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Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of TP53, RB1, and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of PTEN (n = 3), ATM (n = 2), and CDKN2A/B (n = 2) among other genes. Whole exome sequencing identified a TP53 variant in one case and an ATRX variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) represent a significant number of sarcomas arising within the paratesticular region. DDLPS is notorious for a broad histologic spectrum, but epithelioid morphology is rare. Herein, we describe a unique case of paratesticular DDLPS with prominent epithelioid features and molecular confirmation. The patient is 71-year-old-male who presented with multiple paratesticular masses. Morphologic review of the resection specimen revealed a biphasic adipocytic neoplasm consistent with DDLPS. Additionally, epithelioid foci with acinar and nested architecture and focal keratin expression were noted. These areas raised the possibility of a secondary neoplasm including sex cord stromal tumor, germ cell tumor, and paraganglioma. However, MDM2 immunohistochemistry and FISH showed these areas to express MDM2 and exhibit MDM2 amplification, respectively, confirming that they represented a component of DDLPS. This case further highlights the morphologic diversity of DDLPS as well as the utility of MDM2 studies.

A 54-year-old man referred to our hospital for abdominal distension. He had no medical history. On physical examination, he complained lower abdominal distention, and had no spontaneous pain or tenderness. The blood tests showed that CEA and CA19-9 levels were within normal limits. Colonoscopy revealed a submucosal tumor with irregularities and mucosal defects in the descending colon. Computed tomography (CT) showed a 3-cm-diameter mass in the descending colon and ascites. Due to the presence of ascites, laparoscopic examination was performed, which revealed multiple peritoneal seeding of the tumor. Given the presence of peritoneal dissemination, the tumor was determined to be unresectable, and a histological examination was performed from the disseminated nodule. Pathologically, atypical spindle cells were observed and infiltrated into adipose tissue. Additional immunohistochemistry revealed positive expression for Murine double minute 2 (MDM2) and Cyclin-dependent kinase 4 (CDK4), and fluorescence in situ hybridization showed amplification of MDM2. Thus, the tumor was diagnosed with a dedifferentiated liposarcoma of the descending colon. Liposarcoma is a type of soft-tissue sarcoma that arises from soft tissues such as the extremities or retroperitoneum. Here, we report an extremely rare case of a dedifferentiated liposarcoma of the colon., (© 2023. Japanese Society of Gastroenterology.)

Sarcomas are rare malignancies, the number of reports is limited, and this rarity makes further research difficult even though liposarcoma is one of major sarcomas. 2D cell culture remains an important role in establishing basic tumor biology research, but its various shortcomings and limitations are still of concern, and it is now well-accepted that the behavior of 3D-cultured cells is more reflective of in vivo cellular responses compared to 2D models. This study aimed to establish 3D cell culture of liposarcomas using two different methods: scaffold-based (Matrigel extracellular matrix [ECM] scaffold method) and scaffold-free (Ultra-low attachment [ULA] plate). Lipo246, Lipo224 and Lipo863 cell lines were cultured, and distinctive differences in structures were observed in Matrigel 3D model: Lipo224 and Lipo863 formed spheroids, whereas Lipo246 grew radially without forming spheres. In ULA plate approaches, all cell lines formed spheroids, but Lipo224 and Lipo863 spheroids showed bigger size and looser aggregation than Lipo246. Formalin fixed, paraffin embedded (FFPE) blocks were obtained from all 3D models, confirming the spheroid structures. The expression of MDM2, Ki-67 positivity and MDM2 amplification were confirmed by IHC and DNAscope™, respectively. Protein and DNA were extracted from all samples and MDM2 upregulation was confirmed by western blot and qPCR analysis. After treatment with MDM2 inhibitor SAR405838, DDLPS spheroids demonstrated different sensitivity patterns from 2D models. Taken together, we believed that 3D models would have a possibility to provide us a new predictability of efficacy and toxicity, and considered as one important process in in vitro pre-clinical phase prior to moving forward to clinical trials., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Background/aim: Dedifferentiated liposarcoma (DDLS) is a type of soft-tissue sarcoma with a poor prognosis due to distant metastasis and resistance to chemotherapy. The antimalarial drug chloroquine (CQ) can induce apoptosis in cancer cells. CQ in combination with rapamycin (RAPA), an mTOR inhibitor, has shown efficacy on osteosarcoma and other types of cancer. In the present study the efficacy of RAPA combined with CQ on the treatment of a DDLS patient-derived orthotopic xenograft (PDOX) model was investigated., Materials and Methods: A patient-derived DDLS was transplanted into the left retroperitoneum of nude mice to establish a DDLS PDOX nude-mouse model. The mice were randomly divided as follows: untreated control group; CQ group; RAPA group; combined CQ and RAPA group (n=7 for all groups). During the treatment period, tumor volume was measured every 3-4 days with calipers. After 2 weeks treatment, the mice were sacrificed, and H&E staining was performed for histological evaluation. The TUNEL assay was performed to detect apoptosis., Results: The combination of CQ and RAPA arrested tumor growth in the DDLS PDOX compared to the untreated control (p=0.009) and was significantly more effective than RAPA alone (p=0.009). RAPA alone slowed tumor growth, but the difference was not statistically significant (p>0.05). CQ was not active alone (p>0.05). The number of apoptotic TUNEL-positive cells was significantly higher in the CQ plus RAPA group than in the other groups (p=0.02)., Conclusion: Combination therapy with CQ and RAPA arrested tumor growth in a DDLS PDOX model by inducing apoptosis., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Dedifferentiated liposarcoma (DDLPS) is morphologically characterized by well-differentiated liposarcomas associated with high-grade non-lipogenic sarcoma and molecularly characterized by the coamplification of MDM2 and CDK4(12q14-15). DDLPS is highly aggressive, and effective systemic chemotherapy has not been developed yet. In this study, we established a novel DDLPS cell line, NCC-DDLPS6-C1, as a potential tool for the development of novel therapies. NCC-DDLPS6-C1 cells were established from surgically resected tumor tissues of a patient with DDLPS. Amplification and overexpression of MDM2 and CDK4 were observed in NCC-DDLPS6-C1 cells. NCC-DDLPS6-C1 cells proliferated rapidly, invaded aggressively, and formed spheroids. Moreover, NCC-DDLPS6-C1 cells formed tumors in mice. These observations suggested that the malignant potentials that may reflect the original features of DDLPS were retained in the NCC-DDLPS6-C1. Anticancer drugs that significantly reduced the proliferation of NCC-DDLPS6-C1 cells were identified by drug library screening. Thus, NCC-DDLPS6-C1 may recapitulate the original genotypes and phenotypes, and we conclude that the NCC-DDLPS6-C1 cell line is a useful resource for the study of DDLPS., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

