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PubMed1999

Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and chi2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.

Adult↗
PubMed2001

Atypical lipoma of the tongue.

We report an atypical lipoma arising in the tongue of a 43-year-old man who presented with an indolent dorsal lingual swelling. Atypical lipomas contain multivacoulated lipoblasts, which distinguishes them from benign lipomas. The superficial location in this case distinguishes this tumour from well-differentiated liposarcoma, which is biologically similar in lacking the propensity for metastasis. The superficial location of atypical lipoma allows a complete resection, which is often not possible for the deep-seated counterpart. Atypical lipoma and well-differentiated liposarcoma, if left in situ, may undergo transition to de-differentiated liposarcoma. Atypical lipoma should be completely excised with a cuff of normal tissue in order to prevent repeated local recurrence and the possibility of de-differentiation.

Adult↗
PubMed2001

[Spindle cell lipoma and 13q deletion: diagnostic utility of cytogenetic analysis].

AIM: Spindle cell lipomas are rare adipose tissues tumors. Histologically, these lesions are composed of mature adipocytes and spindle cells associated with collagen bundles. Spindle cell lipomas are benign tumors that can be difficult to distinguish from malignant tumors such as spindle cell liposarcomas, myxoid liposarcomas or well-differentiated liposarcomas. RESULTS: We report herein the description of two new cases. The first case was a deeply situated and infiltrating tumor located in the retromastoidian area. The karyotype showed the presence of two chromosomal abnormalities, a partial deletion of the long arm of chromosome 13, del(13)(q12) and a balanced reciprocal translocation t(2;6)(p16~21;p21). The second case was a subcutaneous tumor of posterior cervical localization. The karyotype showed a 13q deletion associated with a complex rearrangement of chromosomes 5, 6 and 10. The presence of the 13q deletion allowed us to confirm the diagnosis of spindle cell lipoma in both cases. This deletion has been previously described in six out the eleven published karyotype reports. The 13q deletion is usually associated with partial monosomy 16. The present case confirms that it can occur independently. The 6p21 rearrangement may also play a role in the pathobiology of this tumor, as suggested by the positive HMGIY expression detected by immunohistochemistry. CONCLUSION: Our study further illustrates that spindle cell lipomas can infiltrate the surrounding muscle and emphasizes the usefulness of cytogenetic analysis in the differential diagnosis of soft tissue tumors.

Chromosome Aberrations↗
PubMed1992

Genomic alterations in sarcomas: a histologic correlative study with use of oncogene panels.

Amplification and rearrangement of cellular proto-oncogenes are two of the several possible genetic alterations implicated in carcinogenesis and tumor progression. Although morphologically similar tumors may be heterogeneous at the level of the genome, some tumor types have shown relatively frequent and consistent abnormalities of specific oncogenes. In order to determine the frequency of oncogene amplification and rearrangement in several types of human sarcomas and to determine if histologically similar tumors have common genetic alterations, we analyzed 26 primary sarcomas by Southern hybridization. The oncogene probes utilized were N- and H-ras, sis, EGF-R (erb-B-1), neu (erb-B-2), fos, N- and c-myc, mos, and yes. The tumors studied included: five rhabdomyosarcomas (one alveolar, four embryonal), six malignant fibrous histiocytomas, six leiomyosarcomas, four liposarcomas, two Ewing's sarcomas, one osteosarcoma, and two fibrosarcomas. Oncogene abnormalities were identified in three tumors. One rhabdomyosarcoma showed 12-fold amplification and concurrent rearrangement of sis. This particular tumor also revealed rearrangement of H-ras and 15-fold amplification of c-myc. A second rhabdomyosarcoma revealed rearrangement of neu. A liposarcoma had a sis rearrangement. These findings suggest that many sarcomas show no common structural oncogene abnormalities. The presence of differing oncogene alterations within the rhabdomyosarcoma group indicates genetic heterogeneity among histologically similar sarcomas. The finding of a sis rearrangement in both a liposarcoma and a rhabdomyosarcoma, however, may suggest common oncogenesis among different tumor types.

Adolescent↗
PubMed1986

[In vitro phase II-III study by clonogenic assay: the combined effects of mitomycin C with alpha-interferon].

