Intravascular lipomas are rare benign tumors composed of adipose tissue that originate from the walls of blood vessels. They most commonly arise from veins, are typically asymptomatic, and rarely occur in the lower extremities. When large, these tumors can cause symptoms related to venous obstruction, such as swelling and pain. We report a case of a 75-year-old man with an intravascular lipoma in the right common femoral vein, identified during evaluation of lower extremity swelling and poorly healing ulcers. Surgical resection was ultimately required. This case contributes to the few published reports of pathologically proven symptomatic intravascular lipomas involving the lower extremity veins. Comprehensive preoperative imaging played a critical role in characterizing the lesion. The case facilitates a discussion of key differential diagnoses, such as atypical lipomatous tumors/well-differentiated liposarcoma and leiomyosarcoma. · Intravascular lipomas are rare and generally asymptomatic masses that most often arise in the veins of the upper extremity and thorax.. · The differential diagnosis for a fatty intravascular mass includes benign lipoma, atypical lipomatous tumor (ALT)/well-differentiated liposarcoma, and leiomyosarcoma.. · Benign lipomas usually demonstrate homogeneous fat signal with thin fibrous septa and minimal nonadipose components.. · Imaging features suggestive of ALT/well-differentiated liposarcoma are reduced and/or heterogeneous fat composition, thickened septa, and nodular nonadipose tissue..

Atypical lipomatous tumor is a well-differentiated liposarcoma which is locally aggressive but does not typically metastasize. Atypical lipoma of the forearm is a very rare condition with unknown incidence. The management of atypical lipoma of the forearm is controversial, with some authors suggesting en bloc excision of the tumor. We report a case of atypical lipoma of the forearm in a 36-year-old female treated by marginal excision. The patient had no evidence of recurrence in medium-term follow-up. We conclude that marginal excision is an accepted method for the management of atypical lipoma of the forearm, which has no evidence of neurovascular encroachment.

Background and Objectives: Primary mesenteric liposarcoma (LPS) is an exceptionally rare malignancy, with most literature data limited to isolated case reports or small series. This papers aims to evaluate the clinicopathological features, treatment outcomes, and prognostic factors in patients with mesenteric LPS. Materials and Methods: Thirteen patients diagnosed with primary mesenteric LPS between 2010 and 2022 were retrospectively analyzed. Data included demographics, tumor location, histological subtype, surgical treatment, recurrence, and survival. Results: The median age was 56 years (range, 22-74), with a slight male predominance (53.8%). Most tumors arose from the small bowel (53.8%) and colonic (38.5%) mesenteries, with one involving the gastric mesentery. The predominant histological subtypes were myxoid (46.1%) and dedifferentiated (23.1%). R0 resection was achieved in 76.9% of patients. During a median follow-up of 55.2 months, nine patients (69.2%) developed recurrence. Mortality was higher in patients with dedifferentiated LPS (66.7%) than in those with myxoid LPS (40%). Five-year survival rate was 100% in patients without recurrence and 28.6% in those with recurrence (p = 0.112, not significant). Patients who received adjuvant chemoradiotherapy suggested longer survival (110.7 vs. 46.2 months; p = 0.620). Conclusions: This 12-year study highlights the aggressive nature of mesenteric LPS, particularly the dedifferentiated subtype which showed the poorest prognosis. Complete resection remains the primary treatment; however, it has high recurrence rates. To diminish the catastrophic poor results of the postoperative period, multidisciplinary treatment strategies become a keystone.

The addition of pembrolizumab to preoperative radiotherapy (RT) improved disease-free survival (DFS) for patients with stage III undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated/pleomorphic liposarcoma (LPS) in the randomized SU2C-SARC032 trial. To precisely identify patients who benefit from pembrolizumab and RT, we performed comprehensive multi-omics profiling of pre- and post-treatment tumor and blood samples, including bulk RNA-seq, flow cytometry, and cytometry by time of flight. Additionally, we built a single-cell RNA-seq atlas spanning 65,786 cells from UPS and LPS to recover single-cell states in bulk tumor samples using digital cytometry. Two opposing tumor microenvironments (TMEs), immune-cold sarcoma ecotype 1 (SE1) and immune-hot sarcoma immune class E (SIC E), benefited from pembrolizumab. Pembrolizumab combined with RT depleted PD-1+ exhausted T cells in SIC E sarcomas and increased effector memory CD4+ T cells in SE1 sarcomas with an overall increase in CD8+ early activated T cells, CD4+ follicular helper T cells, and T cell receptor diversity. Matrix-remodeling stromal and epithelial-like sarcoma cell programs were associated with worse outcomes and diminished with pembrolizumab and RT. Our findings identify different mechanisms of response to pembrolizumab in localized, high-risk UPS/LPS and suggest that sarcoma TME signatures may identify patients most likely to benefit from adding pembrolizumab to preoperative RT.

