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From the archives of the AFIP: imaging of musculoskeletal liposarcoma with radiologic-pathologic correlation.

Liposarcoma is the second most common type of soft-tissue sarcoma, accounting for 10%-35% of these lesions. The World Health Organization has categorized soft-tissue liposarcomas into five distinct histologic subtypes: well differentiated, dedifferentiated, myxoid, pleomorphic, and mixed type. Well-differentiated liposarcomas frequently demonstrate a diagnostic appearance on computed tomographic (CT) or magnetic resonance (MR) images, with a largely lipomatous mass (>75% of the lesion) and nonlipomatous components in thick septa or focal nodules. The CT or MR imaging finding of a nodular dominant focus (>1 cm in size) of nonlipomatous tissue in a well-differentiated liposarcoma suggests dedifferentiated liposarcoma, and biopsy should be directed at the nonadipose component. The high water content of myxoid liposarcoma seen at pathologic analysis and constituting the majority of the lesion is reflected at sonography, CT, and MR imaging. However, the detection of a small amount of adipose tissue in the septa or as small nodular foci superimposed on the background of myxoid tissue allows prospective diagnosis in 78%-95% of myxoid liposarcomas. Pleomorphic liposarcomas are high-grade sarcomatous lesions and typically appear as heterogeneous soft-tissue masses, although small amounts of fat are seen on MR images in 62%-75% of cases, findings that suggest the diagnosis. Mixed-type liposarcomas have features representing a combination of the other subtypes. Primary liposarcoma of bone is exceedingly rare and usually demonstrates aggressive nonspecific features, although fat may be seen. Understanding and recognition of the spectrum of appearances of the various types of musculoskeletal liposarcoma, which reflect their underlying pathologic characteristics, improves radiologic assessment and is vital for optimal patient management.

Adolescent↗

[Anatomopathology, computerized tomography, and magnetic resonance correlations in soft tissue liposarcoma].

Liposarcomas are one of the most common soft tissue malignant tumors; they can be differentiated in four histologic subtypes: well-differentiated, myxoid, round cell and pleomorphic liposarcomas. The search of differential CT and MR patterns to better classify the lesions in the proper histologic subtype is justified by the different histologic features, clinical course and especially prognosis, of every lesion subtype. From 1990 to 1995, 50 liposarcoma patients were examined preoperatively with CT and MRI in our Institute of Radiology. We found 7 well-differentiated liposarcomas (14%), twenty myxoid liposarcomas (40%), ten round cell liposarcomas (20%) and, finally, 13 pleomorphic liposarcomas (26%). The thigh was the most common tumor site (60%). The following parameters were considered: lesion margins, tissue homogeneity, fat tissue ratio and the presence of calcifications. Well-differentiated liposarcomas presented well-defined and regular margins (72%), mildly heterogeneous appearance (44%) and more than 75% fat tissue (72%). Myxoid liposarcomas presented well-defined and regular margins (65%), heterogeneous appearance (65%) and less than 25% fat tissue (95%). The diagnosis of myxoid liposarcoma can be made in the presence of myxoid tissue, which has very low CT attenuation values and mildly hypointense signal on T1-weighted and progressively hyperintense signal on T2-weighted MR images. Round cell and pleomorphic liposarcomas are high-grade malignancies and they cannot be distinguished from other malignant soft tissue lesions. In these cases, the diagnosis can be made only at histology.

Adult↗

PET evaluation of fatty tumors in the extremity: possibility of using the standardized uptake value (SUV) to differentiate benign tumors from liposarcoma.

