Liposarcoma Research Articles

LDH and hemoglobin outperform systemic inflammatory indices as prognostic factors in patients with soft tissue sarcoma undergoing neoadjuvant treatment

BackgroundThe current understanding of the prognostic value of routine pre-treatment laboratory parameters in patients with high-risk soft tissue sarcoma (HR-STS) is limited. We sought to analyze several inflammatory biomarkers in a large cohort of HR-STS patients undergoing neoadjuvant therapy followed by curative surgical resection.Methods123 patients with locally advanced high-risk undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), and synovial sarcoma (SS) who underwent preoperative chemotherapy and regional hyperthermia (RHT) between 2014 and 2022 were retrospectively evaluated. The association of several pre-treatment laboratory parameters with radiologic treatment response, event-free survival (EFS), and overall survival (OS), were analyzed.ResultsLow pre-treatment hemoglobin (HR 2.51, p = 0.018; HR 2.78, p = 0.030) and lactate dehydrogenase (LDH, HR 0.29, p = 0.0044; HR 0.23, p = 0.010) were significantly associated with EFS and OS in the multivariable analysis. Systemic inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR) did not have a significant impact on survival. Low C-reactive protein (CRP) and high albumin values were associated with poor radiologic response according to RECIST (p = 0.021 and p = 0.010, respectively).ConclusionPre-treatment LDH and hemoglobin are strong independent predictors of survival in HR-STS patients. Systemic inflammatory indices based on circulating immune cells may not serve as reliable prognostic factors for HR-STS patients undergoing curative-intent treatment. Higher pre-treatment albumin levels and lower CRP values may reflect a reduced inflammatory status and could be associated with a poorer radiologic response to preoperative treatment.

Aged mice overexpressing cellular repressor of E1A-stimulated genes 1 in adipose tissues exhibited increased liposarcoma incidence and shortened lifespan.

Aged mice overexpressing cellular repressor of E1A-stimulated genes 1 in adipose tissues exhibited increased liposarcoma incidence and shortened lifespan.

Differentiation of Atypical Lipomatous Tumors from Lipomas: Our Experience with Visual Analysis of Conventional Magnetic Resonance Imaging.

Differentiating atypical lipomatous tumors (ALTs) from lipomas using imaging techniques is a challenge, and the biopsy with immunohistochemical determination of murine double minute 2 (MDM2) oncogene is the gold standard. We are looking for a management algorithm with the visual analysis of magnetic resonance images in these two fatty soft tissue tumors that allow us to avoid some biopsies. Two radiologists, blinded to the final diagnosis, independently assessed various features on conventional magnetic resonance imaging (MRI), in 79 patients with pathologically confirmed fatty tumors as either lipoma (MDM2 negative) or ALT (MDM2 positive). Results: The interobserver agreement for the most MRI features was moderate and the musculoskeletal radiologist accuracy for final diagnosis was 90% sensitivity and 66% specificity. Tumors with homogeneous fat signals and a maximum size < 8 cm were always lipomas (p < 0.001), and the tumors with septa thickness ≥ 2 mm, or more than one non-fat nodule, and a maximum size ≥ 12.8 cm were typically ALTs. While those tumors with septa < 2 mm or one non-fat nodule, independently of maximum size, the diagnosis of lipoma versus ALT is uncertain and a biopsy is required.

Epigenetic dysregulation of metabolic programs mediates liposarcoma cell plasticity.