While liposarcoma is one of the most common soft tissue sarcomas, it is rarely seen within the gastrointestinal tract, and even less frequently seen within the colon. Dedifferentiated liposarcoma is a subtype of liposarcoma, which along with the pleomorphic subtype is considered a high-grade, aggressive tumor; both possess the ability to metastasize and are associated with decreased survival. Despite complete resection, recurrence is common. While surgical excision is the cornerstone of treatment for liposarcoma of the colon, there is no consensus on adjuvant therapies. We present the case of a 66-year-old woman who presented with abdominal pain with rectal bleeding and was found on colonoscopy to have a high-grade dedifferentiated liposarcoma of the transverse colon. She underwent robotic segmental colectomy. Due to absence of nodal involvement or distal metastasis, adjuvant therapy was not administered. On 1-year follow-up, the patient remains disease free.

Background: While soft-tissue sarcomas (STSs) are rare tumors, liposarcomas are among the most common type of STS and are divided into four main subtypes: atypical lipomatous tumor/well-differentiated liposarcoma; dedifferentiated liposarcoma; myxoid/round-cell liposarcoma (MLPS); and pleomorphic liposarcoma (PLPS). The four different subtypes of liposarcomas have varying underlying molecular pathology, clinical behavior, and treatment sensitivity., Summary: Surgical resection is the mainstay of treatment for patients with localized liposarcoma. Radiotherapy is often used in conjunction with surgery for improving local control of liposarcoma, with MLPS being the most radiosensitive of the four subtypes. For unresectable, advanced, or metastatic disease, the effectiveness of chemotherapy can vary by subtype, with MLPS and PLPS being considered to be chemo-sensitive; however, median survival is low at around 2 years. Current first-line treatment options for patients with liposarcoma include local treatment with or without doxorubicin, ifosfamide, or a doxorubicin-ifosfamide combination, while second-line (and beyond) treatment options include ifosfamide, gemcitabine-based combinations, trabectedin, eribulin, and possibly pazopanib as established therapies. A number of other experimental treatment options are being evaluated, including mouse double minute 2 homolog antagonists, cyclin-dependent kinase 4/6 inhibitors, immune checkpoint modulators, nuclear export inhibitors, multi-kinase inhibitors, peroxisome proliferator-activated receptor gamma agonists, or various combination regimens. This review discusses established systemic therapies and emerging experimental treatment options for the treatment of patients with liposarcoma., Key Message: New treatments are needed to effectively treat liposarcomas. Results from trials exploring experimental therapeutic options will further define the role that these new treatments will play in the management of the different subtypes of liposarcoma., (© 2022 S. Karger AG, Basel.)

Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well-differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra-tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good-prognosis and the poor-prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]-log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P < .001) and poor distant metastasis-free survival (DMFS) (P < .001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis., (© 2020 Wiley Periodicals LLC.)

