Dedifferentiated liposarcoma with "homologous" lipoblastic (pleomorphic liposarcoma-like) differentiation: clinicopathologic and molecular analysis of a series suggesting revised diagnostic criteria.

PubMed

Mariño-Enríquez, Adrián; Fletcher, Christopher D M; Dal Cin, Paola; Hornick, Jason L

2010-08-01

Dedifferentiated liposarcoma (LPS) is a malignant adipocytic neoplasm defined as the transition from well-differentiated LPS to a nonlipogenic sarcoma. Heterologous differentiation is seen in 5% to 10% of dedifferentiated LPS, usually with myogenic or osteo/chondrosarcomatous elements. Adipocytic differentiation in the dedifferentiated component is incompatible with the current definition of dedifferentiated LPS. Pleomorphic LPS is a high-grade sarcoma containing lipoblasts. At least in areas, pleomorphic LPS can be indistinguishable from dedifferentiated LPS, except for the presence of lipoblasts in pleomorphic LPS and well-differentiated LPS areas in dedifferentiated LPS. We evaluated 12 unusual liposarcomas: 11 cases with pleomorphic LPS-like morphology affecting patients with concomitant or previous well-differentiated/dedifferentiated LPS, and 1 case resembling inflammatory "MFH" with scattered lipoblasts. Clinical and histologic features were reviewed. Immunohistochemistry for MDM2 and CDK4 was carried out. Amplification of 12q13 to q15 was studied by FISH analysis of the HMGA2 locus. The tumors arose in the retroperitoneum (7), proximal lower extremity (3), chest wall (1), and neck (1) of 9 males and 3 females (median age 66 y; range 49 to 76). Size ranged from 9 to 32 cm (median 23 cm). In 3 cases, there was an abrupt transition between well-differentiated LPS and sheets of pleomorphic lipoblasts, indistinguishable from pleomorphic LPS. Four cases consisted of otherwise typical dedifferentiated LPS (with adjacent well-differentiated LPS), except for the presence of lipoblasts in the high-grade component. One case contained both nonlipogenic spindle cell areas and an inflammatory "MFH"-like component with numerous admixed lipoblasts. Four cases were composed exclusively of pleomorphic LPS-like areas developing in 1 of the recurrences or metastases of a prior typical dedifferentiated LPS. Two cases also showed heterologous smooth muscle differentiation. MDM2

Dedifferentiated liposarcoma with homologous lipoblastic differentiation: expanding the spectrum to include low-grade tumours.

PubMed

Liau, Jau-Yu; Lee, Jen-Chieh; Wu, Chen-Tu; Kuo, Kuan-Ting; Huang, Hsuan-Ying; Liang, Cher-Wei

2013-04-01

Dedifferentiated liposarcoma (DDLPS) is traditionally defined as a non-lipogenic high-grade sarcoma arising from a well-differentiated liposarcoma that confers metastatic potential. Recently, DDLPSs with lipoblastic differentiation, i.e. morphologically lipogenic DDLPSs, were reported. Because of the lipoblastic differentiation, these tumours caused confusion, and were reported under different names. However, cytogenetic and molecular studies have revealed their DDLPS nature. So far, the cases reported have been high-grade pleomorphic liposarcoma-like tumours. In this study we have collected another series that contains low-grade tumours, and expand the histological spectrum. Eighteen cases of DDLPS with lipoblastic differentiation from various anatomical locations were analysed by routine histology, immunohistochemistry, and MDM2 fluorescence in-situ hybridization. Two main histological patterns were seen: one featured a spindle cell sarcoma containing lipoblasts with variable nuclear pleomorphism, and the other a pleomorphic liposarcoma-like tumour including the epithelioid variant. Two cases showed low nuclear grade and lipogenic activity in the metastatic foci. CDK4, MDM2 and p16(INK) (4a) overexpression was seen in all except one case. MDM2 amplification was found in all 16 cases tested. We have expanded the spectrum of this variant of DDLPS to include low-grade tumours, in which a careful search for increased mitotic activity is essential. Like conventional DDLPS, these tumours are capable of metastasis. © 2012 Blackwell Publishing Ltd.

High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features.

PubMed

Sciallis, Andrew P; Bedroske, Patrick P; Schoolmeester, John K; Sukov, William R; Keeney, Gary L; Hodge, Jennelle C; Bell, Debra A

2014-09-01

The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as

High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality.

PubMed

Eilber, Fritz C; Rosen, Gerald; Nelson, Scott D; Selch, Michael; Dorey, Frederick; Eckardt, Jeffery; Eilber, Frederick R

2003-02-01

To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy.

Primary Culture of Undifferentiated Pleomorphic Sarcoma: Molecular Characterization and Response to Anticancer Agents

PubMed Central

Recine, Federica; Mercatali, Laura; Miserocchi, Giacomo; Spadazzi, Chiara; Liverani, Chiara; Bongiovanni, Alberto; Pieri, Federica; Casadei, Roberto; Riva, Nada; Fausti, Valentina; Amadori, Dino; Ibrahim, Toni

2017-01-01

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm with no specific line of differentiation. Eribulin, a novel synthetic microtubule inhibitor, has shown anticancer activity in several tumors, including soft tissue sarcomas (STS). We investigated the molecular biology of UPS, and the mechanisms of action of this innovative microtubule-depolymerizing drug. A primary culture from a patient with UPS was established and characterized in terms of gene expression. The activity of eribulin was also compared with that of other drugs currently used for STS treatment, including trabectedin. Finally, Western blot analysis was performed to better elucidate the activity of eribulin. Our results showed an upregulation of epithelial mesenchymal transition-related genes, and a downregulation of epithelial markers. Furthermore, genes involved in chemoresistance were upregulated. Pharmacological analysis confirmed limited sensitivity to chemotherapy. Interestingly, eribulin exhibited a similar activity to that of standard treatments. Molecular analysis revealed the expression of cell cycle arrest-related and pro-apoptotic-related proteins. These findings are suggestive of aggressive behavior in UPS. Furthermore, the identification of chemoresistance-related genes could facilitate the development of innovative drugs to improve patient outcome. Overall, the results from the present study furnish a rationale for elucidating the role of eribulin for the treatment of UPS. PMID:29292724

Dedifferentiated liposarcoma and pleomorphic liposarcoma: a comparative study of cytomorphology and MDM2/CDK4 expression on fine-needle aspiration.

PubMed

Mariño-Enríquez, Adrián; Hornick, Jason L; Dal Cin, Paola; Cibas, Edmund S; Qian, Xiaohua

2014-02-01

Dedifferentiated liposarcoma (DDLPS) and pleomorphic liposarcoma (PLPS) are distinct high-grade liposarcomas. DDLPS is a nonlipogenic sarcoma characterized by amplification of MDM2 and CDK4. PLPS is a high-grade sarcoma containing lipoblasts, characterized by a complex karyotype and a more aggressive clinical course. Rarely, DDLPS shows lipogenic differentiation, mimicking PLPS. The cytomorphologic features of DDLPS and PLPS and the utility of ancillary studies have not been systemically analyzed. Cytologic preparations of 25 DDLPS and 13 PLPS, all histologically confirmed, were retrospectively reviewed along with clinical and cytogenetic data. Sample cellularity, vascular architecture, background material, predominant cell morphology, quality of the cytoplasm, and nuclear pleomorphism were compared for both tumor types. Immunohistochemistry for MDM2 and CDK4 was performed on cell blocks and/or core needle biopsies. Fine-needle aspirate smears from both DDLPS and PLPS were variably cellular, composed of cellular clusters and noncohesive cells. Abundant myxoid stroma was present in ∼25% of DDLPS and PLPS cases, whereas branching curvilinear vessels were more common in DDLPS than in PLPS (7 of 25 versus 2 of 13). Tumors were composed of predominantly spindled (18 of 25 DDLPS versus 3 of 13 PLPS) or epithelioid cells (7 of 25 DDLPS versus 6 of 13 PLPS). Pleomorphic cells were predominant in 3 PLPS, and were frequent in both (13 of 25 DDLPS versus 10 of 13 PLPS). The cytoplasm was mostly fibrillary and often vacuolated in both entities. Other features included necrosis, mitoses, and a prominent inflammatory infiltrate. The main cytologic differences were the presence of marked pleomorphism, abundant lipoblasts, and cells with microvacuolated cytoplasm in most PLPS. A total of 24 (96%) and 20 (80%) cases of DDLPS expressed MDM2 and CDK4, respectively, whereas none of the PLPS expressed both markers. Six DDLPS tested showed ring or giant marker chromosomes and/or MDM2

Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-09

Metastatic Angiosarcoma; Metastatic Epithelioid Sarcoma; Metastatic Fibrosarcoma; Metastatic Leiomyosarcoma; Metastatic Liposarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Pleomorphic Rhabdomyosarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma; Undifferentiated (Embryonal) Sarcoma

Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-06-20

Dedifferentiated Liposarcoma; Gastrointestinal Stromal Tumor; Metastatic Liposarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Pleomorphic Liposarcoma; Stage III Bone Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Bone Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Bone Sarcoma AJCC v7; Stage IVB Bone Sarcoma AJCC v7; Unresectable Liposarcoma

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2016-06-09

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

Non-lethal Clostridium sordellii bacteraemia in an immunocompromised patient with pleomorphic sarcoma.

PubMed

Bonnecaze, Alex K; Stephens, Sarah Ellen Elza; Miller, Peter John

2016-08-03

Clostridium sordellii is a spore-forming anaerobic Gram-positive rod that has rarely been reported to cause disease in humans. Resultant mortality from infection is estimated at nearly 70% and is most often correlated with gynaecological procedures, intravenous drug abuse or trauma. C. sordellii infection often presents similarly to toxic shock syndrome (TSS); notable features of infection include refractory hypotension, haemoconcentration and marked leucocytosis. Although clinically similar to TSS, a notable difference is C. sordellii infections rarely involve fever. The organism's major toxins include haemorrhagic (TcsH) and lethal factor (TcsL), which function to disrupt cytoskeletal integrity. Current literature suggests treating C. sordelli infection with a broad-spectrum penicillin, metronidazole and clindamycin. We present a case of C. sordellii bacteraemia and septic shock in an immunocompromised patient who was recently diagnosed with pleomorphic gluteal sarcoma. Despite presenting in critical condition, the patient improved after aggressive hemodynamic resuscitation, source control and intravenous antibiotic therapy. 2016 BMJ Publishing Group Ltd.

High-grade squamous intraepithelial lesion (HSIL) of the cervix with bizarre cytological appearances ('pleomorphic HSIL'): a review of 19 cases.

PubMed

Stewart, Colin J R

2017-08-01

Cervical high-grade squamous intraepithelial lesions (HSILs) are typically characterised by a proliferation of immature basaloid cells with relatively uniform hyperchromatic nuclei. In this report we describe 19 cases of HSIL exhibiting focal but very marked nuclear atypia often associated with multinucleation ('pleomorphic HSIL'). The bizarre cytological changes mainly involved the basal epithelium particularly in endocervical crypts where the neoplastic cells undermined the native glandular epithelial cells. Superficially invasive squamous cell carcinoma (SISCCA) was present in three cases (16%) and while this was more common than in a comparative series of 40 'conventional' HSIL excision specimens (5%), the difference was not statistically significant. All three invasive cases demonstrated additional histological features that have been associated with increased risk of SISCAA (expansile crypt involvement by HSIL, luminal necrosis, and/or intraepithelial squamous maturation), and the invasive foci were associated microanatomically with conventional-type rather than pleomorphic HSIL. The bizarre cells expressed p16 and p63 proteins but usually lacked mitotic activity and showed less Ki-67 labelling than adjacent conventional HSIL. These findings suggest that pleomorphic epithelial changes in HSIL do not necessarily indicate more aggressive biological behaviour and may, in some cases, represent a degenerative phenomenon. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2017-11-29

Myxofibrosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Leiomyosarcoma; Recurrent Liposarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Undifferentiated Pleomorphic Sarcoma; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7

Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

NASA Astrophysics Data System (ADS)

Lou, Sha; Balluff, Benjamin; Cleven, Arjen H. G.; Bovée, Judith V. M. G.; McDonnell, Liam A.

2017-02-01

Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival ( m/z 180.9436 and 241.0118) and metastasis-free survival ( m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial.

PubMed

Gronchi, Alessandro; Ferrari, Stefano; Quagliuolo, Vittorio; Broto, Javier Martin; Pousa, Antonio Lopez; Grignani, Giovanni; Basso, Umberto; Blay, Jean-Yves; Tendero, Oscar; Beveridge, Robert Diaz; Ferraresi, Virginia; Lugowska, Iwona; Merlo, Domenico Franco; Fontana, Valeria; Marchesi, Emanuela; Donati, Davide Maria; Palassini, Elena; Palmerini, Emanuela; De Sanctis, Rita; Morosi, Carlo; Stacchiotti, Silvia; Bagué, Silvia; Coindre, Jean Michelle; Dei Tos, Angelo Paolo; Picci, Piero; Bruzzi, Paolo; Casali, Paolo Giovanni

2017-06-01

Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland. Eligible patients were aged 18 years or older with localised, high-risk (high malignancy grade, 5 cm or longer in diameter, and deeply located according to the investing fascia), soft-tissue sarcoma of the extremities or trunk wall and belonging to one of five histological subtypes: high-grade myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma. Patients were randomly assigned (1:1) to receive three cycles of full-dose standard chemotherapy (epirubicin 60 mg/m 2 per day [short infusion, days 1 and 2] plus ifosfamide 3 g/m 2 per day [days 1, 2, and 3], repeated every 21 days) or histotype-tailored chemotherapy: for high-grade myxoid liposarcoma, trabectedin 1·3 mg/m 2 via 24-h continuous infusion, repeated every 21 days; for leiomyosarcoma, gemcitabine 1800 mg/m 2 on day 1 intravenously over 180 min plus dacarbazine 500 mg/m 2 on day 1 intravenously over 20 min, repeated every 14 days; for synovial sarcoma, high-dose ifosfamide 14 g/m 2 , given over 14 days via an external infusion pump, every 28 days; for malignant peripheral nerve sheath tumour, intravenous etoposide 150 mg/m 2 per day (days 1, 2, and 3) plus intravenous ifosfamide 3 g/m 2 per day (days 1, 2, and 3), repeated every 21 days; and for undifferentiated pleomorphic sarcoma, gemcitabine 900 mg/m 2 on days 1 and

Doxorubicin With Upfront Dexrazoxane Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2018-02-08

Sarcoma, Soft Tissue; Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Liposarcoma; Synovial Sarcoma; Myxofibrosarcoma; Angiosarcoma; Fibrosarcoma; Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma

Diagnostic utility of IDH1/2 mutations to distinguish dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone.