Using the human tumor clonogenic assay technique, the combined effects of mitomycin C (MMC) with alpha-interferon (HLBI) were surveyed in comparison with 33 fresh human tumor specimens. Tumors in this study were 16 gastric cancers, five breast cancers, four liposarcomas, three colon cancers, two gall bladder cancers, two esophageal cancers, and one hepatoma. When the survival fraction observed in drug combination was smaller than the multiplication of each survival fraction observed in each drug alone, the combined effects were considered to be synergistic. Twenty-two of 33 tumors (gastric cancer 11/16, breast cancer 5/5, liposarcoma 2/4, colon cancer 1/3, gall bladder cancer 2/2, esophageal cancer 1/2, and hepatoma 0/1) formed adequate colony numbers for the evaluation of combined drug effects. Synergistic effects were observed in seven tumors (three gastric cancers, one breast cancer, one gall bladder cancer, one liposarcoma and one esophageal cancer), although three tumors (one gastric cancer, one gall bladder cancer, and one colon cancer) exhibited antagonistic effects.

Cell Division↗
PubMed1996

The value of nuclear DNA and texture analysis by digital image processing in the diagnosis of lipomatous and leiomyomatous tumours.

The present study investigates whether the quantitative chromatin pattern description carried out by means of the digital cell image analysis of Feulgen-stained nuclei can contribute valuable diagnostic information on sarcomas. A series of 77 soft tissue tumours was consequently studied. This series included 9 benign lipomas versus 26 malignant liposarcomas and 26 benign leiomyomas versus 16 malignant leiomyosarcomas. Of the 26 liposarcomas, 14 were primary and 12 recurrent tumours. Of the 16 leiomyosarcomas, 13 were primary and three recurrent tumours. The results show that the combined use of principal-components analysis and the discriminant analyses of digital data obtained by means of the computer-assisted microscope analysis of Feulgen-stained nuclei made it possible to obtain a clear-cut distinction between the three histopathological groups relating to the lipoma/liposarcoma group of soft tumours. In contrast, while a clear-cut distinction could be made between the recurrent leiomyosarcomas and the primary leiomyosarcomas, such a distinction was not possible between the benign leiomyomas and the malignant primary leiomyosarcomas. This feature, along with previous ones obtained through DNA ploidy level determination, suggests to us that leiomyomas, or at least some of them, are in the process of malignant transformation. In other words, leiomyomas might be the pre-malignant counterpart of leiomyosarcomas, a feature that the present results do not suggest for lipomas versus liposarcomas.

Adult↗
PubMed1997

Familial aggregation of soft tissue sarcomas: a report of three cases from a Li-Fraumeni-like family.

Three rare cases of familial aggregation of soft tissue sarcomas (malignant fibrous histiocytoma in a mother and liposarcomas in her two children) are described. The mother developed a late onset of malignant fibrous histiocytoma in her right thigh. Her son and daughter both developed retroperitoneal liposarcomas at the ages of 38 and 33 years, respectively. The mother also developed gastric carcinoma as a second malignancy after a 2-year interval. These clinical features closely resemble those of Li-Fraumeni syndrome, but do not fulfill the exact diagnostic criteria. Genetically, the germline mutation of the p53 gene between exons 4 and 9 was not detected by sequencing DNA obtained from the peripheral blood of the mother. Immunohistochemically, p53 protein was found only in the liposarcoma of the daughter. These results strongly suggest that this familial aggregation of soft tissue sarcomas is very rare, and that it is a unique feature of a familial cancer syndrome that to our knowledge has not been defined or described previously.

Adult↗
PubMedDate not supplied

p53/MDM-2 immunohistochemical expression correlated with proliferative activity in different subtypes of human sarcomas: a ten-year follow-up study.

The aim of this study was the evaluation of p53/MDM-2 protein overexpression in different subtypes of human sarcomas, and their correlation with proliferative activity and patient outcome. We selected 40 cases of human sarcomas comprising 6 malignant fibrous histiocytomas (MFH), 1 fibrosarcoma, 1 dermatofibrosarcoma protuberans, 5 liposarcomas, 9 leiomyosarcomas, 1 rhabdomyosarcoma, 3 synovial sarcomas, 2 osteosarcomas, 1 chondrosarcoma, 4 Ewing's sarcomas, 2 Kaposi's sarcomas, 1 malignant haemangiopericytoma, 1 phylloides cystosarcoma, 1 neuroblastoma, 1 chordoma and 1 unclassified sarcoma. All the immunohistochemical markers, which had been used for the characterization of these sarcomas were re-examined. Additionally, the Streptavidin-Biotin peroxidase method was performed on paraffin sections using the monoclonal antibodies: anti-p53 antibody DO7, anti-MDM-2 antibody IF2 and anti-Ki-67 antibody MIB-1. According to our results, p53 protein nuclear expression was detected in 20% (8/40) of the tumours (1 fibrosarcoma, 2 liposarcomas, 1 leiomyosarcoma, 1 rhabdomyosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). MDM-2 nuclear staining was determined in 7.5% (3/40) of the cases (1 MFH and 2 liposarcomas). A high proliferative index was demonstrated in 27.5% (11/40) of the tumours (2 MFH, 4 leiomyosarcomas, 1 rhabdomyosarcoma, 1 osteosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). p53 overexpression was associated with high tumour grade (p < 0.05) and MIB-1 expression was correlated with reduced survival (p < 0.05), but p53 overexpression was not significantly associated with either MIB-1 score or with overall survival of the patients. In conclusion, from this limited and heterogeneous sample of cases, we suggest that the p53/MDM-2 pathway is involved in the tumourigenesis of several sarcoma subtypes, but it is unclear if the overexpression of these genes may become prognostic marker for patients affected with these highly aggressive tumours.

