An overview on liposarcoma subtypes: Genetic alterations and recent advances in therapeutic strategies.

Liposarcoma (LPS) is a rare malignancy of adipocytic differentiation. According to World Health Organization classification, LPS comprises of four principle subtypes Atypical lipomatous tumor/Well-differentiated liposarcoma (ATL/WDLPS), Dedifferentiated liposarcoma (WDLPS), Myxoid liposarcoma (MLPS), and Pleomorphic liposarcoma (PLPS). Each subtype can develop at any location and shows distinct clinical behavior and treatment sensitivity. ATL/ WDLPS subtype has a higher incidence rate, low recurrence, and is insensitive to radiation and chemotherapy. DDLPS is the focal progression of WDLPS, which is aggressive and highly metastasizing. MLPS is sensitive to radiation and chemotherapy, with a higher recurrence rate and metastasis. PLPS subtype is highly metastasizing, has a poor prognosis, and exhibiting higher recurrence rate. Initial histological analysis provides information for the characterization of LPS subtypes', further molecular and genetic analysis provides certain subtype specifications, such as gene amplifications and gene fusions. Such molecular genetic alterations will be useful as therapeutic targets in various cancers, including the LPS subtypes. A wide range of novel therapeutic agents based on genetic alterations that aim to target LPS subtypes specifically are under investigation. This review summarizes the LPS subtype classification, their molecular genetic characteristics, and the implications of genetic alterations in therapeutics.

Detection of MDM2 gene amplification on tissue microarray-based Fluorescence In-Situ Hybridization (FISH) in well-differentiated and dedifferentiated liposarcomas, displaying a wide morphological spectrum: A validation study at a tertiary cancer referral centre.

BACKGROUND: Liposarcomas including atypical lipomatous tumors (ALT)/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPSs) display a histomorphological spectrum with their several diagnostic mimics. Murine double minute 2(MDM2) gene amplification characterizes ALT/WDLPS and DDLPS. Presently, there is no documented study from our subcontinent on the validation of MDM2 gene testing in these tumors. MATERIAL AND METHODS: Twenty-eight cases, diagnosed as ALT/WDLPS (n = 5) and DDLPSs (n = 23), along with 10 other tumors were tested for MDM2 gene amplification, using fluorescence in situ hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, diagnosed as ALT/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 immunostaining. Twenty tumors were tested for p16INK4a immunostaining. RESULTS: FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as DDLPSs, 19 displayed MDM2 gene amplification. Among the 5 cases diagnosed as ALT/WDLPS, four showed MDM2 gene amplification. Finally, 19 cases were confirmed as DDLPS and 4 as ALT/WDLPS. Furthermore, 7/19 cases confirmed as DDLPS and all 4 cases as ALT/WDLPS tested for MDM2 immunostaining, displayed its diffuse immunoexpression, while a single case of DDLPS showed its focal immunostaining. None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 DDLPSs and 4 cases of ALT/WDLPS displayed p16INK4a immunostaining. The sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in ALT/WDLPS, and specificity was 100%. The sensitivity for MDM2 gene amplification was 94.7% in cases of DDLPS and 100% in cases of ALT/WDLPS. The sensitivity for p16INK4a was 100%. CONCLUSION: This constitutes the first sizable study on MDM2 testing in ALT/WDLPS and DDLPS from our subcontinent using TMAs. MDM2 gene amplification testing continues as the diagnostic gold standard for ALTs/WDLPSs and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 clone) and p16INK4a immunostaining, together seem useful for triaging cases for FISH.

Targeting abundant survivin expression in liposarcoma: subtype dependent therapy responses to YM155 treatment.