OBJECTIVE: The relative utility of various preoperative diagnostic imaging modalities, including PET (utilizing FDG and FMT), CT, and MR imaging, for evaluation of lipoma and liposarcoma, especially well-differentiated liposarcoma, was investigated. METHODS: Imaging findings in 32 patients with histopathologically documented lipoma, including one with fibrolipoma and one with angiolipoma, and 25 patients with liposarcomas whose subtypes included 10 well-differentiated, 10 myxoid, and 5 other types were reviewed retrospectively. Pre-operative imaging included FDG-PET (n = 44), FMT-PET (n = 21), CT (n = 25), and MR imaging (n = 53). RESULTS: Statistically significant imaging features of MR images favoring a diagnosis of liposarcoma involved lesions containing less than 75% fat (p < 0.001) as well as the presence of septa (p < 0.001). As compared with well-differentiated liposarcoma, benign lesions were differentiated significantly only by the presence of septa (p < 0.001), which also provided significant differentiation on CT (p < 0.05). The mean SUVs for malignant tumors were significantly higher than those for benign lesions in both FDG- and FMT-PET analyses (p < 0.0001, p = 0.0011, respectively). By using a cut-off value for FDG- and FMT-PET set at 0.81 and 1.0 respectively, which provided the highest accuracy, benign lesions were differentiated significantly from liposarcomas (p < 0.001, and p < 0.02). Furthermore, benign tumors and the three subtypes of liposarcoma were divided significantly into four biological grades by FDG- and FMT-accumulation rates (rho = 0.793, p < 0.0001; and rho = 0.745, p = 0.0009, respectively). A cut-off value of 0.81 for FDG-PET provided significant differentiation between benign lesions and well-differentiated liposarcoma (p < 0.01). CONCLUSIONS: The presence of septa on MR images differentiated lipomas from liposarcoma, even well-differentiated type. PET analysis, especially FDG-PET, quantitatively provided not only the differentiation but also the metabolic separation among subtypes of liposarcoma. Interpretation of the visual diagnostic modalities requires extensive experience and carries a risk of ignoring a critical portion of malignancy. PET metabolic imaging may be an objective and useful modality for evaluating adipose tissue tumors preoperatively.

Adult↗

Gains of 13q are correlated with a poor prognosis in liposarcoma.

Liposarcomas are a phenotypical heterogeneous group of tumors divided into four main subtypes: well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic. The aim of this study was to compare DNA sequence copy number changes of these subtypes as investigated by comparative genomic hybridization in 36 patients. Comparative genomic hybridization revealed genomic imbalances in tumors of 27 patients (mean 5.6 imbalances per tumor). The most frequent gains were within single regions of 1q, 12q, and 13q. We found a significant correlation of poor overall survival and gain of 13q21 (P=0.0221), 13q22 (P=0.0341), 13q31 (P=0.0410), and 13q32 (P=0.0074). The univariate Cox regression analysis revealed an increased risk of tumor-related death for patients whose liposarcomas possess with gains of 13q21 and 13q32 simultaneously (P=0.010; RR=7.1; 95% CI 1.6-31.7). Furthermore, 12 high-level amplifications were found in tumors of seven patients. In four cases 12q14-q15 and in two cases 13q32-q33 were amplified. We identified in different liposarcoma subtypes characteristic genomic changes: Gains and high-level amplifications of 12q occurred in all 11 investigated well-differentiated liposarcomas, and these changes were often present simultaneously with gains of 1q (mean 5.5 changes). In the two dedifferentiated liposarcomas, gains of 1q in both liposarcomas, and a high-level amplification of 13q were striking. Only eight of the 17 patients with myxoid/round cell liposarcomas showed changes in DNA copy number (mean 3.4 imbalances). In four of these eight cases gains of 13q occurred. The six pleomorphic liposarcomas possessed the most frequent genomic imbalances (mean number 16.3) of all liposarcoma subtypes investigated. These imbalances were in almost all chromosomal regions detected predominantly as over-representations of chromosomes 1, 5p, 13q, and 22q. Summarizing, all subtypes but well-differentiated liposarcomas showed gains of 13q, which were associated with a poor prognosis.

Adult↗

Primary liposarcoma of the skin: a rare neoplasm with unusual high grade features.

