Radiosensitivity translates into excellent local control in extremity myxoid liposarcoma

BACKGROUND:

Myxoid liposarcoma has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The authors report the results of multidisciplinary treatment of extremity myxoid liposarcoma compared with a contemporary cohort of other STS subtypes with an emphasis on the role of radiotherapy (RT) in improving local control.

METHODS:

Between 1989 and 2004, 691 patients were identified from a prospective STS database who underwent combined management for localized extremity STS and were followed for a minimum of 12 months or until death. All patients underwent surgery together with pre or postoperative RT, depending on their presenting characteristics and resection margins. Demographics and outcomes were compared between patients with myxoid liposarcoma and other STS subtypes (other‐STS).

RESULTS:

Of 691 patients, 88 patients had myxoid liposarcoma and 603 had other STS subtypes (other‐STS). Median age was 48 and 60 years for the myxoid liposarcoma and other‐STS groups, respectively. Median follow‐up was 86 and 61 months, respectively. For myxoid liposarcoma and other‐STS groups, preoperative RT was used in 57% versus 61% of patients and postoperative RT in 43% versus 39%, respectively. The 5‐year local recurrence‐free survival was 97.7% for patients with myxoid liposarcoma compared with 89.6% for patients with other‐STS tumors (P = .008). High‐grade tumors were present in 7% and 59% of myxoid liposarcoma and other‐STS patients, respectively (P = .0003). Two myxoid liposarcoma patients with local recurrence had positive resection margins, whereas only 33% of patients in the other‐STS group who developed a local recurrence had positive resection margins. No patients with myxoid liposarcoma required amputation as primary management, whereas 8 (1.3%) required amputation as primary management in the other‐STS group. Systemic disease control was superior in myxoid liposarcoma compared with other‐STS patients, with 5‐year overall and metastasis‐free survival rates of 93.9% versus 76.4% (P = .0008) and 89.1% versus 66.0% (P = .0001) respectively. Of 12 myxoid liposarcoma patients with distant metastases, 7 appeared in nonpulmonary sites. In comparison, 205 (34%) patients with other‐STS tumors developed systemic disease but 78% had pulmonary metastases.

CONCLUSIONS:

Multidisciplinary management of extremity STS achieves high rates of local control. Myxoid liposarcoma is associated with higher rates of local control compared with other STS subtypes, after combined surgery and radiation, suggesting a particular radiosensitivity that can be exploited to improve oncologic outcome in appropriate cases. Cancer 2009. © 2009 American Cancer Society.     

Spinal metastases from myxoid liposarcoma warrant screening with magnetic resonance imaging

BACKGROUND: Myxoid liposarcoma (MLS) has an unusual tendency for extrapulmonary metastasis, particularly to the spine and soft tissues. The objective of this study was to determine the prevalence of spinal metastasis, treatment outcomes, and optimal screening method for spinal metastasis in patients with MLS. METHODS: Data from patients with had spinal metastases were obtained from the authors' institutional soft tissue sarcoma database. The accuracy with which positron emission tomography (PET) scans and bone scans identified metastatic lesions was compared with the accuracy of magnetic resonance imaging (MRI). Clinical response to treatment was based on pain, neurologic scores, and survivorship analysis. RESULTS: There were 33 patients who developed spinal metastasis after a median 36 months of follow-up (range, from 7.5 months to 33 years). Known spinal metastases were detected by bone scans in 16% of patients and by PET scans in 14% of patients. Patients who underwent surgery had high-grade spinal cord compression more often than patients who did not undergo surgery (72% vs 19%, respectively; P = .002). Pain and neurologic function were improved or maintained in all patients who received radiation alone (n = 8 patients) and in all but 1 patient who underwent surgery (n = 18 patients). The median overall survival was 51.4 months from the time of primary diagnosis and 21.9 months from the time of first metastasis. CONCLUSIONS: Bone scans and PET scan lack sufficient sensitivity to detect spinal metastasis from MLS. Treatment of metastasis is palliative, but local treatment can yield long-term disease control in select patients. Screening with whole-spine MRI may lead to the earlier detection of spinal metastasis.     

Localized and metastatic myxoid/round cell liposarcoma

BACKGROUND.

Myxoid liposarcoma (MLPS), a disease especially of young adults with potential for local recurrence and metastasis, currently lacks solid prognostic factors and therapeutic targets. The authors of this report evaluated the natural history and outcome of patients with MLPS and commonly deregulated protein biomarkers.

METHODS.