PURPOSE: Liposarcoma (LPS) represent the largest group of malignant soft tissue tumours comprising a heterogeneous group of subtypes in which the degrees of chemoresistance and radiosensitivity strongly vary. Consequently, it is of utmost interest to establish novel therapeutic regimens based on molecular targets. METHODS: Immunohistochemical staining of survivin was performed in tissue microarrays comprising 49 primary LPS specimens. LPS cell lines were treated with survivin antagonist YM155 and doxorubicin or etoposide alone as well as in combination. Changes in cell viability were investigated and the synergistic effect of a combined therapy analysed. RESULTS: Immunohistochemistry revealed an abundant expression of survivin in LPS that significantly concurred with less-differentiated tumour subtypes and grading. In vitro, we demonstrated the impact of the survivin inhibitor YM155 on dedifferentiated LPS (DDLPS) and, even more imposing, pleomorphic LPS (PLS) tumour cell viability with a strong induction of apoptosis. A combined treatment of doxorubicin or etoposide with YM155 augmented the cytotoxic effects on DDLPS and PLS cells. CONCLUSION: These findings support the significant role of survivin in the oncogenesis and progression of LPS subtypes providing a rationale to target survivin in eligible in-vivo models and to pioneer clinical applications of survivin-specific substances unfolding their therapeutic potential in LPS patients prospectively.

Clinicopathological and histopathological review of dedifferentiated liposarcoma: a comprehensive study of 123 primary tumours.

AIMS: Dedifferentiated liposarcoma (DDLS) has varying histopathological features, but their significance for the biological behaviour of this disease has not been fully clarified. The aim of this study was to elucidate the prognostic factors for DDLS by clinicopathologically reviewing a large case series. METHODS AND RESULTS: We clinicopathologically reviewed 123 cases of primary de-novo DDLS without preoperative treatment, including 81 in the internal trunk (internal DDLS) and 42 in peripheral sites (peripheral DDLS). Univariate and multivariate analyses of their features were also performed for all cases, the internal DDLS group, and the peripheral DDLS group. The results showed that, in all three groups, distant metastasis was significantly associated with shorter overall survival (OS) (univariate analysis, P < 0.0001, P = 0.0011, and P = 0.0101, respectively), whereas local recurrence showed no significant effect on prognosis. Histopathologically, a high mitotic count and the presence of round tumour cells were significantly associated with shorter OS in multivariate analysis of the internal DDLS group [respectively: P = 0.0022, hazard ratio (HR) 4.39, 95% confidence interval (CI) 1.71-11.28; and P = 0.0014, HR 7.19, 95% CI 2.14-24.16]. In the peripheral DDLS group, necrosis and high-grade histological components were significantly associated with shorter OS (univariate analysis, P = 0.0068 and P = 0.0174, respectively). CONCLUSIONS: The presence of round tumour cells may be one of the histological factors associated with a worse prognosis of DDLS patients, as previous studies indicated. This study also suggests that distant metastasis may be predictive of prognosis for both internal and peripheral DDLS, rather than local recurrence.

Myxoid pleomorphic liposarcoma-a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma.

Myxoid pleomorphic liposarcoma is a recently defined subtype of liposarcoma, which preferentially involves the mediastinum of young patients and shows mixed histological features of conventional myxoid liposarcoma and pleomorphic liposarcoma. While myxoid pleomorphic liposarcoma is known to lack the EWSR1/FUS-DDIT3 fusions characteristic of the former, additional genetic data are limited. To further understand this tumor type, we extensively examined a series of myxoid pleomorphic liposarcomas by fluorescence in situ hybridization (FISH), shallow whole genome sequencing (sWGS) and genome-wide DNA methylation profiling. The 12 tumors occurred in 6 females and 6 males, ranging from 17 to 58 years of age (mean 33 years, median 35 years), and were located in the mediastinum (n = 5), back, neck, cheek and leg, including thigh. Histologically, all cases consisted of relatively, bland, abundantly myxoid areas with a prominent capillary vasculature, admixed with much more cellular and less myxoid foci containing markedly pleomorphic spindled cells, numerous pleomorphic lipoblasts and elevated mitotic activity. Using sWGS, myxoid pleomorphic liposarcomas were found to have complex chromosomal alterations, including recurrent large chromosomal gains involving chromosomes 1, 6-8, 18-21 and losses involving chromosomes 13, 16 and 17. Losses in chromosome 13, in particular loss in 13q14 (including RB1, RCTB2, DLEU1, and ITM2B genes), were observed in 4 out of 8 cases analyzed. Additional FISH analyses confirmed the presence of a monoallelic RB1 deletion in 8/12 cases. Moreover, nuclear Rb expression was deficient in all studied cases. None showed DDIT3 gene rearrangement or MDM2 gene amplification. Using genome-wide DNA methylation profiling, myxoid pleomorphic liposarcomas and conventional pleomorphic liposarcomas formed a common methylation cluster, which segregated from conventional myxoid liposarcomas. While the morphologic, genetic and epigenetic characteristics of myxoid pleomorphic liposarcoma suggest a link with conventional pleomorphic liposarcoma, its distinctive clinical features support continued separate classification for the time being.

