Liposarcoma Research Articles

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

As differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility. Three study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists. The validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85). The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics. Hanarth fonds.

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor: A Review and Update.

Atypical spindle cell/pleomorphic lipomatous tumor (ASCPLT) is a rare and recently described adipocytic neoplasm that primarily occurs in the subcutis of the limbs and limb girdles, particularly of middle-aged adults. It has locally recurrent potential if incompletely excised but no risk for distant metastasis. ASCPLT is histologically similar to spindle cell/pleomorphic lipoma and atypical lipomatous tumor and shows a mixture of atypical spindle cells, adipocytes, lipoblasts, floret-like multinucleated giant cells, and/or pleomorphic cells. It has been recently recognized that ASCPLT can undergo sarcomatous transformation. However, the biological significance of morphological sarcomatous transformation in ASCPLT remains uncertain. Immunohistochemically, the tumor cells show variable expression of CD34, S-100 protein, and desmin. Loss of nuclear Rb expression is observed in the majority of cases. ASCPLT lacks MDM2 gene amplification but can show RB1 gene deletion in a significant subset of cases. Complete surgical excision is the treatment of choice. This review provides an overview of the current knowledge on the clinicoradiological features, pathogenesis, histopathology, and treatment of ASCPLT. In addition, we will discuss the differential diagnosis of this new entity.

Unveiling spindle cell lipoma: a radiological case report

BackgroundSpindle cell lipoma is a benign adipocytic tumour, commonly occuring in the subcutis of posterior neck, upper back and shoulder, particularly in middle aged males. It is often composed of relatively equal ratio of fat and spindle cells, yet either component may predominate. Because of its variable ratio, a spindle cell lipoma may mimic liposarcoma radiologically. This article aimed to describe the MRI characteristics that assist in diagnosing spindle cell lipoma.Case presentation:A 45-year-old female presented with a gradually progressive neck swelling along the posterior aspect over a period of 2 years. Physical examination revealed a firm, mobile, non-tender mass in the left suboccipital region. Radiographic imaging showed a well-defined heterogeneous, minimally enhancing soft tissue swelling with areas of macroscopic fat and multiple macrocalcifications in the left suboccipital region extending to the left parapharyngeal space, showing loss of fat plane with adjacent muscles. Differential diagnoses of soft tissue neoplasms such as atypical lipoma and low-grade liposarcoma were considered. Surgical excision confirmed a myxoid variant of spindle cell lipoma upon histopathological examination.ConclusionSpindle cell lipomas, commonly found in the posterior neck, have varied imaging features that are not distinctive. Despite their non-specific nature, radiologists should recognize these features, as the tumor can be treated effectively with simple excision. When encountering a well-defined, complex fatty mass in the subcutaneous tissue of the posterior neck, consider a diagnostic possibility of spindle cell lipoma.

SP9.10 - The Sarcoma Hub and Spoke Diagnostic Service Can be Safely and Effectively Rolled-Out and Continued

Abstract Aims To understand the safety and effectiveness of the newly established Sarcoma Hub and Spoke Service (SHSS) in detecting malignancies through assessment of the performance of one Spoke Service in triaging lesions of concern. Methods Patients referred to our Diagnostic Service on the 2 week-wait pathway (2WW) and have had their lesion(s) of interest removed between an 18-month period were identified from our Hospital Information System. Data was collected for post-op histology, suspicion of diagnosis in the pre-op MDT, compatibility between the two, and whether patient was cleared from suspicion of malignancy before removal of the lesion. Results 119 patients meeting the criteria were identified. 90 had been cleared of suspicion for malignancy prior to surgery. 83/90 of these had samples sent for histology, yielding 82 benign and 1 malignant (dermatofibrosarcoma protruberans) results. Of the 29 patients who had excision biopsy on the 2WW, 5/29 returned histology for risk of (e.g. possible sarcoma or atypical lipoma) or confirmed malignancies. 46/119 cases were discussed at our SHSS MDT and have both pre-op MDT diagnosis records and histology results; 37/46 of these were compatible – all correctly predicted benign pathologies. Where pre-op MDT diagnosis and histology were incompatible, 1/9 predicted benign diagnosis but returned malignant histology. Conclusion Our SHSS Diagnostic Service’s process of triaging lesions concerning for sarcoma, including our MDT and surgical excision biopsies, is accurate. Preliminary data shows that the Sarcoma Hub and Spoke Service is a safe way to aid in diagnosing or ruling out soft tissue sarcoma.