Medical records were retrospectively reviewed for patients who presented to the authors' institution with localized (n = 207) or metastatic (n = 61) MLPS (1990 to 2010). A tissue microarray of MLPS patient specimens (n = 169) was constructed for immunohistochemical analysis of molecular markers.

RESULTS.

The 5‐year and 10‐year disease‐specific survival rates among patients with localized disease were 93% and 87%, respectively; male gender, age >45 years, and recurrent tumor predicted poor outcome. The local recurrence rate was 7.4%, and the risk of local recurrence was associated with recurrent tumors and nonextremity disease location. Male gender was the main risk factor for metastatic disease, which occurred in 13% of patients. Forty percent of patients who had localized disease received chemotherapy, mostly in the neoadjuvant setting. Immunohistochemical analysis revealed significantly higher expression of C‐X‐C chemokine receptor type 4 (CXCR4) and platelet‐derived growth factor beta (PDGFR‐β) in metastatic lesions versus localized lesions. Tumors with a round cell phenotype expressed increased levels of CXCR4, p53, adipophilin, PDGFR‐α, PDGFR‐β, and vascular endothelial growth factor relative to myxoid phenotype. Only the receptor tyrosine kinase encoded by the AXL gene (AXL) was identified as a prognosticator of disease‐specific survival in univariate analysis.

CONCLUSIONS.

In this study, the authors identified clinical and molecular outcome prognosticators for patients with MLPS as well as several potential therapeutic targets. Cancer 2013. © 2013 American Cancer Society.     

Metastatic patterns of extremity myxoid liposarcoma and their outcome

BACKGROUND AND OBJECTIVES: Extremity myxoid liposarcomas have a unique extrapulmonary metastatic potential. We studied the metastatic pattern of extremity liposarcomas to determine what types of posttreatment imaging may be of value in the follow-up these patients. METHODS: Twenty-two patients from a total of 128 patients with primary extremity liposarcoma were treated at a tertiary care institution for subsequent metastases from January 1981 to January 2000. Median follow-up was 45 months (range: 6-270 months). Data on these patients was prospectively collected and then retrospectively analyzed for effect of metastatic pattern and treatment on outcome. RESULTS: Of these 22 patients, extrapulmonary metastases developed in 10, combined pulmonary and extrapulmonary metastases developed in 6, and isolated pulmonary metastases developed in 6. Of the 16 patients with extrapulmonary metastases, 13 were of the myxoid subtype. Of the 49 patients with extremity myxoid liposarcomas, metastases developed in 14 (29%). The most common sites of metastases among these 14 patients include: the retroperitoneum, 10 patients (71)%; intra-abdominal extra-hepatic, 7 patients (50%); spinal/paraspinal, 6 patients (43%). Only 3 of the patients are alive and disease free and all 3 of these patients are from the subgroup of 10 patients with only extra-pulmonary metastases (2 intra-abdominal and 1 retroperitoneal). CONCLUSIONS: Extremity myxoid liposarcomas have an unusually high predilection for extra-pulmonary metastases, frequently without any pulmonary metastases. After treatment of the primary tumor, these patients should be followed with periodic chest X-ray and abdominal/pelvic computed tomography (CT) scans. Any back or neurologic complaints should prompt additional imaging of the appropriate spinal area. Consideration should be given to surgical and adjuvant treatment of metastatic disease when appropriate.     

转移性心包黏液样脂肪肉瘤1例报道并文献复习

原发性心包恶性肿瘤较为少见,以心包恶性间皮瘤居多,原发性心包脂肪肉瘤极为罕见,目前国内外报道甚 少[1-2],而继发性心脏恶性病变的患病率是原发性心脏恶性肿瘤的20～40倍.为进一步提高对原发性心包恶性肿瘤的认识,避免临床漏诊及误诊,现结合相关文献,就1例转移性心包黏液样脂肪肉瘤(myxoid liposarcoma,...     

Prognostic value of nuclear morphometry in myxoid liposarcoma

Myxoid liposarcoma (MLS) accounts for 20%-30% of liposarcoma and the round cell component (RCC) is believed to be a specific poor prognostic factor. However, the RCC assessment criteria are vaguely defined and, therefore, are inconsistently employed by pathologists. In this study, we modified and applied two established grading systems to evaluate nuclear atypia (namely, the World Health Organization/International Society of Urological Pathology and the Fuhrman grading in renal cell carcinoma) in 64 MLS cases. Detailed software-based assessments of the morphology and the cellularity were performed. DNA mutation analysis, comprehensive mRNA expression analysis, and immunohistochemistry were also performed. Our findings revealed that the high–nuclear-grade group according to the modified Fuhrman grading system exhibited a significantly poor disease-free survival (hazard ratio: 4.43; 95% confidence interval: 0.9-22.6; p = 0.047). On the other hand, the cellularity was significantly higher in the modified Fuhrman high-grade group (p = 0.010 at the percentage of the hypercellular area; p = 0.003 at the maximum cell density) but did not qualify per se as a poor prognostic factor in the survival analyses. Furthermore, the modified Fuhrman high-grade group significantly expressed the cell cycle–related genes (such as FOXM1, PLK1, and CDK1). In conclusion, our analyses suggest that an evaluation focusing on nuclear morphology (rather than on cellular density) can be more reliable in predicting the MLS prognosis.     