Histologic Subtype Defines the Risk and Kinetics of Recurrence and Death for Primary Extremity/Truncal Liposarcoma.

OBJECTIVE: We sought to define the prognostic significance of histologic subtype for extremity/truncal liposarcoma (LPS). BACKGROUND: LPS, the most common sarcoma, is comprised of 5 histologic subtypes. Despite their distinct behaviors, LPS outcomes are frequently reported as a single entity. METHODS: We analyzed data on all patients from a single-institution prospective database treated from July 1982 to September 2017 for primary, nonmetastatic, extremity or truncal LPS of known subtype. Clinicopathologic variables were tested using competing risk analyses for association with disease-specific death (DSD), distant recurrence (DR), and local recurrence (LR). RESULTS: Among 1001 patients, median follow-up in survivors was 5.4 years. Tumor size and subtype were independently associated with DSD and DR. Size, subtype, and R1 resection were independently associated with LR. DR was most frequent among pleomorphic and round cell LPS; the former recurred early (43% by 3 years), and the latter over a longer period (23%, 3 years; 37%, 10 years). LR was most common in dedifferentiated LPS, in which it occurred early (24%, 3 years; 33%, 5 years), followed by pleomorphic LPS (18%, 3 years; 25%, 10 years). CONCLUSIONS: Histologic subtype is the factor most strongly associated with DSD, DR, and LR in extremity/truncal LPS. Both risk and timing of adverse outcomes vary by subtype. These data may guide selective use of systemic therapy for patients with round cell and pleomorphic LPS, which carry a high risk of DR, and radiotherapy for LPS subtypes at high risk of LR when treated with surgery alone.

Value of clinical, ultrasonographic and MRI signs as diagnostic differentiators of non-benign lipomatous tumours.

Suspicion of malignant change within a lipoma is a common and increasing workload within the UK Sarcoma multidisciplinary team (MDT) network, and a source of considerable patient anxiety. Currently, there is no lipoma-specific data, with regard to which clinical or radiographic features predict non-benign histology, or calculate an odds-ratio specific to a lipomatous lesion being non-benign. We performed a 9-year, double-blind, unmatched cohort study, comparing post-operative histology outcomes (benign versus non-benign) versus 15 signs across three domains: Clinical (size of tumour, depth, growth noticed by patient, previous lipoma, patient felt pain), Ultrasonographic (size, depth, vascularity, heterogenous features, septae) and MRI (size, depth, vascularity, heterogenous features, septae, complete fat signal suppression). Receiver operating characteristic (ROC) analysis, odds ratios and binary logistic regression analysis was performed double-blind. When each sign is considered independently, (ROC analysis, followed by binary logistic regression) only Ultrasound depth is a significant predictor (p = 0.044) of a histologically non-benign lipoma. Ultrasonographically determined vascularity and septation were not statistically significant predictors. None of the clinical signs were statistically significant (p > 0.05). Of the MRI signs none was statistically significant (p > 0.05). However, heterogeneous MRI features fared better than MRI depth. Ultrasound signs (Pseudo R-Square = 0.105) are more predictive of the post-operation histology outcome than Clinical signs (Pseudo R-Square = 0.082) or MRI tests (Pseudo R-Square = 0.052) Ultrasound and Clinical tests combined (Pseudo R-Square = 0.147) are more predictive of the post-operation histology outcome than MRI tests (Pseudo R-Square = 0.052). This work challenges the traditional perception of "red-flag" signs when applied to lipomatous tumours. We provide accurate data upon which an informed choice can be made, and provides a robust bases for expedited risk/benefit. The importance of an experienced and cohesive MDT network is emphasised.

