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Atypical lipomatous tumors (ALTs) are locally aggressive adipocytic malignancies that frequently occur in middle-aged adults. We report the rare case of an ALT of the thigh that occurred in a 4-year-old girl. Since the tumor was initially diagnosed as a lipoblastoma by incisional biopsy, marginal resection was performed. Histopathological findings of the surgical specimen revealed the proliferation of mature and variously sized adipocytes, as well as ectopic ossification; these features differ from the typical findings of lipoblastoma. Immunohistochemical findings showed nuclear positivity for a murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) and negativity for pleomorphic adenoma gene 1 (PLAG1). Fluorescence in situ hybridization showed abnormal amplification of the MDM2 gene. The patient was thus finally diagnosed as having an ALT. No signs of local recurrence or metastasis were noted 1 year postoperatively. This case is instructive in the differential diagnosis of primary adipocytic tumors. Lipoblastomas are the most common adipocytic tumors in children, but if a tumor is located in the deep tissue or imaging findings are not typical, the possibility of ALT should be considered and immunohistochemistry for MDM2 and CDK4 should be added.

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Background/Aim: Lipomatous tumors, including lipomas, atypical lipomatous tumors (ALTs), myxoid liposarcomas (MLs), and dedifferentiated liposarcomas (DLs), are often diagnosed using magnetic resonance imaging (MRI). Differential diagnosis of lipomas and ALTs by MRI is often challenging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has recently been used for the diagnosis and evaluation of tumor staging and recurrence of soft tissue tumors. The maximum standardized uptake value (SUVmax) is positively associated with malignant grade in several cancers. This study aimed to evaluate SUVmax of 18F-FDG PET/CT in the differential diagnosis of lipomatous tumors. Patients and Methods: Patients who underwent 18F-FDG PET/CT for the diagnosis of lipomatous tumors between January 2013 and September 2021 were included in the study. Patients with lipomatous tumors, confirmed by pathological diagnosis or surgical specimens, were evaluated for lipomatous tumor SUVmax. Results: This study included 44 patients with lipomas (n=19), ALTs (n=12), MLs (n=9), and DLs (n=4). The mean SUVmax of lipomas, ALTs, MLs, and DLs was 0.99±1.41, 1.92±0.95, 5.21±4.94, and 9.29±1.43, respectively. Lipomas showed a significantly lower SUVmax than did ALTs, MLs, and DLs (p<0.05). ALTs demonstrated a significantly lower SUVmax than did MLs and DLs (p<0.05). No significant differences were observed between MLs and DLs. Conclusion: Lipomas or ALTs had a significantly lower SUVmax than lipomatous sarcomas. Lipomas had a significantly lower SUVmax than ALTs, aiding in their preoperative differentiation. 18F-FDG-PET/CT could serve as a potent tool for the differential diagnosis of lipomatous tumors.

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Background: Liposarcomas originating in the supraclavicular fossa are exceptionally rare, with only a few documented cases in the medical literature. Methods: We present a unique case involving a remarkably large indolent, atypical lipomatous tumor or well-differentiated liposarcoma situated in the right supraclavicular region, measuring 18 cm × 18 cm × 17 cm. To our knowledge, this represents the largest liposarcoma found in the supraclavicular fossa reported in the literature. This unique case highlights the effective management of a remarkably large supraclavicular liposarcoma through complete surgical resection. Result and Conclusion: Our findings further support the existing consensus that complete surgical removal is often curative for well-differentiated liposarcoma.

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Segmentation and image intensity discretization impact on radiomics workflow. The aim of this study is to investigate the influence of interobserver segmentation variability and intensity discretization methods on the reproducibility of MRI-based radiomic features in lipoma and atypical lipomatous tumor (ALT). Thirty patients with lipoma or ALT were retrospectively included. Three readers independently performed manual contour-focused segmentation on T1-weighted and T2-weighted sequences, including the whole tumor volume. Additionally, a marginal erosion was applied to segmentations to evaluate its influence on feature reproducibility. After image pre-processing, with included intensity discretization employing both fixed bin number and width approaches, 1106 radiomic features were extracted from each sequence. Intraclass correlation coefficient (ICC) 95% confidence interval lower bound ≥ 0.75 defined feature stability. In contour-focused vs. margin shrinkage segmentation, the rates of stable features extracted from T1-weighted and T2-weighted images ranged from 92.68 to 95.21% vs. 90.69 to 95.66% after fixed bin number discretization and from 95.75 to 97.65% vs. 95.39 to 96.47% after fixed bin width discretization, respectively, with no difference between the two segmentation approaches (p ≥ 0.175). Higher stable feature rates and higher feature ICC values were found when implementing discretization with fixed bin width compared to fixed bin number, regardless of the segmentation approach (p < 0.001). In conclusion, MRI radiomic features of lipoma and ALT are reproducible regardless of the segmentation approach and intensity discretization method, although a certain degree of interobserver variability highlights the need for a preliminary reliability analysis in future studies.

