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PubMed2026

Pleomorphic Liposarcoma: Comprehensive Genomic Analysis of 39 Cases With Comparison to Other Genomically Complex Sarcomas.

Pleomorphic liposarcoma (PLPS) is an aggressive high-grade sarcoma that often shows diverse morphological features and can mimic high-grade undifferentiated pleomorphic sarcoma (UPS)/spindle cell sarcoma or myxofibrosarcoma (MFS), especially when pleomorphic lipoblasts are sparse. The molecular profile of PLPS is distinct from well differentiated/dedifferentiated liposarcoma and myxoid liposarcoma. In this study, we investigate 39 cases of PLPS by comprehensive genomic profiling, occurring in 32 patients with available molecular data. Cases were reviewed and morphologic parameters-lipoblastic component, UPS-like, and MFS-like areas were estimated. The genomic findings were collected and compared to UPS and MFS groups studied using the same platform. The cohort included 15 females and 17 males, with a median age of 56.5 (range, 34-78). The lower extremity (n = 17) was the most common site involved, followed by upper extremity (n = 5) and pelvis (n = 5). UPS-like and MFS-like patterns were the most common morphologic variants, ranging from 15% to 95% and 20% to 90%, respectively. TP53 (87%) and RB1 (51%) mutations and copy number alterations were the most common alterations seen, followed by ATRX (36%). Compared to UPS and MFS, TP53 and RB1 gene alterations were significantly more common in PLPS. Conversely, CDKN2A/B deletions were infrequent in PLPS. Survival analysis showed that MYC amplification was associated with significantly shorter overall survival in PLPS. Among histologic variants, CYSLTR2 alterations were found to be highest in cases with predominantly pleomorphic lipoblasts; additionally, strong correlations were found between gene alteration frequencies of MFS and MFS-like PLPS, and between UPS and UPS-like PLPS. RB1 allele-specific copy number analysis showed loss of heterozygosity in 82% of cases. Our cohort of PLPS showed a complex molecular landscape with distinct genetic alterations, histologic correlations, and clinical outcomes, highlighting its unique position among genomically complex sarcomas and providing insights that may inform future diagnostic and therapeutic approaches.

Humans↗
PubMed1995

Multicentric liposarcoma: report of two cases.

We present herein two unusual cases of multicentric liposarcoma which highlight the problems associated with the management of this disease entity. When the surgeon is confronted with multicentric liposarcomas, it is necessary to define whether they are secondary tumors or independently arising multicentric liposarcomas, since the latter situation merits a more aggressive approach. Guidelines for this differentiation are suggested in the discussion following the case reports. Surgery, which is often multiple, remains the mainstay of treatment, although adjuvant chemotherapy and radiotherapy are also usually required.

Abdominal Neoplasms↗
PubMed1999

Myxoid liposarcoma with transition to round-cell lesion-cell cycle regulator genes and telomerase activity characterizing tumor progression: a case report.

A mixed myxoid/round cell liposarcoma was macrodissected in its 2 histologic components and investigated for genetic differences between its low-grade myxoid and the high-grade round-cell region. For both, we failed to detect p53 gene mutations, loss of heterozygosity at the p53 or Rb genes, and p53 protein expression. The round-cell component showed a high telomerase activity, and an elevated c-myc mRNA and protein expression. The myxoid component was characterized by a lack of telomerase activity and low c-myc mRNA expression, and immunohistochemistry failed to detect the c-myc protein. There was a higher Mib-1 proliferation index in the round-cell portion. The same specific translocation t(12;16) and the fusion transcript type II in both components confirmed the close relationship between myxoid and round-cell liposarcomas. Telomerase activity and increased c-myc expression seem to be helpful molecular markers for characterizing tumor progression in myxoid liposarcoma.

Abdominal Neoplasms↗
PubMed1999

Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation.

