Different mRNA expression profile during tumor progression in a well-differentiated liposarcoma--A microdissection approach

Like malignant fibrous histiocytoma (MFH), dedifferentiated liposarcoma represents a distinct subtype of liposarcoma and is characterized by an abrupt transition from well-differentiated liposarcoma (WDL) to highgrade dedifferentiated liposarcoma (DDL) . In addition, specific cytogenetic aberrations support the close biological relationship between WDL and DDL. Recent observations indicated the significance of cell cycle aberrations in tumor progression from the low-malignant, well differentiated to its dedifferentiated form, the prognosis of which is poor. Thus, alterations of mdm2 and p53 genes belong to the most frequently reported alterations in these two subtypes of liposarcoma. In previous investigations, we reported that loss of heterozygosity at the Rb gene locus, telomerase activity, hTERT, and c-Myc expression were associated with tumor progression in liposarcomas. In this study, we report on a case of a WD/DDL, in which both tumor components were separated using laser microdissection (P.A.L.M.) for the investigation of hTERT mRNA expression on a LightCycler. Macroscopically selected and histologically proven cryosections of low malignant and highly malignant tumor areas were cytogenetically investigated to confirm the diagnosis and to find additional chromosomal alterations with tumor progression.     

DISTINCT mdm2/p53 EXPRESSION PATTERNS IN LIPOSARCOMA SUBGROUPS: IMPLICATIONS FOR DIFFERENT PATHOGENETIC MECHANISMS

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated–dedifferentiated (WD–DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD–DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD–DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD–DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas. © 1997 by John Wiley & Sons, Ltd.     

Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing amplicons at 12q13–22

It has recently been shown that mdm2 overexpression with stabilization of p53 represents a characteristic of retroperitoneal well-differentiated-dedifferentiated, here renamed evolved (WD-E), liposarcomas at the immunocytochemical, molecular, and cytogenetic level. This make-up appears to be confined to half the cases in non-retroperitoneal well-differentiated liposarcomas. Since in different tumours MDM2 amplification involves amplicons encompassing flanking genes, such as CDK4, the possibility was investigated that in these tumours, CDK4 could act as an alternative or additional gene involved in the transformation mechanism. Forty-one retroperitoneal (R)/non-retroperitoneal (NR) well-differentiated-dedifferentiated (WD-DD) and 33 myxoid/round cell liposarcomas were reanalysed by immunocytochemical, molecular (nine cases) and fluorescence in situ hybridization (FISH) (one case) techniques. The results showed that all but one R WD-E cases carried the mdm2+, p53+, cdk4+ immunophenotype. In NR-WD liposarcomas, this immunophenotype was shared in five cases and the remainder showed mdm2+, p53−, cdk4+ in four and mdm2−, p53−, cdk4+ in one case, showing ring chromosomes by FISH analysis. TP53 mutations are confirmed to be closely correlated with NR-DD liposarcomas and no CDK4 involvement was found in the myxoid/round cell liposarcoma group. As well as confirming the synergistic effect of MDM2 and CDK4, these results are consistent with the concept that amplicon(s) excluding MDM2 may contribute to transformation and support a role of CDK4 in opposing p53 function, particularly in NR WD liposarcoma. © 1998 John Wiley & Sons, Ltd.     

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.     

Immunoreactivity of p53, mdm2, and p21WAF1 in dedifferentiated liposarcoma: special emphasis on the distinct immunophenotype of the well-differentiated component

