Patient: Male, 68-year-oldFinal Diagnosis: Pleomorphic lipomaSymptoms: Shoulder massClinical Procedure: Excision of the left upper extremity massSpecialty: SurgeryObjective: Challenging differential diagnosisBackgroundPleomorphic lipoma is a rare benign adipocytic tumor that can closely mimic, radiologically and histologically, malignant soft tissue neoplasms, particularly atypical lipomatous tumor or liposarcoma. Despite is benign nature, pleomorphic lipoma poses a diagnostic challenge because of its significant histologic overlap with malignant entities. Accurate diagnosis is essential to prevent unnecessary wide surgical resections or overtreatment. Recognition of its distinctive clinical, histologic, and immunohistochemical features is therefore critical.Case ReportA 68-year-old man presented with a progressively enlarging, painful mass in the left upper arm. Ultrasound demonstrated a lobulated subdermal soft tissue lesion measuring 4.7×1.0×2.5 cm with a small hypoechoic component, raising concern for an atypical lipomatous tumor. Surgical excision was performed for definitive diagnosis and symptom relief. Gross examination demonstrated a well-circumscribed, yellow, lobulated mass. Histopathologic evaluation showed a lipomatous lesion composed of atypical spindle cells with pleomorphism and multinucleation, intermixed with variably sized adipocytes within a fibrotic and myxoid stroma. Immunohistochemical studies were positive for CD34 and negative for MDM2 and CDK4, with loss of RB1 expression and a low Ki-67 proliferation index (<1%), confirming the diagnosis of pleomorphic lipoma. The postoperative course was uneventful, and the patient remained symptom-free on follow-up.ConclusionsThis case highlights the diagnostic challenges associated with pleomorphic lipoma due to its rarity and resemblance to malignant soft tissue tumors. It underscores the importance of thorough histopathologic evaluation and immunohistochemical profiling to establish an accurate diagnosis and avoid unnecessary aggressive treatment. Complete surgical excision remains essential for diagnosis and management.

Diagnostic work-up of lipomatous tumors : A decision-making analysis across European sarcoma centers

Lipomas are the most common benign soft tissue tumors, yet their occurrence within deep muscular compartments (intramuscular lipomas) is relatively rare. Unlike superficial subcutaneous lipomas, intramuscular variants often display an infiltrative growth pattern, leading to significantly higher recurrence rates if not adequately and completely excised. We present a compelling case of a 40-year-old female with a recurrent giant intramuscular lipoma located in the left vastus medialis muscle. The patient had undergone a surgical excision of a mass in the same anatomical location ten years prior. Clinical examination, plain radiography, and magnetic resonance imaging (MRI) revealed a deep-seated, 8.2-cm lipomatous mass engaging the quadriceps musculature. The patient was treated with an extended marginal re-excision. This report discusses the diagnostic challenges, radiological characteristics, and surgical management of recurrent deep-seated lipomas. We emphasize the absolute necessity of preoperative MRI to distinguish these lesions from atypical lipomatous tumors and the importance of adequate surgical margins to prevent recurrence in infiltrative subtypes.

Syndromes Aassociated with Lipomatous Tumors (SALT): A comprehensive review.

1717 MDM2 Amplification Testing in Well-Differentiated Lipomatous Tumors of the Trunk and Extremities: Frequency, Yield, and Potential Overuse

Background: The necessity of a pre-therapeutic biopsy for soft tissue tumors is assessed differently depending on imaging. We examined the concordance of histopathological and radiological imaging-based diagnoses of soft tissue tumors in a monocentric, multidisciplinary sarcoma board. Methods: From October 2022 to December 2024, we prospectively included 184 patients presenting with preoperative imaging but without prior histology who are presented at the multidisciplinary sarcoma board of the University Hospital of Erlangen. We evaluated tumor dignity (benign/malignant) and most probable tumor subtype based on cross-sectional imaging assisted by the demographic and anatomic characteristics of individual cases. This assessment was then compared with the final pathological results. Results: We classified 75 tumors as benign and 109 tumors as malignant. Of the 75 patients with a suspected benign tumor, 66 (88%) had a benign diagnosis confirmed by pathological assessment, while two (2.7%) had a malignant tumor and seven (9.3%) an intermediate biology tumor. Of the 109 patients with suspected malignant tumors, 69 (63.3%) had a malignant pathology, while 30 (27.5%) had a benign pathology, and 10 (9.2%) an intermediate tumor. Matching the multidisciplinary sarcoma board's assessment with the pathological results revealed significant sensitivity and a negative predictive value for malignant tumors, as well as a significant positive predictive value and specificity for benign tumors. Conclusions: The study shows that, despite the high degree of predictability at an experienced sarcoma center, imaging cannot completely replace biopsies and caution should be exercised when deciding against a biopsy. It is emphasized that the decision not to perform a biopsy can only be made in cases where lipomatous tumors appear benign in imaging procedures, and only in an experienced center.