Sarcomas are rare connective tissue cancers thought to arise from aberrant mesenchymal stem cell (MSC) differentiation. Liposarcoma (LPS) holds valuable insights into dysfunctional differentiation given its well- and dedifferentiated histologic subtypes (WDLPS, DDLPS). Despite well-established differences in histology and clinical behavior, the molecular pathways underlying each subtype are poorly understood. Here, we performed single-nucleus multiome sequencing and spatial profiling on carefully curated human LPS samples and found defects in adipocyte-specific differentiation within LPS. Loss of insulin-like growth factor 1 (IGF1) and gain of cellular programs related to early mesenchymal development and glucagon-like peptide-1 (GLP-1)-induced insulin secretion are primary features of DDLPS. IGF1 loss was associated with worse overall survival in LPS patients. Through in vitro stimulation of the IGF1 pathway, we identified that DDLPS cells are deficient in the adipose-specific PPARG isoform 2 (PPARG2). Defects in IGF1/PPARG2 signaling in DDLPS led to a block in differentiation that could not be fully overcome with the addition of exogenous IGF1 or the pro-adipogenic agonists to PPARG and GLP-1. However, we noted upregulation of the IGF1 receptor (IGF1R) in the setting of IGF1 deficiency, which promoted sensitivity to an IGF1R-targeted antibody-drug conjugate that may serve as a novel therapeutic strategy in LPS. In summary, lineage-specific defects in adipogenesis drive dedifferentiation in LPS and may translate into selective therapeutic targeting in this disease.

Management Algorithm for Atypical Lipomatous Tumours: A Retrospective Case Series.

Atypical lipomatous tumours (ALTs), or low-grade well-differentiated liposarcomas (WDLs), can be identified using radiological complex septations and histological atypia. In our view, this is a confusing name that underestimates the risk of local recurrence of such tumours. Defining a management algorithm for differentiating a lipoma from an ALT is important for considering the best management of these patients. This study aims to evaluate the clinical, radiological, and histological features of ALT presentation and propose a management algorithm for these lesions. A retrospective case series of a prospectively maintained database at Tallaght University Hospital, Dublin, Ireland was carried out on all patients with ALTs from 2013 to 2019. The group demographics, tumour characteristics, radiological features, treatment, and recurrence were described. From 2013 to 2019, 607 lipomatous tumours were resected; 40 lesions in 37 patients were classified as ALTs.The mean age of this subgroup of patients was 56.15 ± 13.64 years (range: 25-83 years). The most common location was the lower limb. All patients underwent clinical, radiological, and histological workups prior to surgery. Angio-embolisation prior to surgery was required in two (5%) patients; three (7.5%) patients developed local recurrence requiring a second surgical resection. Characteristics of ALTs and a management algorithm are proposed. It is important for a practitioner to differentiate a suspected ALT from a lipoma. Increased intratumoural vascularity and septation in ALT are reflected in the MRI findings and may play a key role in the acquisition of a malignant phenotype in adipocytic tumours. The proposed management algorithm for these lesions aims to help stratify these subcutaneous lesions.

Group IV Bimetallic MOFs Engineering Enhanced Metabolic Profiles Co-Predict Liposarcoma Recognition and Classification.

The rarity and heterogeneity of liposarcomas (LPS) pose significant challenges in their diagnosis and management. In this work, a series of metal-organic frameworks (MOFs) engineering is designed and implemented. Through comprehensive characterization and performance evaluations, such as stability, thermal-driven desorption efficiency, as well as energy- and charge-transfer capacity, the engineering of group IV bimetallic MOFs emerges as particularly noteworthy. This is especially true for their derivative products, which exhibit superior performance across a range of laser desorption/ionization mass spectrometry (LDI MS) performance tests, including those involving practical sample assessments. The top-performing product is utilized to enable high-throughput recording of LPS metabolic fingerprints (PMFs) within seconds using LDI MS. With machine learning on PMFs, both the LPSrecognizer and LPSclassifier are developed, achieving accurate recognition and classification of LPS with area under the curves (AUCs) of 0.900-1.000. Simplified versions are also developed of the LPSrecognizer and LPSclassifier by screening metabolic biomarker panels, achieving considerable predictive performance, and conducting basic pathway exploration. The work highlights the MOFs engineering for the matrix design and their potential application in developing metabolic analysis and screening tools for rare diseases in clinical settings.

