Search Results (14)

Background and Clinical Significance: Retroperitoneal tumors are a rare and diverse group of neoplasms, accounting for less than 1% of adult solid tumors. Retroperitoneal lipomas are particularly uncommon, with fewer than 20 cases described in the literature. Their asymptomatic growth and lack of clear anatomical boundaries can result in delayed diagnosis and substantial tumor size at clinical presentation. This case highlights a rare retroperitoneal lipoma with atypical extension into the right thigh through the muscular lacuna, mimicking a femoral hernia and compressing the femoral nerve—a presentation scarcely reported and clinically significant due to its surgical complexity and risk of recurrence. Case Presentation: We report the case of a 65-year-old woman from an urban setting who presented with progressive right thigh discomfort and lower limb pain during ambulation. The mass had been initially identified two years prior as a small, asymptomatic right inguinal formation during imaging to exclude an inguinal hernia. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed a large retroperitoneal lipomatous tumor extending to the anteromedial right thigh. Surgical excision was performed through a dual approach: midline laparotomy and thigh incision. A 30 × 30 cm encapsulated lipoma was removed without injuring adjacent nerves or vessels. Histopathological evaluation confirmed a mature lipoma without atypia but with a lipogranulomatous reaction. The patient’s postoperative course was favorable, with minimal residual paresthesia and complete wound healing. Conclusions: Although benign, retroperitoneal lipomas can mimic other pathologies and present surgical challenges when they extend beyond their typical boundaries. Early recognition and coordinated surgical management are crucial for optimal outcomes and prevention of recurrence. Full article

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. Full article

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. Full article

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. Full article

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. Full article

Lipomatous tumors are the most frequent soft tissue neoplasms. Sometimes their differential diagnosis is difficult to perform only by microscopic analysis. This study aims to create a histopathological scoring system and highlight the impact of intratumoral microvascular density. This study was conducted over 10 years. We analyzed the main pathogenic pathways (MDM2 and CDK4), as well as the tumor microvascularization (CD31 and CD34) by immunohistochemical tests. We also analyzed the status of the MDM2 gene by CISH. These data, together with the clinical and histopathological information, were statistically analyzed by appropriate tests. We identified 112 eligible cases, with most of the patients being in their sixth decade of life, with a slight predominance of the female sex. We found important associations like tumor location linked to nuclear pleomorphism severity and microvascularization density correlated with atypia severity. Also, we observed that a maximum diameter of a tumor of at least 69 mm is associated with the presence of tumor necrosis. The score designed in this study shows an increased sensitivity and specificity for the diagnosis of lipomas (100%, respectively, 97%), atypical lipomatous tumors (93.8%, respectively, 82.3%), and liposarcomas (100%, respectively, 90.5%). This present study enhances the present data by bringing to attention the histopathological score with a role in differential diagnosis, as well as in the prediction of immunohistochemical and genetic tests. Also, we highlighted the importance of microvascular density, especially in the diagnosis of liposarcomas. Full article

Background: The aim of this study was to develop and validate radiogenomic models to predict the MDM2 gene amplification status and differentiate between ALTs and lipomas on preoperative MR images. Methods: MR images were obtained in 257 patients diagnosed with ALTs (n = 65) or lipomas (n = 192) using histology and the MDM2 gene analysis as a reference standard. The protocols included T2-, T1-, and fat-suppressed contrast-enhanced T1-weighted sequences. Additionally, 50 patients were obtained from a different hospital for external testing. Radiomic features were selected using mRMR. Using repeated nested cross-validation, the machine-learning models were trained on radiomic features and demographic information. For comparison, the external test set was evaluated by three radiology residents and one attending radiologist. Results: A LASSO classifier trained on radiomic features from all sequences performed best, with an AUC of 0.88, 70% sensitivity, 81% specificity, and 76% accuracy. In comparison, the radiology residents achieved 60–70% accuracy, 55–80% sensitivity, and 63–77% specificity, while the attending radiologist achieved 90% accuracy, 96% sensitivity, and 87% specificity. Conclusion: A radiogenomic model combining features from multiple MR sequences showed the best performance in predicting the MDM2 gene amplification status. The model showed a higher accuracy compared to the radiology residents, though lower compared to the attending radiologist. Full article