Pleomorphic sarcomas are a heterogeneous group of mesenchymal neoplasms with widely varied clinical behavior but overlapping histologic appearances. The following guidelines are helpful when approaching the diagnosis of a pleomorphic sarcoma. (1) Be aware of the relative incidence of the various sarcoma types: several pleomorphic sarcomas are relatively common (e.g., dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma), whereas others are exceptionally rare. (2) Pay attention to anatomic location: some pleomorphic sarcomas have a predilection for somatic soft tissues, especially the thigh (e.g., undifferentiated pleomorphic sarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma), whereas other pleomorphic sarcomas most often arise in the retroperitoneum (e.g., dedifferentiated liposarcoma). (3) Carefully sample the resection specimen, paying particular attention to areas with differences in gross appearances (e.g., fleshy, fibrous, mucoid, or gritty). (4) Search for histologic clues (i.e., myxoid stroma, lipoblasts, and osteoid matrix, in order to diagnose myxofibrosarcoma, pleomorphic liposarcoma, and extraskeletal osteosarcoma, respectively); these critical diagnostic features may be limited in extent. (5) Apply immunohistochemistry judiciously, after generating a differential diagnosis; always exclude metastatic sarcomatoid carcinoma and melanoma before diagnosing a pleomorphic sarcoma. This review will present an approach to the diagnosis of pleomorphic sarcomas, emphasizing differential diagnosis and the application of ancillary studies (immunohistochemistry and FISH), when relevant., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction:Soft tissue sarcomas are rare tumors comprising 1 percent of solid malignancies. The latest edition of WHO soft tissue pathology lists 94 benign and malignant soft tissue tumors. Many of these show a large degree of morphological overlap. Immunohistochemistry has been shown to be reliable in many cases for differential diagnosis of lesions, although cytogenetic tests are considered the gold standard for many entities.Fluorescence in-situ hybridization (FISH) is a cytogenetic technique that uses fluorescent probes that bind to only those parts of the chromosome which have a high degree of sequence complementarity. Many soft tissue tumors show recurrent genetic mutations that are now being used as diagnostic markers. Knowledge of the molecular identity allows prediction of behavior, prognosis and treatment response. Objective:The aim of this study was to identify genetic mutations in soft tissue sarcomas using FISH testing and to assess correlations with histological diagnosis. Material and methods:A total of 25 cases of different soft tissue sarcomas diagnosed on histology with the help of immunohistochemical staining and for which FISH studies were requested were included in this study. Three pathologists with a special interest in soft tissue sarcomas reviewed the cases. FISH tests for EWS, the X:18 translocation, FOXO1 and MDM2 were respectively applied for 8 cases of Ewing sarcoma, 8 cases of synovial sarcoma, 2 cases of rhabdomyosarcoma and 7 cases of dedifferentiated liposarcoma and atypical lipomatous tumors/well differentiated liposarcomas. Results:EWS gene fusion was detected in 7 out of 8 cases of Ewing sarcoma and the X:18 translocation was positive in 3 of the 8 cases of synovial sarcoma. FOXO1 was not detected in either of the two rhabdomyosarcomas. MDM2 by FISH was detected in only one out of 5 cases of atypical lipomatous tumors and 1 out of 2 dedifferentiated liposarcomas. Conclusion: FISH is a useful adjunct in the diagnostic assessment of different types of soft tissue sarcomas. It is easy to set up, is relatively inexpensive and has the ability to diagnose sarcomas with great accuracy, especially in cases which can not be accurately classified even after thorough histological and immunohistochemical evaluation. It may play a very important role in the accurate diagnosis and correct management of patients., (Creative Commons Attribution License)

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

In the 10 years that have elapsed since trabectedin was first granted approval in Europe for treatment of advanced soft tissue sarcoma (STS), other cytotoxic agents and targeted therapies have been approved and numerous randomized controlled trials have been completed or are underway. As an academic exercise and positive proof of the advances in STS management that have occurred during the past decade, it is interesting to compare current and future treatment approaches. In this review, present and future treatment approaches are examined by case study for three STS subtypes: uterine leiomyosarcoma, abdominal dedifferentiated liposarcoma and malignant solitary fibrous tumor.

Primary sarcomas and sarcoma metastases are a rarity in the spleen. We report on the case of a 69-year-old male patient presenting with unclear abdominal symptoms and computed tomography (CT) revealed a tumor mass in the spleen. Histologically the tumor mass predominantly showed features of a spindle cell sarcoma with lymphoid infiltrates. The expression and amplification of MDM2 could be demonstrated by means of immunohistochemistry and fluorescence in situ hybridization (FISH). Furthermore, staging examinations did not reveal indications of any other primary tumors. These preliminary findings were suggestive of a dedifferentiated liposarcoma; however, in the further diagnostic work-up the tumor showed strong expression of CD21 and CD23 and was ultimately diagnosed as a follicular dendritic cell sarcoma (FDCS). The case emphasizes that MDM2 expression represents a possible pitfall in the diagnosis of spindle cell tumors. The differential diagnostic distinction between FDCS and a dedifferentiated liposarcoma is discussed.