Alteration of the p53/mdm2 pathway has been reported in the well-differentiated liposarcoma (WDLS)/dedifferentiated liposarcoma (DDLS) group. We investigated the immunoreactivity of p53, mdm2, and p21WAF1, along with the MIB-1-labeling index (MIB-1-LI) in 21 WDLS and 21 DDLS cases, to clarify the association of these markers with the morphologic changes and the biological factors responsible for the aggressiveness of DDLS. Within DDLS, p53 and p21WAF1 expression and mdm2 overexpression were significantly more prevalent in the dedifferentiated (DD) components than in the well-differentiated (WD) components. The mdm2 overexpression and p21WAF1 expression was significantly associated with sclerosing liposarcomas in both WDLS and the WD components of DDLS. There was no significant difference in the immunoreactivity of p53, mdm2, or p21WAF1 or MIB-1-LI between WDLS and the WD components of DDLS. An association was found between p53 expression and mdm2 overexpression in the WD group (comprising WDLS and WD components of DDLS) and in the DD group, significantly so in the WD group. Notably, this correlation was found in the subtype of sclerosing liposarcoma but not in that of lipoma-like liposarcoma. Within DDLS, the clinical outcome of the nonaccessible soft tissue (non-AST: comprising retroperitoneum and mediastinum) group was significantly worse than that of the accessible soft tissue (AST: comprising extremities, buttocks, axilla, and scrotum) group; however, the immunophenotypes of p53, mdm2, and p21WAF1 and the MIB-1-LI showed no correlation with survival in the AST group alone, in the non-AST group alone, or in the 2 together. This study suggests that the immunoreactivity of p53, mdm2, and p21WAF1 is associated with the morphologic changes, but not with the biological factors responsible for the aggressiveness of DDLS.     

Biochemical uncovering of mdm2/p53 complexes in liposarcomas parallels their immunohistochemical detection.

Recent observations indicate the existence of pathogenetically distinct groups of well-differentiated (WD) dedifferentiated (DD) liposarcomas. In the retroperitoneal WD-DD liposarcomas, the predominant phenotype is represented by the aberrant (overexpressed) mdm2+/p53+ wild-type profile. At the nonretroperitoneal site, the WD liposarcomas present a wider association of MDM2/P53 gene expression; i.e., mdm2+/p53+, mdm2+/p53-, mdm2-/p53+ and mdm2-/p53-, and TP53 mutations seem to correlate with the dedifferentiation process. A biochemical study of mdm2-p53 association in 11 tumor samples characterized by the presence of different mdm2 and p53 immunophenotypes was performed. Immunoprecipitation assays using a p53-specific antibody were performed on tumor tissue and surrounding normal tissue; the immunoprecipitated material was then investigated for the presence of p53 (control) and of coimmunoprecipitated mdm2. This biochemical analysis showed that, in mdm2+/p53+/wild-type retroperitoneal liposarcomas, a band corresponded to mdm2 protein in the cellular lysates immunoprecipitated with a p53-directed antibody. In contrast, the mdm2+/p53- liposarcoma did not evidence the presence of mdm2 protein nor was p53 protein available to direct immunoprecipitation, as in the p53 mutant tumor samples with mdm2-/p53+ and mdm2-/p53- phenotypes. From the normal counterpart of retroperitoneal liposarcoma lysates, no p53 protein was immunoprecipitated. The findings in this study agree with the molecular data and they show the physical association of mdm2 and p53 in fresh liposarcoma surgical specimens.     

Distinction between lipoma and liposarcoma by MDM2 alterations: a case report of simultaneously occurring tumors and review of the literature

We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The hypothesis tested was if there is a continuum in the development from lipoma to liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53 protein expression, as well as by mdm2 amplification and mdm2 protein expression. p53 mutation and p53 LOH were found neither in the well-differentiated nor in the dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an increase in mdm2 protein expression were found to be associated with malignancy and dedifferentiation, whereas p53 protein expression was only slightly increased. These findings indicate that mdm2 constitutes one of the most common targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker distinguishing between ordinary lipoma and well-differentiated liposarcoma, and that the genesis of these tumors is different.     

Distinction Between Lipoma and Liposarcoma by MDM2 Alterations: A Case Report of Simultaneously Occurring Tumors and Review of the Literature

We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The hypothesis tested was if there is a continuum in the development from lipoma to liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53 protein expression, as well as by mdm2 amplification and mdm2 protein expression. p53 mutation and p53 LOH were found neither in the well-differentiated nor in the dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an increase in mdm2 protein expression were found to be associated with malignancy and dedifferentiation, whereas p53 protein expression was only slightly increased. These findings indicate that mdm2 constitutes one of the most common targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker distinguishing between ordinary lipoma and well-differentiated liposarcoma, and that the genesis of these tumors is different.     