Background: Discrimination between benign and atypical lipomatous tumors (ALT) is important due to potential local complications and recurrence of ALT but can be difficult due to the often-similar imaging appearance. Using a standardized MRI protocol, this study aimed to rank established and quantitative MRI features by diagnostic value in the differentiation of benign and atypical lipomatous tumors and to develop a robust scoring system. Methods: Patients with clinical or sonographic suspicion of a lipomatous tumor were prospectively and consecutively enrolled from 2015 to 2019 after ethic review board approval. Histology was confirmed for all ALT and 85% of the benign cases. Twenty-one demographic and morphologic and twenty-three quantitative features were extracted from a standardized MRI protocol (T1/T2-proton-density-weighting, turbo-inversion recovery magnitude, T2* multi-echo gradient-echo imaging, qDIXON-Vibe fat-quantification, T1 relaxometry, T1 mapping, diffusion-weighted and post-contrast sequences). A ranking of these features was generated through a Bayes network analysis with gain-ratio feature evaluation. Results: Forty-five patients were included in the analysis (mean age, 61.2 ± 14.2 years, 27 women [60.0%]). The highest-ranked ALT predictors were septation thickness (gain ratio merit [GRM] 0.623 ± 0.025, p = 0.0055), intra- and peritumoral STIR signal discrepancy (GRM 0.458 ± 0.046, p < 0.0001), orthogonal diameter (GRM 0.554 ± 0.188, p = 0.0013), contrast enhancement (GRM 0.235 ± 0.015, p = 0.0010) and maximum diameter (GRM 0.221 ± 0.075, p = 0.0009). The quantitative features did not provide a significant discriminatory value. The highest-ranked predictors were used to generate a five-tiered score for the identification of ALTs (correct classification rate 95.7% at a cut-off of three positive items, sensitivity 100.0%, specificity 94.9%, likelihood ratio 19.5). Conclusions: Several single MRI features have a substantial diagnostic value in the identification of ALT, yet a multiparametric approach by a simple combination algorithm may support radiologists in the identification of lipomatous tumors in need for further histological assessment. Full article

MDM2 amplification represents the leading oncogenic pathway and diagnostic hallmark of liposarcoma, whose assessment is based on Fluorescence In Situ Hybridization (FISH) analysis. Despite its diagnostic relevance, no univocal interpretation criteria regarding FISH assessments of MDM2 amplification have been established so far, leading to several different approaches and potential diagnostic misinterpretations. This study aims to address the most common issues and proposes troubleshooting guidelines for MDM2 amplification assessments by FISH. We retrospectively retrieved 51 liposarcomas, 25 Lipomas, 5 Spindle Cell Lipoma/Pleomorphic Lipomas, and 2 Atypical Spindle Cell Lipomatous Tumors and the corresponding MDM2 FISH analysis. We observed MDM2 amplification in liposarcomas cases only (43 out of 51 cases) and identified three MDM2-amplified patterns (scattered (50% of cases), clustered (14% of cases), and mixed (36% of cases)) and two nonamplified patterns (low number of signals (82% of cases) and polysomic (18% of cases)). Based on these data and published evidence in the literature, we propose a set of criteria to guide MDM2 amplification analysis in liposarcoma. Kindled by the compelling importance of MDM2 assessments to improve diagnostic and therapeutic liposarcoma management, these suggestions could represent the first step to develop a univocal interpretation model and consensus guidelines. Full article