Adolescent↗
PubMed1987

Chromosomal changes in soft-tissue sarcomas. A new diagnostic parameter.

A cytogenetic study was performed on short-term cultures from fresh surgical specimens obtained from 41 patients with soft-tissue sarcomas of various histologic origins. The results demonstrated that myxoid liposarcomas (five tumors) were associated with a specific translocation between chromosomes 12 and 16 and that synovial sarcomas (six tumors) were associated with a specific translocation between the X chromosome and chromosome 18. These chromosomal data have been used to differentiate myxoid liposarcoma from other myxoid tumors exhibiting a non-characteristic histologic picture, as well as to ascertain the diagnosis of synovial sarcoma in undifferentiated soft-tissue sarcomas. The results to date indicate that identification of specific chromosomal changes in sarcomas may provide a new diagnostic criterion for these tumors and possibly improve prognostication with regard to survival and response to treatment.

Adult↗
PubMed1999

Fine-needle aspiration cytology of spindle cell lesions of the breast.

BACKGROUND: Fine-needle aspiration biopsy (FNA) has been successful in diagnosing epithelial lesions of the breast. Its role in the evaluation of spindle cell and mesenchymal lesions of the breast, which include a variety of benign and malignant conditions, is less clear. This article discusses the cytologic features and differential diagnosis of these lesions, as well as the potential diagnostic pitfalls associated with them. METHODS: FNAs of the breast, in which a spindle cell or mesenchymal component was a key or dominant feature, were retrieved. Fibroadenomas without cellular stroma and typical lipomas were excluded. RESULTS: Forty-six aspirates (0.87%) in a series of 5306 breast FNAs contained a significant spindle cell or mesenchymal component. The aspirates were classified into 4 categories: 1) reactive conditions, including 2 diabetic mastopathies, 3 granulation tissue specimens, and 7 granulomatous lesions; 2) benign neoplastic conditions, including 1 mammary hamartoma, 1 dermatofibroma, 1 fibromatosis, 2 granular cell tumors, 2 angiolipomas, and 7 cellular fibroadenomas; 3) low grade malignant neoplastic lesions, including 10 low grade phyllodes tumors; and 4) high grade malignant neoplastic lesions, including 1 metaplastic carcinoma with chondroid stroma, 1 pleomorphic liposarcoma, 2 malignant fibrous histiocytomas, 2 osteosarcomas, and 4 metastatic melanomas. A specific diagnosis was rendered in 38 cases (82.6%). The mammary hamartoma was diagnosed as fibrocystic changes; the dermatofibroma as benign spindle cell lesion, not otherwise specified (NOS); and the primary osteosarcoma as an atypical spindle cell proliferation, NOS. The reactive ductal epithelial cells in one of the granulomatous mastitis specimens, as well as the hyperplastic ductal epithelial cells in one of the phyllodes tumors, were interpreted as atypical ductal proliferation. The marked cytologic atypia displayed by one granular cell tumor was interpreted as low grade adenocarcinoma and the primary liposarcoma as poorly differentiated carcinoma. CONCLUSIONS: Breast lesions with a significant spindle cell or mesenchymal component are rarely encountered in FNA and constitute a heterogeneous group that may pose a diagnostic dilemma. FNA should be the initial diagnostic procedure for investigating these lesions, as a specific diagnosis was rendered in the majority of cases. Cancer (Cancer Cytopathol)

Adult↗
PubMed1998

Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes and MorPhology.

With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups.

Adult↗
PubMed2004

ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications.

Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high-level amplifications of the 12q14-q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen-activated protein kinase kinase kinase of the JNK-MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors.

Abdominal Neoplasms↗
PubMed1980

Lipoblastic tumours of somatic soft tissues: a xerographic evaluation of 67 cases.