Growth Rate and Outcomes in Locally Recurrent Extremity and Truncal Soft Tissue Sarcoma.

Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS). To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS. This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024. Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation. The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk. The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P < .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P < .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P < .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.

Clinical features and surgical strategy of retroperitoneal liposarcoma involving the kidney capsule: a retrospective comparative cohort study.

Valid and generalizable data on the clinical features and surgical strategies for retroperitoneal liposarcoma (LPS) involving the kidney capsule remain scarce. This study aimed to investigate the clinical characteristics, morbidity, mortality, and long-term survival of patients with retroperitoneal LPS involving the kidney capsule. The authors analyzed a prospectively maintained database of patients who underwent surgical resection for retroperitoneal LPS between 2015 and 2020. The patients were categorized into kidney capsule or no kidney capsule groups based on the presence or absence of kidney capsule involvement. A kidney-sparing strategy for retroperitoneal LPS involving the kidney capsule was developed. The primary outcome measure was overall survival (OS). The cumulative event probability curve was estimated using the Kaplan-Meier, and differences between groups using the Log-Rank. The study population consisted of 128 patients-54 with and 74 without kidney capsule involvement. Of these patients, 70 were female (54.7%) and 58 were male (45.3%), with a median age of 55. The median follow-up duration was 35 months. Postoperative morbidity, mortality, length of hospital stay, length of ICU stay, OS, and recurrence-free survival (RFS) did not differ significantly between the groups. Eleven patients developed postoperative acute kidney injury (AKI), and one patient required dialysis during the follow-up period. In multivariable logistic regression analysis, only nephrectomy was independently associated with postoperative AKI. Subgroup analysis of patients with kidney capsule involvement showed that nephrectomy did not improve OS or RFS but significantly decreased postoperative estimated glomerular filtration rate. Nephrectomy was associated with an increased risk of postoperative AKI after retroperitoneal LPS resection. A kidney-sparing strategy for retroperitoneal LPS involving the kidney capsule achieved optimal clinical outcomes.

Diagnostic Accuracy of Immunohistochemical Expression of p16, MDM2, and CDK4 in Well-Differentiated and De-Differentiated Liposarcoma in MDM2 Fluorescent in situ Hybridisation Confirmed Cases.

To establish the diagnostic utility of immunohistochemistry markers p16 along with MDM2 and CDK-4 in confirming the diagnosis of well-differentiated and de-differentiated liposarcoma while taking Fluorescent in situ Hybridisation (FISH) as a gold standard. A cross-sectional study. Place and Duration of the Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from 30th January 2022 to 30th June 2023. A standard panel of three immunohistochemistry markers p16, MDM2, and CDK4 were applied to 36 cases of atypical lipomatous tumours, well-differentiated liposarcoma (WDLPS), and de-differentiated liposarcoma (DDLPS), on which the gold standard FISH was already performed. The sample size was calculated with the help of a WHO calculator taking prevalence 1-2% in Pakistani population. Qualitative variables such as gender and site of tumour were presented by calculating frequency and percentages and comparison of Immunohistochemistry results with FISH was done by using a 2x2 table. The sensitivity and specificity of this triple marker panel for detecting WDLPS/DDLPS were 43.47% and 15.38%, respectively. The sensitivity and specificity of CDK4 for detecting WDLPS / DDLPS were 82.6% and 15.4%, those of MDM2 were 73.9% and 61.5 %, and those of p16 were 60.9% and 53.8%, respectively. Among all three markers, CDK4 was the most sensitive and MDM2 was the most specific marker for detecting WDLPS-DDLPS. It also showed that a combination of these three markers improves the diagnostic credibility of the immunohistochemistry in diagnosing DDLPS and WDLPS but FISH is the most reliable and confirmatory method. De-differentiated liposarcoma, Well-differentiated liposarcoma, P16, CDK4, MDM2.