A Well-Differentiated Liposarcoma with History of Benign Prostatic: A Case Report

Liposarcoma, a malignant tumor originating from fat cells, is a rare occurrence in the retroperitoneal region. Surgical resection is the standard method for treating this cancer. This type of tumor is classified into common subtypes, which include well-differentiated liposarcoma and dedifferentiated liposarcoma. A 53-year-old male patient presented with lower left quadrant (LLQ) pain and melena for two weeks. Further diagnostic evaluation, including colonoscopy, revealed a 50 mm polyp in the hepatic flexure or distal of the ascending colon. The pathological assessment of the mass demonstrated a lipomatous lesion with a nuclear atypical lipomatous tumor, which was diagnosed as well-differentiated liposarcoma. The patient underwent surgical treatment and was discharged following his recovery.

Atypical large congenital lipoma of the scalp: Case report of a 7-month-old infant

Atypical large congenital lipoma of the scalp: Case report of a 7-month-old infant

[Translated article] Epidemiology of musculoskeletal tumors in a reference unit

[Translated article] Epidemiology of musculoskeletal tumors in a reference unit

Dedifferentiated Liposarcoma of the Parotid Gland: A Rare Presentation.

Dedifferentiated liposarcoma (DDLPS) is a nonlipogenic sarcoma arising in association with well-differentiated liposarcoma (LPS), and represents 10% of liposarcomas. Most of the cases of dedifferentiated liposarcoma arise in the retroperitoneal region, followed by deep soft tissue of the extremities, trunk, mediastinum, spermatic cord, and the head and neck region. We report a case of a 35 year old male patient who had DDLPS of the left parotid gland.

Liposarcoma: A Journey into a Rare Tumor's Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies.

Sarcomas are a heterogeneous group of neoplasms that develop from bone and soft tissue. Approximately 80% of sarcomas affect soft tissue, with liposarcoma being one of the most common types, accounting for approximately 13-20% of all soft-tissue sarcomas. Per the World Health Organization, liposarcoma can be broadly classified into four different subtypes based on histologic examination: well-differentiated liposarcoma (WDLS)/atypical lipomatous tumors (ALT), dedifferentiated liposarcoma (DDLS), myxoid liposarcoma (MLS), and pleomorphic liposarcoma (PLS). WDLS/ALT is the most common liposarcoma subtype, accounting for approximately 31-33% of liposarcomas; DDLS accounts for 20%; MLS accounts for 19%; and PLS, the least common subtype, represents 7-8% of liposarcomas. Sarcoma diagnosis is challenging because of its rarity, intrinsic complexity, and diagnostic technological complexity. Sarcomas are misdiagnosed in approximately 30% of cases, leading to delays in diagnosis and access to appropriate therapy and clinical trials. Furthermore, treatment options are limited for those diagnosed with liposarcoma. This review discusses the epidemiology, pathology, and treatment options currently available for liposarcoma.

Intracranial pleomorphic liposarcoma misclassified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier: illustrative case.

Recently, it has been shown that DNA methylation arrays and German Cancer Research Center (Deutsches Krebsforschungszentrum) methylation classifiers are useful aids in brain tumor diagnosis for cases in which histopathological diagnosis is difficult. However, not enough is known about diagnostic aids for intracranial liposarcoma (LPS). An 18-year-old woman with a history of natural killer/T-cell lymphoma, which had been treated with a bone marrow transplant and total body irradiation at age 11 years, presented with diplopia. Magnetic resonance imaging revealed a brain tumor in the posterior left temporal lobe, which was removed by craniotomy. The tumor was initially diagnosed as pleomorphic xanthoastrocytoma through histopathological and DNA methylation examination. She also had a soft tissue tumor in her left thigh, which was removed. It contained spindle cells with oval nuclei and highly pleomorphic cells and was diagnosed as radiation-induced LPS. Histopathological re-examination of the brain tumor led to a final diagnosis of pleomorphic LPS. In this report, the authors describe the case of a patient with an intracranial pleomorphic LPS that was initially classified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier. Although DNA methylation classifiers are useful as diagnostic aids in cases in which definitive pathology is difficult to determine, there is a risk of misdiagnosis in some types of tumors. https://thejns.org/doi/10.3171/CASE24465.