PubMed

Chen, Shaoxiong; Fritchie, Karen; Wei, Shi; Ali, Naser; Curless, Kendra; Shen, Tiansheng; Brini, Anna T; Latif, Farida; Sumathi, Vaiyapuri; Siegal, Gene P; Cheng, Liang

2017-07-01

Histologically, it is nearly impossible to distinguish the dedifferentiated component of dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma (UPS) of bone when the low-grade cartilaginous component is absent. Previous studies have revealed that isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are present in a significant number of cartilaginous tumors including most conventional chondrosarcomas and dedifferentiated chondrosarcomas. These mutations have not been studied in UPSs of bone. We sought to investigate whether an IDH1 or IDH2 mutation signature could be used as a clinically diagnostic marker for the distinction of dedifferentiated component of chondrosarcoma from UPS of bone. Sixty-eight bone tumor cases, including 31 conventional chondrosarcomas, 23 dedifferentiated chondrosarcomas, and 14 UPSs of bone, were collected for IDH1/2 mutation analysis either using the Qiagen IDH1/2 RGQ PCR Kit or using whole-exome sequencing. IDH1/2 mutations were detected in 87% (20/23) of dedifferentiated chondrosarcomas and 30% (6/20) of conventional chondrosarcomas. No mutations were detected in the IDH1/2 codon 132 or codon 172 among 14 UPSs of bone. Identification of IDH1 or IDH2 mutations supports the diagnosis of dedifferentiated chondrosarcoma rather than UPS of bone while also providing some insight into the pathogenesis of these 2 lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade.

PubMed

Chao, C; Al-Saleem, T; Brooks, J J; Rogatko, A; Kraybill, W G; Eisenberg, B

2001-04-01

Vascular endothelial growth factor (VEGF), an endothelial-specific mitogen overexpressed in various epithelial malignancies is thought to be a potent regulator of angiogenesis. We hypothesized that some soft tissue sarcomas, due to their high propensity for hematogenous metastases (1) would overexpress VEGF, (2) that the degree of expression may represent a significant biologic predictor for disease-specific survival, and (3) that recurrent tumor would express as high or higher VEGF compared with the primary tumor. Selected paraffin-embedded tissue of surgical specimens from 79 patients with soft tissue sarcomas, treated between 1989 and 1995 were stained with a rabbit polyclonal anti-VEGF antibody at a concentration of 2 microg/ml. Slides were assessed for VEGF expression as high or low by two investigators blinded to the clinicopathologic data. Twelve patients had VEGF expression of their primary tumors, and their recurrent tumors were compared. The Fishers' exact test assessed for differences in VEGF expression; survival analyses were performed according to the methods of Kaplan and Meier. Seventy-eight percent (29 of 37) of patients who died of disease had high VEGF expression. However, VEGF expression was not an independent predictor of either overall or disease-free survival. Tumor grade correlated with VEGF expression significantly. For the low-grade tumors, 7 of 13 expressed low VEGF, whereas for high-grade tumors, 53 of 66 expressed high VEGF (P = .016). Seven of the 12 paired tumor samples expressed identical VEGF immunostaining. The majority of high-grade soft tissue sarcomas in this study have high intensity VEGF expression. This finding may provide useful information on individual soft tissue sarcomas and offer the basis for therapeutic and biologic targeting in high-risk patients using anti-angiogenesis strategies. However, in our analysis, after accounting for tumor grade, VEGF does not seem to be an independent predictor of clinical outcome.

PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue - prognostic implications and rationale for immunotherapy.

PubMed

Boxberg, Melanie; Steiger, Katja; Lenze, Ulrich; Rechl, Hans; von Eisenhart-Rothe, Rüdiger; Wörtler, Klaus; Weichert, Wilko; Langer, Rupert; Specht, Katja

2018-01-01

Therapies targeting programmed death 1-(PD-1) or its ligand (PD-L1), promoting antitumor T-cell activity have been successfully introduced into clinical practice. Clinical response correlates with PD-L1 expression by tumor cells or immune cells within the tumor microenvironment. The PD-L1/PD-1 axis and tumor microenvironment has been rarely studied in high-grade sarcomas of soft tissue (hSTS), a group of rare, genetically heterogenous and clinically aggressive tumors. We examined PD-L1 protein and CD274/PD-L1 gene copy number variations in 128 primary resected, therapy-naive hSTS using immunohistochemistry and fluorescence-in-situ hybridization. Frequency of tumoral PD-L1 expression varied widely in different disease subentities, with highest rates of positivity (40%) seen in undifferentiated pleomorphic sarcomas (UPS) and rare positivity detected in synovial sarcomas (6%). Amplification of the CD274/PD-L1 gene occurred in 14% of UPS and was rare in other subtypes. PD-L1 protein expression was significantly more frequent in CD274/PD-L1 amplified cases (p = 0.015). The subgroup of UPS was further characterized regarding the interaction between PD-L1 and the immunologic tumor microenvironment. High density of CD3+ and CD8+ tumor infiltrating lymphocytes (TILs) was significantly correlated with the presence of PD-L1 expression and seen more frequently in tumors with lower TNM stage (p = 0.024). Both, PD-L1 expression and high density lymphocytic infiltration were independent prognostic factors for a favorable overall (p = 0.001, HR 6.105 (2.041-8.258)), disease-specific (p = 0.003, HR 10.536 (2.186-50.774)) and disease-free survival (p = 0.020, HR 3.317 (1.209-9.106); values for CD8) in this particular subgroup of hSTS, whereas PD-L1 expression in TILs or CD274/PD-L1 gene amplification were not associated with outcome. These findings represent novel insights into the immune landscape of soft tissue sarcomas, in particular UPS and strengthen the rationale for

CT scans for pulmonary surveillance may be overused in lower-grade sarcoma.

PubMed

Miller, Benjamin J; Carmody Soni, Emily E; Reith, John D; Gibbs, C Parker; Scarborough, Mark T

2012-01-01

Chest CT scans are often used to monitor patients after excision of a sarcoma. Although sensitive, CT scans are more expensive than chest radiographs and are associated with possible health risks from a higher radiation dose. We hypothesized that a program based upon limited CT scans in lower-grade sarcoma could be efficacious and less expensive. We retrospectively assigned patients to a high-risk or low-risk hypothetical protocol. Eighty-three low- or intermediate-grade soft tissue sarcomas met our inclusion criteria. Eight patients had pulmonary metastasis. A protocol based on selective CT scans for high-risk patients would have identified seven out of eight lesions. The incremental cost-effectiveness ratio for routine CT scans was $731,400. A program based upon selective CT scans for higher-risk patients is accurate, spares unnecessary radiation to many patients, and is less expensive.

Total Artificial Heart Implantation After Undifferentiated High-Grade Sarcoma Excision.

PubMed

Kremer, Jamila; Farag, Mina; Arif, Rawa; Brcic, Andreas; Sabashnikov, Anton; Schmack, Bastian; Popov, Aron-Frederik; Karck, Matthias; Dohmen, Pascal M; Ruhparwar, Arjang; Weymann, Alexander

2016-11-02

BACKGROUND Total artificial heart (TAH) implantation in patients with aggressive tumor infiltration of the heart can be challenging. CASE REPORT We report on a patient with a rare primary undifferentiated high-grade spindle cell sarcoma of the mitral valve and in the left atrium, first diagnosed in 2014. The referring center did a first resection in 2014. In the course of 17 months, computer tomography (CT) scan again showed massive invasion of the mitral valve and left atrium. Partial resection and mitral valve replacement was not an option. We did a subtotal heart excision with total artificial heart implantation. In this report we discuss complications, risk factors, and perioperative management of this patient. CONCLUSIONS Patients with aggressive tumors of the heart can be considered for TAH implantation.

Polymorphous low grade adenocarcinoma has a consistent p63+/p40- immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma.