p53 Expression in Canine Liposarcoma Correlates With Myxoid Variant and Higher Proliferative Activity.

Canine liposarcoma is classified as well differentiated (WDL), dedifferentiated (DDL), myxoid (ML), and pleomorphic (PL). Overexpression of the protooncogene MDM2 has been reported in WDL and DDL, but little is known regarding the role of p53 in their tumorigenesis. The aim of this study was to assess p53 expression in canine liposarcoma and compare it with subtype, grade, mitotic count (MC), Ki67 labeling index (LI), and MDM2 expression. Forty-seven cases were included (13 WDL, 3 DDL, 7 ML, and 24 PL); 17 were MDM2-positive (13 WDL, 3DDL, and 1ML). Five were p53-positive (4 ML and 1 WDL) but DDL and PL were consistently negative. p53 expression correlated with higher Ki67-LI, higher MC, and myxoid histotype. No correlation was found with grade and MDM2 expression. Based on these results canine liposarcoma seems to embody a group of neoplasms whose subtypes, especially ML, may represent distinct diseases rather than morphological variants of the same entity.

New defining body (Ugras body) in polypoid dedifferentiated liposarcoma of the vallecula. Histomorphological, immunohistochemical and molecular genetic findings.

This is a description of a dedifferentiated liposarcoma seen in a 27-year-old female patient. The tumor originated from the vallecula and contains distinctive bodies. These bodies, which are formed by the aggregation of tumor cells, contain collagen in several regions and are oval or elongated in shape. Immunohistochemically, the tumor cells showed staining for MDM2, p16, Vimentin, beta catenin, smooth muscle actin, bcl-2 and p53. Ki-67 ratio was 17% in hypercellular areas of the tumor. Molecular genetic studies have found copy number increase for CDK4 and MDM2 genes. Final histopathological diagnosis was dedifferentiated liposarcoma with unique bodies. Although meningothelial-like whorls is defined in dedifferentiated liposarcoma, this body has not been defined until now. To our knowledge, this is the first case of a DDL containing a cellular spindle cell component seen as rare sheet-like areas and distinctive ball-like, or elongated, serpiginous formations in the middle of paucicellular, collagenous areas.

Diagnostic importance of clinicopathologic features and p16, CD34, MDM2 expression in differential diagnosis of adipocytic tumors.

OBJECTIVE: The aim of this study was to investigate the immunohistochemical stain profiling of adipocytic tumors. METHODS: From our archive files between the years of 2012-2018, excised, formalin-fixed and paraffin-embedded adipocytic tumors were retrospectively screened and 61 subjects were selected. The gender, age, tumor location and tumor diameter were evaluated. The cases were investigated in terms of p16, CD34, MDM2 expression and clinicopathological information. RESULTS: Of the 61 patients included in the study, we found that 2 had hibernoma, 4 had lipoblastoma, 14 had spindle cell lipoma (SCL), 10 had lipoma, 20 had atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDL), and 11 had dedifferentiated liposarcoma (DDL). In terms of diameter, ALT/WDL and DDL were significantly different from the others (p=0.001, p=0.001, respectively). There was a significant difference between the groups according to the location (p=0.001). 35% (7/20) of ALT/WDLs were in the lower extremities (thighs) and 35% (7/20) were located in the retroperitoneal region. 70% of DDLs (7/11) were located in the retroperitoneum. When CD34 expression was evaluated among the groups, a significant difference was observed (p=0.001). CD34 was positive in 92.9% of SCL cases. p16 immunoreactivity was significantly different between the groups (p=0.001). p16 expression was observed in 50.5% of ALT / WDL cases and 79% of DDL cases. CONCLUSION: p16 and CD34 expression are valuable in the differential diagnosis of lipomatous tumors when radiological and clinical considerations do not help to differential diagnosis of adipocytic tumors. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