Liposarcoma is one of the most common soft tissue sarcomas found in adults, and it usually occurs in the retroperitoneum and the extremities. Here, we describe a case of dedifferentiated liposarcoma originating from a well-differentiated liposarcoma of the mesorectum that presented as a protruding mass in the rectal lumen. Hartmann's operation with total mesorectal excision was performed and the tumor was removed radically. No management guidelines are currently available for liposarcoma of the rectum. We propose that complete surgical resection be required for the treatment of rectal liposarcoma and that a long-term detailed follow up is necessary.

Background: Dedifferentiated liposarcoma (DDLPS) is a rare mesenchymal cancer originating from the adipose tissue, with poor survival rates for most patients, highlighting the critical need for novel treatment options. Case description: This report examines the efficacy and safety of sequential pre-treatment with the marine-derived alkaloid trabectedin followed by checkpoint inhibition using the anti-PD-1 antibody nivolumab in a 63-year-old male patient with unresectable retroperitoneal DDLPS. Treatment was initiated at the time of the seventh relapse as part of the NitraSarc phase 2 multicenter trial for inoperable soft tissue sarcoma conducted by the German Interdisciplinary Sarcoma Group (GISG-15, NCT03590210). The patient demonstrated an immediate tumor response, and in combination with minor surgery, achieved R0 resection status, which was subsequently maintained without the need for further therapy for the past 52 months. Correlative molecular analyses revealed a sustained DNA damage repair machinery and downregulation of PD-1 protein expression in post-treatment tumor samples. Conclusion: This report provides exemplary insight on the feasibility and efficacy of sequential pre-treatment with trabectedin as a priming strategy for PD-1 inhibition in advanced DDLPS. Full trial results from NitraSarc are pending for publication. [ABSTRACT FROM AUTHOR]

Dedifferentiated liposarcoma is a malignant lipomatous tumor that rarely occurs in the gastrointestinal tract, including the ileocecal region. In this case, computed tomography and magnetic resonance imaging showed no fatty mass located in the mesenteric or submucosal lesion, and positron emission tomography–computed tomography showed a high maximum standardized uptake value, collectively indicating the gastrointestinal stroma tumor and lymphoma. The pathological findings resemble leiomyosarcoma; the immunohistochemistry findings including mouse double minute 2 homolog and cyclin D-dependent kinase-4 and amplification of mouse double minute 2 homolog in fluorescence in situ hybridization just favored the diagnosis of dedifferentiated liposarcoma with leiomyosarcoma phenotype and not leiomyosarcoma. Recently, a new inhibitor for mouse double minute 2 homolog and cyclin D-dependent kinase-4 has been developed, and clinical trials for dedifferentiated liposarcoma are currently ongoing. This could change the treatment strategy drastically compared with other soft tissue sarcomas. Hence, a correct diagnosis of dedifferentiated liposarcoma is required. [ABSTRACT FROM AUTHOR]

This correspondence addresses the article published by Nie et al. titled "Primary extraskeletal osteosarcoma of sigmoid mesocolon: a case report and a review of the literature". Their report highlighted an extremely rare case of extraskeletal osteosarcoma (EO) in the sigmoid mesocolon that was diagnosed through imaging and histopathological findings. Diagnosing EO has certain challenges; one of them being the lack of characteristic image findings of EO and the other being the lack of appropriate immunohistochemical (IHC) markers in the histopathological findings. Recently, special AT-rich sequence-binding protein 2 (SATB2) has been proposed as an IHC marker for osteoblastic differentiation; however, it has low specificity. Some cases of EO may show findings such as mouse double minute protein 2 expression and deletion of histone H3 lysine 27 trimethylation (H3K27me3), which are similar to those of other soft tissue sarcomas. Therefore, it is essential to consider other soft tissue sarcomas, especially dedifferentiated liposarcoma, before the accurate diagnosis of EO. [ABSTRACT FROM AUTHOR]

The article discusses the novel role of MDM2 in the diagnosis and treatment of dedifferentiated liposarcoma, a subtype of liposarcoma that often occurs in the retroperitoneum. It highlights the importance of MRI, histopathology, and treatment strategies in managing this condition. The study emphasizes the significance of MDM2 and CDK4 in immunohistochemistry and fluorescence in situ hybridization for accurate diagnosis and potential therapeutic targets. The research provides insights into the clinical features, diagnostic challenges, and treatment options for dedifferentiated liposarcoma, contributing to advancements in the field of oncology. [Extracted from the article]