PubMed

Rooper, Lisa; Sharma, Rajni; Bishop, Justin A

2015-03-01

Polymorphous low grade adenocarcinoma (PLGA) is a tumor of minor salivary glands that exhibits considerable morphologic overlap with adenoid cystic carcinoma and cellular pleomorphic adenoma, especially in small biopsy specimens. Unlike these other tumor types. PLGAs do not harbor a myoepithelial component, yet their frequent positivity for p63 diminishes the usefulness of this particular myoepithelial marker as a discriminating immunostain. p40 is an antibody that recognizes ΔNp63, a p63 isoform that is more specific for true myoepithelial differentiation. As such, p40 immunostaining could help distinguish PLGAs from adenoid cystic carcinomas and pleomorphic adenomas. In this study, p63 and p40 immunohistochemistry was performed on paraffin embedded, formalin fixed tissue from 11 PLGAs, 101 adenoid cystic carcinomas, and 31 pleomorphic adenomas. All 11 PLGAs (100 %) were positive for p63 but completely negative for p40. Among adenoid cystic carcinomas, 91 of 101 (90 %) were positive for p63 and 90/101 (89 %) were positive for p40. The single discordant p63+/p40- adenoid cystic carcinoma exhibited solid architecture and high grade features not typically seen in PLGA. Among pleomorphic adenomas, 21/31 (68 %) were positive for p63 and 13/31 (42 %) were positive for p40. For the pleomorphic adenomas, the discordant p63+/p40- staining pattern was seen only in the overtly mesenchymal chondromyxoid stroma. The cellular epithelial component of the pleomorphic adenomas demonstrated concordant p63+/p40+ or p63-/p40- immunophenotypes. PLGA consistently exhibits a p63+/p40- immunophenotype that can help distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma, tumors that characteristically demonstrate concordant p63 and p40 immunostaining patterns. A p63/p40 immunohistochemical panel can provide a valuable tool for making the distinction between these morphologically similar but clinically divergent entities.

Total Artificial Heart Implantation After Undifferentiated High-Grade Sarcoma Excision

PubMed Central

Kremer, Jamila; Farag, Mina; Arif, Rawa; Brcic, Andreas; Sabashnikov, Anton; Schmack, Bastian; Popov, Aron-Frederik; Karck, Matthias; Dohmen, Pascal M.; Ruhparwar, Arjang; Weymann, Alexander

2016-01-01

Background Total artificial heart (TAH) implantation in patients with aggressive tumor infiltration of the heart can be challenging. Case Report We report on a patient with a rare primary undifferentiated high-grade spindle cell sarcoma of the mitral valve and in the left atrium, first diagnosed in 2014. The referring center did a first resection in 2014. In the course of 17 months, computer tomography (CT) scan again showed massive invasion of the mitral valve and left atrium. Partial resection and mitral valve replacement was not an option. We did a subtotal heart excision with total artificial heart implantation. In this report we discuss complications, risk factors, and perioperative management of this patient. Conclusions Patients with aggressive tumors of the heart can be considered for TAH implantation. PMID:27803495

EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas.

PubMed

Braun, Alexcia Camila; de Mello, Celso Abdon Lopes; Corassa, Marcelo; Abdallah, Emne Ali; Urvanegia, Ana Cláudia; Alves, Vanessa Silva; Flores, Bianca C T C P; Díaz, Mônica; Nicolau, Ulisses Ribaldo; Silva, Virgilio Souza E; Calsavara, Vinicius; Paterlini-Brechót, Patrizia; Chinen, Ludmilla Thomé Domingos

2018-06-03

Soft tissue Sarcomas (STS) are rare malignances, with high mortality rates. Half of patients develop metastasis. The presence of isolated Circulating Tumor Cells (CTCs) and Circulating Tumor Microemboli (CTM) in the blood may be early markers of tumor invasion. Epidermal Growth Factor (EGF) family receptors can also influence this process. to quantify CTCs and identify CTM as well as the EGF Receptor (EGFR) protein expression in these cells and correlate with clinical outcome in metastatic STS. Approximately 8mL of blood was prospectively collected from patients with different types of high-grade STS, before the beginning of chemotherapy. The samples were processed and filtered by ISET (Rarecells, France) for the isolation and quantification of CTCs and CTMs. EGFR expression was analyzed by immunocytochemistry (ICC) on CTCs/ CTMs. We analyzed 18 patients with median age of 49 years (18-77 y). The positivity for EGFR protein expression in CTCs was observed in 93.75% of the patients. This result shows that targeting EGFR positive CTCs from STS origen can be translated in clinical benefit for some patients. In addition, if target therapy is chosen, the EGFR expression in CTCs can be used in follow-up to measure treatment effectiveness. This is the first study to demonstrate the expression of EGFR protein in CTCs from sarcoma patients. It may open an area for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of EGFR in sustaining tumor metastasis in sarcomas.

Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

ClinicalTrials.gov

2017-11-01

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated Pleomorphic Sarcoma; Malignant Adult Hemangiopericytoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PubMed

Sargos, P; Charleux, T; Haas, R L; Michot, A; Llacer, C; Moureau-Zabotto, L; Vogin, G; Le Péchoux, C; Verry, C; Ducassou, A; Delannes, M; Mervoyer, A; Wiazzane, N; Thariat, J; Sunyach, M P; Benchalal, M; Laredo, J D; Kind, M; Gillon, P; Kantor, G

2018-04-01

The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

PubMed

Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

2017-07-01

CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.

PubMed

Tawbi, Hussein A; Burgess, Melissa; Bolejack, Vanessa; Van Tine, Brian A; Schuetze, Scott M; Hu, James; D'Angelo, Sandra; Attia, Steven; Riedel, Richard F; Priebat, Dennis A; Movva, Sujana; Davis, Lara E; Okuno, Scott H; Reed, Damon R; Crowley, John; Butterfield, Lisa H; Salazar, Ruth; Rodriguez-Canales, Jaime; Lazar, Alexander J; Wistuba, Ignacio I; Baker, Laurence H; Maki, Robert G; Reinke, Denise; Patel, Shreyaskumar

2017-11-01

with synovial sarcoma. No patients with leiomyosarcoma (n=10) had an objective response. Two (5%) of 40 patients with bone sarcoma had an objective response, including one (5%) of 22 patients with osteosarcoma and one (20%) of five patients with chondrosarcoma. None of the 13 patients with Ewing's sarcoma had an objective response. The most frequent grade 3 or worse adverse events were anaemia (six [14%]), decreased lymphocyte count (five [12%]), prolonged activated partial thromboplastin time (four [10%]), and decreased platelet count (three [7%]) in the bone sarcoma group, and anaemia, decreased lymphocyte count, and prolonged activated partial thromboplastin time in the soft-tissue sarcoma group (three [7%] each). Nine (11%) patients (five [12%] in the bone sarcoma group and four [10%] in the soft-tissue sarcoma group) had treatment-emergent serious adverse events (SAEs), five of whom had immune-related SAEs, including two with adrenal insufficiency, two with pneumonitis, and one with nephritis. The primary endpoint of overall response was not met for either cohort. However, pembrolizumab showed encouraging activity in patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. Enrolment to expanded cohorts of those subtypes is ongoing to confirm and characterise the activity of pembrolizumab. Merck, SARC, Sarcoma Foundation of America, QuadW Foundation, Pittsburgh Cure Sarcoma, and Ewan McGregor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications

PubMed Central

Pasquali, Sandro; Gronchi, Alessandro

2017-01-01

Soft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments. PMID:28607580

MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma

PubMed Central

Bach, Marisa; Kind, Peter; Helbig, Doris; Quaas, Alexander; Utikal, Jochen; Marx, Alexander; Gaiser, Maria Rita

2018-01-01

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC/CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC/CEP8 ratio ≥ 1.2−< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions. PMID:29765529

MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma.