[PET/CT imaging manifestations of different pathological subtypes of liposarcoma].

OBJECTIVE: To analyze PET/CT imaging manifestations of different pathological subtypes of liposarcoma. METHODS: The 18F-fluorodeoxyglucose(FDG) PET/CT features of 13 patients pathologically confirmed as liposarcoma were retrospectively reviewed. The metabolism degree and distribution of different subtypes of liposarcoma were compared. RESULTS: The well-differentiated liposarcoma showed fat density mass with septa and irregular strip with mild FDG uptake. The myxoid liposarcoma showed cystic or cystic solid mass, single or multiple with mild-moderate FDG uptake heterogeneously or homogeneously. The dedifferentiated liposarcoma showed mixed soft tissue mass with high FDG uptake heterogeneously, larger lesion with necrosis centrally. The mixed type contained well differentiated type and dedifferentiated type, and showed multiple lesion with combined imaging manifestations. There were local invasions in 12 cases, no lymph node matastasis, and the recurrence of dedifferentiated liposarcoma with lung metastasis in 1 case. The maximum standard values (SUVmax) of FNCCLE grade G1, G2 and G3 liposarcoma were 3.00, 5.67 and 10.33, respectively; there was significant difference between G1 and G3 groups, G2 and G3 groups (all P<0.05). CONCLUSIONS: PET/CT manifestations of liposarcoma of various pathological subtypes are different. Preoperative PET/CT examination can clarify the pathological types, scope of tumor invasion and metastasis of liposarcoma, which provides more information for clinical decision-making and is helpful for the preparation of surgical plan.

Atypical Lipomatous Tumors: Does Our Inconsistent Terminology Have Patient Repercussions? Results of a Meta-Analysis.

OBJECTIVES: Misnaming low-grade lipomatous tumors poses a clinical and medicolegal challenge, potentially subjecting patients to expensive and unnecessary surgeries. The terms atypical lipomatous tumor (ALT) and "well-differentiated" liposarcoma (WDL) have been used interchangeably in pathology reports, scholarly works and consensus recommendations, creating vagaries between low-virulence extremity tumors and retroperitoneal disease with metastatic potential. METHODS: A systematic review was performed on all studies that reported on the local recurrence rate and metastasis of ALTs and WDLs in living human subjects. Local recurrence and metastases were compared using Fisher's Exact Test. RESULTS: In total, 20 studies evaluated ALTs (n=936), whereas 13 studied WDLs (n=626). Mean follow-up was 6.6±2.0 years (median, 7.0 y). No metastatic disease was observed among ALTs, whereas 15 patients with WDLs (2.7%, P<0.0001) had metastases. The local recurrence rate of ALTs was significantly lower than WDLs after both marginal (15.1%, 141/936 vs. 46.0%, 288/626, P<0.0001) and wide excisions (3.3%, 2/59 in ALT vs. 17.4%, 19/109, P=0.007). CONCLUSIONS: ALT should be reserved for extremity lesions meeting appropriate histopathologic criteria that represent nonmetastatic disease, reducing over-diagnosis, over-treatment, and patient risk.

[Soft tissue tumors : Epidemiology, classification and staging]. / Weichteiltumoren : Epidemiologie, Klassifikation und Stadieneinteilung.