Hounsfield Unit on Preoperative Computed Tomography as an Indicator of Prognosis in Patients with Liposarcoma.

Liposarcoma (LPS) is classified into 4 subtypes. As some subtypes have a high recurrence rate, knowing the risk of recurrence before surgery is important. Here, we aimed to investigate the relationship between Hounsfield units (HU) derived from preoperative computed tomography (CT) and the prognosis of patients undergoing surgery. We included 32 patients who underwent surgery for LPS between 2014 and 2022. Preoperative plain CT images were collected, and the HU value of each LPS was measured. The association between 2 HU categories (HU < cut-off vs. ≥ cut-off) and clinical variables was assessed. The optimal cut-off value was determined using statistical methods. We used the Kaplan-Meier method to determine the differences between the 2 HU categories at 2 endpoints: recurrence-free survival (RFS) and overall survival (OS). The dedifferentiated subtype showed significantly higher HU values than the other subtypes (P < .001). The optimal cut-off value for HU was 20. HU < 20 was associated with young age, low-performance status, low Charlson Comorbidity Index, and well-differentiated pathology. The Kaplan-Meier curves demonstrated that RFS and OS were significantly shorter in patients with HU ≥ 20 than in those with HU < 20 (P = .007 and .04, respectively). However, when stratified based on subtype, no significant differences were observed between dedifferentiated and other subtypes. HU ≥ 20 on preoperative CT was associated with poor prognosis in LPS patients. Our findings suggest that preoperative CT-derived HU values may serve as useful predictors of prognosis.

MDM2 Testing In Lipomatous Tumors: An Institutional Experience with 1,161 Neoplasms

Abstract Introduction/Objective Amplifications of the MDM2 gene is a well-recognized central molecular event in atypical lipomatous tumors, well-differentiated liposarcomas, and dedifferentiated liposarcomas. However, given the fact that most adipocytic neoplasms are benign, the specific testing approaches that will maximize the detection of MDM2 amplified tumors in an accurate and cost-efficient manner remains unclear. The purpose of this study is to present our experience with MDM2 testing by FISH in a large cohort of lipomatous neoplasms. Methods/Case Report The pathologic database of an academic medical center was queried for all lipomatous tumors as well as all tumors for which MDM2 testing was performed during a three-year period. At our center, MDM2 testing for well differentiated adipocytic neoplasms is triggered by the so-called “traditional criteria”: a deep tumor and/or tumor size &amp;gt;10 cm and/or recurrence. We also take an expanded approach for a variety of indications that may include equivocal atypia or clinical/imaging concern, among others. Testing is also performed on overt malignancies for which dedifferentiated liposarcoma is a plausible consideration after review of morphologic features. Clinicopathologic data, including patient age of diagnosis, tumor size, depth of tumor, results from MDM2 testing [when performed], anatomic location(s) and recurrence [where applicable], were collected for each patient. Results (if a Case Study enter NA) 1161 cases were assessed, 456 of whom underwent MDM2 testing, and 108 of which were ultimately classified as MDM2 amplified. Standardized bivariable comparisons found that a deep tumor location (p=0.0014) and older age (p=0.0002), but not tumor size at the &amp;gt;10 cm cut off were associated with MDM2 positivity. However, a logistic regression model showed that neither size, depth or age were significantly associated with MDM2 positivity. Among the MDM2-positive cohort, 91% had tumor sizes &amp;lt;10 cm, 14% were superficial, 23% were non-recurrent and 15% were less than the median cohort patient age of 58 years. If the aforementioned “traditional criteria” were used as the sole basis for MDM2 testing, 50 (46.29%) of the 108 cases that were ultimately classified as MDM2 positive would not have been tested. Conclusion Our findings suggest that a strict adherence to “traditional criteria” may result in a significant subset of MDM2 positive tumors not being tested in lipomatous tumors. A more expansive approach that incorporates additional indications for testing, should be evaluated.