High YEATS4 expression characterizes MDM2-amplified liposarcoma.

Tumours of the ischiofemoral region: The largest case series.

The tRNA Editing Complex ADAT2/3 Promotes Cancer Cell Growth and Codon-biased mRNA Translation.

Undifferentiated pleomorphic sarcoma (UPS) remains one of the most clinically aggressive and poorly characterized soft-tissue sarcoma subtypes. To uncover distinctive molecular traits for UPS, a multiomics analysis of UPS compared with leiomyosarcoma (LMS) and liposarcoma (LPS) was performed. Transcriptomic profiling revealed that UPS exhibits overexpression of genes encoding succinate dehydrogenase (SDH) subunits, particularly SDHB, SDHC, and SDHD, distinguishing it from LMS and dedifferentiated LPS. This finding was validated using The Cancer Genome Atlas Sarcoma dataset. High SDHB expression in UPS was significantly associated with shorter overall survival, shorter recurrence-free survival, and shorter overall survival from the date of first metastasis. IHC validated elevated SDHB protein levels in UPS and LMS relative to dedifferentiated LPS. Despite overexpression of SDH subunits, metabolomic profiling demonstrated a significantly higher succinate-to-fumarate ratio in UPS, suggesting functional impairment of SDH enzymatic activity potentially due to posttranslational modifications, altered assembly of SDH subunits, or imbalanced tricarboxylic acid flux. This paradoxical phenotype of SDH overexpression with enzymatic dysfunction defines a unique molecular and metabolic subtype of UPS with prognostic significance. Recognition of this distinct SDH-associated molecular and metabolic phenotype provides insights into UPS pathogenesis, identifies a potential novel prognostic biomarker, and suggests a new avenue for metabolic-targeted therapy.Significance:This study identified a paradoxical phenotype of SDH subunit overexpression with functional impairment in UPS, defining a molecular/metabolic subtype associated with poor prognosis. It offers new data on UPS pathogenesis and treatment.

Introduction: Liposarcoma (LPS) is the most common soft tissue sarcoma in adults, yet its presentation as a primary mass in the inguinal region is exceedingly rare. This atypical location poses a significant diagnostic challenge, as the clinical signs often mimic more common benign conditions such as inguinal hernia or lipoma, which can lead to delayed diagnosis or inadequate initial management. This report details a case of well-differentiated liposarcoma (WDLS) in the inguinal canal, highlighting the clinical, radiological, and pathological nuances critical for accurate diagnosis and definitive treatment. Case Illustration: A 49-year-old male presented with a one-month history of a right inguinal lump that had rapidly enlarged over the preceding week, accompanied by intermittent pain. Physical examination revealed a mobile, tender mass measuring approximately 2x3 cm. Ultrasound imaging was pivotal, identifying a solid, heterogeneous, vascularized lesion, which raised the suspicion of a neoplasm beyond a simple lipoma. The patient subsequently underwent a wide excisional biopsy.Histopathological examination revealed a tumor composed of mature adipocytes with scattered atypical, hyperchromatic stromal cells and neoplastic lipoblasts, confirming the diagnosis of well-differentiated liposarcoma. A notable and potentially misleading feature was the presence of a prominent "chicken wire" vascular pattern within the stroma, a finding more classically associated with myxoid liposarcoma.1 Discussion: This case underscores the importance of maintaining a high index of suspicion for malignancy in patients presenting with atypical inguinal masses. Preoperative imaging, particularly ultrasound with Doppler, is invaluable for identifying features suggestive of sarcoma, thereby guiding appropriate surgical planning toward a wide excision rather than a simple enucleation. The finding of a "chicken wire" vascular pattern within a WDLS represents a significant diagnostic pitfall, emphasizing the need for comprehensive morphological assessment and, in equivocal cases, ancillary molecular testing to avoid misclassification and subsequent inappropriate adjuvant therapy. Wide surgical excision with negative margins remains the cornerstone of treatment for localized WDLS. Conclusion: Well-differentiated liposarcoma is an essential, albeit rare, differential diagnosis for solid inguinal masses. Optimal patient outcomes are contingent on a multidisciplinary approach encompassing astute clinical suspicion, appropriate imaging, meticulous pathological evaluation, and definitive surgical management. Given the high risk of local recurrence and the potential for dedifferentiation into a more aggressive sarcoma, a structured protocol of long-term, lifelong surveillance is mandatory following initial treatment. Keywords: Liposarcoma, Well-Differentiated Liposarcoma, Inguinal Tumor, Spermatic Cord, Soft Tissue Sarcoma.

