GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases.

GLI1(12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS). The 12q amplicon can occasionally include GLI1, a gene in close proximity to CDK4. We hereby describe the first cohort of GLI1/MDM2/CDK4 coamplified WD/DDLPS. The departmental database was queried retrospectively for all cases of WD/DDLPS having undergone next-generation (MSK-IMPACT) sequencing with confirmed MDM2, CDK4, and GLI1 coamplification. Clinicopathologic data was obtained from a review of the medical chart and available histologic material. Four hundred eighty-six WD/DDLPS cases underwent DNA sequencing, 92 (19%) of which harbored amplification of the GLI1 locus in addition to that of MDM2 and CDK4. These included primary tumors (n = 60), local recurrences (n = 29), and metastases (n = 3). Primary tumors were most frequently retroperitoneal (47/60, 78%), mediastinal (4/60, 7%), and paratesticular (3/60, 5%). Average age was 63 years, with a male:female ratio of 3:2. The cohort was comprised of DDLPS (86/92 [93%], 6 of which were WDLPS with early dedifferentiation) and WDLPS without any longitudinal evidence of dedifferentiation (6/92, 7%). One-fifth (13/86, 17%) of DDLPS cases showed no evidence of a well-differentiated component in any of the primary, recurrent, or metastatic specimens. Dedifferentiated areas mostly showed high-grade undifferentiated pleomorphic sarcoma-like (26/86,30%) and high-grade myxofibrosarcoma-like (13/86,16%) morphologies. A disproportionately increased incidence of meningothelial whorls with/without osseous metaplasia was observed as the predominant pattern in 16/86 (19%) cases, and GLI1-altered morphology as described was identified in a total of 10/86 (12%) tumors. JUN (1p32.1), also implicated in the pathogenesis of WD/DDLPS, was coamplified with all 3 of MDM2, CDK4, and GLI1 in 7/91 (8%) cases. Additional loci along chromosomal arms 1p and 6q, including TNFAIP3, LATS1, and ESR1, were also amplified in a subset of cases. In this large-scale cohort of GLI1 coamplified WD/DDLPS, we elucidate uniquely recurrent features including meningothelial whorl-like and GLI-altered morphology in dedifferentiated areas. Assessment of tumor location (retroperitoneal or mediastinal), identification of a well-differentiated liposarcoma component, and coamplification of other spatially discrete genomic segments (1p and 6q) might aid in distinction from tumors with true driver GLI1 alterations.

Sclerosing well-differentiated liposarcoma: two diagnostically challenging mimicker cases and a literature review.

Liposarcoma is a malignant soft tissue tumor with several subtypes, the most common of which is well-differentiated liposarcoma (WDL) or atypical lipomatous tumor (ALT). WDL/ALTs are further divided into three histological subtypes, including lipoma-like, sclerosing, and inflammatory. While the majority of these tumors are predominantly fatty, the sclerosing variant demonstrates diverse histologic and radiographic characteristics, including variable amounts of fibrosis and fat. Because of this histological variability and relative rarity, the sclerosing WDL/ALT can present diagnostic dilemmas. We present two cases of sclerosing WDL/ALT, both of which demonstrated high degrees of fibrosis and a paucity of fat, mimicking desmoid fibromatosis and other fibrotic soft tissue tumors. Thus, it is important for radiologists to be aware of the subtypes of liposarcoma and their unique characteristics, and to consider sclerosing WDL/ALT in cases of fibrotic soft tissue tumors.

MDM4 amplification in atypical lipomatous tumors/well-differentiated liposarcoma: Private event or alternative oncogenic mechanism?

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

Atypical lipomatous tumour/well-differentiated liposarcoma found in the buccal mucosa: A rare case report.

Oral liposarcomas are uncommon diseases, the most predominant histopathological subtype being atypical lipomatous tumour/well-differentiated liposarcoma. In regard to its clinical aspects in the oral cavity, it is challenging to confirm a diagnosis and develop a treatment plan. In this case report, we present a rare case of atypical lipomatous tumour/well-differentiated liposarcoma in the right cheek of a 77-year-old male patient. Conservative surgery was performed considering the histopathological subtype of the neoplasm. Knowledge of the clinical and histopathological characteristics of this rare disease is essential to maintaining function and aesthetics through conservative treatment in older patients.

Lessons learnt from MDM2 fluorescence in-situ hybridisation analysis of 439 mature lipomatous lesions with an emphasis on atypical lipomatous tumour/well-differentiated liposarcoma lacking cytological atypia.