Fusion of TLS/FUS and CHOP gene by reciprocal translocation t(12;16)(q32;q16) is a common genetic event found in myxoid and round-cell liposarcomas. Characterization of this genetic event was performed by three methods, Southern blot, RT-PCR, and genomic long-distance PCR in nine myxoid and three round-cell liposarcomas. All but one tumors showed genetic alternations indicating the fusion of TLS/FUS and CHOP gene. Two novel types of fusion transcripts were found, of which one lacked exon 2 sequence of CHOP gene, and the other lacked 3' half of exon 5 of TLS gene. The latter case was caused by a cryptic splicing site which was created by the genomic fusion. Detailed analyses genomic fusion points revealed several sequence characteristics surrounding the fusion points. Homology analyses of breakpoint sequences with known sequence motifs possibly involve in the process of translocation uncovered Translin binding sequences at both of TLS/ FUS and CHOP breakpoints in two cases. Translocations were always associated with other genetic alterations, such as deletions, duplications, or insertions. Short direct repeats were almost always found at both ends of deleted or duplicated fragments some of which had apparently been created by joining of sequences that flank the rearrangement. Finally, consensus topoisomerase II cleavage sites were found at breakpoints in all cases analysed, suggesting a role of this enzyme in creating staggered ends at the breakpoint. These data suggested that sequence characteristics may play an important role to recruit several factors such as Translin and topoisomerase II in the process of chromosomal translation in liposarcomas.

Artificial Gene Fusion↗
PubMed1998

Iodine-123 BMIPP and Ga-67 scintigraphy in liposarcoma.

A patient with recurrent retroperitoneal liposarcoma had multiple suspected metastases. I-123 BMIPP imaging showed areas of increased uptake due to accumulation in the myxoid components of the liposarcoma. Ga-67 showed accumulation in the undifferentiated components. The well-differentiated components showed little accumulation of either I-123 BMIPP or Ga-67. Differences in the accumulation of these radionuclides may reflect differences in cell densities, fatty acid metabolism, and the degree of malignancy. I-123 BMIPP and Ga-67 scintigraphy may be useful in determining the prognosis of liposarcoma.

Abdomen↗
PubMed1998

Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas. In this study, we conducted a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16 myxoid and round cell liposarcoma cases, the fusion transcripts could be identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using the PCR products confirmed that the detected messages were derived from either type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant (80%). The results were consistent in primary and recurrent lesions of the same patients and in paraffin-embedded and snap-frozen samples from the same tumors. In two negative specimens, transcripts of the beta-actin gene could not be detected by RT-PCR, and intact mRNA including the fusion messages might have been degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded material of other types of tumors with myxoid morphology (seven myxoid malignant fibrous histiocytomas and four lipomas with myxoid change). These results indicate that this molecular assay can be applied to formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.

Adolescent↗
PubMed2000

p27(kip1) protein expression correlates with survival in myxoid and round-cell liposarcoma.

PURPOSE: The p27(kip1) protein (p27) is a cyclin-dependent kinase inhibitor that has been shown to be an independent prognostic factor in a variety of human neoplasms. Low expression of p27 tends to occur in more aggressive neoplasms. The role of p27 as an independent prognostic factor in the spectrum of myxoid and round-cell liposarcomas has not been examined. MATERIALS AND METHODS: Forty-seven cases of myxoid and round-cell liposarcomas were examined. Clinicopathologic features and immunohistochemical expression of p27 and Ki-67 antigen were studied in all cases. Survival analysis was performed using the log-rank test and the Cox multivariate regression model. RESULTS: The male:female ratio was 1. 4:1, and the mean age at diagnosis was 45 years. The tumors were located in the lower extremities (94%) and retroperitoneum (6%). The median tumor size was 13.5 cm. The median follow-up was 6.3 years, and the overall 5- and 10-year survival rates were 76% and 67%, respectively. Low expression of p27 was identified in 34 cases (72%) and correlated with decreased metastasis-free (P =.026) and overall survival (P =.008). In a multivariate analysis, only round-cell differentiation and low expression of p27 independently predicted decreased metastasis-free and overall survival. CONCLUSION: p27 expression predicts the clinical behavior of myxoid and round-cell liposarcomas, even in neoplasms with few or no round-cell differentiation.

Adult↗
PubMed2004

Prognostic significance of MRI findings in patients with myxoid-round cell liposarcoma.

