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Characterization of centromere alterations in liposarcomas.

Supernumerary ring and large marker chromosomes are a characteristic of atypical lipomas and well-differentiated liposarcomas (ALP-WDLPS) and are composed of amplified 12q14-15 sequences in association with variable segments from other chromosomes. Although stably transmitted, these chromosomes contain centromeric alterations, showing no detectable alpha-satellite sequences. We performed C-banding, fluorescence in situ hybridization, and immunostaining with anti-centromere antibodies in 8 cases of liposarcomas with supernumerary rings and large markers, including 5 ALP-WDLPS and 3 dedifferentiated-LPS and high-grade LPS. Our results with alpha-satellite probes and anti-CENPB antibodies confirm the lack of detectable alpha-satellite sequences in the five ALP-WDLPS supernumerary chromosomes, whereas centromeric activity was proved by the detection of kinetochores by using anti-CENPC antibodies. In contrast, the high grade and dedifferentiated liposarcomas showed a different pattern. In 2 cases, amplified chromosome 12 sequences, including amplification of alpha-satellite 12 sequences in 1 case, were present on chromosomes with typical centromeres. In another case, the rings were similar to WDLPS-ALP rings, but a large marker contained a chromosome 5 centromere and amplified alpha-satellite sequences from chromosome 8. ALP-WDLPS is the first example of a tumor class for which the presence of stable analphoid chromosomes is a constant and specific abnormality. Formation of newly derived centromeres, so-called neocentromeres, could be an original and effective way to maintain a selective advantage in neoplastic cells by conferring stability to the supernumerary chromosomes of ALP-WDLPS. The activation of normally non-centromeric sequences might be obtained by an epigenetic mechanism due to the peculiar chromatin conformation of these highly complex chromosomes.

Blotting, Southern↗

Analysis of human telomerase reverse transcriptase mRNA (hTERT) expression in myxoid liposarcomas using LightCycler real-time quantitative reverse transcriptase-polymerase chain reaction.

We describe a convenient, nonradioactive reverse transcription--polymerase chain reaktion (RT-PCR) method for the rapid and accurate quantitative detection of the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) mRNA. The LightCycler TeloTAGGG hTERT Quantification Kit (Roche Molecular Biochemicals) was designed to be used for the highly sensitive and quantitative detection of hTERT mRNA relative to the house-keeping gene porphobilinogen deaminase (PBGD). As a tumor progression model, we investigated 26 myxoid liposarcomas (11 pure myxoid grade I, 15 myxoid/round cell grade II/III) for the hTERT expression level and compared the results of the new method with former measurements performed in silver-stained polyacrylamide gels. Both methods revealed similar results, with real-time RT-PCR being the more accurate quantification technique, which also saves time and material. Elevated hTERT expression (cut-off ratio x 100 at 1.3) was an indicator of round cell components and hence for tumor progression in myxoid liposarcoma. The new method is capable of differentiating between pure myxoid and myxoid/round cell liposarcomas for hTERT-expression more accurately.

Computer Systems↗

Well-differentiated liposarcoma of the paratesticular area: report of a case with fine-needle aspiration preoperative diagnosis and review of the literature.

This article presents a rare case of well-differentiated liposarcoma of the paratesticular area (spermatic cord) with a preoperative cytological diagnosis. A 0.6-mm fine-needle aspiration biopsy (FNAB) of a paratesticular lump showed many spindle and polygonal atypical cells with numerous cytoplasmic vacuoles. On the basis of a diagnosis of "malignant mesenchymal neoplasia consistent with liposarcoma," the patient underwent radical orchiectomy. A 8 x 7 x 8.5 cm, whitish mass was found, which was histologically classified as a "well-differentiated liposarcoma" (with lipoma-like, sclerosing, and myxoid areas), according to the classification of Enzinger and Weiss. A review of the literature is presented.

Aged↗

Collision tumor of the thyroid: a case report of metastatic liposarcoma plus papillary thyroid carcinoma.