Liposarcoma is the most common soft tissue sarcoma in adults. It presents in three main forms: well-differentiated liposarcoma (which includes adipocytic, sclerosing, inflammatory, spindle cell, and dedifferentiated subtypes), myxoid/round cell liposarcoma, and pleomorphic liposarcoma. Anatomic distribution depends largely on histologic subtype, but the deep soft tissue of the extremities and the retroperitoneum are most frequently affected. Whereas it is accepted that liposarcoma rarely occurs in the subcutaneous soft tissue, the dermis seems to represent an exceedingly rare site of occurrence. The clinicopathologic features of a series of seven primary cutaneous liposarcomas (two atypical lipomatous tumors/well-differentiated liposarcomas, one myxoid/round cell liposarcoma, and four pleomorphic liposarcomas) are analyzed here. Clinically, all of the patients were adults (four men, three women) with a median age of 72 years, and four of seven cases arose on the scalp. Local recurrences occurred in two patients, but no distant metastases or disease-related deaths have been observed. Although follow-up is relatively short, it appears that, exceptionally, liposarcoma occurs primarily in the skin and, despite an apparent tendency to show high-grade morphologic features, it seems to exhibit relatively indolent clinical behavior in this location.

Adipose Tissue↗

Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma.

CONTEXT: beta-Catenin is an adhesion molecule that also plays a role in the Wnt signaling pathway. Objective.-To analyze beta-catenin mutation and accumulation in a series of liposarcomas and malignant fibrous histiocytomas. DESIGN: beta-Catenin mutation in exon 3 was studied using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30 formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12 dedifferentiated liposarcomas, characterized by both high-grade anaplastic components and well-differentiated liposarcoma components, plus 18 well-differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2 components of dedifferentiated liposarcomas were analyzed independently. beta-Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell-proliferation marker, MIB-1 labeling index) were examined immunohistochemically. Nine storiform-pleomorphic-type malignant fibrous histiocytomas were also studied. RESULTS: Dedifferentiated liposarcomas showed mutation in 2 cases (17%) and accumulation in 5 cases (42%). One of the 2 cases that showed mutations had a mutation in the well-differentiated component; this mutation was silent. The other case had mutations that differed between the 2 components. In well-differentiated liposarcomas, mutation was not seen in any of the cases (0/18; 0%); however, accumulation was seen frequently in the sclerosing-type cases (5/8; 63%), but not in the lipoma-like cases (0/10; 0%). Malignant fibrous histiocytomas showed mutation and accumulation in 5 (56%) and 4 (44%) cases, respectively, without any exact correlation between the cases. Cases with accumulation had a higher MIB-1 labeling index than those without, among both the sclerosing-type well-differentiated liposarcomas (P <.05) and the malignant fibrous histiocytomas. CONCLUSIONS: Our results suggest the possible involvement of beta-catenin activation caused by beta-catenin mutation in liposarcoma and malignant fibrous histiocytoma, but the contribution would seem to be different, depending on the tumor type. beta-Catenin accumulation is also thought to be related to cell proliferation in some of the cases.

Adult↗

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Adult↗

Lipoblastoma and liposarcoma in children: an analysis of 9 cases and a review of the literature.

OBJECTIVES: To review the experience at a children's hospital of lipoblastoma and liposarcoma and to identify any factors that would differentiate one type of tumour from the other. DESIGN: A retrospective case series. SETTING: British Columbia's Children's Hospital a tertiary-care pediatric centre. PATIENTS: All patients with a pathological diagnosis of lipoblastoma and liposarcoma recorded over 12 years. MAIN OUTCOME MEASURES: The frequency of lipoblastoma and liposarcoma, identified from biopsy specimens of pediatric adipose tumours. The clinical, pathological and cytogenetic variables between lipoblastoma and liposarcoma. RESULTS: One hundred and forty-nine adipose tumours were recorded. Seven (4.7%) were lipoblastomas and 2 (1.3%) were liposarcomas. All tumours presented as asymptomatic, slow-growing, soft-tissue masses. The children with lipoblastoma tended to be younger, but 29% were over 3 years of age. The liposarcoma patients were aged 9 and 14 years. One liposarcoma was of myxoid type and the other was a round cell variant. Karyotypes were reported for 1 lipoblastoma and 1 liposarcoma. The myxoid liposarcoma karyotype was 46,XY,t(12;16)(q13;p11), and the lipoblastoma was reported as 46,XY,der(8)?t(8q;?),+mar. CONCLUSIONS: Lipoblastoma is an unusual childhood neoplasm and liposarcoma is very rare in children. Both tumours may present in a similar fashion, and differentiating them histologically can be difficult. Age cannot be relied upon to accurately predict their behaviour. The tumour karyotype is very helpful in differentiating these neoplasms.