The role of xeroradiography for the diagnosis and the clinical evaluation of lipoblastic tumours of somatic soft tissues was investigated in 67 patients. Xeroradiography improved the visibility of soft tissues over film radiography in 20 out of the 23 cases in which both examinations were performed. The xeroradiographic characters of a lipoblastic tumour depend on its nature, thus irregular and infiltrative masses are usually liposarcomas, while regular and rounded nodes are usually pure or mixed lipomas. Moreover, pure lipomas are always radiolucent and liposarcomas are always radiopaque. Xeroradiography is regarded as a promising first technique in the diagnosis of lipoblastic tumours, before more complex investigations, like computed tomography (CT) scanning or arteriography, are undertaken.

Evaluation Studies as Topic↗
PubMed1998

MR and CT findings in a case of hibernoma of the thigh extending into the pelvis.

Review of the literature shows no report of hibernoma of the thigh extending into the pelvis. Herein we report a case of hibernoma which appeared on CT and MR as a well-defined pelvic mass with contrast enhancement extending through the obturator foramen into the thigh. Fat was demonstrated by CT, whereas MR, using multiplanar sections, better analyzes the extension of the mass. This case demonstrates that hibernoma as liposarcoma can extend through the obturator foramen. However, no definite diagnosis could be made by CT or MR and the tumor must be considered as a "potential" malignant liposarcoma.

Adipose Tissue↗
PubMed2006

Perioperative outcome in sarcoma surgery.

INTRODUCTION: Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of all malignancies. Although disease-specific surgical management is increasingly important, only few data are available for STS. Here, we analyze a single institution setting focusing on perioperative surgical and clinical parameters. METHODS: Prospectively gathered data of all adult patients undergoing surgery for STS including gastrointestinal stroma tumors (GIST) between October 2001 and October 2004. Patients undergoing only biopsy or ambulatory surgery were excluded. Statistical analysis was performed using SAS(R) software and patient's data from a computerized sarcoma registry. RESULTS: 159 patients with a median age of 60.2 years underwent a total of 179 operations. Three major sites of occurrence were notified: the visceral cavity (VIS) (36.3%), the retroperitoneum (RET) (31.3%), and the extremities (EXT) (27.4%). GIST (53.9%) were the most common type in the VIS, liposarcoma (62.5%) in the RET, and either liposarcoma (30.6%) or malignant fibrous histiocytoma (28.6%) in the EXT. Recurrence was treated in more than half of the patients with RET STS, and in almost one third of the EXT lesions, while primary occurrence dominated in the VIS. Median operation times in the VIS, RET, and EXT were 210, 240, and 120 min, respectively. Blood loss was 300, 500, and 50 ml for VIS, RET, and EXT operations. Morbidity was 26.2, 30.4, and 34.7% in VIS, RET, and EXT operations, respectively (reoperation rates were 9.4, 5.4, and 14.3%). Mortality was 1.5, 8.9, and 2.0% for VIS, RET, and EXT. Length of hospital stay in the groups was comparable. CONCLUSION: STS surgery of a single surgical unit contains predominantly VIS, RET, and EXT tumors. The STS subtype varies with location, as does length of operation, blood loss, morbidity, mortality, and reoperation rate. These data are helpful for planning the perioperative management of adult patients with STS and can be used for prognostic analyses.

Aged↗
PubMed1996

A rare case of burn scar malignancy.

Malignant changes in burn scars have long been reported in the literature. Most cases are squamous cell carcinomas and some other epithelial cell carcinomas. Soft tissue tumours are considered rare. A rare case of sarcoma arising in a scar on the sole of the foot in a 64-year-old male is reported. He had suffered fire burns 25 years previously. Histological findings indicated that the tumour was a pleomorphic liposarcoma. Amputation was performed, but he died 3 months after the operation. To our knowledge, this is only the second case of liposarcoma developing in a burn scar.

Burns↗
PubMed2004

Current soft-tissue sarcoma classifications.

In order to analyse the impact of modern sarcoma classification criteria, pathological material from 281 extremity soft-tissue sarcomas (STS) was reviewed. The cases were originally diagnosed between 1972 and 1994, and the most frequent diagnoses then were malignant fibrous histiocytoma (MFH) (26%), liposarcoma (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the proportions had changed significantly, with the largest group now being leiomyosarcomas (20%), liposarcomas (17%), synovial sarcomas (14%), and sarcomas "not otherwise specified" (NOS) (11%). The original diagnosis was changed in 57% of the cases; in particular, the number of fibrosarcomas was reduced from 32 to 6, and MFHs from 72 to 2, with 22 renamed as myxofibrosarcomas; 20 (7%) were found not to be sarcomas. The main reasons for these results are the recent advances in immunohistochemistry (IHC) together with changes in nomenclature. The findings have obvious implications, in particular for retrospective research.

Fibrosarcoma↗

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