Dedifferentiated myxoid liposarcoma: a clinicopathological study suggesting a closer relationship between myxoid and well-differentiated liposarcoma

Myxoid/round cell liposarcoma is arguably the commonest type of liposarcoma occurring in the extremities and may show gradual progression from low-grade, pure myxoid liposarcoma to high-grade round cell liposarcoma. Rarely myxoid/round cell liposarcoma is associated with areas of well-differentiated or pleomorphic liposarcoma (mixed liposarcoma). We describe the clinicopathological features of three unusual myxoid/round cell liposarcomas which showed morphological features of de novo dedifferentiation. All patients were male and were aged 66, 70 and 76 years, respectively. One lesion each arose in the retroperitoneum, inguinal region and peritoneal cavity. Histologically, in one case the myxoid/round cell component was juxtaposed to a high-grade non-lipogenic component resembling non-pleomorphic storiform 'malignant fibrous histiocytoma' ('MFH'), one case showed a combination of myxoid liposarcoma and a high-grade myxofibrosarcoma-like component (so-called myxoid 'MFH'), and in the third case, a well-differentiated myxoid liposarcoma with a discontinuous micronodular pattern of dedifferentiation was seen. Follow-up information of 30, 28 and 26 months revealed two recurrences each in two patients. These patients died of postoperative pulmonary embolism and abdominal haemorrhage, respectively; systemic metastases were not noted. These cases demonstrate that myxoid/round cell liposarcoma can show, albeit very rarely, histological features of dedifferentiation. Cases like these, combined with the occurrence of mixed-type liposarcoma (well-differentiated/myxoid liposarcoma) and the vicinity of chromosomal regions involved by specific karyotypic aberrations in these tumours, suggest that myxoid/round cell liposarcoma and well-differentiated liposarcoma (including its dedifferentiated variant) are more closely related in biological terms than is generally believed.     

Crystalline inclusions in oligodendroglial cells

Liposarcomas are among the most common soft tissue sarcomas. It is recognized that dedifferentiation can occur within a well-differentiated liposarcoma, but there is limited information concerning the ultrastructure of the dedifferentiated cells. A series of 8 cases has been studied by light and electron microscopy and compared with well-differentiated, myxoid, and pleomorphic liposarcomas. No definite evidence of lipoblastic differentiation could be found in the dedifferentiated cases. The tumor cells resembled atypical cells in the well-differentiated liposarcomas, supporting the close relationship between these two types of tumors. However, since no conclusive line of differentiation could be found in the dedifferentiated cases, this study supports the contention that these neoplasms are undifferentiated counterparts of well-differentiated liposarcomas.     

The Ultrastructure of Liposarcomas with Attention to “Dedifferentiation”

Liposarcomas are among the most common soft tissue sarcomas. It is recognized that dedifferentiation can occur within a well-differentiated liposarcoma, but there is limited information concerning the ultrastructure of the dedifferentiated cells. A series of 8 cases has been studied by light and electron microscopy and compared with well-differentiated, myxoid, and pleomorphic liposarcomas. No definite evidence of lipoblastic differentiation could be found in the dedifferentiated cases. The tumor cells resembled atypical cells in the well-differentiated liposarcomas, supporting the close relationship between these two types of tumors. However, since no conclusive line of differentiation could be found in the dedifferentiated cases, this study supports the contention that these neoplasms are undifferentiated counterparts of well-differentiated liposarcomas.     

Molecular aberrations of the G1-S checkpoint in myxoid and round cell liposarcoma.