Adolescent↗

High telomerase activity and high HTRT mRNA expression differentiate pure myxoid and myxoid/round-cell liposarcomas.

Molecular markers characterizing the transition of a myxoid to a more round-cell liposarcoma have not been described. To examine whether telomerase activity, hTRT and hTR mRNA expression were associated with tumor progression in myxoid liposarcoma, we investigated a total of 28 myxoid liposarcomas (13 pure myxoid tumors, 14 mixed-type tumors, and 1 pure round-cell variant) from 19 patients. Telomerase activity was detected by using the fluorescent PCR-based TRAP-assay. Expression of hTRT and hTR mRNAs was determined by the semi-quantitative RT-PCR. On the basis of only one tumor sample per patient, telomerase activity was found in 9 of 9 myxoid/round-cell liposarcomas and in 3 of 10 pure myxoid tumors. Elevated hTRT expression was found in 13 of 17 liposarcomas. All telomerase-positive tumors showed hTRT expression, whereas there were 3 cases showing hTRT expression without telomerase activity. HTR mRNA expression was elevated in all 19 liposarcomas. Thus, only the levels of telomerase activity and of hTRT mRNA expression differentiated pure myxoid liposarcoma and myxoid/round-cell liposarcoma (p < 0.003 and p = 0.029, respectively). We believe that high levels of telomerase activity and of hTRT expression are associated with tumor progression from low-grade pure myxoid to higher-grade malignant round-cell liposarcoma, and may consequently represent a useful prognostic marker for this histological sub-type of soft-tissue tumors.

Biomarkers↗

A study of inter-alpha-trypsin inhibitor chains expression in liposarcomas.

AIM: Liposarcoma is common soft tissue sarcoma that is sometimes difficult to treat, besides its good prognosis. The inter-alpha-trypsin inhibitor heavy chains (HCs) has been reported to be linked to hyaluronan, which play important roles in tumour progression and metastasis. In this study, clinical significance of HCs in patients with liposarcoma was investigated. METHODS: HC expression was studied by immunohistochemistry on resected specimens of 33 liposarcoma patients and 10 lipoma patients. The expression of HC mRNA was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Serum concentration of HC was determined with enzyme-linked immunosorbent assay (ELISA). RESULTS: Prominent positive staining of HC was observed in extracellular matrix of pleomorphic and myxoid liposarcoma. In well-differentiated liposarcoma and lipoma, faint staining was seen with HC. No products of HC could be detected by RT-PCR. Serum concentration of HC was not up-regulated in any subtypes of liposarcoma. HC expression was not significantly correlated with tumour subtypes and prognosis. CONCLUSION: HC was strongly accumulated in pleomorphic and myxoid liposarcoma, however, was not locally synthesized in liposarcoma. HC might play roles in stabilizing extracellular matrix, such as hyaluronan (HA), in liposarcoma.

Alpha-Globulins↗

FUS/TLS-CHOP chimeric transcripts in liposarcoma tissues.

Myxoid liposarcoma and malignant fibrous histiocytoma (MFH) are common soft tissue sarcomas of adulthood. Histopathologically they often show intratumor heterogeneity. In some cases, differential diagnosis of liposarcoma and MFH is difficult. It has been reported that myxoid liposarcomas are characterized by chromosomal translocation t (12; 16) (q13; p11), and that this results in two types (type I and type II) of FUS/TLS-CHOP fusion transcripts. In this study, the FUS/TLS-CHOP chimeric transcripts in seven malignant soft tissue tumors of Asian patients were analyzed by reverse transcription-polymerase chain reaction, DNA blot hybridization and nucleotide sequencing. One myxoid liposarcoma and two round cell liposarcomas possessed a chimeric transcript whose fusion point was the same as that of the type I fusion transcript reported previously for myxoid liposarcoma. We were thus able to detect the type I FUS/TLS-CHOP fusion transcript in clinical specimens of liposarcoma from Asian patients, including the first examples of round cell liposarcoma. These results suggest that the detection of FUS/TLS-CHOP chimeric transcripts or chimeric genes can be used as a diagnostic tool for the pathological diagnosis of liposarcomas.