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The classification and work-up of adipocytic neoplasms remains challenging and sometimes controversial. Since its initial description by Dr. Enterline, the variety of subtypes and morphological appearances considered to represent the spectrum of atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDL) has expanded, resulting in significant morphologic overlap with other entities, including the recently described atypical spindle cell/pleomorphic lipomatous tumor (ASPLT), conventional spindle cell/pleomorphic lipoma (SPL), and so-called "low-grade" forms of dedifferentiated liposarcoma (DL). Nevertheless, the distinction of most examples of ALT/WDL from lipomas/lipoma-like lesions is easily performed on routine histologic examination but can be problematic if the characteristic atypical cells are poorly represented, particularly in small biopsy specimens, obscured by other cellular elements (inflammation), or simply not recognized. The discovery that lipomatous tumors harbor specific and unique karyotypes and molecular events has resulted in ancillary tests that can help provide more accurate diagnoses, especially in less-than-optimal scenarios. Confirmation of MDM2 immunohistochemical over-expression and detection of the MDM2 gene rearrangement via fluorescent in situ hybridization (FISH) have proven particularly reliable and useful. While FISH analysis for MDM2 gene amplification may be helpful for confirming (or excluding) ALT/WDL, it also can lead to overutilization and overdependence. Furthermore, a small subset of otherwise typical ALT/WDL lack MDM2 gene amplification, employing alternative molecular pathways. The recent recognition of ASPLT has introduced a tumor easily mistaken morphologically for ALT/WDL, often exhibiting bizarre and pleomorphic lipoblasts, but lacking the underlying molecular abnormalities and subsequent risk of dedifferentiation. ASPLT also have overlapping features with the better-established SPL but with a greater tendency to locally recur and more frequent involvement of the distal extremities. The precise criteria separating cellular forms of ALT from what some consider "low grade" forms of DL remains controversial and inconsistently applied, even among individual pathologists within institutions. Given their underlying shared cytogenetic abnormality, molecular testing has no utility in this distinction. Herein is a comprehensive historical overview of ALT/WDL, with updates on its distinction from other similar lipomatous tumors and DL, including practical evidence-based criteria for the appropriate cost-effective use of MDM2 testing.

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Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is usually a solitary adipocytic tumor. ALT/WDLPS shows no potential for metastasis unless it undergoes dedifferentiation. No case of multiple ALT/WDLPS has been reported in recent years. We present a rare case of multiple recurrent liposarcomas. A 71-year-old man with a history of scrotal ALT/WDLPS at 61 years presented with multiple large tumors spread throughout the body. The patient was bedridden and severely limited in his activities of daily living (ADL) due to multiple large tumors in the trunk and lower extremities. Radiological examination revealed multiple adipocytic tumors, mainly in the soft tissues of the trunk and extremities, with several visceral lesions. Tumors were resected in stages, starting with large tumors directly related to disability. Repeated palliative resections improved the patient's ADL; he regained ambulation and was discharged 18 months after admission. Twelve surgeries were performed to remove 44 adipocytic tumors from the testis, left chest wall, perigastric area, ileum, left inguinal region, both buttocks, thighs, and lower legs. Histological examination revealed dedifferentiated components in five tumors, while 39 tumors were diagnosed as ALT/WDLPS. At the age of 76 years, the patient developed an unresectable dedifferentiated liposarcoma between the heart and aorta, leading to fatality at 79 years. The patient's clinical course suggested multiple metastases of ALT/WDLPS of scrotal origin or ALT/WDLPS of multicentric origin. Although multicentric ALT/WDLPS or ALT/WDLPS metastases are rare, they should be considered when multiple large adipocytic tumors are found throughout the body. Despite the presence of numerous large malignant tumors, surgical treatments of the lesions can improve ADL and prolong life if the tumors are of low-grade malignancy.

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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.