Myxoid and round cell liposarcoma represents a morphological spectrum in which tumor progression from low-grade myxoid to high-grade round cell areas is frequently observed. A distinctive t(12;16)(q13;p11) reciprocal translocation rearranges the CHOP gene localized to 12q13 in most cases. Data concerning the occurrence of cell cycle aberrations in this subset of mesenchymal malignancies are very limited. Therefore, we analyzed a histologically homogeneous series of 21 cases of myxoid and round cell liposarcoma. The p53 pathway was studied by investigating the TP53 gene and protein, mdm2 protein, and p21Waf1 protein. The Rb-cyclin D pathway was analyzed by studying the pRb protein, the p16MTS1 gene, cyclin D1, cyclin D3, p27Kip1, cdk4, and cdk6 proteins. In contrast with the rare involvement of the TP53 gene in well differentiated liposarcoma, aberrations of the TP53 gene were observed in approximately 30% of cases of myxoid and round cell liposarcoma. Notably, mdm2 overexpression was seen in 56% of cases and correlated with histological grade, therefore indicating a possible role in tumor progression. Abnormalities involving the Rb-cyclin D pathway were observed in more than 90% of cases. pRb loss was present in one-third of cases and, at variance with that observed in other subsets of sarcoma, overexpression of cyclin Ds represented a rare event. Interestingly, upregulation of either cdk4 or cdk6 was demonstrated in 85% of cases.     

Dedifferentiated liposarcoma of the pyriform sinus: report of a case and review of the literature

Laryngeal and hypopharyngeal liposarcomas are extraordinarily infrequent tumors. To the best of our knowledge there are fewer than 40 well-documented cases reported to date. Almost all of them are well-differentiated liposarcomas, with only 2 laryngeal-hypopharyngeal dedifferentiated liposarcomas. Dedifferentiated liposarcoma is defined as a well-differentiated liposarcoma with areas of high-grade spindle cell nonlipogenic sarcoma. The well-differentiated areas may be of a lipoma-like, sclerosing, or mixed type, and the dedifferentiated areas most frequently are of malignant fibrous hystiocytoma-like type. Despite its commonly pleomorphic histology, dedifferentiated liposarcoma does not behave as aggressively as most pleomorphic sarcomas of adulthood; however, it has the capacity to metastasize, in contrast to its well-differentiated counterpart. We present a case of dedifferentiated liposarcoma arising in the pyriform sinus, an event only twice reported previously in the literature.     

c‐Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme

Genomic amplification of c‐Jun and its upstream kinases have been implicated as a mechanism of progression from well‐differentiated to dedifferentiated liposarcoma. To further define the role of c‐Jun in liposarcoma progression, we performed immunohistochemistry for c‐Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c‐Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c‐Jun amplification. c‐Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well‐differentiated components (59%), but only in the minority of pure well‐differentiated liposarcomas (27%). When c‐Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c‐Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c‐Jun in c‐Jun‐amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c‐Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

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.     

Aberrant calreticulin expression is involved in the dedifferentiation of dedifferentiated liposarcoma

Liposarcomas are a representative group of soft tissue sarcomas with variably hampered adipogenesis, which is most exemplified by its dedifferentiated subtype. However, the factor(s) responsible for inhibiting adipocyte differentiation remains unknown. A recent gene expression profiling study identified several unique genes that were highly expressed in dedifferentiated liposarcoma, and the gene encoding calreticulin (CALR), a major Ca(2+)-buffering protein that can inhibit adipocyte differentiation, was found to be overexpressed. Thus, we investigated the expression of calreticulin in 45 cases of liposarcomas, including 15 dedifferentiated tumors, at both the protein and mRNA levels. Immunohistochemically, calreticulin was consistently expressed in the dedifferentiated areas of dedifferentiated liposarcomas and commonly observed in atypical stromal cells and/or lipoblasts in the well-differentiated areas (87%), whereas large vacuolated adipocytic cells in either the tumors or normal fat were essentially negative. These results were further supported by the findings of Western blot and quantitative RT-PCR analyses. Although abnormalities in 19p13.1-13.2 where CALR is localized were uncommon in the dedifferentiated liposarcomas examined by fluorescence in situ hybridization, expression of miR-1257, a putative microRNA that targets calreticulin, was suppressed in the dedifferentiated subtype. The down-regulation of calreticulin by small-interfering RNA could induce adipogenesis in dedifferentiated liposarcoma cells and reduce cell proliferation. Our results therefore suggest that aberrantly expressed calreticulin in dedifferentiated liposarcoma is involved in its dedifferenitation and/or tumor progression.     