Background: Pulmonary nodules in patients with soft tissue sarcomas are likely pulmonary metastases, whereas synchronous primary pulmonary sarcomas are rare. Without surgery, determining whether a solitary pulmonary nodule is a primary or metastatic nodule is difficult. Herein, we report a rare case of a primary pulmonary sarcoma that presented synchronously with a primary dedifferentiated liposarcoma. Case presentation: A 77-year-old man presented to another hospital with left inguinal swelling and a suspected recurrent inguinal hernia. Computed tomography revealed a left inguinal mass and pure-solid nodule in the left lung and the patient was referred to our hospital for detailed examination and treatment. The inguinal mass was pathologically diagnosed as a dedifferentiated liposarcoma using needle biopsy, whereas bronchoscopic biopsy revealed histological findings suggestive of a sarcoma; however, the primary site could not be determined. Positron emission tomography–computed tomography revealed no high-accumulation lesions except for the two sarcomas. We decided to perform surgery on both sarcomas for diagnostic and curative purposes. The surgical specimens showed that the two sarcomas were different. Based on the immunohistochemical staining findings of MDM2, a left inguinal dedifferentiated liposarcoma and primary pulmonary unclassified sarcoma were diagnosed. The patient displayed no evidence of recurrence 1 year after surgery. Conclusions: We encountered a rare case of synchronous multiple primary sarcomas, one presenting in the lung and the other in the soft tissue. Surgery was required to achieve a definitive diagnosis for the patient, who achieved disease-free survival at 1 year. This case suggests that proactive resection of pulmonary nodules in patients with soft tissue sarcomas may be feasible as a diagnostic treatment if complete resection is achieved. [ABSTRACT FROM AUTHOR]

Background: Dedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated. Methods: This retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed. Results: A total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes. Conclusions: This is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted. [ABSTRACT FROM AUTHOR]

BackgroundDedifferentiated liposarcoma (DDLPS) is a rare mesenchymal cancer originating from the adipose tissue, with poor survival rates for most patients, highlighting the critical need for novel treatment options.Case descriptionThis report examines the efficacy and safety of sequential pre-treatment with the marine-derived alkaloid trabectedin followed by checkpoint inhibition using the anti-PD-1 antibody nivolumab in a 63-year-old male patient with unresectable retroperitoneal DDLPS. Treatment was initiated at the time of the seventh relapse as part of the NitraSarc phase 2 multicenter trial for inoperable soft tissue sarcoma conducted by the German Interdisciplinary Sarcoma Group (GISG-15, NCT03590210). The patient demonstrated an immediate tumor response, and in combination with minor surgery, achieved R0 resection status, which was subsequently maintained without the need for further therapy for the past 52 months. Correlative molecular analyses revealed a sustained DNA damage repair machinery and downregulation of PD-1 protein expression in post-treatment tumor samples.ConclusionThis report provides exemplary insight on the feasibility and efficacy of sequential pre-treatment with trabectedin as a priming strategy for PD-1 inhibition in advanced DDLPS. Full trial results from NitraSarc are pending for publication.

Introduction: Liposarcomas are the most common of all sarcomas. A well-differentiated liposarcoma can transform into a dedifferentiated liposarcoma with myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of MDM2 gene is then characteristic. Treatment usually involves surgical resection to radically remove the tumor. Other treatments such as chemotherapy and radiotherapy may also be used. Case report: A 60-year-old patient was admitted to the hospital for surgical treatment of a left renal mass. The true location of the tumor was discovered only intraoperatively. The lesion was completely removed laparoscopically with preservation of the capsule. Genomic amplification of MDM2 gene was confirmed. One and a half years after surgery, despite the removal of the tumor without the surrounding margin of healthy tissue, the patient remains without recurrence. Conclusion: Dedifferentiated liposarcoma with osteosarcomatous differentiation is a sporadic case and may occur in various locations of the retroperitoneal space, also mimicking a renal tumor. The laparoscopic technique is a safe surgical treatment for tumors of unclear origin. Removal of dedifferentiated liposarcoma with osteosarcomatous differentiation tumor with preservation of the lesion capsule without maintaining a margin of healthy tissue also allows for long-term cure. Precise immunohistochemical and molecular studies may have an impact on the effectiveness of further treatment and the prognosis of the patient. A patient after surgical treatment of liposarcoma requires constant outpatient follow-up for the reason of the high risk of local and distant recurrence. [ABSTRACT FROM AUTHOR]

Primary liposarcoma of the breast is an uncommon soft tissue malignant tumor, comprising only 0.003% of all malignant breast tumors. The main differential diagnosis of this mass consists of malignant phyllodes tumor and metaplastic breast carcinoma. The objective of this paper is to report a case of dedifferentiated breast liposarcoma, therapeutic approach and outcome. We present a case of a 79-year-old woman complaining of a large mass in her left breast which had increased in size over the last 6 months. Physical examination revealed an enlarged left breast, and a total body CT scan showed a large tumor in contact with the musculature of the anterior thoracic wall, with no metastatic lesions. The histopathology report of a fine needle biopsy described a high-grade sarcoma. The Oncological Tumor Board recommended neoadjuvant radiotherapy sessions and reevaluation by MRI and CT scans. The patient underwent radical mastectomy with latissimus dorsi myo-cutaneous flap reconstruction. The final histopathology diagnosis was a grade 3 dedifferentiated liposarcoma (FNCLCC), with certain response to radiotherapy and positive MDM2, CDK4 markers. The postoperative period was uneventful; 12 months after surgery, the follow-up CT scan showed multiple pulmonary lesions with metastatic characteristics. Liposarcoma is a very rare type of breast cancer, and the most important treatment for breast sarcoma is surgery, the role of axillary lymph node removal, chemotherapy and radiotherapy still being controversial. Considering such cases are scarce and the development of surgical guidelines is difficult, reporting any new case is crucial. [ABSTRACT FROM AUTHOR]

