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PubMed1984

Malignant mediastinal myxoid tumor and renal cell carcinoma.

A 69-year-old man with a malignant mediastinal myxoid tumor and a right renal cell carcinoma died from bilateral compression atelectasis after a two months' clinical course. The mediastinal tumor simulated a myxoid malignant fibrous histiocytoma (MFH) because of great pleomorphism of tumor cells, although the histological differential diagnosis of myxoid MFH, other myxoid sarcomas, and metastatic renal cell carcinoma was very difficult. Three reported cases of primary mediastinal MFH are briefly reviewed.

Adenocarcinoma↗
PubMed1997

Cloning of P2XM, a novel human P2X receptor gene regulated by p53.

Through cloning of functional p53-binding sites (p53-tagged sites) from the human genome, we isolated a novel gene inducible by wild-type p53. Its cDNA sequence contained an open reading frame encoding a 431-amino acid peptide that showed a significant homology with members of the P2X family. This protein also revealed a similarity to RP-2, a gene activated in thymocytes undergoing programmed cell death. Northern blot analysis showed that it was expressed predominantly in skeletal muscle. Hence, we designated the gene P2XM (P2X specifically expressed in skeletal muscle). P2XM was localized to chromosomal band 22q11, where frequent loss of heterozygosity has been observed in rhabdoid tumors. Although we detected no genetic alteration in the coding sequences, one of four rhabdomyosarcoma cell lines examined had completely lost expression of this gene. Furthermore, a minor splice variant lacking a part of exon 1 that would encode residues corresponding to transmembrane domain M1 was relatively more abundant in two of seven sarcoma cell lines, one of which was derived from a rhabdomyosarcoma, and the other was derived from an osteosarcoma. The results suggest that P2XM may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and that its altered expression may be involved in the development of some sarcomas.

Alternative Splicing↗
PubMed1999

Epidemiological aspects of soft tissue sarcomas (STS)--consequences for the design of clinical STS trials.

The purpose of the study was to gain insight into epidemiological aspects of soft tissue sarcomas (STS), based on the population-based cancer registry of the Comprehensive Cancer Center North-Netherlands (CCCN), and to provide data for the development of future STS clinical trials. 456 primary STS (Kaposi, urogenital and gastro-intestinal STS excluded), registered from 1989 to 1995 by the cancer registration of the Comprehensive Cancer Center North-Netherlands (CCCN), were analysed. The annual, age-adjusted, STS incidence was 3.6 per 100,000. Incidence increased with age. Half of the patients were over the age of 65 years. Malignant fibrous histiocytomas and liposarcomas were most frequently encountered. At presentation, nodal involvement was rare (3-8%). Distant metastases were more frequently encountered (9-14%), and appeared to be related to tumour size and site. Above 70 years of age, 16% of patients received no treatment at all, especially for metastatic disease.

Adult↗
PubMed1991

Soft tissue sarcomas in Iceland 1955-1988. Analysis of survival and prognostic factors.

From 1955 to 1988 a total of 129 cases (69 males and 60 females) of soft tissue sarcomas were diagnosed in Iceland, four at autopsy. The median age was 55 years (0-91). All the cases have been reviewed clinically and histopathologically and graded on both a three- and a four-point scale. The average age-standardized incidence was 1.8/100,000 for males and 1.6 for females. The tumour was most often localized in the thigh and retroperitoneal space. The most common histologic subtypes were malignant fibrous histiocytoma (22.5%), liposarcoma (18.6%) and leiomyosarcoma (16.3%). The 5- and 10-year survival rates (n = 125) were 38% and 29% respectively. Cox's multivariate analysis was performed on the following prognostic factors: age, sex, tumour localization, histopathologic subtype, tumour size, malignancy grade and year of diagnosis. The strongest prognostic factor was malignancy grade (IV vs I; p less than 0.001 and RR = 5.35 and III vs I; p = 0.017 and RR = 2.01) followed by tumour size (pT2 vs pT1; p less than 0.001 and RR = 3.09 and pT3 vs pT1; p = 0.002 and RR = 3.40) and year of diagnosis (p = 0.003 and RR = 0.96; corresponding to a 54% reduction in mortality risk during a 20-year period).