PubMed

Gaiser, Timo; Hirsch, Daniela; Orouji, Azadeh; Bach, Marisa; Kind, Peter; Helbig, Doris; Quaas, Alexander; Utikal, Jochen; Marx, Alexander; Gaiser, Maria Rita

2018-04-20

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC /CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC /CEP8 ratio ≥ 1.2-< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions.

Constant p53 Pathway Inactivation in a Large Series of Soft Tissue Sarcomas with Complex Genetics

PubMed Central

Pérot, Gaëlle; Chibon, Frédéric; Montero, Audrey; Lagarde, Pauline; de Thé, Hugues; Terrier, Philippe; Guillou, Louis; Ranchère, Dominique; Coindre, Jean-Michel; Aurias, Alain

2010-01-01

Alterations of the p53 pathway are among the most frequent aberrations observed in human cancers. We have performed an exhaustive analysis of TP53, p14, p15, and p16 status in a large series of 143 soft tissue sarcomas, rare tumors accounting for around 1% of all adult cancers, with complex genetics. For this purpose, we performed genomic studies, combining sequencing, copy number assessment, and expression analyses. TP53 mutations and deletions are more frequent in leiomyosarcomas than in undifferentiated pleomorphic sarcomas. Moreover, 50% of leiomyosarcomas present TP53 biallelic inactivation, whereas most undifferentiated pleomorphic sarcomas retain one wild-type TP53 allele (87.2%). The spectrum of mutations between these two groups of sarcomas is different, particularly with a higher rate of complex mutations in undifferentiated pleomorphic sarcomas. Most tumors without TP53 alteration exhibit a deletion of p14 and/or lack of mRNA expression, suggesting that p14 loss could be an alternative genotype for direct TP53 inactivation. Nevertheless, the fact that even in tumors altered for TP53, we could not detect p14 protein suggests that other p14 functions, independent of p53, could be implicated in sarcoma oncogenesis. In addition, both p15 and p16 are frequently codeleted or transcriptionally co-inhibited with p14, essentially in tumors with two wild-type TP53 alleles. Conversely, in TP53-altered tumors, p15 and p16 are well expressed, a feature not incompatible with an oncogenic process. PMID:20884963

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 2-Uncommon Sarcomas.

PubMed

Levy, Angela D; Manning, Maria A; Miettinen, Markku M

2017-01-01

Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but important group of malignancies. Recent changes to the World Health Organization classification of soft-tissue tumors include the movement of gastrointestinal stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the most common intraperitoneal sarcoma. Liposarcoma is the most common retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST, liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered in the abdomen and pelvis and are discussed in part 1 of this article. Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly arise in the abdomen and pelvis and the abdominal wall. Although these lesions are rare sarcomas and their imaging features overlap, familiarity with the locations where they occur and their imaging features is important so they can be diagnosed accurately. The anatomic location and clinical history are important factors in the differential diagnosis of these lesions because metastasis, more-common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors), and endometriosis have imaging findings that overlap with those of these uncommon sarcomas. In this article, the clinical, pathologic, and imaging findings of uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall are reviewed, with an emphasis on their differential diagnosis.

Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway

PubMed Central

Matushansky, Igor; Hernando, Eva; Socci, Nicholas D.; Mills, Joslyn E.; Matos, Tulio A.; Edgar, Mark A.; Singer, Samuel; Maki, Robert G.; Cordon-Cardo, Carlos

2007-01-01

Malignant fibrous histiocytoma (MFH), now termed high-grade undifferentiated pleomorphic sarcoma, is a commonly diagnosed mesenchymal tumor, yet both the underlying molecular mechanisms of tumorigenesis and cell of origin remain unidentified. We present evidence demonstrating that human mesenchymal stem cells (hMSCs) are the progenitors of MFH. DKK1, a Wnt inhibitor and mediator of hMSC proliferation, is overexpressed in MFH. Using recombinant proteins, antibody depletion, and siRNA knockdown strategies of specific Wnt elements, we show that DKK1 inhibits hMSC commitment to differentiation via Wnt2/β-catenin canonical signaling and that Wnt5a/JNK noncanonical signaling regulates a viability checkpoint independent of Dkk1. Finally, we illustrate that hMSCs can be transformed via inhibition of Wnt signaling to form MFH-like tumors in nude mice, and conversely, MFH cells in which Wnt signaling is appropriately reestablished can differentiate along mature connective tissue lineages. Our results provide mechanistic insights regarding the cell of origin of MFH, establish what we believe is a novel tumor suppressor role for Wnt signaling, and identify a potential therapeutic differentiation strategy for sarcomas. PMID:17948129

The Value of Surgery for Retroperitoneal Sarcoma

PubMed Central

Gholami, Sepideh; Jacobs, Charlotte D.; Kapp, Daniel S.; Parast, Layla M.; Norton, Jeffrey A.

2009-01-01

Introduction. Retroperitoneal sarcomas are uncommon large malignant tumors. Methods. Forty-one consecutive patients with localized retroperitoneal sarcoma were retrospectively studied. Results. Median age was 58 years (range 20–91 years). Median tumor size was 17.5 cm (range 4–41 cm). Only 2 tumors were <5 cm. Most were liposarcoma (44%) and high-grade (59%). 59% were stage 3 and the rest was stage 1. Median followup was 10 months (range 1–106 months). Thirty-eight patients had an initial complete resection; 15 (37%) developed recurrent sarcoma and 12 (80%) had a second complete resection. Patients with an initial complete resection had a 5-year survival of 46%. For all patients, tumor grade affected overall survival (P = .006). Complete surgical resection improved overall survival for high-grade tumors (P = .03). Conclusions. Tumor grade/stage and complete surgical resection for high-grade tumors are important prognostic variables. Radiation therapy or chemotherapy had no significant impact on overall or recurrence-free survival. Complete surgical resection is the treatment of choice for patients with initial and locally recurrent retroperitoneal sarcoma. PMID:19826633

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 2—Uncommon Sarcomas

PubMed Central

Manning, Maria A.; Miettinen, Markku M.

2017-01-01

Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but important group of malignancies. Recent changes to the World Health Organization classification of soft-tissue tumors include the movement of gastrointestinal stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the most common intraperitoneal sarcoma. Liposarcoma is the most common retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST, liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered in the abdomen and pelvis and are discussed in part 1 of this article. Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly arise in the abdomen and pelvis and the abdominal wall. Although these lesions are rare sarcomas and their imaging features overlap, familiarity with the locations where they occur and their imaging features is important so they can be diagnosed accurately. The anatomic location and clinical history are important factors in the differential diagnosis of these lesions because metastasis, more-common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors), and endometriosis have imaging findings that overlap with those of these uncommon sarcomas. In this article, the clinical, pathologic, and imaging findings of uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall are reviewed, with an emphasis on their differential diagnosis. PMID:28493803

EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma.