Epigenetic alteration of p16INK4a gene in dedifferentiation of liposarcoma

The atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) is a locally aggressive subtype of liposarcoma unless dedifferentiation occurs. The mechanism driving this progression is not clear. Loss of p16 is believed to be an early and critical event in tumor progression. Gene silencing by methylation of p16INK4a gene promoter has been reported in several soft tissue sarcomas. The aim of this study is to study the role of p16INK4a gene promoter methylation and p16 expression in tumor progression (dedifferentiation) and recurrence of ALT/WDLPS. Four cases of dedifferentiated liposarcomas (DDLPS) and three cases of recurrent well-differentiated liposarcomas (WDLPS) were collected, and methylation status of p16INK4a gene promoter was analyzed using methylation-specific PCR (MSP) on DNA extracted from paraffin blocks. p16 expression was examined by immunohistochemistry on the same blocks. Methylation of p16INK4a gene promoter was seen in the dedifferentiated (DD) components only, in two out of four (2/4, 50%) DDLPS. The other two DDLPS and three recurrent WDLPS were not methylated. Both WD and DD components in all four DDLPS cases showed strong nuclear p16 expression. All three recurrent WDLPS showed positive p16 expression with similar intensity between primary and recurrent tumors. Even though linear correlation between p16 promoter hypermethylation and p16 protein expression was not present, there appears to be a role for p16INK4a gene promoter hypermethylation in DDLPS and not in recurrent WDLPS.     

Dedifferentiated liposarcoma with rhabdomyoblastic differentiation

Dedifferentiated areas of dedifferentiated liposarcoma (DDL) usually show malignant fibrous histiocytoma (MFH)- or fibrosarcoma-like features and lack any histologic signs of specific differentiation. However, some reports have demonstrated specific differentiation in these areas, with histologic features resembling those of rhabdomyosarcoma, leiomyosarcoma, and osteosarcoma. We report here a pathologic and genetic analysis of three cases of DDLs with rhabdomyosarcomatous areas. MFH- or fibrosarcoma-like areas of one primary DDL and two recurrent DDLs contained various amounts of rhabdomyoblasts, which were immunoreactive for desmin, myoglobin, muscle actin (HHF-35), and myogenin. An ultrastructural examination demonstrated rhabdomyoblasts with abundant cytoplasm containing thin and thick filaments and Z-bands. By real-time PCR, amplification of mdm2 and cdk4 was confirmed in both well-differentiated and dedifferentiated areas with rhabdomyoblasts of all cases. To our knowledge, only seven cases of DDLs with rhabdomyosarcomatous components have been reported, and furthermore, the genetic profiles of the rhabdomyosarcomatous components in DDLs have not been investigated. This study demonstrates that DDLs with rhabdomyosarcomatous areas have genetic alterations that are common to well-differentiated/dedifferentiated liposarcomas.     

Histologically low-grade dedifferentiated liposarcoma of the retroperitoneum

A low-grade dedifferentiated liposarcoma in the retroperitoneum of a 52-year-old woman is described. The excised specimens contained six nodules of lipoma-like well-differentiated liposarcoma and a nodule of dedifferentiated liposarcoma. The latter was composed predominantly of loosely arranged, benign-appearing spindle cells and fat cells. A small number of cells with irregularly shaped nuclei were scattered. There were no mitotic figures. The fat cells showed slight variation of size and shape, and a few multivacuolated lipoblasts were found. The spindle cell areas occupied approximately 60% of the tumor. The stroma was somewhat fibrous and myxoid and no dense collagenous matrix was found. The stroma vascularity was not prominent. Immunohistochemically, the spindle cells were positive for vimentin but negative for S-100 protein, desmin, muscle actin, and alpha-smooth muscle actin. Follow up for 5 months showed no evidence of recurrence or metastasis. The tumor, in which the benign-appearing spindle cell component was predominant, was considered to be a low-grade dedifferentiated liposarcoma. Close and long-term follow up is required. In retroperitoneal lipoma-like well-differentiated liposarcomas, spindle cell components like the present tumor, which represent dedifferentiation, should not be overlooked.