BackgroundAtypical lipomatous tumors (ALTs) are aggressive fat cell tumors that are distinguished from benign lipomas (SL) mainly through histopathology. Biopsy is needed for suspicious cases but can miss malignancy, so complete surgical removal and examination are essential. MRI is used but often can't differentiate ALT from SL. We introduce a machine learning method for tumor classification.PurposeTo characterize the classification performance of a Bayesian additive regression trees (BART) model, built from MR radiomic features, and compare it to the readings of a musculoskeletal radiologist in classifying atypical lipomatous tumors (ALTs) from simple lipomas.Materials and MethodsRetrospective data were collected from 5 medical institutions in North America, for a total of 437 patients; the mean age was 58 years ±12 years, with 248 men and 287 women. At each institution, at least T1-MRI images without contrast were collected from patients with suspected ALT prior to surgery. Histopathology was used as the reference standard. Radiomic features extracted from the MRI images were used to train the BART model and a random forest model for comparison of classification performance using a 10-fold cross-validation. Both models were compared with the classifications of an experienced (>10 years) musculoskeletal radiologist who scored the images on a 5-point scale.ResultsA cohort of 423 patients was included, and 1132 radiomic features were extracted from each MR study. The BART model had an accuracy, sensitivity, and specificity of 77.07% (72.76%-80.99%), 77.67% (71.36%-83.16%), and 76.50% (70.28%-81.97%), respectively, when utilizing all predictors and aggregating training and testing data from all the cohorts, approximating the human reader at 78.72% (74.51%-82.53%), 76.21% (69.80%-81.85%), and 81.11% (75.25%-86.09%), respectively. In the external validation, the average area under the curve (AUC) value across cohorts between the BART model and the human reader differed by 0.04 AUC points. From the receiver operating characteristic curve, the AUC was calculated to be 84.72% (81.00%-88.50%) and 84.74% (81.00%-88.50%) for the BART and human reader, respectively.ConclusionThis study demonstrated that the BART model can distinguish ALT from lipoma with diagnostic performance comparable to an experienced human observer.

Expression of antibody-drug conjugate targets in soft tissue sarcomas.

Whole-body magnetic resonance imaging in myxoid liposarcoma: Toward a new standard?

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

Soft tissue sarcomas are a diverse group of rare cancers, with approximately 15%-20% found in the retroperitoneum. Liposarcomas (LPS) make up approximately half of all retroperitoneal (RP) sarcomas, with most cases classified as either well-differentiated (WD) or dedifferentiated (DD). DD LPS is more aggressive, with a higher local recurrence rate and risk of distant metastasis compared to WD LPS. The purpose of this review is to outline surgical management of RP LPS and highlight the multimodal treatment strategies for both primary and recurrent disease, along with considerations for their effective implementation. The current medical literature was reviewed for studies focused on retroperitoneal liposarcoma and its treatment with surgery, radiation, and chemotherapy. The data was interpreted and compiled in the context of expert clinical experience. Along with histopathologic analysis, tumor biology can inform patient prognosis. Surgery, the standard treatment for RP LPS, can be either curative or palliative. In primary disease, an attempt should be made to achieve wide surgical margins when feasible. Surgery for recurrent disease requires careful timing and an understanding of the potential benefit versus risk. Neoadjuvant radiation therapy can improve local control of RP LPS; however, data supporting the use of neoadjuvant chemotherapy are currently lacking. Multimodality treatment of RP LPS is complex and requires consideration of tumor biology and extent of disease, along with individual patient characteristics. Multidisciplinary team collaboration is critical for improving outcomes in patients with RP LPS.

Clinical presentation, management and outcome of 11,132 patients with liposarcoma patients: a population-based study from the NETSARC+ registry

Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a few cases have been reported in the thigh. We report the case of a 36-year-old female patient on the 11th day of the puerperium after a cesarean section. The patient presented to the gynecology ward owing to the sudden appearance of a tumor in the medial part of her right thigh. The lesion was non-painful, mobile, soft, approximately 20 cm in diameter, and protruded above the level of the rest of the thigh surface. A suspicion of hematoma was raised. The final diagnosis was high-grade MLPS. An MLPS diagnosis is uncommon in female patients and even rarer during pregnancy. This case represents a novel occurrence, as the first instance in which symptoms manifested during the puerperium. Proper treatment and early detection could improve disease outcomes.