PubMed

Ferrari, Stefano; Bielack, Stefan S; Smeland, Sigbjørn; Longhi, Alessandra; Egerer, Gerlinde; Sundby Hall, Kirsten; Donati, Davide; Kevric, Matthias; Brosjö, Otte; Comandone, Alessandro; Werner, Mathias; Monge, Odd; Palmerini, Emanuela; Berdel, Wolfgang E; Bjerkehagen, Bodil; Paioli, Anna; Lorenzen, Sylvie; Eriksson, Mikael; Gambarotti, Marco; Tunn, Per-Ulf; Jebsen, Nina L; Cesari, Marilena; von Kalle, Thekla; Ferraresi, Virginia; Schwarz, Rudolf; Bertulli, Rossella; Kasparek, Anne-Katrin; Grignani, Giovanni; Krasniqi, Fatime; Sorg, Benjamin; Hecker-Nolting, Stefanie; Picci, Piero; Reichardt, Peter

2018-01-01

The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study. The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

Clinicopathological relevance of tumour grading in canine osteosarcoma.

PubMed

Loukopoulos, P; Robinson, W F

2007-01-01

Tumour grading assesses biological aggressiveness and is of prognostic significance in many malignancies. The clinicopathological features of 140 primary canine osteosarcomas and their metastases were analysed, and the interrelations between them and an established grading system and its constituent parameters (mitotic index, necrosis, pleomorphism) were examined. Of these tumours, 35% were grade III (high-grade), 37% grade II and 28% grade I. Primary tumours that had metastasized were of significantly higher grade than non-metastatic osteosarcomas. Osteosarcomas belonging to the osteoblastic minimally productive subtype, but not chondroblastic or telangiectatic subtypes, differed from fibroblastic osteosarcomas in being associated with a significantly higher number of high-grade cases. Dogs younger than 4 years of age had osteosarcomas with higher grade, score and mitotic index than did older animals. Appendicular differed from axial tumours in having a higher mitotic index; distal differed from proximal tumours in being of higher grade; cranial tumours differed from tumours in most other sites in being of lower grade and lower mitotic index. Rib osteosarcomas showed a particularly high degree of necrosis. The mitotic index varied widely between tumour locations. Pleomorphism did not have prognostic merit when examined separately, as most osteosarcomas were highly pleomorphic.

Intraoperative versus postoperative electrochemotherapy in high grade soft tissue sarcomas: a preliminary study in a spontaneous feline model.

PubMed

Spugnini, Enrico P; Baldi, Alfonso; Vincenzi, Bruno; Bongiorni, Franco; Bellelli, Corrado; Citro, Gennaro; Porrello, Alessandro

2007-02-01

Feline soft tissue sarcomas are spontaneous, rapidly growing, and aggressive neoplasms that mimic their human counterpart. The purpose of this study was to evaluate the feasibility and efficacy of electrochemotherapy (ECT) in an adjuvant fashion for the treatment of feline sarcomas, and the possibility of repeated treatments in the case of recurrence. Cats with fibrosarcoma (FSA) were assigned to receive surgery or surgery plus ECT. Feline patients recruited in the ECT study were enrolled in a microscopic arm (39 patients) or a macroscopic arm (19 patients) on the basis of their tumor status (absence or presence of gross disease). Patients received local injection of bleomycin followed by bursts of eight biphasic pulses at a voltage of 1,300 V/cm for postoperative and of 800 V/cm for intraoperative treatments. The median time to recurrence was 4 months for cats treated with surgery alone, 19 months for the postoperative cohort, and 12 months for the intraoperative group. Moreover, ten patients with recurring neoplasms were retreated and experienced responses lasting 6 to 28+ months. Side effects were minimal. Of interest, the metastatic rate (1.7%) in our patients was negligible: only one cat had distant spread. The results suggest that ECT is a well tolerated and potentially useful addition to surgery in controlling high-grade sarcomas. On the basis of these results, additional evaluations are warranted in pets and in humans.

Treatment of low-grade endometrial stromal sarcoma in a nulligravid woman.

PubMed

Michael Straughn, J; Boitano, Teresa; Smith, Haller J; Dilley, Sarah E; Liang, Margaret I; Novak, Lea

2018-06-07

A 32 year-old nulligravid woman with a uterine mass underwent exploratory laparotomy with myomectomy. Final pathology revealed a low-grade endometrial stromal sarcoma (ESS) with positive margins. She subsequently underwent definitive robotic hysterectomy and bilateral salpingectomy with ovarian preservation. She was diagnosed with a stage IB low-grade ESS. She is currently undergoing observation. Discussion of classification, surgical options, and adjuvant therapy is presented. Copyright © 2018 Elsevier Inc. All rights reserved.

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blum, R.H.; Greenberger, J.S.; Wilson, R.E.

1979-08-01

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M/sup 2/ day 1, Adriamycin (ADR) 60 mg/M/sup 2/ day 2, and DTIC 400 mg/M/sup 2/ days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M/sup 2/. Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks,more » and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment.« less

PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

PubMed

Vincenzi, Bruno; Santini, Daniele; Schiavon, Gaia; Frezza, Anna Maria; Silletta, Marianna; Crucitti, Pierfilippo; Casali, Paolo; Dei Tos, Angelo P; Rossi, Sabrina; Rizzo, Sergio; Badalamenti, Giuseppe; Tomasino, Rosa Maria; Russo, Antonio; Butrynski, James E; Tonini, Giuseppe

2012-04-01

Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. Copyright © 2011 Wiley Periodicals, Inc.

Rare Aggressive Behavior of MDM2-Amplified Retroperitoneal Dedifferentiated Liposarcoma, with Brain, Lung and Subcutaneous Metastases.

PubMed

Ben Salha, Imen; Zaidi, Shane; Noujaim, Jonathan; Miah, Aisha B; Fisher, Cyril; Jones, Robin L; Thway, Khin

2016-09-05

Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, non-lipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo . DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct) liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2 -amplified retroperitoneal liposarcoma.

Scoring nuclear pleomorphism using a visual BoF modulated by a graph structure

NASA Astrophysics Data System (ADS)

Moncayo-Martínez, Ricardo; Romo-Bucheli, David; Arias, Viviana; Romero, Eduardo

2017-11-01

Nuclear pleomorphism has been recognized as a key histological criterium in breast cancer grading systems (such as Bloom Richardson and Nothingham grading systems). However, the nuclear pleomorphism assessment is subjective and presents high inter-reader variability. Automatic algorithms might facilitate quantitative estimation of nuclear variations in shape and size. Nevertheless, the automatic segmentation of the nuclei is difficult and still and open research problem. This paper presents a method using a bag of multi-scale visual features, modulated by a graph structure, to grade nuclei in breast cancer microscopical fields. This strategy constructs hematoxylin-eosin image patches, each containing a nucleus that is represented by a set of visual words in the BoF. The contribution of each visual word is computed by examining the visual words in an associated graph built when projecting the multi-dimensional BoF to a bi-dimensional plane where local relationships are conserved. The methodology was evaluated using 14 breast cancer cases of the Cancer Genome Atlas database. From these cases, a set of 134 microscopical fields was extracted, and under a leave-one-out validation scheme, an average F-score of 0.68 was obtained.

Low-grade sinonasal sarcoma with neural and myogenic features: a clinicopathologic analysis of 28 cases.