Adult↗

Liposarcoma occurring in children. An analysis of 17 cases and review of the literature.

Liposarcoma, one of the most common malignant mesenchymal neoplasms affecting adults, has rarely been documented to arise in children. Therefore, in this retrospective study, the clinicopathologic features of 17 liposarcomas retrieved from the files of the Armed Forces Institute of Pathology (AFIP) which occurred in patients between the ages of eight months and 15 years were analyzed. In contrast to the slight male prevalence verified in most studies of adult liposarcoma, this group of 17 cases disclosed a distinct female majority (65%). The tumor had a predilection for the lower extremity (41%), particularly the thigh; the remaining examples, which included cases from the neck, back, axilla, buttock, and forearm, reflected a seemingly random anatomic distribution. The retroperitoneum, a very common primary location for adult liposarcoma, accounted for only one example in the group. The histologic variants of liposarcoma coincided with the types delineated in most generally accepted classifications employed for liposarcoma in adults, but their distribution varied considerably from that found in most extensive series of adult liposarcomas. Specifically, there were 13 myxoid liposarcomas, two well-differentiated liposarcomas, and one each of the round cell and mixed variants. Follow-up information, obtained for 15 cases, revealed local recurrence in three patients, one of whom eventually died as a result of direct tumor extension into the pleural cavity.

Adolescent↗

[liposarcoma. Aspects of pathomorphology--an analysis of 209 tumos].

BACKGROUND: Among the heterogeneous group of adult soft tissue sarcomas, liposarcomas represent the largest entity along with malignant fibrous histiocytomas (MFH). PATIENTS AND METHODS: This article summarizes the results of pathomorphological data on 209 liposarcomas resected over a 10-year period. RESULTS: The most common tumor site was the thigh, and the peak age incidence was in the 5th and 6th decades. In general, three major subtypes of liposarcoma can be distinguished in terms of pathomorphology: well-differentiated/dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. Well-differentiated liposarcomas represent malignancy grade 1 tumors without biological potential to metastasize, but which are able to relapse locally in cases of incomplete resection. When a local relapse has occurred, the liposarcoma may show dedifferentiation and may metastasize. CONCLUSIONS: In the pathologic-anatomical diagnosis of liposarcomas, conventional light-microscopic findings are decisive. Additional methods of molecular pathology may help in single cases to gain further insights.

Adult↗

Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation.

We studied 155 cases of dedifferentiated liposarcoma to define its clinicopathologic features and behavior, in particular how the extent and grade of dedifferentiation affected outcome. Tumors occurred in late adult life (median, 61.5 years: range, 21-92 years), most commonly in the retroperitoneum (106 cases), extremities and trunk (32 cases), and scrotum/spermatic cord (13 cases). The majority of dedifferentiated liposarcomas presented as de novo lesions, whereas the remainder developed as a late complication of a preexisting well-differentiated liposarcoma after an average interval of 7.7 years. At the time of presentation, most of the dedifferentiated liposarcomas displayed extensive areas of high-grade dedifferentiation resembling malignant fibrous histiocytoma or high-grade fibrosarcoma, whereas a minority contained only areas of low-grade dedifferentiation resembling fibromatosis or well-differentiated fibrosarcoma. Divergent myosarcomatous or osteosarcomatous differentiation was observed focally in six cases. The behavior of dedifferentiated liposarcomas was that of a high-grade sarcoma with a local recurrence rate of 41%, a metastatic rate of 17%, and disease-related mortality of 28%. The most important prognostic factor was location in that retroperitoneal tumors had significantly worse survival than those in other sites. Tumors were divided into those having less than or those with more than 25% dedifferentiation, and dedifferentiated zones were classified into low grade or high grade. Neither low-grade dedifferentiation nor a low percentage of dedifferentiation was associated with an improved outcome for the tumors examined in this study; however, in no cases was the absolute size of the dedifferentiated focus <2 cm. Therefore, this study did not determine a minimum, or threshold, amount of dedifferentiation below which outcome was more favorable. The behavior of liposarcomas in which the dedifferentiated component was entirely low grade was more similar to that of traditional dedifferentiated liposarcoma than to that of well-dedifferentiated liposarcoma. Our study supports the expansion of the definition of dedifferentiated liposarcoma to include tumors with low-grade dedifferentiation and also suggests that low-grade dedifferentiation represents a precursor lesion of high-grade dedifferentiation.