Benign, intermediate and malignant soft tissue tumors can be differentiated histologically. Furthermore, the tumors can be subdivided according to their linear differentiation. In the new World Health Organization (WHO) classification of soft tissue tumors from 2013 changes have been made relating to the allocation of known entities, e. g. undifferentiated sarcomas have been formed into a new subgroup and are no longer assigned to the fibrohistiocytic tumors. The term malignant fibrous histiocytoma has been replaced by the undifferentiated sarcoma. Furthermore, two new subgroups were incorporated, the nerve sheath tumors and gastrointestinal stromal tumors. These were previously included in the tumor classification of other organ systems. These changes in the new classification are related to the rapid increase in knowledge of the genetics and the cell biology of soft tissue tumors. Malignant soft tissue tumors only represent 1% of all malignant tumors in adults. The largest subgroup of soft tissue tumors in adults is the adipocytic tumors. The liposarcoma, which belongs to this subgroup is one of the most common malignant soft tissue tumors in adults. In childhood malignant soft tissue tumors represent 15% of malignant tumors and rhabdomyosarcoma is the most common malignant soft tissue tumor.

Current Concepts in Non-Gastrointestinal Stromal Tumor Soft Tissue Sarcomas: A Primer for Radiologists.

Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist.

Liposarcoma: Multimodality Management and Future Targeted Therapies.

There are 3 biologic groups of liposarcoma: well-differentiated and dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. In all 3 groups, complete surgical resection is central in treatment aimed at cure and is based on grade. Radiation can reduce risk of local recurrence in high-grade lesions or minimize surgical morbidity in the myxoid/round cell liposarcoma group. The groups differ in chemosensitivity, so adjuvant chemotherapy is selectively used in histologies with metastatic potential but not in the resistant subtype dedifferentiated liposarcoma. Improved understanding of the genetic aberrations that lead to liposarcoma initiation is allowing for the rapid development of targeted therapies for liposarcoma.

MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance.

This study of 140 cases assessed the incidence of MDM2/CDK4 gene amplification in lipomatous neoplasms with histological features of a lipoma but which were of clinical concern due to large size (≥50 mm) and/or deep-seated (subfascial) location. Univariate and multivariate statistical analyses were used to identify clinical, radiological and pathological predictors of gene amplification. Differences in local recurrence rates between amplified and non-amplified cases were assessed using survival analysis. The findings indicate that the incidence of MDM2/CDK4 amplification in this setting is low at 5% (95%CI 1.4-8.6%). Variables associated with amplification on univariate analysis were tumour site (thigh, p = 0.004), size (>100 mm, p = 0.033) and presence of equivocal atypia (p = 0.001). Independent predictors on multivariate analysis were size (OR 3.9, 95%CI 1.4-11.3, p = 0.012) and presence of equivocal atypia (OR 12.5, 95%CI 1.9-80.3, p = 0.008). There was no significant difference in local recurrence rates between amplified and non-amplified cases (p = 0.461) based on a median follow-up time of 31 months. Assessment for MDM2/CDK4 amplification, therefore, should be considered in 'lipomas' which are >100 mm in size, show equivocal atypia and arise in the thigh. However, the clinical significance of gene amplification in this setting is unclear and requires confirmation in larger studies.

Accuracy of preoperative percutaneous biopsy for the diagnosis of retroperitoneal liposarcoma subtypes.