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Liposarcomas originating in the urinary bladder are extremely rare. Only six cases of bladder liposarcoma have been reported, and all have been described as myxoid liposarcomas. Notably, none of the patients underwent molecular testing. Here, we report a dedifferentiated liposarcoma (DDL) that occurred in the urinary bladder, primarily in a 69-year-old Chinese woman, with infrequent low-grade dedifferentiation. Computed tomography (CT) revealed an ill-defined solid mass in the anterior bladder wall. The patient underwent a partial bladder resection. Histologically, the tumor cells with mild-to-moderate nuclear atypia were arranged in fascicular and storiform patterns, mimicking a low-grade fibroblastic tumor. In addition, scattered small foci of typical lipoma-like well-differentiated components were identified. Immunohistochemically, the tumor tested positivity for MDM2, CDK4, and p16. Fluorescence in situ hybridization revealed MDM2 gene amplification in the neoplastic cells. Whole-exome sequencing showed that this tumor also harbored CDK4, TSPAN31, and JUN amplification. At the latest follow-up (85 months after surgery), the patient was alive, with no evidence of disease. To the best of our knowledge, this is the first example of a molecularly confirmed primary bladder liposarcoma and the first case of DDL at this site.

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Adipocytic neoplasms are frequently encountered in clinical practice. Atypical lipomatous tumor (ALT) is a locally aggressive but non-metastasizing adipocytic neoplasm that primarily occurs in the proximal extremities of middle-aged to older adults. Histologically, ALT is divided into adipocytic (lipoma-like), sclerosing and inflammatory subtypes. The sclerosing subtype is an unfavorable prognostic factor for local recurrence. ALT is characterized by supernumerary ring and/or giant rod chromosomes. These rings and giant markers invariably contain amplified sequences originating from the long arm of chromosome 12, including the MDM2 proto-oncogene (MDM2) and cyclin-dependent kinase 4 (CDK4) gene. MDM2 and/or CDK4 nuclear immunopositivity is present in most cases. Confidently differentiating deep-seated ALT from deep-seated ordinary lipoma is often difficult on imaging. Moreover, the sclerosing subtype may mimic a higher grade liposarcoma. Detection of MDM2 amplification by fluorescence in situ hybridization would be helpful diagnostically for ALT in more difficult cases. The standard treatment for deep-seated ALT is surgery. Although there is no consensus on the best surgical approach for deep-seated ALT of the extremities, the use of marginal resection is acceptable to preserve musculoskeletal function. This review provides an overview of the current knowledge on the clinical and imaging characteristics, pathogenesis, histopathology, and management of deep-seated ALT of the extremities.

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INTRODUCTION: The distinction between lipoma and well-differentiated liposarcoma (WDLPS), or "atypical lipomatous tumor" (ALT), is crucial as it impacts patient management. A group of European experts led by Benjamin Moulin recently issued a consensus report to define the role of radiology in managing these lesions. It describes an algorithm defining the criteria prompting a diagnostic biopsy of deep lipomatous tumors of the limbs and chest wall. The primary aim of this study was to evaluate the algorithm's diagnostic performance. MATERIALS AND METHODS: Between 2012 and 2019, all biopsies of deep fatty tumors of the limbs or chest wall with a pre-biopsy MRI assessment were recorded at our institution. The MRI scans were reviewed by two radiologists. Each lesion was classified according to biopsy status by applying the algorithm of the European panel. The algorithm's diagnostic performance was assessed by calculating the sensitivity, specificity, positive predictive value and negative predictive value. Inter-rater agreement was also assessed. RESULTS: Of the 156 tumors in our study, 148 (94.9%) required a biopsy, and the algorithm's sensitivity for detecting ALT/WDLPS was 100% with specificity of 6.3% and a PPV of 20.3%. Inter-rater agreement was almost perfect with a kappa value of 0.882. CONCLUSION: The European algorithm demonstrates perfect sensitivity, an important criterion for a screening examination such as MRI in this setting. The algorithm's low specificity, however, emphasizes the need for further studies to redefine the optimum size cut-off value, especially for lesions without atypical criteria or an anatomical location at risk of post-surgical recurrence.