Lipomatous tumors are among the most common soft tissue tumors (STTs). Magnetic resonance imaging (MRI) is a state-of-the-art diagnostic tool used to differentiate and characterize STTs. Radiological misjudgment can lead to incorrect treatment. This was a single-center retrospective study. Two hundred and forty lipomatous tumors were included. MRI diagnoses were categorized as benign, intermediate, or malignant and were compared with histological diagnoses. Tumor volumes were measured by MRI and from surgical specimens. The tumor was correctly categorized 73.3% of the time. A total of 21.7% of tumors were categorized as more malignant in MRI reports than they were by histology, and vice versa for 5.0% of tumors. Volume measured by MRI was not different from actual tumor size in pathology. Atypical lipomatous tumors (ALTs) and liposarcomas (LPSs) were larger when compared with lipomata and occurred in older patients. Based on the MRI-suspected tumor entity, surgical treatment can be planned. Large lipomatous tumors in elderly patients are more likely to be ALTs. However, a safe threshold size or volume for ALTs cannot be determined. Full article

Dedifferentiated liposarcoma (DDL) is defined as the transition from well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) to non-lipogenic sarcoma, which arises mostly in the retroperitoneum and deep soft tissue of proximal extremities. It is characterized by a supernumerary ring and giant marker chromosomes, both of which contain amplified sequences of 12q13-15 including murinedouble minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) cell cycle oncogenes. Detection of MDM2 (and/or CDK4) amplification serves to distinguish DDL from other undifferentiated sarcomas. Recently, CTDSP1/2-DNM3OS fusion genes have been identified in a subset of DDL. However, the genetic events associated with dedifferentiation of WDL/ALT remain to be clarified. The standard treatment for localized DDL is surgery, with or without radiotherapy. In advanced disease, the standard first-line therapy is an anthracycline-based regimen, with either single-agent anthracycline or anthracycline in combination with the alkylating agent ifosfamide. Unfortunately, this regimen has not necessarily led to a satisfactory clinical outcome. Recent advances in the understanding of the pathogenesis of DDL may allow for the development of more-effective innovative therapeutic strategies. This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology and treatment of DDL. Full article

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

The classification of soft tissue tumors has evolved considerably in the last decade, largely due to advances in understanding the pathogenetic basis of many of these, sometimes rare, tumors. Deletion of Retinoblastoma 1 (RB1), a well-known tumor suppressor gene, has been implicated in the tumorigenesis of a particular group of soft tissue neoplasms. This group of so-called “RB1-deleted soft tissue tumors” has been rapidly expanding in recent years, currently consisting of spindle cell/pleomorphic lipoma, atypical spindle cell/pleomorphic lipomatous tumor, pleomorphic liposarcoma, myofibroblastoma, cellular angiofibroma, and acral fibromyxoma. Most of these neoplasms, except pleomorphic liposarcoma, are considered benign entities and are mainly described in the older adult population. This article will review the currently known morphological, immunohistochemical, and molecular features of this heterogeneous group of mesenchymal tumors with an emphasis on differential diagnosis. Full article

After Evans and colleagues identified the lipomatous tumor with a well-differentiated liposarcoma in a subcutaneous location or within a muscle layer, namely, atypical lipomatous tumor (ALT), this malignancy has been investigated to clarify the characteristics of clinical behavior and genomic changes. As one of the important issues for clinicians, it is a hot topic of how to distinguish ALT from benign lipoma in the clinical aspect. Recent studies revealed novel findings to clarify the risk factor for the diagnosis of ALT and molecular targets for the treatment of ALT. Clinical characteristics of superficial-type ALT well reflect the subcutaneous location of the tumor and are slightly different compared to deep-type ALT, such as tumor size. In addition, there has been a recent discovery of novel findings in ALT-related genes, namely, HMG2A (high mobility group protein 2a), YEATS4 (YEATS domain containing 4), and CPM (Carboxypeptidase M). Recent updates on treatment for advanced ALT are well developed including immunotherapy and conducting clinical trials. Finally, this review introduces one of the hot topics of ALT research focused on epigenetic changes: their attention in recent updates on clinical characteristics and the novel discovery of related genes, treatment, and epigenetic modifications in atypical lipomatous tumors. Full article