AIMS: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia. METHODS AND RESULTS: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17 of 75 (22.6%) ALTs/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features, consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis, or blood vessels. These cells matched the cells in which FISH showed MDM2 amplification. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL on the basis of histology lacked MDM2 amplification and were reclassified following the FISH findings. CONCLUSIONS: We conclude that a subset of lipoma-like ALTs/WDLs are not associated with any of the features typically described in ALT/WDL. Our study also showed that tumours >100 mm are more likely to be ALT/WDL; however, a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.

MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics.

Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests. Recognizing the important role that microRNAs (miRNAs) play in tumorigenesis and their potential utility in tumor classification, we analyzed routine clinical tissue samples of benign and malignant lipomatous tumors, as well as other sarcoma mimics, to identify distinguishing miRNA-based signatures that can aid in the differential diagnosis of these entities. We discovered a 6-miRNA signature that separated lipomas from WDLPS with high confidence (AUC of 0.963), as well as a separate 6-miRNA signature that distinguished DDLPS from their more aggressive histologic mimics (AUC of 0.740). Functional enrichment analysis unveiled possible mechanistic involvement of these predictive miRNAs in adipocytic cancer-related biological processes and pathways such as PI3K/AKT/mTOR and MAPK signaling, further supporting the relevance of these miRNAs as biomarkers for adipocytic tumors. Our results demonstrate that miRNA expression profiling may potentially be used as an adjunctive tool for the diagnosis of benign and malignant adipocytic tumors. Further validation studies are warranted.

Recent developments in gastroesophageal mesenchymal tumours.

The pathologist's approach to gastroesophageal mesenchymal tumours has changed dramatically during the last 25 years. In particular, gastrointestinal stromal tumour (GIST) has evolved from a wastebasket mesenchymal tumour category to a precisely defined entity with an increasingly detailed genetic subclassification. This subclassification has brought gastrointestinal mesenchymal neoplasia into the realm of precision medicine, with specific treatments optimised for particular genetic subtypes. Molecular genetic data have also greatly improved our understanding of oesophageal mesenchymal tumours, including the discovery that so-called 'giant fibrovascular polyps' in fact represent a clinically distinctive presentation of well-differentiated liposarcoma. Here, we will focus on gastroesophageal mesenchymal tumours for which there have been recent developments in classification, molecular genetics or tumour biology: granular cell tumour, 'giant fibrovascular polyp'/well-differentiated liposarcoma, plexiform fibromyxoma, gastroblastoma and, of course, GIST.

Image-Guided Core Needle Biopsy of Adipocytic Tumors: Diagnostic Accuracy and Concordance With Final Surgical Pathology.

OBJECTIVE. Diagnostic accuracy of core needle biopsy (CNB) for adipocytic tumors can be low because of sampling error from these often large, heterogeneous lesions. The purpose of this study was to evaluate the diagnostic accuracy of image-guided CNB for various adipocytic tumors in comparison with excisional pathology. MATERIALS AND METHODS. Adipocytic tumors (n = 77) of all adult patients undergoing image-guided CNB and subsequent surgical excision of an adipocytic tumor at a tertiary referral center between 2005 and 2019 were studied. To determine concordance, we compared pathologic diagnoses based on CNB to the reference standard of pathologic diagnoses after surgical excision. Tumors were divided into three categories (benign lipomatous tumors [lipoma, lipoma variants, hibernomas], atypical lipomatous tumors [ALTs] or well-differentiated liposarcomas [WDLs], and higher grade liposarcomas [myxoid, dedifferentiated, pleomorphic]), and diagnostic accuracy was calculated for each category. RESULTS. In 73 of 77 adipocytic tumors (95%), diagnosis at CNB and diagnosis after excision were concordant. Accuracy of diagnosis was poorer for ALTs and WDLs than for the other two categories, and the difference was statistically significant (p < .002). For the 29 benign lipomatous tumors and the 27 higher-grade liposarcomas, diagnoses at CNB and after excision were concordant in all cases (100%). Seventeen of the 21 tumors (81%) diagnosed as ALTs or WDLs at CNB had a concordant diagnosis after excision; four of the 21 were upgraded (dedifferentiated liposarcoma, n = 3; myxoid liposarcoma, n = 1). CONCLUSION. CNB provides high diagnostic accuracy for adipocytic tumors, particularly for benign lipomatous tumors and higher grade liposarcomas. However, though still high at 81%, diagnostic accuracy of CNB is not as high for tumors diagnosed as ALTs or WDLs. Awareness of this limitation is important when determining management, particularly of cases of ALT or WDL for which surgery is not planned.