To synthesize magnetic resonance imaging (MRI) features and their reported diagnostic performance that differentiate benign from malignant soft-tissue tumors in alignment with the 2020 World Health Organization classification. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials were searched through July 2024. Eligible studies reported MRI feature frequencies or diagnostic accuracy for common soft-tissue tumor subtypes. Reviews, case reports, duplicates, non-English publications, and studies outside the scope were excluded. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Seventy-six studies met inclusion criteria. In lipomatous tumors, homogeneous fat signal and thin septa supported lipoma, whereas thick or nodular septa and enhancement favored atypical or well-differentiated liposarcoma. Myxofibrosarcoma often demonstrated an infiltrative fascial "tail." Vascular lesions included angioleiomyoma with a reticular T2 pattern and glomus tumor with marked T2 hyperintensity and avid enhancement. In peripheral nerve sheath tumors, lower apparent diffusion coefficient values and peritumoral edema favored malignancy. Heterogeneity in imaging protocols precluded meta-analysis; results were summarized descriptively by subtype. Consolidated MRI patterns-such as septal morphology in lipomatous tumors, the fascial tail in myxofibrosarcoma, characteristic T2 patterns in vascular lesions, and diffusion and edema cues in nerve sheath tumors-support differentiation of benign and malignant entities, enhance reader confidence, and inform biopsy and management. Standardized prospective studies are needed to validate these thresholds and improve generalizability.

Atypical lipomatous tumors (also known as well-differentiated liposarcoma) are locally aggressive, low-malignant soft tissue tumors composed of mature adipocytes and stromal cells with nuclear atypia. Although these tumors do not metastasize, they exhibit a significant risk for local recurrence and potential for dedifferentiation into high-grade liposarcomas. Despite consensus that complete surgical excision is the gold standard, the impact of positive margins remains unclear. This study evaluated the role of surgical margins in atypical lipomatous tumor recurrence. We retrospectively reviewed medical records of patients who underwent marginal resection of atypical lipomatous tumors between 2005 and 2025 at a single center. Demographic data, tumor characteristics, surgical treatment, pathology reports, recurrence rates, and risk of dedifferentiation were analyzed. Recurrence-free survival was estimated using Kaplan-Meier analysis, and factors associated with recurrence were evaluated using multivariate Cox proportional hazards regression. Fifty-four patients were included in the study. The median follow-up period was 24.5 months (range 6-172 months). Complete (R0) resection was achieved in 32 patients, whereas 22 patients had microscopically positive margins (R1). Local recurrence occurred in 11 patients (20.4%) with a median time to recurrence of 31.8 months (range 11-65.7 months). Recurrence occurred in 18.8% of R0 and 22.7% of R1 resections, with no significant difference in recurrence-free survival (P = .42). No cases of distant metastasis were observed. Dedifferentiation to grade 2 liposarcoma occurred in 2 patients (3.7%). Marginal resection of atypical lipomatous tumors offers an acceptable local recurrence rate while allowing the preservation of critical structures and function. Regular postoperative surveillance enables early identification of tumor recurrence and potential dedifferentiation.