Introduction: Liposarcomas are the most common of all sarcomas. A well-differentiated liposarcoma can transform into a dedifferentiated liposarcoma with myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of MDM2 gene is then characteristic. Treatment usually involves surgical resection to radically remove the tumor. Other treatments such as chemotherapy and radiotherapy may also be used. Case report: A 60-year-old patient was admitted to the hospital for surgical treatment of a left renal mass. The true location of the tumor was discovered only intraoperatively. The lesion was completely removed laparoscopically with preservation of the capsule. Genomic amplification of MDM2 gene was confirmed. One and a half years after surgery, despite the removal of the tumor without the surrounding margin of healthy tissue, the patient remains without recurrence. Conclusion: Dedifferentiated liposarcoma with osteosarcomatous differentiation is a sporadic case and may occur in various locations of the retroperitoneal space, also mimicking a renal tumor. The laparoscopic technique is a safe surgical treatment for tumors of unclear origin. Removal of dedifferentiated liposarcoma with osteosarcomatous differentiation tumor with preservation of the lesion capsule without maintaining a margin of healthy tissue also allows for long-term cure. Precise immunohistochemical and molecular studies may have an impact on the effectiveness of further treatment and the prognosis of the patient. A patient after surgical treatment of liposarcoma requires constant outpatient follow-up for the reason of the high risk of local and distant recurrence.

Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity. ● The mean time to dedifferentiation was 101 months in dedifferentiation type. ● The 5-year local recurrence and metastasis-free survival were 71.6% and 75.7%. ● The 5-year disease-specific survival rate was 84.7%. ● Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. ● Grade, extension, and margin in the dedifferentiated area are critical to outcomes. [ABSTRACT FROM AUTHOR]

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

Dedifferentiated liposarcoma is a nonlipogenic sarcoma of variable histological grade that frequently arises in association with a well-differentiated liposarcoma. Dedifferentiation occurs in approximately 10% of well-differentiated liposarcomas and is most commonly encountered in the retroperitoneum. Dedifferentiated liposarcoma of the upper respiratory tract is an extremely rare occurrence. Herein, we report a very rare case of low-grade dedifferentiated liposarcoma of the pharynx that presented as a polyp mimicking a benign process clinically and microscopically. We discuss the relevant molecular findings and review the current literature. [ABSTRACT FROM AUTHOR]

Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of liposarcoma that is morphologically defined as a transition from a well-differentiated lipomatous component to a non-lipogenic one. Curative therapy for DDLPS is complete resection, and the benefits of current systemic chemotherapy remain marginal. Although DDLPS is molecularly characterized by co-amplification of MDM2 and CDK4 (12q14-15) and detailed genomic analyses have been conducted by multiple research groups, the effects of molecular targeted drugs are marginal, and novel therapeutic modalities are required. Although patient-derived cell lines are pivotal for cancer research, no DDLPS cell lines are currently available from public cell repositories. Accordingly, in this study, we established a novel DDLPS cell line, NCC-DDLPS5-C1, using surgically resected tumor tissues from a patient with DDLPS. NCC-DDLPS5-C1 cells exhibited typical gene amplification, overexpression of MDM2 and CDK4, and other DNA copy number alterations. The NCC-DDLPS5-C1 cells were capable of rapid cell proliferation, aggressive invasion, and spheroid formation, but not tumor formation in mice. We reported the utility of NCC-DDLPS5-C1 cells for a drug–response assay to detect anticancer drugs that significantly attenuated cell proliferation. Thus, we concluded that the NCC-DDLPS5-C1 cell line could be a useful resource for the study of DDLPS. Considering the diversity of disease in terms of clinical outcomes, continuous efforts are required to develop more patient-derived cancer models with different clinical and pathological backgrounds. [ABSTRACT FROM AUTHOR]