PubMed

Lewis, Jason T; Oliveira, Andre M; Nascimento, Antonio G; Schembri-Wismayer, David; Moore, Eric A; Olsen, Kerry D; Garcia, Joaquin G; Lonzo, Melissa L; Lewis, Jean E

2012-04-01

Sarcomas of the sinonasal region are rare. We describe a distinct spindle cell sarcoma of the sinonasal region characterized by concomitant neural and myogenic differentiation. Consultation files and surgical cases from Mayo Clinic were reviewed. Twenty-eight cases were identified that met the inclusion criteria. Clinical data were collected from medical records, consultation letters, and referring pathologists. Reverse transcriptase-polymerase chain reaction for synovial sarcoma fusion transcripts was performed on 18 cases. Cytogenetic studies were performed on 2 cases. The 21 female and 7 male patients ranged in age from 24 to 85 years (mean, 52 y). All cases showed a characteristic histology, which included a cellular spindle cell neoplasm with uniform, elongate nuclei and an infiltrative growth pattern. All tumors demonstrated expression of S-100 with actin positivity in 96% of cases tested. Reverse transcriptase-polymerase chain reaction for synovial sarcoma fusion transcripts was negative in all cases tested. Cytogenetic studies conducted on 2 cases demonstrated the chromosomal translocation t(2;4). The nasal cavity (54%) and ethmoid sinus (57%) were the most commonly involved areas, singly or in combination. Follow-up information was available for 57% (16/28) of cases, with a mean of 8.3 years. Of these, 44% (7/16) experienced at least 1 recurrence. No patient has developed metastases or died of disease. We describe a unique tumor with a characteristic morphologic, immunophenotypic, and cytogenetic profile. On the basis of the locally aggressive nature of this lesion we believe it is best considered a low-grade sarcoma and suggest the term low-grade sinonasal sarcoma with neural and myogenic features.

A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes.

PubMed

Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

2015-01-01

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST.

A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes

PubMed Central

Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

2015-01-01

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST. PMID:26839509

Prognostic value of proliferation in pleomorphic soft tissue sarcomas: a new look at an old measure.

PubMed

Seinen, Jojanneke M; Jönsson, Mats; Bendahl, Pär-Ola O; Baldetorp, Bo; Rambech, Eva; Åkerman, Måns; Rydholm, Anders; Nilbert, Mef; Carneiro, Ana

2012-12-01

Though proliferation has repeatedly shown a prognostic role in sarcomas, it has not reached clinical application. We performed a comprehensive evaluation of the prognostic role of 5 proliferation measures in a large series of soft tissue sarcomas of the extremities and the trunk wall. One hundred ninety-six primary soft tissue sarcomas of the extremities and the trunk wall were subjected to DNA flow cytometry for quantification of S-phase fraction and to immunohistochemical evaluation of Ki-67, Top2a, p21, and p27Kip1. In univariate analysis, positive expression of Ki-67 (hazard ratio = 4.5, CI = 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Management of Breast Sarcoma.

PubMed

Hsu, Cary; McCloskey, Susan A; Peddi, Parvin F

2016-10-01

Breast sarcomas are exceptionally rare mesenchymal neoplasms composed of many histologic subtypes. Therapy is guided by principles established in the management of extremity sarcomas. The anatomic site does influence treatment decisions, particularly the surgical management. Surgery should be undertaken with the aim of achieving a widely negative margin. Selected patients can be managed with breast-conserving surgery. Breast reconstruction is increasingly being undertaken for selected patients. Radiation therapy and chemotherapy are used selectively for large, high-grade sarcomas for which there is significant concern for local and distant recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone.

PubMed

Palmerini, E; Jones, R L; Marchesi, E; Paioli, A; Cesari, M; Longhi, A; Meazza, C; Coccoli, L; Fagioli, F; Asaftei, S; Grignani, G; Tamburini, A; Pollack, S M; Picci, P; Ferrari, S

2016-04-20

Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Patients receiving G 900 mg/m(2) d 1, 8; D 75 mg/m(2) d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51%) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49%) patients had metastases limited to lungs, 26 (51%) multiple sites. 40 (78%) osteosarcoma, 11 (22%) HGS. Eight (16%) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46%, and significantly better for patients with ECOG 0 (ECOG 0: 54% vs ECOG 1: 43% vs ECOG 2: 0%; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75% vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56% vs HGS 18%; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13%) patients had a partial response (PR), 20 (43%) had stable disease (SD) and 20 (43%) had progressive disease (PD). The 1-year OS was 30%: 67% for PR, 54% for SD and 20% for PD (p = 0.005). GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

Optimizing Local Control in High‐Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment

PubMed Central

Annede, Pierre; Gouy, Sébastien; Mazeron, Renaud; Bentivegna, Enrica; Maroun, Pierre; Petit, Claire; Dumas, Isabelle; Leary, Alexandra; Genestie, Catherine; Lhommé, Catherine; Deutsch, Eric; Morice, Philippe; Pautier, Patricia; Haie‐Meder, Christine

2017-01-01

Abstract Purpose. The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT). Material and Methods. We conducted a single‐center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high‐grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined. Results. Median follow‐up time was 5.5 years. A total of 98 pts with high‐grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High‐dose rate, low‐dose rate, and pulsed‐dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow‐up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I‐III disease, 5‐year overall survival was 77% (95% confidence interval: 67%–87%) and 5‐year survival without locoregional failure was 91% (83%–98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects. Conclusion. Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high‐grade US. Implications for Practice. This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional

[A rare primary tumor of the mediastinum: pleomorphic liposarcoma].

PubMed

Msaad, S; Yangui, I; Ayedi, L; Ketata, W; Sellami, T; Ayoub, A; Jlidi, R

2007-12-01

Liposarcoma of the mediastinum is a rare tumor with various histologic features. We report a case of mediatinal pleomorphic liposarcoma in a 37-year-old man who complained of chest pain. Computed tomography showed an anterior expansive process within the mediastinum. Histological diagnosis was established by a trans-thoracic computed tomography guided core-needle biopsy. Despite a first cure of chemotherapy with gemcitabin/cisplatin, disease progression led to death 3 months after diagnosis. Mediastinal pleomorphic liposarcoma is an exceptional invading tumor affecting the middle-aged adult. This tumor, usually giant, becomes symptomatic by compression of mediastinal structures. Surgery is the best treatment when possible. The role of radiotherapy and chemotherapy are discussed. Prognosis depends both on the quality of resection and the grade malignancy.

Molecular classification of soft tissue sarcomas and its clinical applications

PubMed Central

Jain, Shilpa; Xu, Ruliang; Prieto, Victor G; Lee, Peng

2010-01-01

Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the morphology and type of tissue that they resemble, such as rhabdomyosarcoma, which resembles skeletal muscle. However, the cell of origin is unclear in numerous sarcomas. Molecular genetics analyses have not only assisted in understanding the molecular mechanism in sarcoma pathogenesis but also demonstrated new relationships within different types of sarcomas leading to a more proper classification of sarcomas. Molecular classification based on the genetic alteration divides sarcomas into two main categories: (i) sarcomas with specific genetic alterations; which can further be subclassified based on a) reciprocal translocations resulting in oncogenic fusion transcripts (e.g. EWSR1-FLI1 in Ewing sarcoma) and b) specific oncogenic mutations (e.g. KIT and PDGFRA mutations in gastrointestinal stromal tumors) and (ii) sarcomas displaying multiple, complex karyotypic abnormalities with no specific pattern, including leiomyo-sarcoma, and pleomorphic liposarcoma. These specific genetic alterations are an important adjunct to standard morphological and immunohistochemical diagnoses, and in some cases have a prognostic value, e. g., Ewing family tumors, synovial sarcoma, and alveolar rhabdomyosarcoma. In addition, these studies may also serve as markers to detect minimal residual disease and can aid in staging or monitor the efficacy of therapy. Furthermore, sarcoma-specific fusion genes and other emerging molecular events may also represent potential targets for novel therapeutic approaches such as Gleevec for dermatofibrosarcoma protuberans. Therefore, increased understanding of the molecular biology of sarcomas is leading towards development of newer and more effective treatment regimens. The review focuses on recent advances in molecular genetic alterations having an impact on diagnostics, prognostication and clinical management of selected sarcomas. PMID:20490332

FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways.