BACKGROUND: The term collision tumor represents the proximal coexistence of two histologically distinct tumors. Collision tumors within the thyroid are extremely rare, and reported cases are usually of mixed histologies of papillary and medullary carcinomas. Metastatic disease to the thyroid is also an uncommon scenario but may develop after long disease-free intervals. Carcinomas, most commonly renal cell carcinoma, are the likeliest group of neoplasms to metastasize to the thyroid. Soft tissue sarcomas metastasize to the thyroid with a much lower frequency. METHODS: We are reporting this highly unusual case of metastatic liposarcoma from the thigh to thyroid, which harbored a collision tumor of papillary thyroid carcinoma. This 86-year-old woman had undergone an initial resection for liposarcoma of the thigh two decades before being seen with a thyroid mass. RESULTS: Histologically, the thyroid mass was a metastatic myxoid liposarcoma, identical to the primary neoplasm. Papillary thyroid carcinoma was present within this metastasis and in the adjacent thyroid. CONCLUSION.: For any patient seen with a thyroid mass with a history of prior malignancy, no matter how remote, metastatic disease should be considered in the differential diagnosis.

Aged↗

Hypermethylation of the APC promoter but lack of APC mutations in myxoid/round-cell liposarcoma.

The adenomatous polyposis coli (APC) protein is a key component of the WNT signalling pathway wherein it acts as a scaffolding protein in controlling the level of the proto-oncoprotein beta-catenin. Although APC has been shown to be genetically or epigenetically inactivated in a variety of carcinomas, little is known about its role in sarcoma. Liposarcomas (LPSs) are the second most common soft tissue sarcoma in adults. Despite different histology and malignancy, the myxoid and round-cell LPSs belong to one tumour entity characterized by a specific chromosomal translocation. We assessed the extent of genetic and epigenetic inactivation of the APC gene in myxoid/round-cell LPS. Sequencing of the mutation cluster region, the protein truncation test and a loss of heterozygosity (LOH) analysis did not reveal any genetic alterations of the APC gene in all of the liposarcoma samples. Methylation of the APC promoter was detected by methylation-specific PCR in 9 of 20 (45%) tumours. Analysis of APC expression by semiquantitative RT-PCR in a subset of the samples demonstrated that tumours with a methylated APC promoter showed a downregulation of the APC transcript. However, APC downregulation was not correlated with a stabilisation of the beta-catenin protein. Thus, the epigenetic regulation of the APC gene might play an important role in the pathogenesis of myxoid/round-cell LPS. However, the impact of APC methylation on liposarcoma development is quite likely not mediated through WNT signalling.

Adult↗

Liposarcoma: a population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content.

Different conceptions exist regarding the epidemiology and prognosis of liposarcoma, and several classification systems are in use. We analyzed a population-based, 25-year series of 43 patients with liposarcoma of the extremity or trunk wall. Follow-up was complete. The annual incidence was 0.12/10(5). The thigh was the most common location. One of 6 tumors was subcutaneous. Deep-seated tumors were larger than s.c. tumors. Among the 42 surgically treated patients, grade II (4-grade scale) was the most common malignancy grade. Four tumors were well-differentiated, 24 were predominantly myxoid, 4 predominantly round-cell, and 10 were predominantly of pleomorphic type. The 5-year metastasis-free survival rate was 69%. By univariate analysis increasing malignancy grade, tumor necrosis, vascular invasion, mitotic count, subtype other than well-differentiated, and high cellularity were prognostic for metastatic disease. However, in the multivariate analysis only tumor necrosis was an independent risk factor. Tumor necrosis should be considered when prognosis of liposarcoma of the extremity and trunk wall is evaluated.

Abdominal Muscles↗

Liposarcoma of hepatic hilum in childhood: report of a case and review of the literature.

Liposarcoma in childhood has seldom been documented. The rare occurrence of this tumor has resulted in a lack of information about its natural history, prognosis, and management. The differential diagnosis with lipoblastomatosis is obligatory. A 2 year 4 month-old white male child presented at the Hospital das Clinicas of Medical School of Ribeirão Preto, University of São Paulo, with fever, jaundice, and coluria secondary to a tumoral mass of the hepatic hilum causing obstruction of the biliary tree. Histologic and immunohistochemical study at autopsy disclosed a liposarcoma. A literature review found 64 other reported cases. Special attention was given to age, sex, anatomic localization, and histologic aspects of the literature cases. Liposarcoma involving the hepatic hilum and causing obstruction of the biliary tree in childhood was not previously reported in the literature.

Bile Ducts, Intrahepatic↗

Significance of loss of heterozygosity of the RB1 gene during tumour progression in well-differentiated liposarcomas.