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Spindle cell lipoma (SCL) is a benign adipocytic tumor that primarily occurs in the subcutis of the posterior neck, upper back, and shoulder, particularly of middle-aged males. SCL and pleomorphic lipoma (PL) represent a morphological spectrum of one disease process. The lesion typically presents as a relatively small (<5 cm), mobile, slow-growing, painless mass. Magnetic resonance imaging reveals the lesion to be a well-defined subcutaneous mass with a mixture of adipose and non-adipose components. Intense enhancement of the non-adipose component is seen after contrast administration. Histologically, SCL is composed of variable distributions of mature adipocytes, bland spindle cells and ropey collagen bundles and PL also contains pleomorphic and multinucleated floret-like giant cells. By immunohistochemistry, the spindle and pleomorphic/floret-like giant cells of SCL/PL are diffusely positive for CD34 and show loss of nuclear RB transcriptional corepressor 1 (RB1) expression. Recent cytogenetic and molecular genetic studies have shown heterozygous deletions of 13q14, including the RB1 gene. SCL/PL can be successfully treated with simple excision, with a very low recurrence rate. Knowledge of these peculiar tumors is important because it can mimic a variety of benign and malignant soft-tissue tumors. This review provides an updated overview of the clinical, radiological, histopathological, cytogenetic, and molecular genetic features of SCL/PL.

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INTRODUCTION: Liposarcomas are thought to be the most prevalent kind of soft tissue sarcoma in adults. A well-differentiated liposarcoma that has a higher incidence of a local recurrence following surgical excision is referred to as an atypical lipomatous tumor. The incidence are extremely rare in which <1 % of head and neck sarcoma cases. This is unusual liposarcoma localization warrants great interest in reporting such a case. PRESENTATION OF CASE: In this report we present a case of a 50-year-old male complained with difficulty swallowing solid food and continuous presence of lump in the throat. Fiber Optic Laryngoscopy (FOL) showed a tumor filled the hypopharynx and CT scan suggested a benign mass that was most likely a fibrolipoma. DISCUSSION: Tumor was found infiltrating the lateral pharyngeal wall and protruding into the hypopharyngeal lumen. Because the tumor had spread to the right thyroid lobe, surgical excision via a transcervical approach was combined with a right thyroidectomy. There was a positive margin at the end of resection, thus a chemoradiation was added. Two years post-operative evaluation shows no sign of recurrence. CONCLUSION: The main treatment for hypopharyngeal liposarcoma is based on surgery, either through an endoscopic or transcervical approach which determined by the size of the tumor and surgical field. Adjuvant chemoradiation is given to help prevent the recurrence.

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Adipocytic tumors are the most common mesenchymal tumors in soft tissues. Among them, a diagnostic challenge relies in the distinction between lipoma and atypical lipomatous tumor (ALT)/well differentiated liposarcoma (WDLPS), as both entities are often undistinguishable not only from a radiological point of view, but also at the microscopic level and particularly when dealing with small tumor specimen. Thus, detection of recurrent MDM2 amplifications may be the only criteria to discriminate malignant tumors from lipomas. In this study, we report the case of a patient diagnosed with a well differentiated, adipocytic tumor located in the inferior limb and lacking MDM2 amplification, whose diagnosis was reclassified for ALT/WDLPS after identification of an alternative MDM4 amplification by comparative genomic hybridization profiling, whole exome sequencing and fluorescence in situ hybridization (FISH). Screening of a cohort of 37 large, deep-seated, well-differentiated adipocytic tumors previously classified as lipomas using RT-qPCR and FISH failed to detect other cases of MDM4-amplified ALT/WDLPS. This report shows that MDM4 amplification is an exceptional molecular event alternative to MDM2 amplification in ALT/WDLPS. This alteration should be considered and looked for in suspicious adipocytic tumors to optimize their surgical management.

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BACKGROUND: Differentiating atypical lipomatous tumors (ALTs) and well-differentiated liposarcomas (WDLs) from benign lipomatous lesions is important for guiding clinical management, though conventional visual analysis of these lesions is challenging due to overlap of imaging features. Radiomics-based approaches may serve as a promising alternative and/or supplementary diagnostic approach to conventional imaging. PURPOSE: The purpose of this study is to review the practice of radiomics-based imaging and systematically evaluate the literature available for studies evaluating radiomics applied to differentiating ALTs/WDLs from benign lipomas. REVIEW: A background review of the radiomic workflow is provided, outlining the steps of image acquisition, segmentation, feature extraction, and model development. Subsequently, a systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the grey literature was performed from inception to June 2022 to identify size studies using radiomics for differentiating ALTs/WDLs from benign lipomas. Radiomic models were shown to outperform conventional analysis in all but one model with a sensitivity ranging from 68 to 100% and a specificity ranging from 84 to 100%. However, current approaches rely on user input and no studies used a fully automated method for segmentation, contributing to interobserver variability and decreasing time efficiency. CONCLUSION: Radiomic models may show improved performance for differentiating ALTs/WDLs from benign lipomas compared to conventional analysis. However, considerable variability between radiomic approaches exists and future studies evaluating a standardized radiomic model with a multi-institutional study design and preferably fully automated segmentation software are needed before clinical application can be more broadly considered.