IntroductionMultiple symmetric lipomatosis (MSL) is a rare disorder characterized by symmetrical, unencapsulated lipomatous masses, most commonly involving the neck and upper trunk. Beyond cosmetic disfigurement, MSL can be associated with systemic complications such as insulin resistance, type 2 diabetes, peripheral neuropathy, and hepatosplenomegaly. In this report, we present a genetically confirmed syndromic MSL case carrying a homozygous pathogenic variant in the Mitofusin-2 (MFN2) gene, consistent with MSL and axonal sensorimotor neuropathy, together with a homozygous variant in the Gonadotropin-Releasing Hormone Receptor (GNRHR) gene, consistent with hypogonadotropic hypogonadism type 7.Clinical CaseA 52-year-old male patient with type 2 diabetes diagnosed in 2022 (HbA1c: 7.2%) and treated with oral antidiabetics (linagliptin and pioglitazone) presented with bilateral limb weakness, glove-and-stocking paresthesia, cervical swelling, and inadequately controlled diabetes. His medical history included hepatic steatosis and two prior spinal surgeries for benign lipomatous tumors. Family history revealed paternal consanguinity and a sibling with similar neuromuscular symptoms resulting in immobility.Physical examination showed cervical lipomatosis, parotid gland enlargement, scoliosis, and lower extremity motor deficits and a BMI of 23.9 kg/m². Laboratory results demonstrated insulin resistance (C-peptide: 10.1 μg/L), hypertriglyceridemia (229 mg/dL), hypoalbuminemia, and pancytopenia consistent with hypersplenism. Imaging confirmed hepatosplenomegaly, marked cervical subcutaneous lipomatous infiltration, and peripheral neuropathy. Neck MRI revealed bilateral parathyroid region masses, more prominent on the right side, consistent with lipomatous lesions (right: 45×45 mm; left: 40×35 mm).Genetic testing identified a homozygous pathogenic variant in the MFN2 gene (c.2119C>T, p.Arg707Trp), consistent with MSL and axonal sensorimotor neuropathy. Additionally, a homozygous GNRHR variant (c.317A>G, p.Gln106Arg) was detected, consistent with hypogonadotropic hypogonadism type 7. Despite normal testosterone levels, the patient had a history of infertility, and relatives reported delayed puberty.The patient is currently treated with linagliptin and pioglitazone for glycemic control, nutritional support, and symptomatic therapy for neuropathy. Metformin was avoided due to the risk of lactic acidosis in mitochondrial dysfunction, and SGLT-2 inhibitors were contraindicated due to prior SGLT-2–induced urticaria.ConclusionThis genetically confirmed syndromic form of MSL was associated with insulin resistance, hepatic steatosis, and axonal neuropathy. Early diagnosis, genetic counseling, and multidisciplinary management are essential for the recognition of rare familial lipomatosis disorders. As one of the few reported cases with concurrent MFN2 and GNRHR mutations, this case further expands the genotype–phenotype spectrum of MSL.Figure 1:Neck MRI demonstrating extensive bilateral subcutaneous lipomatous infiltration, more prominent on the right side, with masses in the parathyroid regions (right: 45×45 mm; left: 40×35 mm), consistent with multiple symmetric lipomatosis.

Although lipoma is the most common soft tissue tumor, lipoma in the infrapatellar fat pad (IFP) is rare. Herein, we report three cases of lipoma in the IFP that penetrated the joint capsule and extended subcutaneously. All patients presented with unusual MRI findings. Patients 1, 2, and 3 were 63, 74, and 64 years old, respectively, and all were female. Their chief complaint was a knee mass; however, they did not experience pain or limitations in range of motion. The interval from initial awareness of the mass to first consultation was long (3, 8, and 13 years, respectively). MRI revealed that the mass had extended subcutaneously from the IFP through the lateral, medial, and bilateral joint capsules of the patellar tendon, respectively. On MRI, the masses appeared as lipomatous tumors with scattered low signal areas on T1-weighted imaging. The tumors excised after biopsy had long axes of approximately 6, 7, and 7 cm, respectively. Histological examination revealed lipomas with partial fibrosis in all three tumors and cartilage metaplasia in the tumor from patient 3. Lipomas in IFPs often exhibit secondary changes, such as fibrosis and cartilage metaplasia, resulting in MRI findings that differ from those of typical lipomas. In the present cases, biopsy was necessary to differentiate them from atypical lipomatous tumors or Hoffa disease.

Updates in Peripheral Nerve Sheath and Adipocytic Tumors.

A pragmatic approach to lipomatous tumours of the limbs and trunk wall.

Image-intensity normalization approaches on T1-weighted MRI images for lipomatous soft tissue tumors

Abstract The term “atypical spindle cell/pleomorphic lipomatous tumor” was introduced in the WHO Classification of Soft Tissue Tumors in 2020. This tumor is an adipocytic neoplasm of benign or low-grade category, is clinically indolent, has poorly circumscribed margins, and composed of mature adipocytes, lipoblasts, atypical spindle-shaped cells, and multinucleated cells. A 75-year-old male presented with a paratesticular mass. On microscopic examination, the tumor showed a mixture of two components—adipose and fibrous tissue components—which blended with each other along with scattered atypical giant cells. Immunohistochemically, smooth muscle actin showed diffuse positivity in the spindle cells. S100 was negative in the spindle cells and giant cells but was positive in the nuclei of some adipocytes. The Ki-67 index was only 5%. CD34 and desmin were positive in the blood vessel walls—in endothelial cells and muscle layer respectively—and negative in the giant cells. Immunohistochemistry (IHC) with MDM2 (murine double minute 2) and Rb (retinoblastoma) was negative, while CDK4 (cyclin-dependent kinase 4) was variably positive in the nuclei of the spindle cells. The spectrum of adipocytic tumors that show overlapping morphologic features may pose diagnostic difficulty. Precise diagnosis of ASPLT is important, as it can be misdiagnosed as an intermediate grade or malignant lipomatous tumor. A tumor can be diagnosed as ASPLT when it is composed of a heterogeneous mixture of adipocytes, spindle cells with focal atypia, and multinucleated cells. Lipoblasts are not mandatory for diagnosis. IHC with MDM2, Rb1, Ki67, and molecular testing is helpful in differentiating benign ASPLT from other entities and in ensuring a better prognosis. CDK4 is not found to be useful.

Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDL) is a rare low-grade malignant tumor primarily composed of adipose tissue. Although lipomatous tumors commonly develop in the subcutaneous tissues, those originating from the chest wall are infrequently reported. Accurate diagnosis and appropriate treatment are essential, given the tumor's potential for local recurrence despite its low metastatic risk. We report the case of a 45-year-old man with a firm, enlarging, and painless mass in the left anterior lower chest wall. Imaging revealed a well-defined, fat-attenuated mass (4.8 × 5.0 × 5.2cm) located in the left precardial subcostal space. Incisional biopsy suggested a lipomatous neoplasm. Thoracoscopic-assisted total removal excision was performed. Histopathological analysis showed mature adipose tissue with stromal cell atypia and muscle infiltration. Immunohistochemistry was negative for MDM2 and CDK4. Due to close microscopic margins and the tumor's deep location, adjuvant radiation therapy was administered. The final diagnosis was ALT. No recurrence was noted at the about 2-year follow-up, and the patient reported excellent postoperative quality of life. ALT of the chest wall is rare, and its management requires accurate diagnosis, complete resection, and consideration of adjuvant therapy when margins are close. This case contributes to the limited literature on subcostal ALT and emphasizes a multidisciplinary approach.

Background/Objectives: Differentiating atypical lipomatous tumours (ALT) from lipomas remains challenging, as both share similar clinical and radiological features but require different forms of management. We previously proposed a clinical-radiological score integrating routine parameters to improve preoperative discrimination. This study aimed to externally validate the score in an independent cohort and refine it for enhanced robustness. Methods: We retrospectively analysed 119 patients with lipomatous tumours treated between 2022 and 2024 at an external university hospital. Diagnostic performance of the original models was assessed using receiver operating characteristic analysis. Data were then combined with the initial development cohort (n = 106) to recalibrate the models and define new cut-offs. Results: In the external validation cohort, predictive accuracy decreased compared to the derivation cohort, especially in extremity tumours assessed without contrast (AUC 0.830 vs. 0.942). Across four recalibrated models in the combined dataset (n = 225), diagnostic accuracy remained high (AUCs 0.918-0.954). Models combining clinical and imaging parameters consistently outperformed single-parameter approaches, with contrast enhancement providing the greatest incremental value. Accuracy was lower in trunk-localised tumours, highlighting the need for molecular confirmation in selected subgroups. Conclusions: The re-modelled score demonstrated robust diagnostic accuracy and practicality for routine use, offering a resource-efficient tool to support preoperative risk stratification. While molecular testing remains essential in high-risk cases, the refined score may reduce unnecessary testing and facilitate tailored diagnostic strategies. To support clinical adoption, the score is available as a web application that automatically selects the appropriate model and presents results in a colour-coded format.

Rationale:Lipomatous tumors are rare in the pediatric population. Lipomatous tumors may develop at any location throughout the body; however, they are highly uncommon in the retroperitoneal area. Lipomatous tumors represent the predominant category of soft-tissue neoplasms. Only 3 cases of pediatric retroperitoneal lipoma have been reported since 1980. We report a benign retroperitoneal lipomatous tumor and the literature compilation of benign retroperitoneal lesions.Patient concerns:A 2-year-old South Asian female presenting with 13 months of increasing abdominal distention and intermittent fever was referred to our hospital. The child had no trauma or gastrointestinal symptoms like vomiting, diarrhea, or constipation.Diagnoses:An abdominal ultrasound showed a large, echogenic mid-abdomen tumor. The tumor obscured the bowel without calcification or fat necrosis. A color Doppler scan indicated no blood flow in the lesion. The computed tomography scan of the neck, chest, and abdomen with IV contrast showed a well-circumscribed, non-enhancing, heterogeneous hypodense mass from the left hypochondrium to the pelvis on the left abdominal region. The mass measured 18.4 × 14.8 × 13.6 cm, and its Hounsfield units ranged from −66 to −90, indicating adipose tissue. Histopathology showed a benign lipoma made of mature fat cells and thinsultory fibrils with no malignancy, cellular atypia, or necrosis.Interventions:The patient had surgical resection via laparotomy, achieving complete resection with negative margins.Outcomes:The patient was discharged on the 4th day after the procedure, after an uneventful recovery. After 6 weeks, the child was asymptomatic in follow-up.Lessons:The long-term prognosis of the retroperitoneal lipoma among children remains inadequately characterized relative to adults due to a small number of cases. Current literature suggests magnetic resonance imaging, computed tomography scan, and FISH are the most suitable diagnostic options. Extended follow-up is essential in pediatric patients.