Age Factors↗
PubMed1984

Epidemiology of soft-tissue sarcoma in the locomotor system. A retrospective population-based study of the inter-relationships between clinical and morphologic variables.

From all soft-tissue malignancies reported to the Swedish National Cancer Registry in Southern Sweden (1.3 mill. inhabitants) from 1964 through 1978, 278 cases were accepted as sarcomas after histologic re-examination. All these were malignancy-graded on a four-grade scale, without knowledge of the clinical course. A number of clinical and morphological variables were recorded and subjected to uni-, bi- and multi-variate analysis. Follow-up was available in all patients. The annual incidence rate over all ages was 1.4/100,000. The mean age was 58 years and males dominated (1.3/1). Malignant fibrous histiocytoma, liposarcoma and leiomyosarcoma were the most common histologic groups. Three-fourths of the tumors were high-grade malignant (Grade III-IV). Sixty per cent were deep-seated, having a median size of 8 cm compared to 4 cm for the superficial tumors. One third of all tumors were located in the thigh. The histologic groups were characterized by age, tumor depth and size, the occurrence of pain, malignancy grade and five-year survival; it was seen that each group, with respect to at least one of the variables, differed significantly from all the other groups. Thus histologic classification seems to identify different tumor entities. Out of several pair-wise associations the strongest were as follows: histologic groups versus depth, size, malignancy grade and age; depth versus size; and size versus malignancy grade (Grade IV tumors being larger). The proportion of superficial and small tumors in this series is high, compared to several reported series, probably owing to "referral selection" in the previous studies. The inter-relationships found between several variables and conclusions based on selected series may explain, in part, the differing opinions which can be found in the literature regarding prognostic variables in soft-tissue sarcoma.

Adolescent↗
PubMedDate not supplied

Modified staging system for extremity soft tissue sarcomas.

BACKGROUND: The establishment of a universally acceptable staging system for soft tissue sarcomas has been hampered by the low incidence, various grading systems, and lack of consensus regarding the value of different prognostic factors. We aimed to evaluate prognostic factors in patients with extremity soft tissue sarcomas and to test the validity of the AJCC/UICC staging system. METHODS: Prospectively collected data from 316 previously untreated patients with primary extremity soft tissue sarcomas treated at a single institution between 1989 and 1995 were studied. The influence of clinical and pathological factors on local recurrence, distant metastasis, and disease-specific survival was analyzed by univariate and multivariate techniques. RESULTS: Large tumor size and high histological grade were independent adverse prognostic factors for distant metastasis. Large size, high grade, and positive microscopic surgical margins were independent adverse prognostic factors, and liposarcoma histology was an independent favorable prognostic factor for disease-specific survival. Within each histological grade, there was a progressive decline in survival with increasing tumor size, as reflected by an almost linear increase in hazard ratios. Similarly, there was a progressive fall in survival with increasing grade within each size group (<5 cm, 5 to 10 cm, 10 to 15 cm, and > 15 cm). AJCC staging did not correlate well with prognosis. Survival for intermediate-grade tumors smaller than 5 cm (stage IIA) was better than that for low-grade tumors larger than 5 cm (stage IB) (86% vs. 73%). Survival for high-grade tumors smaller than 5 cm (stage IIIA) was better than that for intermediate-grade tumors larger than 5 cm (stage IIB) (72% vs. 57%). A modified staging system was formulated based on the additive influence of size and grade on the estimated hazard ratios for disease-specific survival, as follows: stage IA, G1T1; stage IB, G1T2 or G2T1; stage IIA, G1T3 or G2T2 or G3T1; stage IIB, G1T4 or G2T3 or G3T2; stage IIIA, G2T4 or G3T3; stage IIIB, G3T4; and stage IV, M1 (G1, G2, G3 = low, intermediate, and high grade; T1, T2, T3, T4 = tumor size < 5 cm, 5-10 cm, 10-15 cm, and > 15 cm, respectively). The 5-year disease-specific survivals of stages IA, IB, IIA, IIB, IIIA, and IIIB were 100%, 83%, 74%, 61%, 39%, and 18%, respectively. The 5-year disease-specific survival for stages I, II, III, and IV were 90%, 67%, 31%, and 6% respectively. The survival difference between each stage was statistically significant (P < .001). CONCLUSION: Histological grade and tumor size are equally important determinants of distant metastases and survival. The AJCC/UICC staging system is based primarily on the grade of the tumor, with size used to subgroup each stage. A staging system for extremity soft tissue sarcomas with equal emphasis on grade and size is proposed that correlates extremely well with prognosis.