Solitary fibrous tumor of the stomach

Abstract Introduction/Objective Solitary fibrous tumor (SFT) is an uncommon fibroblastic tumor that originates from the mesenchymal tissue. It has been rarely reported within the stomach. None of these reported tumors have occurred in a background of autoimmune atrophic gastritis as was seen in our patient. Methods/Case Report Case report Results (if a Case Study enter NA) An 85-year-old female with history of anemia and autoimmune atrophic gastritis presented with two-month history of dysphagia and abdominal discomfort. Upper gastrointestinal endoscopy showed a 1 cm subepithelial lesion in the gastric body along the greater curvature. Upper endoscopic ultrasound showed mildly hypoechoic lesion in the submucosa of the stomach with the differential of leiomyoma, neuroendocrine tumor, gastrointestinal stromal tumor, and an atypical looking lipoma. The entire gastric lesion was lifted with submucosal saline injection and then resected using cap endoscopic mucosal resection (EMR) snare cautery. Gross examination showed a well-circumscribed lesion with firm, tan-white cut surface. On microscopy, a bland appearing spindle cell proliferation within a collagenous stroma was seen with alternating hypercellular and hypocellular areas and few dilated vessels. No significant mitosis, nuclear pleomorphism or necrosis was identified. Immunohistochemical stains were performed and the lesional cells were positive for STAT6. Markers for gastrointestinal stromal tumor (CD117, DOG1), smooth muscle tumor (desmin, smooth muscle actin) and schwannoma (S100, SOX10) were negative. Nuclear staining for STAT6 is a sensitive and specific marker for SFTs. This particular SFT was considered to be of low risk and non-malignant considering its small size, lack of mitotic activity and tumor necrosis. The etiology for SFT is not entirely clear but molecular studies have shown that the NAB2::STAT6 translocation in a spindle cell neoplasm is a diagnostic hallmark for SFTs. Conclusion Solitary fibrous tumors have been rarely reported within the stomach. Complete surgical resection with negative margins is the mainstay of treatment as they may recur after an incomplete resection.

A Case of Recurrent Atypical Lipomatous Tumor.

A Case of Recurrent Atypical Lipomatous Tumor.

Characterizing the Transformation and Diagnosis of Atypical Lipomatous Tumor to Dedifferentiated Liposarcoma: Single Institutional Outcomes.

Atypical lipomatous tumor (ALT) in the extremities is a locally aggressive adipocytic tumor with the potential risk of transformation into dedifferentiated liposarcoma (DDLS). Studies seldom differentiate whether DDLS was diagnosed on initial biopsy, final resected specimen, or subsequent recurrence. Our study seeks to characterize how and when patients received their ALT or DDLS diagnoses to better understand the relationship between the two neoplasms. We performed a retrospective review of patients diagnosed with ALT or DDLS of the extremities. Clinical characteristics, including the method of diagnosis of an ALT or DDLS, time between diagnoses, and tumor recurrence was recorded. Univariate/multivariate analysis was performed to identify risk factors. Forty-five patients were diagnosed with ALT after core needle biopsy (CNB) and 41 of them received marginal en bloc excision. Three (7.3%) of these patients had a heterogeneous tumor on final resection, pathology revealed both ALT and DDLS. Four patients (8.2%) were diagnosed with DDLS from CNB and received negative margin en bloc excision. One of these tumors was identified as heterogeneous ALT/DDLS after resection. Fifty-three patients received marginal en bloc resection without CNB after a benign lipomatous mass was suspected on CT/MRI. Among these, one (1.9%) had a tumor with a heterogeneous composition of both ALT and DDLS on pathology. There were 11 (11.7%) ALT recurrences and 1 (1.0%) DDLS recurrence after ALT resection. Obtaining a proper diagnosis whether ALT or DDLS is critical. Our cohort found that amongst those concerning lipomatous lesions biopsied, 7.84% will show biopsy proven DDLS. Additionally, 6.67% of the biopsies will be false negatives and show DDLS on final pathology. Furthermore, our local recurrence for ALT was 11.7% recurring as ALT and 1.0% recurring as DDLS.