Background: Spermatic cord lipomas originate from preperitoneal adipose tissue within the internal spermatic fascia and are found in 20%-70% of all inguinal hernia repairs. Morphologically, spermatic cord lipomas may harbor some atypical features, including increased stromal cellularity with thickened fibrous bands, occasional lipoblasts, and stromal nuclear atypia or hyperchromasia, raising concern for well-differentiated liposarcoma (WDLS) versus reactive-type atypia. Fluorescence in situ hybridization (FISH) for MDM2 amplification would be the gold standard test in such cases. The aim of this study was to evaluate the efficacy and cost-effectiveness of MDM2 FISH in diagnostically discrimination morphologically atypical spermatic cord lipoma cases at our institution.Methods: All cases with “specimen type” labeled as “spermatic cord lipoma” between 2018 and 2023 were retrospectively retrieved from our institutional archives. Cases were included in the study group if they had MDM2 FISH performed. Cases with a prior history of spermatic cord well-differentiated liposarcoma with positive MDM2 amplification were excluded. MDM2 amplification status and corresponding final diagnosis were recorded.Results: Three hundred twenty specimens labelled as spermatic cord lipoma were retrieved from our archives. Forty-three out of 320 had MDM2 FISH performed. All 43 cases demonstrated atypical features and appeared morphologically similar. Only one out of 43 (2.3%) cases demonstrated a positive MDM2 amplification result, thus labeling it as an incidental WDLS (11 cm) in the setting of an inguinal hernia repair for which the patient required a subsequent orchiectomy. The remaining 42 cases (97.7%) harbored reactive-type atypia with negative FISH results and were diagnosed as spermatic cord lipomas.Conclusion: Our results indicate that 2.3% of morphologically atypical specimens labeled as spermatic cord lipoma at our institution are in fact well-differentiated liposarcomas. These findings prove the efficacy of MDM2 FISH in diagnosing WDLS in the setting of atypical spermatic cord lipoma labeled specimens. Although 97.7% of our spermatic cord lipomas harbored reactive-type atypia with negative FISH results, which argues against the cost-effectiveness of such testing, we propose performing FISH analysis in cases greater than 10 cm in size to avoid misdiagnosis and ensure optimal patient care.

ASO Author Reflections: Comparison of Local Recurrence Rates between Wide Resection and Expanded Marginal Excision in Atypical Lipomatous Tumors.

IWS1 is a key assembly factor of the RNA polymerase II (RNAPII) elongation complex, and its overexpression is associated with worse outcomes in patients with liposarcoma (LPS). This study aimed to identify compounds that can disrupt the IWS1/Spt6 interaction and assess their biological effects in dedifferentiated LPS (DDLPS). Using the AlphaFold-predicted structure of IWS1, we identified a core binding region (AA 545–694) for its interaction with Spt6. Through molecular modeling and virtual screening, Ketotifen and Desloratadine were predicted as candidate inhibitors. Both were predicted to mimic Spt6 phenylalanine (F217) and disrupt the complex, which was confirmed by co-immunoprecipitation. Functional assays showed that treatment with either compound reduced migration, invasion, and spheroid formation in DDLPS cell lines. Additionally, increased nuclear localization of IWS1 was observed. These findings suggest Ketotifen and Desloratadine as promising inhibitors of the IWS1/Spt6 interaction, with potential applications in reducing the invasive properties of human LPS.

The incidence of spindle cell/pleomorphic lipomas ranges from 2.2% to 47.2%. Its diagnosis is impeded by its diverse histological features, including adipocytes and myxo-collagenous stroma. Accordingly, we aimed to reexamine oral adipocytic tumors, focusing on RB1-deficient tumors, to reveal the diversity of oral spindle cell lipomas. We selected 30 cases of spindle cell/pleomorphic lipomas and their mimics from 111 oral adipocytic tumors. Subsequently, we performed analysis using immunohistochemistry for CD34 and RB protein (pRB) and RB1 fluorescence insitu hybridization (FISH) in limited cases. Among the included cases, 16 were CD34-positive with pRB and/or the RB1 loss. Among them, 15 were spindle cell lipomas (SCLs) with 27% of them being confirmed through FISH in cases where pRB status was mosaic. These included five low-fat SPLs (including one low-fat pleomorphic lipoma), four conventional SCLs, three fibrous SCLs, two myxoid, and one fat-rich SCL. The remaining case was an atypical spindle cell lipomatous tumor. Only prominent spindle cell and myxoid changes showed significant differences between SCL and fibrous lipoma. Two cases, initially identified as spindle cell lipomas, were reclassified as fibrolipoma and lipoma. Oral spindle cell/pleomorphic lipomas frequently exhibit prominent collagenous stroma, which results in low-fat and fibrous variants that require careful differentiation from fibrous lipomas or non-adipocytic tumors. Given the diverse histological findings, meticulous diagnosis of rare spindle cell lipoma variants and other lipomas in daily surgical pathology is essential. Specifically, it should apply CD34 and retinoblastoma protein immunohistochemistry, as well as RB1 FISH when necessary.