OBJECTIVE: The aims of this study were to determine the prognostic significance of MRI findings in patients with myxoid-round cell liposarcomas and to clarify which MRI features best indicate tumors with adverse clinical behavior. MATERIALS AND METHODS: The initial MRI studies of 36 pathologically confirmed myxoid-round cell liposarcomas were retrospectively reviewed, and observations from this review were correlated with the histopathologic features. MR images were evaluated by two radiologists with agreement by consensus, and both univariate and multivariate analyses were conducted to evaluate survival with a median clinical follow-up of 33 months (range, 9-276 months). RESULTS: Statistically significant MRI findings that favored a diagnosis of intermediate- or high-grade tumor were large tumor size (> 10 cm), deeply situated tumor, tumor possessing irregular contours, absence of lobulation, absence of thin septa, presence of thick septa, absence of tumor capsule, high-intensity signal pattern, pronounced enhancement, and globular or nodular enhancement. Of these MRI findings, thin septa (p < 0.05), a tumor capsule (p < 0.01), and pronounced enhancement (p < 0.01) were associated significantly, according to univariate analysis, with overall survival. Multivariate analysis indicated that pronounced enhancement was associated significantly with overall survival (p < 0.05). CONCLUSION: Contrast-enhanced MRI findings can indicate a good or adverse prognosis in patients with myxoid-round cell liposarcomas.

Adolescent↗
PubMed2005

[Detection of FUS-CHOP fusion gene in paraffin-embedded tissues and its clinicopathologic significance for myxoid/round cell liposarcomas].

OBJECTIVE: To explore the feasibility of detecting FUS-CHOP fusion gene in formalin-fixed, paraffin-embedded tissue and its application in the diagnosis and differential diagnosis of myxoid/round cell liposarcomas (MRCLs). METHODS: Forty-four formalin-fixed, paraffin-embedded MRCL samples and 60 control cases (atypical/well-differentiated liposarcoma, pleomorphic liposarcoma, low-grade myofibrosarcoma, etc.) retrieved from the archival files were studied. Nested reverse transcription-polymerase chain reaction (RT-PCR) technique was employed to detect the FUS-CHOP mRNA expression, followed by DNA sequencing confirmation of the PCR product. Housekeeping gene PGK was used to assess the quality of the mRNA templates. RESULTS: PGK mRNA was detected in 93 of 104 tumor cases (89.4%), including 39 MRCLs cases (39/44, 88.6%) and 90% of the negative control cases. Type II FUS-CHOP fusion transcript was successfully detected in 20 out of 39 (51.3%) MRCL cases. Type I FUS-CHOP fusion transcript was not detected in any MRCLs in this study. All 60 negative control cases were negative for the FUS-CHOP fusion gene transcripts. CONCLUSIONS: (1) Nested RT-PCR can be used to detect FUS-CHOP mRNA in formalin-fixed, paraffin-embedded tissues. (2) FUS-CHOP is considered a specific molecular and genetic hallmark for MRCLs. Nested RT-PCR is a sensitive and specific technique in detecting FUS-CHOP gene, and can be used in the diagnosis and differential diagnosis of MRCLs.

Adolescent↗
PubMed2005

Cytomorphological features of combined myxoid and round cell liposarcoma--a case report.

Fine needle aspiration cytology plays an important role in the preoperative assessment of soft tissue neoplasms. In a 40-year-old man presenting with a large soft tissue mass in the posterior aspect of thigh a diagnosis of myxoid liposarcoma was suggested on FNAC. Scrape smears of the excised mass showed an additional finding of round cell component. Histopathology confirmed combined myxoid and round cell liposarcoma (grade 2), which behaves aggressively when compared to pure myxoid liposarcoma.

Adult↗
PubMed1994

Laryngeal liposarcoma.

Laryngeal liposarcomas are rare, with only 13 previously well-documented cases (to our knowledge). We report an additional case, which documents the use of computed tomography for treatment planning. Laryngeal liposarcomas appear to have a better prognosis than nonlaryngeal liposarcomas; therefore, a critical analysis of reported cases enabled us to identify clinical characteristics that contribute to the favorable prognosis. We also propose a rational therapeutic approach.

Adult↗
PubMed1999

Case of retroperitoneal dedifferentiated mixed-type liposarcoma: comparison of proliferative activity in specimens from four operations.

In a case of retroperitoneal dedifferentiated mixed-type liposarcoma, a dedifferentiated component was observed in the so-called mixed-type liposarcoma consisting of well-differentiated and myxoid components. The proliferative activity was compared among the different components of the tumor by immunohistochemical study using the proliferating cell nuclear antigen (PCNA) and MIB-1 monoclonal antibodies. The dedifferentiated component showed higher positivity than the well-differentiated and myxoid components, and tumor progression was most advanced in the dedifferentiated component. In the chronological examination of each component, the labeling indices of PCNA and MIB-1 were significantly higher at the third recurrence than in the primary lesion in all types, indicating that the proliferative activity of the tumor cells increased gradually. Considering the surgical treatment of liposarcoma, an extended resection encompassing normal adjacent tissues is required in cases containing the dedifferentiated component in comparison to the cases containing only well-differentiated or myxoid components.

Antibodies, Monoclonal↗
PubMed1996

Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect and map the regions of gain, high-level amplification, and loss of DNA sequences in 14 liposarcomas. Thirteen tumors showed DNA sequence copy number changes of one or more genomic regions (mean, six aberrations/tumor; range, 0-17). These aberrations were observed in almost every chromosome but some chromosomal regions were affected more often than others. DNA sequence gains were more frequent than losses. The most common gain was seen at 12q14-21 (50% of tumors). Other frequent gains (29%) were of 1q21-24, 8cen-q21.2, 19q, and 20q. High-level amplification was observed in six (43%) tumors and included as minimal common segments bands 12q15, 1q22, and 1q24. In five (36%) tumors, sequences at 1q21-24 and 1q32 were found to be gained simultaneously with 12q14-21, which means that in 71% of the tumors with gain at 12q, an increase of DNA sequence copy number at 1q was also observed. The most common losses of DNA sequences (21%) occurred from regions 9p21-pter and 13q21-qter. Most of the aforementioned regions have not previously been reported to be altered in liposarcomas. The detection of a novel recurring amplicon at 1q21-24 with high-level amplification at 1q22 and frequent simultaneous DNA sequence gain at 12q14-21 (high-level amplification at 12q15) suggests that genes linked to both these regions may play a significant role in the development and progression of liposarcomas.

Adult↗
PubMed1977

Non-epithelial tumors of the nasal cavity, paranasal sinuses and nasopharynx: a clinicopathologyic study. VIII. Adipose tissue tumors (lipoma and liposarcoma).

In a study of 256 non-epithelial neoplasms involving the nasal cavity, paranasal sinuses and nasopharynx, only two lesions were classified as adipose tissue tumors (one lipoma and one liposarcoma). The lipoma was found incidentally when tissue removed from the maxillary sinus was studied histologically, the patient having been treated with a Caldwell-Luc procedure for maxillary sinusitis. The liposarcoma produced a large mass involving the nasal cavity, maxillary sinus, ethmoid area, hard palate and maxillary, temporal and sphenoid bones. The tumor extended into the cranial cavity and eventually led to the patient's death. The problems involved in histologically differentiating liposarcomas from other lesions are discussed. Even though adipose tissue tumors are among the most common soft tissue neoplasms, these lesions rarely occur in the nasal cavity, paranasal sinuses and nasopharynx.

Adult↗
PubMed1979

Liposarcomas of the head and neck: a review of the literature and addition of four cases.

Liposarcomas of the head and neck are rare. There have been 25 previously reported patients in the literature. Four patients with head and neck liposarcomas, recently treated by the Head and Neck Surgery Service, Walter Reed Army Medical Center, are presented. Less than half of reported patients were noted to be living without evidence of disease. Prognosis generally corresponds to the cell type of the tumor. Intraoral, cheek and orbital tumors seem to have a worse prognosis compared to neck tumors. Wide local excision remains the treatment of choice. Advances in surgical techniques have allowed adequate therapy for most head and neck liposarcomas. Advanced lesions should be managed by conservative surgery and radical radiation therapy.

Adolescent↗
PubMed1993

Liposarcoma in patients younger than or equal to 22 years of age.