Deciphering the prognostic and therapeutic significance of BAG1 and BAG2 for predicting distinct survival outcome and effects on liposarcoma

Liposarcoma (LPS) is the second most common kind of soft tissue sarcoma, and a heterogeneous malignant tumor derived from adipose tissue. Up to now, the prognostic value of BAG1 or BAG2 in LPS has not been defined yet. Expression profiling data of LPS patients were collected from TCGA and GEO database. Survival curves were plotted to verify the outcome differences of patients based on BAG1 or BAG2 expression. Univariate and multivariate Cox regression models were used to analyze the prognostic ability of BAG1 or BAG2. Chaperone’s regulators BAG1 and BAG2 were identified as prognostic biomarkers for LPS patients, which exhibited distinct expression patterns and survival outcome prediction performances. Patients with high BAG2 expression and/or low BAG1 expression had worse prognosis. Enrichment analysis showed that BAG1 was involved in negative regulation of TGF-β signaling. Low expression of BAG1 was associated with high abundance of regulatory T cells (Tregs). The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.

Burden of liposarcoma on patients in the United States and their unmet needs: Interim survey results.

255 Background: Liposarcomas (LPS) are rare tumors that are among the most common soft tissue sarcomas (STS) worldwide. In the US, the incidence rate of LPS is increasing. The variable clinical presentation, prognosis, and response to treatment for the LPS subtypes coupled with the lack of substantial changes to systemic therapy for STS since the 1970s highlight the challenges for patients (pts) in seeking accurate diagnosis and treatment. Data on the impact of LPS on the quality of life (QoL) of pts and their caregivers are limited. Here we present interim results of a survey conducted to help understand the burden of LPS on pts in the US, their diagnostic journey, and the impact on their QoL. Methods: Pts with LPS aged ≥18 years and residing in the US completed an online survey on their experiences with the diagnostic journey, burden of disease and treatment, QoL, and sources of support. Survey enrollment is ongoing. A descriptive statistical analysis was performed. Results: Of 40 pts who completed the survey between 4 Aug 2023 and 1 Mar 2024, 83% were white and 58% lived in a suburban area. Most pts (60%) had employer-provided insurance, and 13% had an individual insurance plan. Collectively, the pts consulted at least 7 types of specialists for initial symptoms and concerns. Most (n=16) consulted with an internal medicine practitioner first and 10 with an oncologist first; many consulted with oncologists second (n=14) or third (n=10). Most pts (60%) were diagnosed by a surgeon or an oncologist. Nearly one third (n=12) of pts were unsure of their LPS stage at diagnosis; 8 noted that it was not discussed. At the time of completing the survey, 53% of pts were in remission and 18% were unsure of their stage. Approximately 25% of pts needed to travel more than 1.5 hours for treatment. In addition, 25% of pts noted that treatment did not improve their QoL. Patients’ greatest concerns about the impact of LPS were physical condition (73%) and financial aspects (53%). Over half of the pts (55%) reported that there were activities they could no longer perform because of LPS. Pts were most comfortable asking their physicians questions related to LPS, followed by physician assistants. Most pts found support resources through Facebook groups and specialists, reporting peer-to-peer support (48%), financial assistance (30%), and mental health resources (28%) as the most useful types of support. Conclusions: The interim findings of this survey underscore the challenges that pts with LPS face while navigating the healthcare system. Consultation of numerous specialists and travel time to receive treatment impact access to timely diagnosis and quality care. The impacts of LPS on QoL and finances were also key unmet needs experienced by pts, which supports an increase in QoL and financial support resources for pts. There is also a need for increased awareness among physicians about LPS and the impact on pts’ QoL as well as for effective treatments that improve QoL.

Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI

Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI