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PubMed2002

Molecular characterisation of soft tissue tumours: a gene expression study.

BACKGROUND: Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers. METHODS: We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition. FINDINGS: Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types. INTERPRETATION: These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.

Gene Expression Profiling↗
PubMed1994

[Results of surgical treatment of recurrent retroperitoneal soft tissue sarcomas].

Thirty patients with locally recurrent retroperitoneal soft tissue sarcomas, whose primary tumors had been previously resected, were surgically treated. Complete resection was achieved in 18 patients (60%), of which 6 underwent en bloc resection of adjacent organs involved by the tumor. The overall 3- and 5-year survival rate for all patients was 39% and 14%, respectively. Survival at 3 and 5 years was 49% and 24% respectively for those undergoing complete resection, compared to 25% and 0% respectively for those undergoing partial resection or biopsy only (P < 0.005). An aggressive surgery aimed at complete resection. in treating recurrent retroperitoneal soft tissue sarcomas is strongly recommended. Prognostic value and clinical significance of factors such as disease-free interval, tumor size, and histologic type were discussed.

Adult↗
PubMed1993

Sonographic evaluation of local recurrences of soft tissue sarcomas.

The aim of our study was to establish whether ultrasonography can be proposed as the main diagnostic technique for the follow-up of soft tissue sarcoma (STS). In 26 patients with previous history of STS, a sonographic examination was carried out using a 5 MHz linear transducer to identify early local recurrences. Sonography was performed every 3 months and a computed tomographic (CT) control was made when the sonogram showed findings strongly suggestive of recurrence. STS recurrences were detected by sonography in 20 of 26 patients (77%) and were confirmed by histologic examination. In six cases, sonographic results were uncertain and in three of these the recurrence was ascertained by biopsy. CT scan provided a correct diagnosis in 16 patients (61.5%) and only in cases with lesions greater than 5 cm in diameter. From our experience we conclude that high frequency sonography is a most accurate noninvasive approach in early detection of STS recurrences. CT plays an important role in the cases amenable to surgery treatment and is recommended to obtain a better assessment of anatomic connection between tumor and adjacent structures.

Adult↗
PubMed2005

Antigens recognized by autologous antibodies of patients with soft tissue sarcoma.

Serological analysis of recombinant cDNA libraries (SEREX) uses high titer IgGs to identify antigens expressed by autologous cancers. In order to identify tumor antigens in soft tissue sarcoma (STS), sera from four patients with malignant fibrous histiocytoma (MFH), gastrointestinal stromal tumor (GIST), pleomorphic liposarcoma, and dedifferentiated liposarcoma were screened against cDNA libraries derived from autologous tumor. We identified 18 antigens encoded by 15 different genes, including DLG7, which is located on chromosome 14q22, a locus previously found to be altered in STS, and the proto-oncogene JUN. Ten of fourteen antigens (71%) do not react with sera from healthy donors, suggesting that antibody recognition takes place during cancer progression. Using oligonucleotide microarray technology, most genes were variably expressed across a panel of 16 benign specimens and 41 STSs of different histologies. DLG7, however, showed restricted expression in testes and cancer, similarly to known germ cell cancer-testis antigens (or germ cell antigens, GCAs). Thus, the current study identified several antigens, including molecules implicated in tumorigenesis that were recognized by high titer IgGs in STS patients. Further studies of these selected novel STS antigens are warranted to identify and characterize potential antigen targets expressed by STS.

Antibodies, Neoplasm↗
PubMed1995

Metastatic liposarcoma in the adrenal gland: report of two cases diagnosed by fine-needle aspiration.

Fine-needle aspiration is now well established in the investigation of retroperitoneal masses. Many of these lesions are first detected in the course of radiological surveys of patients with known or suspected malignancy. It can be difficult to diagnose sarcomas on fine-needle aspiration material as many of these tumour do not show cytological features of malignancy. We describe two cases of metastatic liposarcoma confidently diagnosed on the basis of characteristic cytological features seen in material aspirated from metastatic adrenal tumours.

Adrenal Gland Neoplasms↗
PubMed2003

[Giant retroperitoneal liposarcoma].

Liposarcoma is a malignant tumor that has an embryologic origin from mesodermal tissue depending on fatty tissue. Although liposarcoma is only 0.1% of all human neoplasms, it is the most common histology subtype of retroperitoneal soft tissue sarcomas. This tumor grows slowly. Diffuse abdominal pain is its most frequent symptom and abdominal mass is the most common sign. Aggressive surgical treatment is basic to get a complete resection and a local disease control. This objective is difficult because of the large tumor size it gets in the retroperitoneal location and the multiorgan involvement that require the resection of a high percentage of contiguous organs. We report a case of a giant retroperitoneal liposarcoma presenting like continuous left hemiabdominal pain because of the visceral compression. The right kidney was involved and suffering from renal vessel enlargement without renal function. There is a high probability of microscopic residual disease and a good follow-up of the patients is necessary as well as an adjuvant radiation therapy in some cases.

Abdominal Pain↗
PubMed1990

Metastases of malignant melanoma simulating soft tissue sarcoma. A clinico-pathological, light- and electron microscopic and immunohistochemical study of 21 cases.

Metastases of cutaneous malignant melanoma (MM) of ordinary type can resemble various types of soft tissue sarcoma light microscopically to a degree which has not been previously recognized. Twenty-one cases are described, in which the tumours were originally diagnosed as a soft tissue sarcoma. Seven tumours were predominantly of blue and spindle-cell, fascicular type, resembling malignant peripheral nerve sheath tumour and at times monophasic synovial sarcoma. Ten tumours which were of fascicular and predominantly storiform type, and included uni- and multi-nuleated pleomorphic cells resembled malignant fibrous histiocytoma. Due to the presence of multivacuolated lipoblast-like tumour cells, 2 of these 10 tumours resembled pleomorphic liposarcoma. One had a predominantly myxoid and hypocellular appearance and 5 additional tumours included such areas. The diagnoses were revised after ultrastructural examination with the demonstration of melanosomes in 13 of 16 studied cases and the immunohistochemical demonstration of positivity using anti-S-100 protein antibodies and the anti-melanoma antibody NKI/C3 in all cases. The anti-melanoma antibody HMB 45 gave a positivity in 9 of 21 cases. Light microscopically, sparse amounts of melanin were noted in 7 tumours using the Whartin-Starry technique. Eleven tumours occurred at sites close to major lymph node groups and in 9 of these cases, lymphoid tissue was associated with the tumours, suggesting that they represented lymph node metastases. Following a review of the patients' clinical histories and renewed clinical examination, primary cutaneous MM was demonstrated in 10 of 21 patients and in 1 case an MM in regression was detected. The origin of the 10 tumours without a detected primary is discussed, including the possibility of an overlooked primary, spontaneous regression of a primary and a de novo origin from lymph nodes and soft tissues.

Adolescent↗
PubMed1998

[Imaging findings of primary sarcoma in the kidney].

OBJECTIVE: To reveal the characteristic findings of primary sarcoma of the kidney. METHODS: From December 1988 through February 1996, seven cases of renal sarcoma confirmed by histo-pathology were retrospectively reviewed, including 3 leiomyosarcoma and 1 for each of liposarcoma, fibrosarcoma, malignant fibrous histiocytoma and malignant Schwannoma. Image material: CT in 6 cases, ultrasonography in 6 cases and MRI in 1 case. RESULTS: The tumor was located in renal parenchyma in 6 cases and in renal pelvis in 1 case. On the images, it was commonly a large mass with irregular margin, indefinite, circumscribed and heterogeneous in density with necrosis inside as observed on the CT scan and 2 cases with median to hyperattenuation on the enhanced CT scan; 4/6 cases gave median heterogeneous mixed echo and 2/6 cases appeared as even hypoechoic mass on the ultrasonogram. On MRI, the mass gave isosignal intensity on T1WI and increased signal intensity with moderate heterogeneity was seen on T2WI or became more enhanced and heterogeneous but no more than renal parenchyma on the enhanced T1WI of MRI. Big tumor thrombus in the inferior vena cava and renal vein was noted in the fibrosarcoma. CONCLUSIONS: Primary renal sarcomas give imaging findings characteristic of malignant tumor but without histological specificity and can not be differentiated from renal cell carcinoma. The enhanced CT and MRI capable of providing useful information of the localization, changes in density/signal and extent of invasion of the tumor, are beneficial to the differential diagnosis and managements.

Adolescent↗
PubMed2006

Liposarcoma in adult limbs treated by limb-sparing surgery and adjuvant radiotherapy.

Between December 1995 and March 2003, 38 adult patients with intermediate or high-grade liposarcoma in a limb were treated by limb-sparing surgery and post-operative radiotherapy. The ten-year local recurrence-free survival was 83%, the ten-year metastasis-free survival 61%, the ten-year disease-free survival 51% and the ten-year overall survival 67%. Analysis of failure and success showed no association with the age of the patients, gender, the location of the primary tumour, the type of liposarcoma and the quality of resection. Our results indicate that liposarcoma may recur even ten years after the end of definitive therapy and may spread to unexpected sites as for soft-tissue sarcoma.

Adolescent↗
PubMed1995

Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines.

Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectively, than for the HT-1080 (fibrosarcoma) cell line, which has wild-type pRB. These Rb-/- cell lines exhibited a 2- to 4-fold increase in both dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzyme activities as well as a 3- to 4-fold increase in mRNA levels for these enzymes compared to the HT-1080 (Rb+/+) cells. This increase in expression was not due to amplification of the DHFR and TS genes. Growth inhibition by MTX and FdUrd was increased and DHFR and TS activities and expression were correspondingly decreased in Rb transfectants of SaOS-2 cells. In contrast, there was no significant difference in growth inhibition among these cell lines for the nonantimetabolites VP-16, cisplatin, and doxorubicin. A gel mobility-shift assay showed that parental SaOS-2 cells had increased levels of free E2F compared to the Rb-reconstituted SaOS-2 cells. These results indicate that pRB defective cells may have decreased sensitivity to growth inhibition by target enzymes encoded by genes whose transcription is enhanced by E2F proteins and suggest mechanisms of interaction between cytotoxic agents and genes involved in cell cycle progression.

Antimetabolites, Antineoplastic↗
PubMed1991

High dose hyperfractionated radiotherapy in the treatment of extremity soft tissue sarcomas.

A hyperfractionated radiotherapy schedule has been evaluated in the treatment of 29 adults with limb or limb girdle soft tissue sarcomas. The objective was to increase the total administered dose and possibly improve local control, without increasing late normal tissue damage. Twice daily 1.25 Gy fractions (with a minimum interval of 6 h) have been given over 5 to 6 weeks to 12 patients pre-operatively, 10 post-operatively and 7 palliatively. Five patients received 62.5 Gy in 5 weeks pre-operatively and 3 palliatively. Nineteen of the remaining 21 patients received 75 Gy in 6 weeks with a field size reduction after 5 weeks. Sixteen of 29 tumours were situated in the thigh and only 2 were in the upper limb. Twenty were of high grade. The mean tumour size of those treated radically was 13.1 cm (range 5 to 40 cm). Sixteen patients (76%) given 75 Gy developed moderate or severe skin erythema maximal at 5 weeks. Despite the large field sizes used (mean phase one of 34.5 cm, and phase two of 22.8 cm) only 2 patients failed to complete the planned treatment because of the severity of these reactions. Two other patients developed partial wound breakdowns after the end of treatment--both healing spontaneously. Fourteen patients developed an area of moist desquamation--11 mild, 2 moderate and one severe. There have been four late wound breakdowns requiring surgical intervention; all have since healed well. The median follow up is short at 556 days. Ten of 19 evaluable patients have developed moderate/severe induration, 5/19 mild and 4/19 none.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Myxoid liposarcoma--the frequency and the natural history of nonpulmonary soft tissue metastases.

BACKGROUND: Myxoid liposarcomas (ML) make up the major subset of liposarcomas, which in most series represent the second or third most common type of soft tissue sarcoma. The tendency for ML to metastasize to other soft tissues (STM) in preference to lung parenchyma has been previously described; however, the natural history of this tumor's behavior is poorly documented. Our intent was to analyze the natural history of ML and further quantify the incidence of STM, concentrating on their significance in terms of survival. METHODS: We reviewed the experience at the Royal Marsden Hospital over a 10-year period, documenting the clinicopathological behavior of ML, including the frequency of STM. RESULTS: There were 50 patients, with a median follow-up of 43 months. The actuarial 5-year soft tissue metastasis rate was 31%, and the most common sites of STM were the retroperitoneum, abdominal wall, and abdominal cavity. In those 12 patients who had STM there was a median interval of 23 months after original diagnosis to the time the first metastasis became apparent (range, 0-142 months). Median survival following first metastasis was 35 months; 6 of the 12 patients died between 6 and 50 months. Four patients who had STM remain disease free at 15 to 59 months after their first STM. Any round cell component of the ML was associated with a significantly greater chance of metastatic disease (P = .02). In this series, the overall 5-year and 7-year survival rates were 85% and 68%. Patients with STM had an 11 times greater chance of dying than those who did not. CONCLUSIONS: ML usually is an indolent disease, but there is a subset of patients who develop STM and have a significantly worse prognosis. STM can occur years after the initial diagnosis and can be associated with medium-long-term survival after they occur. STM should be managed aggressively because of this.

Abdominal Neoplasms↗
PubMed1994

[Computed tomography in malignant primary soft tissue tumors].

The results of CT examinations in 36 patients suffering from histologically confirmed malignant primary tumours of the soft tissues are presented (6 rhabdomyosarcomas, 4 leiomyosarcomas, 6 liposarcomas, 4 malignant schwannomas, 5 malignant fibrous histiocytomas, 4 malignant haemangiopericytomas, 3 angiosarcomas, 1 fibrosarcoma, 1 renal sarcoma, 2 malignant mesenchymal tumours without histologically clear classification). The CT image alone will not yield information on the type of tumour or on the tumour status. However, CT continues to rank in the diagnosis of tumours of the soft tissues and is even superior to MR especially in the identification of gas accumulations due to infection in a tumour of the soft tissues that is otherwise unclear. Comparing the literature conclude that MR is now the imaging method of choice in the diagnosis of soft tissue tumours.

Adolescent↗
PubMed1980

Primary lymphomas and sarcomas of the stomach.

The records of patients with primary gastric lymphoma and sarcoma treated at M. D. Anderson Hospital and Tumor Institute between 1945 and 1975 were reviewed. Weight loss, abdominal pain, nausea, and vomiting were the most common presenting symptoms, while palpable abdominal mass was the most common sign. The lymphomas were predominantly located in the distal portion of the stomach, in contrast to the sarcomas, which were commonly located in the body and the proximal portion of stomach. Curative gastric resection was performed in 96% of patients with lymphoma and in 67% of patients with sarcoma. Diffuse histiocytic lymphoma and leiomyosarcoma were the most common histologic types. Patients with lymphoma survived significantly longer than patients with sarcoma (median 75 vs 22 months, P = 0.009). Adjuvant radiotherapy seemed to improve the survival of patients with lymphoma, while curative gastric resection provided the only hope for long-term survival for patients with gastric sarcoma. The place of adjuvant chemotherapy after curative resection of gastric lymphoma and sarcoma remains to be investigated.

Female↗
PubMed1985

Standardized echographic-histopathologic correlations in liposarcoma.

A 57-year-old woman had metastatic liposarcoma of the left orbit that underwent transformation. The primary focus in the abdomen, resected in 1975, was a well-differentiated liposarcoma. Later metastases to the neck and orbit were poorly differentiated, pleomorphic, and highly anaplastic liposarcomas. The ultrasonographic and histopathologic correlations of the different stages of the tumor during the disease process were analyzed and compared. This patient's disease had echopathologic similarities to other orbital sarcomas and adult cavernous hemangiomas.

Abdominal Neoplasms↗