Dedifferentiated liposarcoma (DDLPS) is a highly malignant subtype of liposarcoma, with characteristic amplification of MDM2 and CDK4 (12q14-15). It is caused by the dedifferentiation of well-differentiated liposarcoma. DDLPS is refractory to conventional chemotherapy; thus, surgical resection is the primary treatment modality. However, complete resection of DDLPS is difficult because of its deep location, which results in poor prognosis. Therefore, novel systemic chemotherapy is required to improve the clinical outcome. Patient-derived cell lines are important tools in the development of novel chemotherapy. However, there are no DDLPS cell lines available from public cell banks. In this study, we established a novel DDLPS cell line, NCC-DDLPS3-C1, using a surgically resected specimen from a patient with DDLPS. NCC-DDLPS3-C1 cells retained the characteristic gene amplification of MDM2 and CDK4. In addition, other gene amplifications and losses related to the poor prognosis of DDLPS were also observed in concordance with the original tumor. The cells also exhibited rapid cell proliferation, aggressive invasion ability, spheroid formation ability, and tumorigenic ability in nude mice. Furthermore, a drug-screening test showed significant antiproliferative effects of proteasome inhibitors and HDAC inhibitors. Thus, the NCC-DDLPS3-C1 cell line should be a useful tool for the development of novel chemotherapy for DDLPS. [ABSTRACT FROM AUTHOR]

Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of liposarcoma that is histologically a transition form between an atypical lipomatous tumor/well-differentiated liposarcoma and a non-lipogenic sarcoma. DDLPS is genetically characterized by a complex karyotype with copy number variations and genomic complexity. DDLPS has a poor prognosis, a high local recurrence rate, and refractory behaviors for chemotherapy and radiation, which indicate a requirement for a novel therapeutic strategy for better clinical outcomes. We report here, a novel DDLPS cell line (NCC-DDLPS2-C1) developed from a tumor tissue. NCC-DDLPS2-C1 cells showed an amplified 12q13-15 region and exhibited constant growth, spheroid formation, and invasion. High-throughput drug screening revealed distinct sensitivity between monolayer- and three-dimensional cells. Romidepsin and trabectedin especially showed high anti-proliferative effects in both culture methods of NCC-DDLPS2-C1. Thus, the NCC-DDLPS2-C1 cell line may serve as a useful resource for DDLPS studies. [ABSTRACT FROM AUTHOR]

Abstract Background Sarcomas are malignant heterogeneous tumors of mesenchymal derivation. Dedifferentiated liposarcoma (DDLPS) is aggressive with recurrence in 80% and metastasis in 20% of patients. We previously found that miR-133a was significantly underexpressed in liposarcoma tissues. As this miRNA has recently been shown to be a tumor suppressor in many cancers, the objective of this study was to characterize the biological and molecular consequences of miR-133a underexpression in DDLPS. Methods Real-time PCR was used to evaluate expression levels of miR-133a in human DDLPS tissue, normal fat tissue, and human DDLPS cell lines. DDLPS cells were stably transduced with miR-133a vector to assess the effects in vitro on proliferation, cell cycle, cell death, migration, and metabolism. A Seahorse Bioanalyzer system was also used to assess metabolism in vivo by measuring glycolysis and oxidative phosphorylation (OXPHOS) in subcutaneous xenograft tumors from immunocompromised mice. Results miR-133a expression was significantly decreased in human DDLPS tissue and cell lines. Enforced expression of miR-133a decreased cell proliferation, impacted cell cycle progression kinetics, decreased glycolysis, and increased OXPHOS. There was no significant effect on cell death or migration. Using an in vivo xenograft mouse study, we showed that tumors with increased miR-133a expression had no difference in tumor growth compared to control, but did exhibit an increase in OXPHOS metabolic respiration. Conclusions Based on our collective findings, we propose that in DDPLS, loss of miR-133a induces a metabolic shift due to a reduction in oxidative metabolism favoring a Warburg effect in DDLPS tumors, but this regulation on metabolism was not sufficient to affect DDPLS.

Dedifferentiated liposarcomas are rare; localization of these tumors in the descending colon is extremely uncommon. We describe the case of a 75-year-old man with a dedifferentiated liposarcoma originating from the descending colon that manifested as partial bowel obstruction. The very uncommon presentation of this rare disease contributed to a challenging diagnostic process. The patient was successfully treated by surgical resection of the mass through left hemicolectomy. Although exceptionally unusual, soft tissue sarcomas should be considered in the differential diagnosis for bowel obstruction. Currently, radical resection of the mass is considered to be the first-line treatment. [ABSTRACT FROM AUTHOR]

The efficacy of an immune checkpoint blockade has been demonstrated against various types of cancer, but its suitability has not been fully proven for therapies specifically targeting sarcoma. We conducted a pan-cancer tumor data analysis to identify key immune-related variables strongly associated with sarcoma prognosis, and we explored whether these expected factors are functionally correlated with anti-PD-1 therapy in humanized (Hu) NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice xenografted with dedifferentiated liposarcoma (DDLPS). We found that an abundance of hCD8+ T cells and hNK cells was functionally associated with anti-PD-1 effects in the Hu-NSG DDLPS mice. Phenotypically, these cells were shown to be hCD8+IFNγ+, hCD8+PD-1+, hCD8+Ki-67+, hCD56+IFNγ+, hCD56+PD-1+, and hCD56+Ki-67+ cells and were enriched in splenocytes and tumor-infiltrating lymphocytes (TILs) of Hu-NSG DDLPS mice treated with anti-PD-1 antibody. Moreover, a considerable increase in activated hCD56+NKp46+NKG2D+ NK cells was also detected. Our findings suggest that hCD8+ T and hNK subsets play a pivotal role in anti-DDLPS tumor effects of anti-PD-1 therapy. The results provide clinical reference for advanced anti-PD-1 therapy targeting sarcoma tumors including DDLPS. [ABSTRACT FROM AUTHOR]