Update on genomic and molecular landscapes of well-differentiated liposarcoma and dedifferentiated liposarcoma.

Well-differentiated liposarcoma (WDLPS) is the most frequent subtype of liposarcoma and may transform into dedifferentiated liposarcoma (DDLPS) which is a more aggressive subtype. Retroperitoneal lesions of WDLPS/DDLPS tend to recur repeatedly due to incomplete resections, and adjuvant chemotherapy and radiotherapy have little effect on patient survival. Consequently, identifying therapeutic targets and developing targeted drugs is critical for improving the outcome of WDLPS/DDLPS patients. In this review, we summarised the mutational landscape of WDLPS/DDLPS from recent studies focusing on potential oncogenic drivers and the development of molecular targeted drugs for DDLPS. Due to the limited number of studies on the molecular networks driving WDLPS to DDLPS development, we looked at other dedifferentiation-related tumours to identify potential parallel mechanisms that could be involved in the dedifferentiation process generating DDLPS.

Parosteal osteosarcoma associated with a low-grade component mimicking well-differentiated liposarcoma: a case report.

Parosteal osteosarcomas and well-differentiated liposarcomas are both well-differentiated locally aggressive tumors. They both have simple karyotypes with amplification of the 12q13-15 regions including MDM2 and CDK4 genes. In this report, we describe the case of a parosteal osteosarcoma intertwined with a low-grade component similar to a well-differentiated liposarcoma. The association of a bone component with an adipose component was initially overlooked. We describe the histological, imaging, and molecular characteristics of this tumor stressing the importance of radio-pathological correlation. To our knowledge, this is the second report of a parosteal osteoliposarcoma. Awareness of this rare presentation may allow radiologists and surgeons to recognize the peripheral fatty component as an integral part of the tumor.

Qualitative evaluation of MRI features of lipoma and atypical lipomatous tumor: results from a multicenter study.

OBJECTIVES: The objectives of the study are (1) to distinguish lipoma (L) from atypical lipomatous tumor (ALT) using MRI qualitative features, (2) to assess the value of contrast enhancement, and (3) to evaluate the reproducibility and confidence level of radiological readings. MATERIALS AND METHODS: Patients with pathologically proven L or ALT, who underwent MRI within 3 months from surgical excision were included in this retrospective multicenter international study. Two radiologists independently reviewed MRI centrally. Impressions were recorded as L or ALT. A third radiologist was consulted for discordant readings. The two radiologists re-read all non-contrast sequences; impression was recorded; then post-contrast images were reviewed and any changes were recorded. RESULTS: A total of 246 patients (135 females; median age, 59 years) were included. ALT was histopathologically confirmed in 70/246 patients. In multivariable analysis, in addition to the lesion size, deep location, proximal lower limb lesions, demonstrating incomplete fat suppression, or increased architectural complexity were the independent predictive features of ALT; but not the contrast enhancement. Post-contrast MRI changed the impression in a total of 5 studies (3 for R1 and 4 for R2; 2 studies are common); all of them were incorrectly changed from Ls to ALTs. Overall, inter-reader kappa agreement was 0.42 (95% CI 0.39-0.56). Discordance between the two readers was statistically significant for both pathologically proven L (p < 0.001) and ALT (p = 0.003). CONCLUSION: Most qualitative MR imaging features can help distinguish ALTs from BLs. However, contrast enhancement may be limited and occasionally misleading. Substantial discordance on MRI readings exists between radiologists with a relatively high false positive and negative rates.

Double minute chromosomes harboring MDM2 amplification in a pediatric atypical lipomatous tumor.

Adipocytic tumors are rare in children and are mostly benign. Less than 25 cases of pediatric well-differentiated liposarcoma (WDLPS), atypical lipomatous tumors (ALT), and dedifferentiated liposarcoma (DDLPS) have been reported. Among them, only three cases were genetically analyzed. We describe the genetic features of a rapidly growing adipose tumor that occurred in the thigh of a 7-year-old girl. Histologically, it was composed of mature adipocytic cells with a few atypia. Molecular analysis showed high-level amplification of the 12q13-21 region including MDM2 among 64 amplified genes. MDM2 amplification is a diagnostic hallmark of ALT/WDLPS/DDLPS. In adult cases, it is typically located in ring or giant marker chromosomes. In the present case, extra-copies of MDM2 were located on double minute chromosomes (dmin). This raised the hypothesis of dmin being precursors of adult's rings and giant markers and may provide indications for a better understanding of the mechanisms of adipose tumor oncogenesis.