Tumour progression can be investigated in liposarcomas showing a transition from a low-grade well-differentiated (WD) to a high-grade dedifferentiated (DD) variant. As RB1 gene alterations are common defects in sarcomas, this study examined the frequency of RB1 loss of heterozygosity (LOH) in a group of 14 well-differentiated liposarcomas (WDLs) and 17 well-differentiated/dedifferentiated liposarcomas (WD/DDLs), using a microdissection approach (PALM laser pressure catapulting) that allows the two histological components to be separated for polymerase chain reaction (PCR) analysis. In addition, RB1 protein expression and the Mib1 proliferation index were determined by immunohistochemistry and interphase FISH was performed with an RB1 probe at 13q14. By the use of four intragenic polymorphic RB1 markers (introns 1, 17, 20, and 25) for PCR, allelic losses were found only in the DD parts, but never in the pure WDLs or in the WD components of the WD/DDLs investigated. Furthermore, DD areas characterized by a heterogeneous RB1 protein expression pattern (35-65% immunopositivity), as compared with 90-100% RB1 positivity in WD areas, showed a marked increase in Mib1 proliferation index (19.6% versus 1.8% in WD areas; p<0.001). Interphase fluorescence in situ hybridization (FISH) detected a higher RB1-LOH rate in the DD components of WD/DDLs. Considering the different detection sensitivities of the three methodologies, it is concluded that loss of RB1 function already begins in the WDL, and that the tumour cell population with RB1-LOH starts prevailing in the tumour mass during progression of a WDL.

Adult↗

The behaviour of liposarcoma in tissue culture. A specific growth pattern.

There have been few studies of liposarcoma in tissue culture. We report a study of 27 cases of liposarcoma including examples of all subtypes in tissue culture. All the cases showed a uniform growth pattern of glass adherence by polygonal cells with short processes distributed in a random fashion. The cytoplasm of these cells became progressively loaded with glycogen followed by lipid droplets. These lipid droplets tended to fuse progressively to form a single or dominant vacuole. At the same time, the cells tended to adopt a rounded shape. This pattern of growth, which was seen in all subtypes of liposarcoma with minimal variation, is different from that shown by other soft tissue tumours and is similar to the growth of embryonal fat in tissue culture.

Adult↗

Radiotherapy for liposarcoma of the vulva.

BACKGROUND: Primary liposarcoma of the vulva is extremely rare. We report a case of liposarcoma of the vulva which was treated with local excision and postoperative radiotherapy. CASE: A 21-year-old woman complained of a painless lump in her labium majus which she first noticed 3 years earlier. An initial diagnosis of lipoma of the vulva was made. The patient was treated by surgical removal. On examination of the surgical specimen, the final pathological diagnosis was well-differentiated liposarcoma and the stalk was not excised completely. Radiotherapy was initiated because of the uncertainty of the patient's prognosis. Eighteen months after radiotherapy, no evidence of local recurrence, metastasis, and late complication has been seen. CONCLUSION: This case is suggestive of the contribution of postoperative radiotherapy, although not conclusive, and continued monitoring is necessary because recurrence or metastasis can occur years later.

Adult↗

Liposarcoma complicating pregnancy.

BACKGROUND: An adnexal mass in pregnancy is a common occurrence. Malignancy is uncommon and only seven cases of liposarcoma have been reported in association with pregnancy. CASE: We present a case of a pregnant patient who was diagnosed with an adnexal mass detected by ultrasound at 13 weeks gestation. The mass was surgically removed postpartum, when it was found to be a liposarcoma. Postoperatively she received chemotherapy but eventually succumbed to her disease. CONCLUSIONS: Liposarcoma is rarely found in association with pregnancy and may follow an aggressive course.

Adult↗

Case report 797: "Dedifferentiated" lipoma-like liposarcoma of soft tissue with focal transformation to high-grade "sclerosing" osteosarcoma.

We have presented the first case of a lipoma-like liposarcoma of the soft tissues with high-grade malignant transformation to a high-grade osteosarcoma, the latter component of which responded well to systemic chemotherapy. With 4 months of follow-up the patient is without evidence of disseminated disease. The various types of liposarcoma are listed and several described in some detail. Of particular importance is the potential for development of a highly malignant sarcoma from a relatively indolent low-grade liposarcoma, with even osteosarcoma developing.

Aged↗

Liposarcoma of the breast. Case report and review of the literature.

A case of primary liposarcoma of the breast in a 65-years-old woman is described by light- and electron microscopy. The patient had previously had a cystosarcoma phyllodes removed from the same area. A review of the literature showed 34 previously published cases of liposarcoma of the breast, which regarding age distribution, histological type and pattern of metastasis corresponded to liposarcomas of the lower limbs.