Background: Well- and dedifferentiated liposarcoma (WD/DDLPS) are rare mesenchymal malignant tumors that account for 20% of all sarcomas in adults. The WD form is a low-grade malignancy with a favourable prognosis which may progress to DDLPS, a high-grade aggressive counterpart. WDLPS is referred to as atypical lipomatous tumour (ALT) when localised in extremities, due to its better prognosis. Currently the final differential diagnosis to distinguish between more aggressive and less aggressive form is based on post-surgical histological examination and no molecular biomarkers for early detection are available. Methods: Quantitative polymerase chain reaction (qPCR) analysis of 11 metabolic genes involved in general and adipose tissue-specific metabolism, was performed on ALT (= 8), WDLPS (= 9) and DDLPS (= 20) samples. Subsequent statistical analysis was carried out to determine genes that most accurately can predict DDLPS differential diagnosis. Selected genes were further validated in a separate cohort by qPCR and the data statistically analysed. Deep sequencing was performed on DDLPS specimen from the metastatic patient and on five random WDLPS specimens. Results: We established a three-gene signature based on PNPLA2, LIPE and PLIN1, which identified DDLPS with 100% sensitivity and 90% specificity, even in specimens from the WD component of DDLPS tumors. Interestingly, the PNPLA2 gene is deleted in 45% of DDLPS samples analyzed under TCGA project, and the deletion is associated with significantly lower PNPLA2 expression level. However, other mechanisms causing loss or downregulation of the expression of these three genes may be involved. Moreover, the significantly lower level of PNPLA2 is associated with R1 surgical margins, compare to R0 margins, which suggests the more invasive tumor phenotype in the absence of PNPLA2. Conclusions: The identified metabolic signature allows highly accurate differential diagnosis between WD- and DDLPS even in samples containing lipid droplets, a marker of differentiation, which makes it very suitable for the use on biopsies. In respect to the pathogenesis of the disease, our results give a new insight into possible molecular mechanisms involved and support the recent observation that deletion of PNPLA2 is a novel factor in liposarcoma progression. [ABSTRACT FROM AUTHOR]

Liposarcoma (LS) is the most common soft-tissue sarcoma. Dedifferentiated liposarcoma (DDLS) shows more aggressive biological behavior than that of well-differentiated liposarcoma (WDLS), so advanced therapeutic agents based on molecular mechanism are urgently needed. Here we show that tissue inhibitors of metalloproteinases (TIMPs) from TIMP-1 to TIMP-4 are differently expressed and regulate yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) in LS. Database analysis showed high TIMP-1 expression in DDLS patients correlating with poor prognosis, but high TIMP-4 expression in WDLS patients with better prognosis. Stable TIMP-1 knockdown inactivated YAP/TAZ and inhibited proliferation, colony formation and migration in DDLS cells, which was rescued by a constitutive active YAP. However, stable overexpression of TIMP-1 showed the opposite in WDLS cells. Stable TIMP-4 knockdown activated YAP/TAZ and promoted proliferation and migration in WDLS cells, which was suppressed by YAP/TAZ inhibitor (verteporfin) or knockdown of YAP/TAZ. Recombinant TIMP-4 showed opposite results in DDLS cells. These results indicate that dedifferentiation in LS shifts the expression of TIMPs from type 4 to type 1, inducing more aggressive behavior and poor prognosis through YAP/TAZ activation, which can be prognostic markers and therapeutic targets for LS patients. [ABSTRACT FROM AUTHOR]

Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this context, the recognition of these rare tumor types can be challenging, with significant potential for misdiagnosis as sarcomatoid carcinomas (i.e., anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or neuroendocrine carcinomas, depending upon the dominant histologic patterns. In this review, we address potential pitfalls in diagnosing selected mesenchymal neoplasms arising within or near endocrine organs, including dedifferentiated liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid sarcoma, Ewing sarcoma, and neuroblastoma. For each of these tumor types, we review clinical and pathologic features, histologic clues to distinguish them from endocrine neoplasms, and recently developed immunohistochemical markers that can be particularly useful for establishing the correct diagnosis. [ABSTRACT FROM AUTHOR]

Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, nonlipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct) liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma.

Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, nonlipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct) liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma. [ABSTRACT FROM AUTHOR]