Adult↗

Retroperitoneal liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma-like myxoid areas.

To broaden the knowledge of myxoid morphology in liposarcoma, eight cases of unusual liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma (MFH)-like myxoid areas are reported. The tumors arose as huge retroperitoneal masses in elderly patients, except for one that occurred in the spermatic cord. Three cases had local recurrences, and one of the seven patients who were followed up had died of the tumor. Grossly, the tumors were mostly confluent and multinodular and showed a glistening myxoid appearance in variable proportions, which merged gradually into or were juxtaposed to yellow fatty or sclerotic whitish areas. Microscopically, in addition to areas of well-differentiated lipoma-like or sclerosing liposarcoma, all the tumors contained myxoid portions characterized by scattered multinucleated or bizarre giant cells and a prominent plexiform vascular pattern that resembled myxoid MFH or myxofibrosarcoma. The myxoid areas were associated with discernible lipogenesis. High-grade dedifferentiation was present in one tumor. Cytogenetically, in one case, the myxoid lesion had nonrandom chromosomal aberrations, such as ring and marker chromosomes, characteristic of a well-differentiated variant of liposarcoma. In a nested reverse transcription-polymerase chain reaction analysis using archival paraffin-embedded tissue, it was seen that none of the eight tumors with myxoid MFH-like features had TLS/FUS-CHOP fusion transcripts characteristic of myxoid and round cell liposarcomas. These clinicopathologic and molecular features suggest that the current myxoid tumors are more closely related to well-differentiated liposarcoma rather than to ordinary myxoid liposarcoma despite their unequivocal myxoid morphology. Missense point mutations of the p53 gene were detected in two (25%) cases by single-strand conformation polymorphism and sequence analyses. Immunohistochemical expressions of p53 and mdm2 were observed in 75% of the cases, in which immunoreactive tumor cells were seen more often in the myxoid MFH-like areas. Thus, altered p53 pathways, such as p53 gene mutation and mdm2-mediated inactivation of p53, may play a pathogenetic role in this form of tumor progression showing myxoid MFH-like morphology in liposarcoma, as has been suggested in dedifferentiated liposarcoma.

Aged↗

Paratesticular liposarcoma: a clinicopathologic study.