BACKGROUND: There have been few reported series of liposarcomas in patients younger than or equal to 22 years of age. METHODS: A retrospective analysis of all patients presenting with liposarcoma between 1949-1990 at Memorial Sloan-Kettering Cancer Center with age at diagnosis younger than or equal to 22 years was performed. Variables evaluated for their predictive effect on survival included anatomic location of the primary, size, and completeness of surgical resection. RESULTS: Eighteen patients were identified. Only 1 patient (6%) presented with a high-grade lesion, and in 13 patients (72%), the myxoid subtype was observed. All but one patient undergoing complete resection remain disease-free 1.3-29.1 years after treatment, while all patients with gross residual tumor have died from disease. Two of three patients with microscopic residual at resection are disease-free 2 and 11.8 years after diagnosis with the addition of external beam radiation therapy. CONCLUSIONS: The authors conclude that complete surgical resection is crucial for survival in young patients with liposarcoma and the external beam radiation therapy may be effective against microscopic residual.

Adolescent↗
PubMed1995

Molecular and immunohistochemical p53 status in liposarcoma and malignant fibrous histiocytoma: identification of seven new mutations for soft tissue sarcomas.

BACKGROUND: p53 mutations are the most frequently observed tumor-related genetic changes. Mutational analysis concerns mostly carcinomas and is not comprehensive for soft tissue sarcomas. Among soft tissue sarcomas, malignant fibrous histiocytoma (MFH) and liposarcoma represent the most frequent tumor types. Most of the few identified mutations for soft tissue sarcomas are localized in the core domain of p53. A correlation between p53 positive immunoreactivity, missense mutations, and a poor prognosis is generally assumed. However, the character of p53 mutations and their functional importance for the clinical process is still unknown. METHODS: Sixty-two soft tissue sarcoma samples were investigated for the presence of p53 mutations and for p53 immunoreactivity. Exons 4-9 of the p53 gene were amplified from genomic DNA with the polymerase chain reaction. A prescreen for mutations was performed by nonradioactive single strand conformation polymorphism analysis; striking cases were sequenced directly. For an evaluation of the immunohistochemical status, five p53 antibodies were used. RESULTS: In 10 tumor samples 7 new p53 mutations and one polymorphism were identified. Mutations were detected for five liposarcomas (four patients) and four MFHs (three patients). Of the seven mutations, three were missense point mutations, three were deletions, and one was a complex conversion. All mutations but one were localized in the core domain of p53. Of 62 tumor samples, 56% (14 of 32 liposarcomas and 21 of 30 MFHs) were positive for p53 immunostaining. CONCLUSIONS: The mutations identified in the core domain affect codons that are structurally or functionally involved in DNA binding. A relation between p53 positive immunoreactivity and a poor prognosis, but not with an exclusively high tumor grade, is evident. p53 mutations in soft tissue sarcomas have a similar spectrum to those in carcinomas.

Histiocytoma, Benign Fibrous↗
PubMed2000

LiSa-2, a novel human liposarcoma cell line with a high capacity for terminal adipose differentiation.

LiSa-2 is a stable cell line derived from a poorly differentiated, pleomorphic liposarcoma. In serum-containing medium, LiSa-2 cells are fibroblastoid and rapidly dividing. In a serum-free, chemically defined culture medium containing physiological concentrations of insulin, triiodothyronine and cortisol, LiSa-2 cells divide slower and, extensively storing fat, acquire adipocyte morphology. In contrast to fibroblastoid LiSa-2 cells, these adipocyte-like LiSa-2 cells highly express transcripts for peroxisome proliferator-activated receptor-gamma, lipoprotein lipase, fatty acid synthetase, hormone-sensitive lipase, adipocyte most abundant gene transcript-1, glycerol-3-phosphate-dehydrogenase and the insulin-sensitive glucose transporter-4, all of which are specific for differentiated adipocytes. However, leptin mRNA expression was demonstrated only after preventing DNA methylation by incorporation of 5-aza-deoxycytidine into cellular DNA. Functionally, adipocyte-like LiSa-2 cells show increased insulin-dependent glucose uptake and lipid synthesis and are sensitive to lipolytic agents. This cell line may serve as an in vitro model for studying the regulation of human liposarcoma differentiation and for screening drugs for induction of differentiation-associated growth arrest in liposarcomas.

Adipocytes↗