Primary liposarcoma of the lung: Report of a case

We reported one case of a primary liposarcoma of the lung which has been reported only in six cases to date worldwide, and we added some documented study. A 49-year-old female complained of exertional dyspnea with about 100 ml of hemoptysis. The chest X ray showed a coin lesion at the left upper field. After left pneumonectomy, the histological examination revealed liposarcoma of the lung. Six months after the operation, she died from severe dyspnea; the autopsy revealed the relapse of liposarcoma in the right lung, and no liposarcomas in other organs. This is the seventh case according to a worldwide review of the literature.     

Successful treatment of advanced pancreatic liposarcoma with apatinib: A case report and literature review

Pancreatic liposarcoma is a malignant tumor originated from the pancreas mesenchymal tissue and mostly presented in skin, subcutaneous, periosteum, and long bone on both sides. Both conventional chemotherapy and radiotherapy have limited efficacy and poor prognosis for advanced pancreatic liposarcoma. Here, we reported a case of advanced pancreatic liposarcoma and reviewed the literature specific for liposarcoma of the pancreas and discuss the emerging options of treatment. The patient was treated with apatinib and a cross-line rescue therapy combined with paclitaxel after progressive disease. The therapeutic effect of the combination regimen has been evaluated. Apatinib is an oral tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2 (VEGFR-2), which has dual effects of anti-angiogenesis and anti-tumor cell proliferation. To our knowledge, this is the first case to report the successful use of apatinib for advanced pancreatic liposarcoma.     

Identification of a gene expression driven progression pathway in myxoid liposarcoma

Aim: to investigate the events involved in the progression of myxoid liposarcoma (MLS).Gene expression profiling and immunohistochemical/biochemical analyses were applied to specimens representative of the opposite ends of the MLS spectrum: pure myxoid (ML) and pure round cell (RC) liposarcomas.The analyses revealed the involvement of both coding and non coding RNAs (SNORDs located in DLK1-DIO3 region) and support a model of stepwise progression mainly driven by epigenetic changes involving tumour vascular supply and tumoral cellular component. In this model, a switch in the vascular landscape from a normal to a pro-angiogenic signature and the silencing of DLK1-DIO3 region mark the progression from ML to RC in concert with the acquisition by the latter of the over-expression of YY1/C-MYC/HDAC2, together with over-expression of genes involved in cell proliferation and stemness: MKNK2, MSX1 and TRIM71.Taken together, these findings strongly suggest that to progress from ML to RC liposarcoma the cells have to overcome the epigenetic silencing restriction point in order to reset their new stem-like differentiation signature. Our findings provide a first attempt at identifying the missing links between ML and RC liposarcomas, that may also have broader applications in other clinico-pathological settings characterised by a spectrum of progression.     

Antiangiogenic activity of trabectedin in myxoid liposarcoma: Involvement of host TIMP‐1 and TIMP‐2 and tumor thrombospondin‐1

Trabectedin is a marine natural product, approved in Europe for the treatment of soft tissue sarcoma and relapsed ovarian cancer. Clinical and experimental evidence indicates that trabectedin is particularly effective against myxoid liposarcomas where response is associated to regression of capillary networks. Here, we investigated the mechanism of the antiangiogenic activity of trabectedin in myxoid liposarcomas. Trabectedin directly targeted endothelial cells, impairing functions relying on extracellular matrix remodeling (invasion and branching morphogenesis) through the upregulation of the inhibitors of matrix metalloproteinases TIMP‐1 and TIMP‐2. Increased TIMPs synthesis by the tumor microenvironment following trabectedin treatment was confirmed in xenograft models of myxoid liposarcoma. In addition, trabectedin upregulated tumor cell expression of the endogenous inhibitor thrombospondin‐1 (TSP‐1, a key regulator of angiogenesis‐dependent dormancy in sarcoma), in in vivo models of myxoid liposarcomas, in vitro cell lines and primary cell cultures from patients' myxoid liposarcomas. Chromatin Immunoprecipitation analysis showed that trabectedin displaced the master regulator of adipogenesis C/EBPβ from the TSP‐1 promoter, indicating an association between the up‐regulation of TSP‐1 and induction of adipocytic differentiation program by trabectedin. We conclude that trabectedin inhibits angiogenesis through multiple mechanisms, including directly affecting endothelial cells in the tumor microenvironment—with a potentially widespread activity—and targeting tumor cells' angiogenic activity, linked to a tumor‐specific molecular alteration.     

Challenging surgical treatment of giant retroperitoneal liposarcoma: A case report

Liposarcoma is a rare malignant tumor type and surgical resection is the gold standard treatment. The present study reported on the case of a 51-year-old woman who presented with a mass in the left upper abdomen. Computed tomography revealed a 32-cm giant retroperitoneal liposarcoma. Complete tumor resection was performed without the removal of other organs. Postoperative pathological examination indicated retroperitoneal well-differentiated liposarcoma and immunohistochemistry revealed S-100(−), MDM2(+), vimentin(+), CDK4(+), p16(+) and STAT6(+) results. The patient recovered well after the surgery. Complete tumor resection during the first surgery is key to cure liposarcoma. The present case report will be helpful for clinical oncologists to fully understand giant retroperitoneal liposarcoma and treat it accordingly.     

Cardiac metastasis of liposarcoma

The authors describe a retroperitoneal liposarcoma with secondary involvement of the left ventricle. Therapy has been disappointing, and is guided by the nature of the primary tumor, previous therapy, extent of metastatic spread, and feasibility of cardiac resection. In selected patients whose primary tumor is well-controlled and progressing slowly, with no evidence of widespread disease, resection of the cardiac metastases can be performed when technically feasible.     

Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy

PURPOSE: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). PATIENTS AND METHODS: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. RESULTS: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at > or =5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. CONCLUSION: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.     

骨外黏液样软骨肉瘤的临床病理分析

背景与目的：骨外黏液样软骨肉瘤(extraskeletal myxoid chondrosarcoma,EMC)是一种好发于四肢深部软组织分化不定的恶性肿瘤,以形成多结节样结构、富含黏液为特点。本研究旨在探讨EMC的临床病理特征、诊断及鉴别诊断。方法：对7例EMC进行病理形态学及免疫组化观察,并复习相关文献。结果：7例EMC患者病理巨检显示,灰白色多结节状半透明肿物,边界清楚。镜下卵圆形或短梭形细胞排列成条索,由纤细的纤维组织分隔,呈分叶状,富含黏液样基质但血管稀少。免疫组化肿瘤细胞表达vimentin,部分患者表达S-100及EMA,但不表达CK。结论：EMC是一种罕见的具有独特病理特点的软组织肿瘤,应与脊索瘤、软骨肉瘤等富含黏液样基质或软骨样分化的肿瘤相鉴别。     

Bilateral hypernephroma with solitary pancreatic metastasis

A case of bilateral renal carcinoma with an uncommon solitary metastasis is presented. Therapeutic rationale is discussed.     

Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival in a series of patients treated at a single institution

BACKGROUND: The objective of this study was to investigate prognostic factors and clinical outcome of myxoid/round cell and pleomorphic liposarcoma. METHODS: Three hundred twenty-nine patients with localized myxoid/round cell or pleomorphic liposarcoma who underwent surgery at the Istituto Nazionale per lo Studio e la Cura dei Tumori (Milan, Italy) over 25 years were reviewed. The rates of local recurrence, distant metastases, and survival were studied. RESULTS: Two hundred fourteen patients presented with primary disease, and 115 patients had locally recurrent tumors. The disease-specific survival rate was 75% at 10 years, and the local recurrence and distant metastases incidence were 25% and 15%, respectively. Presentation with recurrent disease, tumor size (>10 cm), tumor grade (French Federation of Cancer Centers grade II or III vs grade I), and positive surgical margins were independent predictors of death. Tumor site and radiation therapy also played a role, mostly related to their effect on local outcome. Pathologic grade and histologic subtype influenced distant metastases. Extrapulmonary metastases were associated with poorer postmetastatic disease-specific survival. CONCLUSIONS: Myxoid/round cell liposarcomas shared similar prognostic factors with other soft tissue sarcomas and had a relatively good clinical outcome. The presence of >5% of round cell component singled out a group of patients at greater risk of metastases and death but with a broad spectrum of disease aggressiveness. Extrapulmonary metastases were a peculiar pattern of myxoid/round cell liposarcoma that require special consideration for treatment and prognosis.