Demonstration of MDM2 amplification is currently recommended to confirm the diagnosis of well-differentiated adipocytic tumors arising in the retroperitoneum, abdomen, and pelvis; recurrent "lipomas"; those with equivocal cytologic atypia; deep extremity tumors >10cm which lack cytologic atypia and occur in patients >50years old, and in special clinical circumstances (Clay et al., 2015 [Clay criteria]). In our practice, fluorescence in situ hybridization studies (FISH) for MDM2 were historically performed for all referred-in testing requests, for all well-differentiated fatty tumors >10cm, and to confirm the diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) in cases with definite atypia. As part of a test utilization review, after exclusion of dedifferentiated liposarcoma, we reviewed 1151 ostensibly fatty tumors on which FISH was successfully performed. After exclusion of 203 cases for which testing was inappropriate or indicated for other reasons, 233/948 (24.6%) fatty tumors met at least one Clay criterion, and 222 (23.4%) had definite nuclear atypia. Among tumors with definite atypia, 152 (68.5%) were ALT/WDL, and 48 (21.6%) were spindle cell/pleomorphic lipoma arising in unusual locations or atypical spindle cell/pleomorphic lipomatous tumors. Thirty (12.9%) cases meeting any Clay criteria were ALT/WDL, and 4/453 (0.9%) tumors not meeting Clay criteria or having atypia were ALT/WDL. The sensitivity of Clay criteria plus nuclear atypia for ALT/WDL was 97.8%, while specificity was 62.7%. We conclude that it is safe to defer MDM2 FISH in well-differentiated fatty tumors not meeting Clay criteria and lacking nuclear atypia.

ABSTRACTSpindle cell lipomas (SCL) and pleomorphic lipomas (PL) are today considered a single tumor entity (SCLPL). Atypical SCLPL, in contrast, represents a recently recognized related but distinct entity. Here we explored the correlation between genomic features and morphological aspects of SCLPL and atypical SCLPL and the role of the RB1 gene in tumor development. Seventy‐one samples from 68 patients with SCLPL or atypical SCLPL, as well as a lipomatous tumor from a retinoblastoma patient with a germline pathogenic variant in the RB1 gene, and two pleomorphic liposarcomas were analyzed using chromosome banding, high‐resolution genomic arrays (SNP array), whole exome sequencing (WES), and/or RNA sequencing (RNA‐seq). Common for all tumors was involvement of 13q; other recurring variants were deletion of 16q, 6q, and 17p. A minimally deleted region that only contained RB1 was found on 13q. A distinction was seen between SCL on the one hand and PL and atypical SCLPL on the other; SCL had fewer copy number aberrations in general, and loss of 17p/TP53 gene or a SNV affecting TP53 was only rarely detected in SCL but seen in the vast majority of PL and atypical SCLPL tumors. Thus, at the molecular level, SCL is different from PL/atypical SCLPL. Furthermore, the finding of the same copy number changes (loss of 13q, 6q, 16q, and 17p) in some pleomorphic liposarcomas raises the possibility that a subset of SCLPL/atypical SCLPL have the potential for malignant transformation.

Lipoma and well-differentiated liposarcoma are clinically differentiated by site of origin and length, and pathologically differentiated by immunostaining with MDM2 and CDK4. An 82-year-old male patient. A retroperitoneal lipomatous tumor which compressed intraabdominal organs was found on CT and MRI scan. Laparotomy for retroperitoneal tumor resection was performed. Lipomatous tumor more than 10 cm was extirpated. The pathological diagnosis was retroperitoneal intramuscular lipoma. One year after surgery, there is no sign of tumor recurrence.