Targeting Asparagine Metabolism in Well-Differentiated/Dedifferentiated Liposarcoma.

mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). Human tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling. Asn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth. Asn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS.

Giant Atypical Spindle Cell Lipomatous Tumor of Retroperitoneal Origin Presenting with Lung Metastasis and Extension to the Thigh: A Case Report with Literature Review

AbstractRetroperitoneal liposarcomas are rare, and their variants, atypical spindle cell lipomatous tumor (ASCLT), are rarer. Though ASCLTs are benign, they have high recurrence despite complete surgical excision. We present a rare case of a 22-year-old male presented with insidious-onset, and gradually progressive swelling over left inguinofemoral, and iliac fossa region. Also, the patients had a history of weight loss, pricking-type pain radiating to left lower limb, and breathlessness on exertion. Contrast-enhanced computed tomography (CECT) abdomen revealed a large well-defined heterogeneously enhancing soft mass located in pelvis, and involving left-sided iliopsoas muscle suggestive of retroperitoneal soft tissue sarcoma and CECT thorax showed metastasis. The CT-guided core biopsy led to the definitive diagnosis of low-grade ASCLT. Subsequently, the patient was initiated on concurrent neoadjuvant chemoradiotherapy followed by complete surgical excision. The findings in this report make it critical to enhance our understanding of this rare tumor, with surgery being the best treatment option.

Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.

As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.

Liposarcoma excision and removal with right total nephrectomy in a large retroperitoneal perinephric liposarcoma involving the right kidney: A case report

An uncommon tumor, retroperitoneal liposarcoma (LPS) occurs in 2.5 out of every million people. Due to the lack of distinct clinical manifestations, early diagnosis is challenging. LPS is a mesenchymal tumor that is malignant and mostly develops into adipose tissue and is a common soft tissue tumor that affects people in their middle years. The thigh, gluteal region, retroperitoneum, leg, and shoulder area are among the areas that are frequently affected. Here, we report the case of a 72-year-old female who had a history of abdominal distension from the past 6 months, occasional retention of urine from the past 3–4 months, and constipation on and off from the past 1 year. The patient was evaluated and diagnosed with a case of right retroperitoneal LPS and treated by surgical resection. To sum up, retroperitoneal LPS is an uncommon condition involving other organs, though occasionally combined resection of other organs is also required.

Epidemiología de los tumores musculoesqueléticos en una unidad de referencia

ObjectiveThe objective of this study was to perform an epidemiological analysis of patients presented to the Musculoskeletal Tumors Committee of a reference hospital. Material and methodA retrospective analysis of patients with sarcomas treated in a reference Sarcoma Unit between 2009 and 2022 was carried out. ResultsA total of 1978 patients were analyzed, of which 1477 (74.67%) were diagnosed as sarcomas. They were divided into 446 (30.20%) bone tumors and 1.031 (69.80%) soft tissue tumors. The most common benign bone tumor was enchondroma (27.23%), giant cell tumor (59.21%) was the most common tumor of intermediate malignancy and the malignant one was osteosarcoma (24.78%). The most frequently observed benign soft tissue tumor was lipoma (50.74%), the atypical lipomatous tumor (53.25%) was the most frequent tumor of intermediate malignancy and the malignant one was sarcoma of uncertain differentiation (38.10%). ConclusionOur study represents the first work on the epidemiology of sarcomas and other musculoskeletal tumors in our country, being very useful to adapt the resources destined for their diagnosis and treatment.