Adipogenesis induces growth inhibition of dedifferentiated liposarcoma.

Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are the most common types of liposarcoma. Although WDLPS and DDLPS patients receive intensive treatment including radical surgery and systemic therapy, their overall 5-year survival rates are 90% and 30%, respectively, indicating that DDLPS is clinically more aggressive. We examined whether adipogenic stimulation induces adipogenesis in human WDLPS/DDLPS cells by using dexamethasone, indomethacin, insulin, and 3-isobutyl-1-methylxanthine (IBMX), all putative medications or drugs. Functional in vitro experiments showed that treatment with these four compounds induced adipogenic potency by transcriptional and translational upregulation of genes related to the maintenance of stemness and adipogenic differentiation. Using in vivo xenograft models, we found that the induction of stemness and adipogenesis inhibited the tumorigenic potency of DDLPS. This study suggests a potential application of drug repositioning in which adipogenesis-inducing compounds could be used to treat DDLPS patients in a clinical setting.

Molecular updates in adipocytic neoplasms✰.

Adipocytic neoplasms include a diversity of both benign tumors (lipomas) and malignancies (liposarcomas), and each tumor type is characterized by its own unique molecular alterations driving tumorigenesis. Work over the past 30 years has established the diagnostic utility of several of these characteristic molecular alterations (e.g. MDM2 amplification in well- and dedifferentiated liposarcoma, FUS/EWSR1-DDIT3 gene fusions in myxoid liposarcoma, RB1 loss in spindle cell/pleomorphic lipoma). More recent studies have focused on additional molecular alterations which may have therapeutic or prognostic impact. This review will summarize several of the important molecular findings in adipocytic tumors that have been described over the past 10 years.

Well-differentiated liposarcoma and dedifferentiated liposarcoma: An updated review.

Well-differentiated liposarcoma (WDL)/atypical lipomatous tumor and dedifferentiated liposarcoma (DDL) together comprise the largest subgroup of liposarcomas, and constitute a histologic and behavioral spectrum of one disease. WDL and DDL typically occur in middle-aged to older adults, particularly within the retroperitoneum or extremities. WDL closely resembles mature adipose tissue, but typically shows fibrous septation with variable nuclear atypia and enlargement. WDL does not metastasize, but can dedifferentiate to DDL, which is associated with more aggressive clinical behavior, with a greater propensity for local recurrence and the capacity for metastasis. Although distant metastasis is rarer in DDL compared with other pleomorphic sarcomas, behavior is related to location, with a significantly worse outcome in retroperitoneal tumors. DDL typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma, and is usually a non-lipogenic sarcoma that is adjacent to WDL, occurs as a recurrence of WDL or which can arise de novo. WDL and DDL share similar background genetic aberrations; both are associated with high-level amplifications in the chromosomal 12q13-15 region, which includes the CDK4 and MDM2 cell cycle oncogenes. In addition, DDL harbor further genetic changes, particularly 6q23 and 1p32 coamplifications. While surgical excision remains the treatment mainstay with limited medical options for patients with aggressive recurrent disease or metastases, novel targeted therapies towards the gene products of chromosome 12 are being evaluated. This review summarizes the pathology of WDL and DDL, discussing morphology, immunohistochemistry, genetics and the differential diagnosis.

[Oesophagus polyps: Giant fibrovascular polyp of the oesophagus disappears!] / Polypes œsophagiens : le polype géant fibrovasculaire de l'œsophage n'existe plus !

The giant fibrovascular polyp of the esophagus is a rare, benign and typical entity described in 1957. This lesion is easily identifiable in its macroscopic and microscopic aspects. However, recent studies question the existence of the giant fibrovascular polyp of the esophagus. The demonstration of an amplification of the MDM2 gene poses the diagnosis of well-differentiated liposarcoma. We describe here a case of an esophagus polyp in a 67-year-old man. The diagnosis of giant fibrovascular polyp of the esophagus was initially retained. Secondly, the immunohistochemical and fluorescence in situ hybridization techniques showed amplification of the MDM2 gene and reclassified the lesion to a well-differentiated liposarcoma. The search for an undifferentiated contingent is essential to not ignore a dedifferentiated liposarcoma, which is a high-grade sarcoma with a poorer prognosis.

Amplification of FRS2 in atypical lipomatous tumour/well-differentiated liposarcoma and de-differentiated liposarcoma: a clinicopathological and genetic study of 146 cases.

AIMS: The aim of this study was to evaluate the frequency of FRS2 amplification and its relationship with the clinicopathological features of atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL)/de-differentiated liposarcoma (DDL). METHODS AND RESULTS: FRS2 and MDM2 fluorescence in-situ hybridisation (FISH) was performed on 146 tumours (70 ALT/WDLs and 76 DDLs). One hundred and eight control samples were included for FRS2 analysis. FRS2 amplification was detected in 136 of 146 (93.2%) ALT/WDL/DDLs, including 63 ALT/WDLs and 73 DDLs. A higher FRS2/CEP12 ratio was observed in DDLs than in ALT/WDLs (P = 0.0005). The FRS2/CEP12 ratio of peripheral tumours was lower than that of central tumours (P = 0.00004). All the ALT/WDL/DDLs showed MDM2 amplification (100%). The MDM2+ /FRS2- series included seven ALT/WDLs and three DDLs. Four of seven (57.1%) MDM2+ /FRS2- ALT/WDLs occurred in peripheral sites, slightly higher than the percentage of MDM2+ /FRS2+ ALT/WDLs (28 of 63, 44.4%). All the three MDM2+ /FRS2- DDLs (100%) were peripheral tumours, a much higher proportion than that of MDM2+ /FRS2+ DDLs (10 of 73, 13.7%). A high percentage of homologous pleomorphic liposarcoma-like DDLs (two of three) were observed in the MDM2+ /FRS2- group. In the control group all the parosteal osteosarcomas (five of five, 100%) were FRS2 amplified, whereas the remaining 103 samples were FRS2 non-amplified. CONCLUSIONS: These findings suggest that FRS2 is amplified consistently in ALT/WDL/DDLs and offer another avenue for the investigation of the biology of this tumour group. MDM2+ /FRS2- cases seem to be associated with certain clinicopathological features, and further investigation is needed.

A clinical review of 11 cases of large-sized well-differentiated liposarcomas.

Well-differentiated liposarcomas of the extremities are one of the most frequent types of malignant soft tissue tumors in adults. These tumors are typically locally aggressive and show a tendency to recurrence after surgical excision even though they do not metastasize and very rarely dedifferentiate. Its clinical presentation is generally a progressively growing mass causing aesthetic, functional, or compressive symptoms depending on the tumor's size and localization. Several authors recommend a wide excision with free margins in order to minimize the risk of recurrence, while others report good results and a low rate of recurrence with more conservative or even marginal excision thereby avoiding complications due to surgical site morbidity. We present a retrospective study of 11 patients with a large-sized well-differentiated liposarcoma of the lower limb with a mean follow-up of 3.2 years. The mean size was 22 × 19 × 17 cm, and a marginal resection was made, respecting the affected neurovascular structures, in all cases. Only one recurrence was found and the functional results were 81.6% according to the MSTS functional scale 1 year after surgery. We believe that the marginal excision is a good alternative when the tumor is located near vascular or nerve structures, and as to our experience, it is not associated with elevated recurrences.

Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study.

BACKGROUND: The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS: Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS: Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION: In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.

Dedifferentiated liposarcoma of the orbit.

Purpose: To present a rare case of dedifferentiated liposarcoma of the orbit. Observations: A 61-year-old male complained of left-sided proptosis, diplopia, and limited ocular motility for two years. Biopsy results at that time were suggestive of an atypical lipomatous neoplasm. Ten years later, he presented with increase in size of the mass and worsening of his symptoms. Imaging showed a multi-lobulated mass in the left orbit involving the intraconal, medial, and anterior orbit. Decompression and orbitotomy with biopsy were performed to debulk the mass. Pathology showed a low-grade well-differentiated liposarcoma and the patient was monitored thereafter annually. Eight years later, he complained of persistent proptosis and mass effect from the tumor resulting in ptosis and diplopia and underwent orbital exenteration. Histopathological analysis of the exenterated orbit revealed a focal area of dedifferentiated liposarcoma. Conclusions and importance: Dedifferentiation of an orbital mass can occur as a late complication years after the diagnosis of well-differentiated liposarcoma. Compared to the previously published cases of orbital liposarcoma, this presentation shows a prolonged timeline prior to dedifferentiation (18 years after initial diagnosis). Symptoms of growth or invasive features could indicate dedifferentiation and should warrant a biopsy.