BACKGROUND: Surgery is the primary treatment for all subtypes of retroperitoneal liposarcoma, but neoadjuvant therapy may be warranted in cases of dedifferentiated liposarcoma (DDLS), which has an increased risk of recurrence and metastasis. Therefore, an accurate subtype-specific diagnosis is vital for appropriate consideration of neoadjuvant therapy. Previous studies assessing the subtype-specific accuracy of percutaneous biopsy are limited. We aimed to analyze the accuracy of preoperative percutaneous biopsy in the subtype-specific diagnosis of retroperitoneal liposarcoma and thus the reliability of percutaneous biopsy in guiding decisions about neoadjuvant treatment. METHODS: We retrospectively reviewed the medical records, including the pathologic reports, interventional radiology reports, and operative reports, of patients registered in the retroperitoneal/well-differentiated liposarcoma (WDLS/DDLS) database at The University of Texas MD Anderson Cancer Center between 1993 and 2013. RESULTS: We identified 120 patients who underwent 137 preoperative percutaneous biopsies followed by surgical resections. Pathologic examination following resection indicated that 74 of the patients had WDLS and 63 had DDLS. The overall diagnostic accuracy of percutaneous biopsy for identifying the subtype of liposarcoma was 62.8 % (86/137); the accuracy for identifying WDLS was significantly higher (85.1 %; 63/74) than that for identifying DDLS (36.5 %; 23/63) (p < 0.01). CONCLUSIONS: Percutaneous biopsy has low accuracy in the diagnosis of retroperitoneal DDLS. This can potentially mislead physicians in the decision to implement neoadjuvant treatment. When developing treatment strategies, including clinical trials for patients with retroperitoneal liposarcoma, physicians should carefully consider the low accuracy of percutaneous biopsy in detecting DDLS.

Computed tomography manifestations of histologic subtypes of retroperitoneal liposarcoma.

OBJECTIVE: Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies, often occurring in deep soft tissue of retroperitoneal space. Accurate preoperative diagnosis is therefore necessary. We explored whether computed tomography (CT) could be used to differentiate between the various types of retroperitoneal liposarcoma (RPLS). METHOD: Forty-seven cases of RPLS, diagnosed surgically and histologically, were analyzed retrospectively. CT features were correlated with postoperative pathological appearance. RESULTS: The study radiologist identified 29, 11, 2, 2 and 3 RPLS as atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL), myxoid/round cell liposarcoma (ML/RCL), pleomorphic liposarcoma (PL) and mixed-type liposarcoma. Analysis of CT scans revealed the following typical findings of the different subtypes of RPLS: ALT/WDL was mainly visible as a well-delineated fatty hypodense tumor with uniform density and integrity margin; DDL was marked by the combination of focal nodular density and hypervascularity. ML/RCL, PL and mixed liposarcoma showed malignant biological behaviour and CT findings need further studies. CONCLUSIONS: CT scanning can reveal important details including internal components, margins and surrounding tissues. Based on CT findings, tumor type can be roughly evaluated and biopsy location and therapeutic scheme guided.

Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?

Dedifferentiated liposarcoma (DDLPS) has been defined as a tumor composed of well-differentiated liposarcoma associated with a nonlipogenic undifferentiated sarcoma and is genetically characterized by a 12q13-15 amplicon with MDM2 amplification. Some peripheral (extremities, trunk wall, head/neck) undifferentiated pleomorphic sarcomas (UPS) without areas of well-differentiated liposarcoma present an MDM2 amplification. We addressed whether they are true DDLPS or not. We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). For a control cohort, we described 153 patients from the Conticabase, with peripheral UPS without expression of MDM2 by IHC. By IHC, tumor cells were positive for MDM2 in 59 conventional DDLPS and in all UPS with MDM2 amplification. FISH analysis and/or quantitative polymerase chain reaction showed amplification of MDM2 in 54 conventional DDLPS and in all UPS with MDM2 amplification. The 2-year overall survival rates of UPS with MDM2 amplification, conventional DDLPS, and UPS without expression of MDM2 were 93.3%, 90.7%, and 73.9%, respectively. Such similarities in the clinical characteristics, morphology, genomic profile, and follow-up of peripheral UPS with MDM2 amplification and peripheral conventional DDLPS strongly suggest that peripheral UPS with MDM2 amplification are in fact DDLPS. Faced with histologic diagnosis of UPS, a systematic IHC evaluation of MDM2 allows a selection of cases for FISH analysis permitting the diagnosis of DDLPS.