Adolescent↗
PubMed2005

[Malignant fibrous histiocytoma: pleomorphic sarcoma NOS or pleomorphic fibrosarcoma].

The entity and nosology of pleomorphic malignant fibrous histiocytoma (MFH) is still ambiguous. The actual WHO-Classification uses pleomorphic malignant fibrous histiocytoma (MFH) and pleomorphic sarcoma NOS (not otherwise specified) synonymously. On the other hand text and illustrations convey the impression, that these tumors also could be pleomorphic lipo-, leio- or rhabdomyosarcomas etc. It would have been more informative to emphasize, that with the above mentioned specific sarcoma types MFH-like appearance may occur. Furthermore it would have been more up to date to consider pleomorphic sarcomas NOS as pleomorphic fibrosarcomas and include them in the chapter of fibroblastic and myofibroblastic tumors. This concept already has been carried out for the former myxoid variant of MFH, nowadays preferentially called myxofibrosarcoma. There is controversial discussion about the clinical significance of exact typing of pleomorphic sarcomas. Problems may also occur due to the lack of standards, which degree of desmin expression signifies leiomyosarcoma or just indicates myofibroblasts in MFH. The requirement of exclusion of other tumor-types before diagnosing pleomorphic fibrosarcoma still remains obligatory. After verification of the diagnosis pleomorphic sarcoma NOS or pleomorphic fibrosarcoma, grading e.g. according to criteria of the FFCCS can be carried out. Most cases of pleomorphic fibrosarcoma will qualify as high grade malignant.

Diagnosis, Differential↗
PubMed2000

[Retroperitoneal sarcoma: report of 6 cases].

Retroperitoneal soft tissue sarcomas (RPS) are uncommon tumors. The diagnosis is frequently made later in the evolution of the disease due to the absence of specific symptomatology. Surgery with total resection of the tumor is the treatment of choice, but is only possible in 38 to 75% of cases. Six cases of RPS have been retrospectively reviewed; the mean time to diagnosis was 5 months; diagnosis was established via CT scan, which determined the retroperitoneal tumor location and its relationship to the neighboring organs. The most common symptoms were the presence of an abdominal mass and accompanying abdominal pain; signs of urinary and vascular compression were not found until later. Surgery with total resection was performed in 4 cases, and with partial resection in 2 cases. The histological findings were as follows: 3 liposarcomas, 2 rhabdomyosarcomas, and 1 fibrosarcoma. Tumor recurrence developed in 2 cases (liposarcomas), necessitating further surgery and complete resection. Two patients were lost to follow-up. RPS are characterized by locoregional relapse and metastases. Disease outcome depends on the histological type, tumor grade, and on the possibility of carrying out complete resection.

Adult↗
PubMed1994

A prospective randomized trial of adjuvant brachytherapy in the management of low-grade soft tissue sarcomas of the extremity and superficial trunk.

PURPOSE: This study was designed to evaluate the impact of adjuvant brachytherapy (BRT) on local and systemic recurrence rates in patients with low-grade sarcoma. PATIENTS AND METHODS: Forty-five patients with histologic low-grade, completely resected soft tissue sarcomas of the extremity or superficial trunk were entered onto this trial. Following resection of all gross disease, patients were randomized to the BRT arm (n = 22) or to the no-BRT arm (n = 23). On the fifth or sixth postoperative day, catheters were loaded with iridium 192 to deliver a dose of 45 Gy to the tumor bed over 4 to 6 days. RESULTS: The two groups were evenly distributed with respect to the distribution of presentation status (primary v recurrent), tumor site (trunk v extremity, proximal v distal extremity), tumor size (< 5 cm v > or = 5 cm), tumor depth (superficial v deep), and microscopic tumor margins (positive v negative). The predominant histopathologic diagnosis in each group was liposarcoma (BRT, 13 of 22 [59%]; no BRT, 14 of 23 [61%]) with other histopathologic subtypes evenly distributed between the two groups. The median follow-up duration among the ongoing survivors is 67 months. One patient in the BRT group developed systemic disease and died of progressive disease. Local recurrence occurred in five of 23 patients (22%) in the no-BRT group and six of 22 patients (27%) in the BRT group (P = .60). CONCLUSION: Adjuvant radiation in the form of BRT does not appear to decrease local recurrence rates following complete resection of low-grade extremity and superficial trunk soft tissue sarcomas. Other adjuvant approaches, such as external-beam radiotherapy, are required to have a significant impact on local recurrence rates in this group of patients.

Brachytherapy↗
PubMed1996

Fusion of the EWS and CHOP genes in myxoid liposarcoma.

The translocation t(12;16)(q13;p11), which cytogenetically characterizes myxoid liposarcomas (MLS), results in a fusion of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a chimeric FUS/CHOP gene. We have identified two cases of MLS with translocations giving rise to recombination between 12q13 and 22q12. The result was a fusion of the N-terminal part of the EWS gene in 22q12, involved in a number of mesenchymal tumor types, with the CHOP gene and the creation of an EWS/CHOP chimeric gene. The presence of the EWS/CHOP chimeric gene in MLS shows that (i) the N-terminal part of FUS may be replaced by the N-terminal part of EWS in a CHOP fusion oncoprotein (ii) the two N-terminal parts, when fused to certain transcription factors, have a common or very similar oncogenic potential and (iii) the tumorigenic process in MLS and the morphogenetically distinctly different EWS-associated tumor types may be related.

Amino Acid Sequence↗
PubMed2005

Pulmonary metastasis from liposarcoma: a clinicopathologic and immunohistochemical study of 24 cases.

A review of the histologic features of pulmonary metastasis and clinical implications of liposarcoma (LS) is given for 24 cases (8 each) of the 3 types of LS: myxoid LS (ML), pleomorphic LS (PL), and dedifferentiated LS (DDL). Most patients were men. Metastatic ML and PL were distributed almost equally among the lung lobes, whereas DDL was more common in the left lower lobe. The metastatic MLs had variable cellularity ranging from singly scattered cells in a hyalinized stroma (treatment-related effect) to hypercellular ML. Most PLs (6/8) were nonlipogenic and resembled an undifferentiated pleomorphic sarcoma. All metastatic DDLs had high-grade histologic features and were predictably nonlipogenic. After pulmonary metastasectomy, 2 patients with ML and 1 with PL were disease-free. The other 6 patients with ML, 7 with PL, and all with DDL had progressive disease. The morphologic features of LS metastatic to the lungs seem diverse but within the spectrum of the histologic type expected from the primary tumor. Overall, the general trend for these LS subsets is progressive disease, metastatic disease for ML and PL with a much shorter interval for PL, and metastatic disease and local recurrence for DDL.

Adolescent↗
PubMed1989

[Retroperitoneal sarcoma].

Clinical experience in the treatment of retroperitoneal soft tissue sarcomas during period 1978-1987 is presented. The material consists of 64 patients with the male predominance (60.94%), and the peak occurrence in the forth and fifth decade of life. The difficulties in the diagnostic of these tumours are mostly caused by unspecific clinical picture, which is usually cleared with the stage of inoperability. Modern diagnostic approach, using echotomography and angiography enables earlier diagnosis. The most often seen histological pictures in this series are: M. Hodgkin (28.14%), Liposarcoma (25%) Lympho and fibrosarcoma (twice 12.5%), and the other forms are rarely encountered (1-3%). The operability is very low, and the radical operation is performed only in 16 cases (25.50%), and exploratory procedures are performed in 44 (68.75%). In the rest of cases a reduction of bulk mass of tumour was performed. The 5 year survival in the radically operated is present in 25% (4 patients) what is in accordance with the literature. In the cases with exploration or partial resection, the average survival is 4.5 months, in spite of some longer survivals in the group with Hodgkin's disease, mostly because of the modern cytostatic treatment. Intermediate postoperative mortality is 3.12% (2 patients). In recent years, the more aggressive surgical approach is advised, resulting in better outcome.

Adolescent↗
PubMed2004

Retroperitoneal soft tissue sarcomas: patterns of recurrence in 167 patients treated at a single institution.

BACKGROUND: The objective of this study was to assess long-term prognosis and patterns of failure in patients with retroperitoneal soft tissue sarcoma who underwent surgery with curative intent at a single institution. Several series of patients with retroperitoneal sarcoma were reported, providing widely variable data regarding local and distant failure. METHODS: Overall, 167 consecutive patients who underwent surgery for retroperitoneal soft tissue sarcoma over a 20 year span at a single referral center were reviewed retrospectively. Eighty-two patients presented with primary disease, whereas 85 patients had recurrent locoregional tumors. Surgical resection was considered macroscopically complete in 147 of 167 patients (88%). RESULTS: Overall survival at 10 years after definitive surgery was approximately 27%, and the disease-free survival was approximately 16%. Only a minority of patients developed distant metastases. The risk of recurrence was correlated with whether patients underwent surgery for primary disease or for recurrent disease; the 10 year disease-free survival rate was 27% in the former group and 4.6% in the latter group. Histotype and malignancy grade were other prognostic factors, with the former found to be predictive of the pattern of failure and the latter predictive of overall survival. CONCLUSIONS: Local recurrence after primary surgery and high-grade malignancy were associated with the worst survival. Histologic subtype appeared to influence the pattern of recurrence, which mainly was local for patients with liposarcoma but was both local and distant for patients with the other histotypes.

Adolescent↗
PubMed2003

Expression of the coxsackievirus and adenovirus receptor in musculoskeletal tumors and mesenchymal tissues: efficacy of adenoviral gene therapy for osteosarcoma.

Recombinant adenovirus is used as a competent vector in a wide spectrum of cancer gene therapies. Adenovirus infection depends on coxsackievirus and adenovirus receptor (CAR)-mediated virus attachment to the cell surface. However, the expression levels of CAR and the efficiency of adenoviral gene transduction in musculoskeletal tumors have not been systematically investigated. To study the feasibility of gene therapy in musculoskeletal tumors, the expression levels of CAR and the antiproliferative effect of an adenovirally transduced wild-type p53 tumor suppressor gene were examined in 15 distinct musculoskeletal tumor cell lines, 19 tumor tissue samples, and the corresponding pathologically unremarkable mesenchymal tissues. The expression levels of the CAR gene were significantly higher in six of seven osteosarcoma cell lines and two of five osteosarcoma tissue samples than in the other cell lines, musculoskeletal tumors, and mesenchymal tissues. CAR expression levels were closely correlated with adenoviral gene transduction efficiency and the antiproliferative effect of a transduced adenoviral p53 gene in the tested cell lines. In addition, an immunocytochemical study confirmed that transfected green fluorescent protein (GFP) borne by Ad-CAG-GFP was expressed at the cell surface of CAR-positive cells. These results indicate that CAR expression is a critical determinant of transduction efficiency in adenovirus-based gene therapy. Most osteosarcomas appeared to express high levels of CAR, and thus adenovirus-mediated p53 gene therapy is likely to be suitable for the treatment of such tumors.

Adenoviruses, Human↗
PubMed2004

Clinical characteristics and overall survival in genitourinary sarcomas treated with curative intent: a multicenter study.

OBJECTIVES: Adult soft tissue sarcomas in general, and those arising from the urological organs in particular, are a group of rare tumours with a generally poor prognosis, only a few studies are available. We report our experience with this type of tumours in a multicenter study carried out in a single region of Central Italy (Tuscany). METHODS: Pre-treatment and follow-up data were obtained from 22 adult patients, all residing in Tuscany, treated consecutively between 1984 and 2002 for primary or locally recurrent genito-urinary sarcomas in 8 urology departments in the area. All cases were classified according to the French Federation of Cancer Center System Grading Scheme for Adult Sarcomas (FFCC) and Broders System. The crude survival probability was estimated by using the Kaplan-Meier method and differences between patient sub-groups were assessed by the log rank test. RESULTS: The study series included 18 males and 4 females. The mean age at diagnosis was 61+/-21.5 years (range: 15.3-89.1). The most common site was paratesticular (n=9, 40.9%), followed by kidney (n=8, 36.4%), prostate (n=3, 13.6%) and penis and bladder (1 case each, 4.6%). 15 cases (68.2%) were classified as FFCC III, and 16 (72.7%) as Broders IV. The most common histological type was leiomyosarcoma (8 cases, 36.7%), followed by liposarcoma (6, 27.3%), rhabdomyosarcoma (3, 13.6%) and other histological types (5, 22.7%). At the last follow-up (mean: 3.66+/-3.25 years; range 0.15-10.0), 11 of the 22 patients (50%) were still alive. The overall survival rate at 1, 3 and 5 years was 85.9%, 62.0% and 48.8%, respectively. There were no significant differences in survival according to sex, age or histological type. When we compared paratesticular vs. kidney and prostate cancer cases, a significant difference in survival emerged (p=0.02). According to size and grade of the tumour we also found a significant difference in survival (p=0.0006 and p=0.01, respectively). CONCLUSIONS: In our representative series, 3 tumor parameters (site, size and grade) appeared to represent the most important prognostic factors in adult genitourinary sarcomas.

Adult↗
PubMed1997

Additional evidence of a variant translocation t(12;22) with EWS/CHOP fusion in myxoid liposarcoma: clinicopathological features.

It is well established that the majority of myxoid/round cell liposarcomas (LPS) are characterized by a reciprocal translocation t(12;16)(q13;p11) which at the molecular level results infusion of the CHOP and FUS/TLS genes. It is assumed that functional characterization of these genes may provide insight into the molecular pathogenesis of this tumour type. This study describes two new cases of myxoid/round cell LPS having a t(12;22). By reverse transcription-polymerase chain reaction (RT-PCR) it has been shown that this leads to fusion between the CHOP and EWS genes, thus indicating involvement of the EWS gene, at least occasionally, in yet another sarcoma type. Combining these two cases with two others which were recently similarly characterized at the molecular level, their clinicopathological features have been compared with cases having the more usual t(12;16). It was not possible to identify any clinical or pathological differences between these molecular genetic subsets. The relevance or significance of these gene fusion products in myxoid/round cell LPS remains to be determined.

Adult↗
PubMed1986

Spermatic cord sarcoma. Leiomyosarcoma and retroperitoneal lymph node dissection.

Two cases of leiomyosarcoma of the spermatic cord are described. The first case is a seventy-eight-year-old white man with a twenty-year history of leiomyosarcoma of the cord. Twice irradiated, he has had some twenty local recurrences. These have been to the contralateral cord, scrotum, suprapubic region, both inguinal regions, and the penis. The second case is a seventy-three-year-old white man who had radical orchiectomy for leiomyosarcoma of the cord one year ago. The patient remains free of recurrence without other therapy. Other adnexal sarcomas are described, the literature is reviewed, the usefulness of retroperitoneal lymph node dissection discussed, and a plan for therapy and follow-up proposed.

Aged↗