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This review examines findings of musculoskeletal neoplasms whose equivocal imaging and/or histopathologic features make it difficult to determine if they will show aggressive behavior. We include both intermediate tumors as defined by the World Health Organization (WHO), and a single low-grade malignancy, low-grade central osteosarcoma, which mimics a benign lesion on imaging and histology. Intermediate tumors are a broad category and are subdivided into tumors that have risk of local recurrence only, and ones that have a risk of distant limb and pulmonary metastases. Difficult intermediate musculoskeletal lesions include atypical cartilaginous tumor/grade 1 chondrosarcoma, atypical lipomatous tumor/grade 1 liposarcoma, and solitary fibrous tumor. We review diagnostic criteria, differential diagnosis, and recommendations for surveillance.

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

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Background: Distinguishing between some benign lipomas (BLs), atypical lipomatous tumors (ALTs), and dedifferentiated liposarcomas (DDLs) can be challenging due to overlapping magnetic resonance imaging characteristics, and poorly understood molecular mechanisms underlying the malignant transformation of liposarcomas. Purpose: To identify metabolic biomarkers of the lipomatous tumor spectrum by examining human tissue specimens using high-resolution 1H magnetic resonance spectroscopy (MRS). Materials and methods: In this prospective study, human tissue specimens were obtained from participants who underwent surgical resection for radiologically-indeterminate lipomatous tumors between November 2016 and May 2019. Tissue specimens were obtained from normal subcutaneous fat (n=9), BLs (n=10), ALTs (n=7) and DDLs (n=8). Extracts from specimens were examined with high-resolution MRS at 17.6T. Computational modeling of pattern recognition-based cluster analysis was utilized to identify significant differences in metabolic signatures between the lipomatous tumor types. Results: Significant differences between BLs and ALTs were observed for multiple metabolites, including leucine, valine, branched chain amino acids, alanine, acetate, glutamine, and formate. DDLs were distinguished from ALTs by increased glucose and lactate, and increased phosphatidylcholine. Multivariate principal component analysis showed clear clustering identifying distinct metabolic signatures of the tissue types. Conclusion: Metabolic signatures identified in 1H MR spectra of lipomatous tumors provide new insights into malignant progression and metabolic targeting. The metabolic patterns identified provide the foundation of developing noninvasive MRS or PET imaging biomarkers to distinguish between BLs, ALTs, and DDLs.

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Hibernomas are soft tissue tumors derived from remnants of brown fat. They are rare masses that can have variable presentations ranging from incidental asymptomatic masses to pain due to nerve compression. We present the case of a 52-year-old male presenting with an atypical lipomatous mass on ultrasound and magnetic resonance imaging. The mass was excised and sent for pathology with the result being a hibernoma. We should be vigilant in the treatment of such tumor presentations as they may be a low grade liposarcoma in disguise. Surgical biopsy or excision is the best treatment for achieving a definite diagnosis.

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Atypical lipomatous tumor or well-differentiated liposarcoma is a rare condition in the laryngopharynx. We present a case of a 63 year-old male with progressive dysphagia who later manifested with a mass that regurgitates outside the oral cavity. Surgical removal was done via a transoral approach, followed by adjuvant radiotherapy.

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BACKGROUND: According to guidelines, every soft tissue tumor (STT) larger than 3 cm should be biopsied before definitive resection. Advances in magnetic resonance imaging (MRI) improve the possibility to give a provisional diagnosis of the tumor's entity. Can lipomas and atypical lipomatous tumors (ALTs) of the extremities therefore be primarily marginally resected based on interpretation of MR images without a previous biopsy?. METHODS: In this retrospective, single-center study, 240 patients with the suspicion of a lipomatous tumor in MRI and surgical treatment in our institution between 2011 and 2020 were included. MR imaging was performed before surgery. All resected specimens underwent histopathological analysis. RESULTS: The collective comprised 142 tumors that were suspected as lipoma or ALT by the radiologist and underwent primary marginal resection (PMR). One case had myxoid liposarcoma that was underestimated on MRI and needed radical follow-up resection. One-hundred forty-one patients were cured after PMR. Ninety-eight patients were biopsied initially and in 93 cases resected afterwards according to the necessary oncological margins. CONCLUSION: In our institution, PMR is performed if a lipoma or ALT is suspected on MR imaging. Our treatment method and the diagnostic algorithm are presented. Primary resection spares patients from one surgical procedure, but a slight risk for underestimation of the tumor remains.

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