portended worse prognosis included RECQL4 (disease-specific survival HR 4.67; p=0.007), MN1 (OS HR=3.38; p=0.013), NOTCH1 (OS HR 2.28, p=0.086), and CNTRL (OS HR 2.42; p=0.090). This is one of the largest retrospective reports analyzing genomic aberrations in relation to clinical outcomes for patients with DDLPS. Our results suggest therapies targeting abnormalities should be explored and confirmation of prognostic markers is needed. Dedifferentiated liposarcoma is one of the most common subtypes of soft tissue sarcoma yet little is known of its molecular aberrations and possible impact on outcomes. The work presented here is an evaluation of genetic abnormalities among a population of patients with dedifferentiated liposarcoma and how they corresponded with survival and risk of metastases. There were notable gene mutations and amplifications commonly found, some of which had interesting prognostic implications.

Rare Ewingoid Dedifferentiated Liposarcoma of the Spermatic Cord Causing Testicular Artery Compression: A Case Report

Liposarcomas of the spermatic cord are rare and often clinically and histologically misdiagnosed, leading to ineffective management and poor outcomes. We present a case of metastatic dedifferentiated liposarcoma of the spermatic cord, which recurred after excision of a misdiagnosed well-differentiated liposarcoma 3 years prior. Due to its size and high-grade metastasis, the tumor was unresectable, leading to treatment with systemic chemotherapy. Complications arose including partial compression of the testicular artery and urethral obstruction secondary to local mass effect. Tumor biopsy was characterized by a unique immunohistochemical profile which helped to explain the unique processes leading to mass effect, vascular and urethral compression, and bilateral scrotal swelling. The patient’s family history of malignancy and 22/22q trisomy identified in the tumor biopsy were also interesting contributors. In conclusion, accurate diagnosis of spermatic cord tumors is essential for effective treatment, and further data collection is required to improve management of advanced metastatic disease.

Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2-p53 interaction has thus garnered interest as a therapeutic target for DDLPS and other malignancies. MDM2 binds p53 via a hydrophobic protein interaction that is easily accessible with synthetic analogues. Multiple agents have been developed, including Nutlins such as RG7112 and small molecular inhibitors including SAR405838 and HDM201. Preclinical in vitro and animal models have shown promising results with MDM2 inhibition, resulting in robust p53 reactivation and cancer cell death. However, multiple early-phase clinical trials have failed to show a benefit with MDM2 pathway inhibition for DDLPS. Mechanisms of resistance are being elucidated, and novel inhibitors and combination therapies are currently under investigation. This review provides an overview of these strategies for targeting MDM2 in DDLPS.

MRI findings to differentiate musculoskeletal dedifferentiated liposarcoma from atypical lipomatous tumor.

This study aimed to assess the efficacy of using MRI findings for differentiating musculoskeletal dedifferentiated liposarcoma (DDLP) from atypical lipomatous tumor (ALT). This study included 22 patients with histopathologically proven DDLP and 35 with ALT in the musculoskeletal areas. All DDLPs were immunohistochemically positive for MDM2. MRI findings for both pathologies were retrospectively reviewed and compared. The maximum lesion diameter was significantly lower in DDLPs than in ALTs (p < 0.01). Ill-defined margin, peritumoral edema, and tail sign were more frequently observed in DDLPs than in ALTs (p < 0.01, respectively). The fatty component was less frequently observed in DDLPs than in ALTs (27 vs. 100%; p < 0.01), whereas the non-fatty component was more frequently observed in DDLPs than in ALTs (100 vs. 11%; p < 0.01). The occupation rate by non-fatty components was significantly higher in DDLPs than in ALTs (p < 0.01). No significant differences were observed in imaging findings associated with fatty component; however, necrosis within the non-fatty component on the contrast-enhanced image was more frequently observed in DDLPs than in ALTs (72 vs. 0%, p < 0.05). DDLPs always had a non-fatty component, whereas ALTs always had fatty component. Ill-defined margin, peritumoral edema, tail sign, and necrosis within non-fatty components were useful MRI features for differentiating musculoskeletal DDLP from ALT.

Retrospective evaluation of the role of gemcitabine-docetaxel in well-differentiated and dedifferentiated liposarcoma.

Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS. All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups. Sixty-five WDLPS/DDLPS patients were included. Seven patients (10.8%) received a gemcitabine-based regimen more than once, totaling 72 treatments. The median age at the start of treatment was 66 years (range 32-80 years). Sixty-five (90.3%) regimens were gemcitabine-docetaxel, and 7 (9.7%) were gemcitabine alone. Majorities of treatments were for disease that was recurrent/metastatic (86.1%), was abdominal/retroperitoneal (83.3%), and had DDLPS components (88.9%), while 25.0% of treatments were for multifocal disease. The overall response rate was 9.7% (7/72). All responses were in patients with documented DDLPS. The median time to progression was 9.2months (95% CI 5.3-12.3months). The median overall survival from the start of therapy was 18.8months (95% CI 13.1-32.4months). Gemcitabine-docetaxel is an efficacious second-line treatment for DDLPS. Though cross study comparisons are not advisable, response to gemcitabine-docetaxel compares favorably to current standard options trabectedin and eribulin. This combination is a valid comparator arm for future second-line trials in DDLPS.

Transcriptome analysis identifies TODL as a novel lncRNA associated with proliferation, differentiation, and tumorigenesis in liposarcoma through FOXM1

Liposarcoma, the most common soft tissue sarcoma, is a group of fat cell mesenchymal tumors with different histological subtypes. The dysregulation of long non-coding RNAs (lncRNAs) has been observed in human cancers including a few studies in sarcoma. However, the global transcriptome analysis and potential role of lncRNAs remain unexplored in liposarcoma. The present investigation uncovers the transcriptomic profile of liposarcoma by RNA sequencing to gain insight into the global transcriptional changes in liposarcoma. Our RNA sequencing analysis has identified that many oncogenic lncRNAs are differentially expressed in different subtypes of liposarcoma including MALAT1, PVT1, SNHG15, LINC00152, and MIR210HG. Importantly, we identified a highly overexpressed, unannotated, and novel lncRNA in dedifferentiated liposarcomas. We have named it TODL, transcript overexpressed in dedifferentiated liposarcoma. TODL lncRNA displayed significantly higher expression in dedifferentiated liposarcoma cell lines and patient samples. Interestingly, functional studies revealed that TODL lncRNA has an oncogenic function in liposarcoma cells by regulating proliferation, cell cycle, apoptosis, differentiation, and tumorigenesis in the murine model. Silencing of TODL lncRNA highlighted the enrichment of several key oncogenic signaling pathways including cell cycle, transcriptional misregulation, FOXM1 network, p53 signaling, PLK1 signaling, FoxO, and signaling Aurora signaling pathways. RNA pull-down assay revealed the binding of TODL lncRNA with FOXM1, an oncogenic transcription factor, and the key regulator of the cell cycle. Silencing of TODL lncRNA also induces adipogenesis in dedifferentiated liposarcomas. Altogether, our finding indicates that TODL could be utilized as a novel, specific diagnostic biomarker, and a pharmacological target for therapeutic development in controlling aggressive and metastatic dedifferentiated liposarcomas.

The Immune Contexture of Liposarcoma and Its Clinical Implications.

Simple SummaryLiposarcomas (LPS) are malignancies arising from adipose tissue. Based on the histological appearance, five subtypes are distinguished: well-differentiated LPS, dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), pleomorphic LPS, and myxoid pleomorphic LPS. Immune cells can infiltrate the tumor microenvironment (TME) of LPS and can either promote an efficient antitumor immune response or mediate immunosuppression paving the way for immune evasion of the tumor. The LPS subtypes display different TME characteristics and vary in regard to immune cell infiltration, ranging from the generally lowly infiltrated MLPS to the highly infiltrated DDLPS where immunological determinants predict response to novel antibody-based immunotherapy. Thus, immune cells in the TME can significantly affect response to therapy, disease progression, and patient survival. This review aims to decipher the immune contexture of LPS as well as its clinical association and highlights differences between the LPS subtypes that may have implications for the design of novel treatment strategies.Liposarcomas (LPS) are the most frequent malignancies in the soft tissue sarcoma family and consist of five distinctive histological subtypes, termed well-differentiated LPS, dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), pleomorphic LPS, and myxoid pleomorphic LPS. They display variations in genetic alterations, clinical behavior, and prognostic course. While accumulating evidence implicates a crucial role of the tumor immune contexture in shaping the response to anticancer treatments, the immunological landscape of LPS is highly variable across different subtypes. Thus, DDLPS is characterized by a higher abundance of infiltrating T cells, yet the opposite was reported for MLPS. Interestingly, a recent study indicated that the frequency of pre-existing T cells in soft tissue sarcomas has a predictive value for immune checkpoint inhibitor (CPI) therapy. Additionally, B cells and tertiary lymphoid structures were identified as potential biomarkers for the clinical outcome of LPS patients and response to CPI therapy. Furthermore, it was demonstrated that macrophages, predominantly of M2 polarization, are frequently associated with poor prognosis. An improved understanding of the complex LPS immune contexture enables the design and refinement of novel immunotherapeutic approaches. Here, we summarize recent studies focusing on the clinicopathological, genetic, and immunological determinants of LPS.