Paratesticular liposarcomas are rare and typically reported as isolated cases or as components of larger studies of liposarcomas. We studied a series of these tumors. All cases of paratesticular liposarcomas were retrieved from the archives of the Royal Marsden Hospital and the Johns Hopkins Hospital. Slides were reviewed and clinical information obtained. There were 30 paratesticular liposarcomas from men aged 41-87 years (mean 63 years; median 65 years) that involved the spermatic cord (23, 76%), testicular tunics (6, 20%), and epididymis (1, 4%). Tumors ranged from 3 to 30 cm (mean 11.7 cm; median 10 cm). Nineteen were well-differentiated liposarcomas (WDLs) and 10 were dedifferentiated liposarcomas (DDLs, five with high-grade and five with low-grade dedifferentiation). One was a myxoid/round cell liposarcoma with 70% round cell areas. All patients were treated by radical orchiectomy. One patient with WDL received radiation after his second recurrence and the myxoid/round cell liposarcoma received radiation and chemotherapy. Follow-up information was available for 16 of the patients, including 10 WDLs (range 24-216 months, mean 106 months), 5 DDLs (14-30 months, median 24 months), and for the myxoid/round cell liposarcoma (14 months) (range for all cases 14 months to 22 years; mean 87 months, median 36 months). Six of the WDLs (60%) recurred at 2, 4, 6, 10, 18, and 21 years (median 8 years). The lesion that recurred at 18 years (case no. 6) displayed foci of high-grade dedifferentiation in the recurrence, although the patient was disease free at 19 years. One patient with WDL had two recurrences at 4 and 7 years, and another had six recurrences over a 17-year period. Only one example of DDL recurred, at 30 months; another patient, who refused therapy for 15 years, had a primary tumor 30 cm in diameter, displayed pulmonary metastases 1 month after excision, and died after 14 months. The patient with MRCL had abdominal metastases after 1 year and was alive at 14 months. In summary, paratesticular WDL had a prolonged course with recurrences in more than half the cases, sometimes late. There were no metastases and the overall prognosis was good. One DDL recurred and only one of five (20%) developed metastases, but the mean follow-up for DDL was only 24 months.

Adult↗

Histologic subtype and margin of resection predict pattern of recurrence and survival for retroperitoneal liposarcoma.

OBJECTIVE: The aim of this study was to determine the pattern of recurrence and prognostic significance of histologic subtype in a large series of patients with primary retroperitoneal liposarcoma. SUMMARY BACKGROUND DATA: Classification of liposarcoma into subtypes, based on morphologic features and cytogenetic aberrations, is now widely accepted. Previous studies have shown that high histologic grade and incomplete gross resection are the most important prognostic factors for survival in patients with retroperitoneal sarcoma and suggest that patients with liposarcoma have a 3-fold higher risk of local recurrence compared with other histologies. METHODS: A prospective database was used to identify 177 patients with primary retroperitoneal liposarcoma treated between July 1982 and June 2002. Histology at primary presentation was reviewed by a sarcoma pathologist and subtyped into 4 distinct groups according to strict criteria. The influence of clinicopathological factors on local recurrence, distant recurrence, and disease-specific survival was analyzed. RESULTS: Of 177 patients with primary retroperitoneal liposarcoma operated on for curative intent, 99 (56%) presented with well-differentiated, 65 (37%) with dedifferentiated, 9 (5%) with myxoid, and 4 (2%) with round cell morphology. The tumor burden was determined by the sum of the maximum tumor diameters. The median tumor burden was 26 cm (5-139). Median follow-up time for 92 (52%) surviving patients was 37 (mean, 0.5-192) months. Multivariate analysis showed that dedifferentiated liposarcoma subtype was associated with a 6-fold increased risk of death compared with well-differentiated histology (P < 0.0001). In addition to histologic subtype, incomplete resection (P < 0.0001), contiguous organ resection (excluding nephrectomy; P = 0.05), and age (P = 0.03) were important independent prognostic factors for survival in retroperitoneal liposarcoma. Retroperitoneal dedifferentiated liposarcoma was associated with an 83% local recurrence rate and 30% distant recurrence rate at 3 years. CONCLUSIONS: The histologic subtype and margin of resection are prognostic for survival in primary retroperitoneal liposarcoma. Dedifferentiated histologic subtype and the need for contiguous organ resection (excluding nephrectomy) was associated with an increase risk of local and distant recurrence. Nephrectomy may be needed to achieve complete resection, but has no measurable influence on disease specific survival.

Databases, Factual↗

H-ras oncogene mutation in dedifferentiated liposarcoma. Polymerase chain reaction-restriction fragment length polymorphism analysis.

Point mutations of the ras gene family (K-ras, H-ras, and N-ras) are thought to be involved in the development of a variety of human tumors. Dedifferentiated liposarcoma is characterized by the coexistence of well-differentiated (WD) and high-grade anaplastic (HG) components. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well-differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently. H-ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases. Our results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma.

Adult↗