Aged↗

Myxoid malignant fibrous histiocytoma versus myxoid liposarcoma. A comparative ultrastructural study.

An ultrastructural comparison of 7 examples of myxoid malignant fibrous histiocytoma (myxoid MFH) with 6 of myxoid liposarcoma is described. Despite certain histological differences between the two, electron microscopy was more valuable in differentiating MFH from liposarcoma. Electron microscopically, MFH contained a variety of cell types including histiocyte-like, fibroblast-like, intermediate-type, xanthomatous, multinucleated tumor giant cells and undifferentiated cells. Liposarcoma was composed mainly of lipoblasts at various stages of differentiation with a minority of undifferentiated cells and fibroblast-like cells. In contrast to the component cells of the MFH, these lipoblasts were characterized by abundant cytoplasmic glycogen, numerous pinocytotic vesicles and a discontinuous basal lamina in addition to large lipid droplets.

Adult↗

Multifactorial analysis of survival in primary extremity liposarcoma.

The treatment of extremity soft tissue sarcoma is now directed at limb preservation with the addition of various adjuvant therapies to improve treatment results. To achieve this goal, a knowledge of prognostic factors for extremity soft tissue sarcoma becomes increasingly critical. The object of this study was to analyze prognostic factors for survival in patients with extremity liposarcoma. Eighty-three patients with primary localized extremity liposarcoma, admitted from 1968 to 1978, were retrospectively reviewed. Surgical resection was the primary mode of treatment. Eleven prognostic factors were analyzed. Tumor factors included: histologic subtype, tumor grade, size, depth, invasion of vital structures, and site; operative factors included: type of operation, and surgical margins; and patient factors included: symptoms, age at diagnosis, and sex. Kaplan-Meier survival curves, and univariate and stratified log-rank tests of association were performed. Independent factors for predicting survival were identified using the Cox model stepwise regression technique. In univariate analysis of the entire group of patients, 5 factors were significant for tumor mortality: tumor grade (p = 0.00005), histologic subtype (p = 0.00025), tumor size greater than or equal to 5 cm (p = 0.005), type of surgery/margin (p = 0.0001), and invasion of vital structures (p = 0.008). When associations among all factors were analyzed, it was found that many factors were interdependent. The independent prognosticators were, therefore, determined according to the Cox model technique. For the multivariate analysis, well-differentiated and lipoblastic liposarcomas were excluded because of lack of survival variation within each group. The former group had no tumor-related deaths and the latter group showed 80% tumor mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Myxoid liposarcoma of the porta hepatis in childhood.

Liposarcoma in childhood is rare. A case of a myxoid liposarcoma arising at the porta hepatis is reported in a 3-year-old boy with initial favourable response to surgery combined with radio- and chemotherapy. Fatal recurrence occurred at age 15 years. The radiological and sonographic findings of liposarcomas are reviewed.

Child, Preschool↗

Liposarcoma of the breast, review of the literature and a report of a case.

A case of gigantic liposarcoma of the breast in a 52-year-old woman was reported. She had a small indolent mass in the left breast for twenty years. The mass grew rapidly from the summer of 1979 and became gigantic and penetrated the skin over the mass. Her general condition on admission was poor but resection of the tumor was carried out. She suddenly died of cardiac failure with electrolytes imbalance 13 days after the operation. The diagnoses of liposarcoma, predominantly myxoid, was made on the basis of light and electron microscopic findings. Forty cases of liposarcoma of the breast were collected from the literature. The possibility of malignant transformation of a benign tumor was suggested.

Breast Neoplasms↗

Renal liposarcoma of the sinus renalis.

We report on 42-month follow-up of a case of renal liposarcoma of the sinus renalis with tumour-free survival. It is a rare condition and occurs generally in the 4th and 6th decades of life. Renal liposarcomas are clinically asymptomatic for a long period of time. Symptoms develop only when the tumours become large enough, as in our case. For the differential diagnosis of renal liposarcoma we performed intravenous urography, computerized tomography and colour flow Doppler ultrasonography. After these diagnostic evaluations the patient underwent right radical nephrectomy. Complete surgical resection was performed. Final diagnosis was made by pathological examination. Because of the poor results of either chemotherapy or radiotherapy, we conclude that 42 months of tumour-free survival is related to complete surgical resection with negative surgical margins.

Humans↗