PubMed

Kelleher, Fergal C; O'Sullivan, Hazel

2016-07-05

FOXM1 is a pro-proliferative transcription factor that promotes cell cycle progression at the G1-S, and G2-M transitions. It is activated by phosphorylation usually mediated by successive cyclin - cyclin dependent kinase complexes, and is highly expressed in sarcoma. p53 down regulates FOXM1 and FOXM1 inhibition is also partly dependent on Rb and p21. Abnormalities of p53 or Rb are frequent in sporadic sarcomas with bone or soft tissue sarcoma, accounting for 36% of index cancers in the high penetrance TP53 germline disorder, Li-Fraumeni syndrome.FOXM1 stimulates transcription of pluripotency related genes including SOX2, KLF4, OCT4, and NANOG many of which are important in sarcoma, a disorder of mesenchymal stem cell/ partially committed progenitor cells. In a selected specific, SOX2 is uniformly expressed in synovial sarcoma. Embryonic pathways preferentially used in stem cell such as Hippo, Hedgehog, and Wnt dominate in FOXM1 stoichiometry to alter rates of FOXM1 production or degradation. In undifferentiated pleomorphic sarcoma, liposarcoma, and fibrosarcoma, dysregulation of the Hippo pathway increases expression of the effector co-transcriptional activator Yes-Associated Protein (YAP). A complex involving YAP and the transcription factor TEAD elevates FOXM1 in these sarcoma subtypes. In another scenario 80% of desmoid tumors have nuclear localization of β-catenin, the Wnt pathway effector molecule. Thiazole antibiotics inhibit FOXM1 and because they have an auto-regulator loop FOXM1 expression is also inhibited. Current systemic treatment of sarcoma is of limited efficacy and inhibiting FOXM1 represents a potential new strategy.

FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways

PubMed Central

Kelleher, Fergal C.; O'sullivan, Hazel

2016-01-01

FOXM1 is a pro-proliferative transcription factor that promotes cell cycle progression at the G1-S, and G2-M transitions. It is activated by phosphorylation usually mediated by successive cyclin – cyclin dependent kinase complexes, and is highly expressed in sarcoma. p53 down regulates FOXM1 and FOXM1 inhibition is also partly dependent on Rb and p21. Abnormalities of p53 or Rb are frequent in sporadic sarcomas with bone or soft tissue sarcoma, accounting for 36% of index cancers in the high penetrance TP53 germline disorder, Li-Fraumeni syndrome. FOXM1 stimulates transcription of pluripotency related genes including SOX2, KLF4, OCT4, and NANOG many of which are important in sarcoma, a disorder of mesenchymal stem cell/ partially committed progenitor cells. In a selected specific, SOX2 is uniformly expressed in synovial sarcoma. Embryonic pathways preferentially used in stem cell such as Hippo, Hedgehog, and Wnt dominate in FOXM1 stoichiometry to alter rates of FOXM1 production or degradation. In undifferentiated pleomorphic sarcoma, liposarcoma, and fibrosarcoma, dysregulation of the Hippo pathway increases expression of the effector co-transcriptional activator Yes-Associated Protein (YAP). A complex involving YAP and the transcription factor TEAD elevates FOXM1 in these sarcoma subtypes. In another scenario 80% of desmoid tumors have nuclear localization of β-catenin, the Wnt pathway effector molecule. Thiazole antibiotics inhibit FOXM1 and because they have an auto-regulator loop FOXM1 expression is also inhibited. Current systemic treatment of sarcoma is of limited efficacy and inhibiting FOXM1 represents a potential new strategy. PMID:27074562

Pleomorphic Hyalinizing Angiectatic Tumour: A Rare Case Report and Discussion of Differential Diagnosis.

PubMed

Chalmeti, Ambica; Arakeri, Surekha U; Javalgi, Anita P; Goyal, Shefali

2017-08-01

Pleomorphic Hyalinizing Angiectatic Tumour (PHAT) is one of the rare soft tissue tumour which is non-metastasizing. The origin of this tumour is yet uncertain. It occurs in adults as a slow growing subcutaneous mass mimicking clinically and histologically to various benign and malignant soft tissue tumours such as schwannoma, haemangioma and malignant fibrous histiocytoma. The microscopic features of this tumour include clusters of ectatic, fibrin containing, hyalinized blood vessels with pleomorphic and spindle shaped tumour cells showing intranuclear inclusions, stromal haemosiderin pigment and a variable inflammatory infiltrate. Despite marked pleomorphism, the lesion behaves as a low grade neoplasm, with frequent recurrences, but no metastases. The incidence of this tumour is very rare with less than 100 cases being published. Hence, awareness of this entity is must for proper management of the patient and to avoid misdiagnosis of the lesion. We report a case of pleomorphic hyalinizing angiectatic tumour in a 50-year-old man who presented with a slow growing mass in the left calf region since two years.

Pleomorphic Hyalinizing Angiectatic Tumour: A Rare Case Report and Discussion of Differential Diagnosis

PubMed Central

Arakeri, Surekha U; Javalgi, Anita P; Goyal, Shefali

2017-01-01

Pleomorphic Hyalinizing Angiectatic Tumour (PHAT) is one of the rare soft tissue tumour which is non-metastasizing. The origin of this tumour is yet uncertain. It occurs in adults as a slow growing subcutaneous mass mimicking clinically and histologically to various benign and malignant soft tissue tumours such as schwannoma, haemangioma and malignant fibrous histiocytoma. The microscopic features of this tumour include clusters of ectatic, fibrin containing, hyalinized blood vessels with pleomorphic and spindle shaped tumour cells showing intranuclear inclusions, stromal haemosiderin pigment and a variable inflammatory infiltrate. Despite marked pleomorphism, the lesion behaves as a low grade neoplasm, with frequent recurrences, but no metastases. The incidence of this tumour is very rare with less than 100 cases being published. Hence, awareness of this entity is must for proper management of the patient and to avoid misdiagnosis of the lesion. We report a case of pleomorphic hyalinizing angiectatic tumour in a 50-year-old man who presented with a slow growing mass in the left calf region since two years. PMID:28969147

Dedifferentiated liposarcoma of the spermatic cord: a series of 42 cases.

PubMed

Kryvenko, Oleksandr N; Rosenberg, Andrew E; Jorda, Merce; Epstein, Jonathan I

2015-09-01

Dedifferentiated liposarcoma (DDL) of the spermatic cord is rare, with limited data regarding morphology and prognosis. We analyzed the morphologic spectrum of DDL of the spermatic cord and its clinical significance in 42 patients from 1990 to 2014. The median age of the patients was 70.5 years (range: 43 to 90 y). The median tumor size was 10.9 cm (range: 3 to 30 cm). Six cases were low-grade DDL, 28 were high-grade DDL, and in 8 cases both coexisted. Five cases had osteosarcoma, and 2 had leiomyosarcoma differentiation. Low-grade DDL had a fibrosarcoma-like (n=11), myxofibrosarcoma-like (n=2), and fibrosarcoma and inflammatory-like (n=1) pattern. High-grade DDL had a fibrosarcoma-like (n=22), undifferentiated pleomorphic sarcoma-like (n=7), myxofibrosarcoma and undifferentiated pleomorphic sarcoma-like (n=4), fibrosarcoma and undifferentiated pleomorphic sarcoma-like (n=2), and myxofibrosarcoma-like (n=1) pattern. Resection margins were positive in 22, negative in 13, and unknown in 7 cases. MDM2 was positive in 24/24 cases. Two patients received neoadjuvant radiotherapy (1 with chemotherapy). Patients received postoperative radiation (n=13), reexcision (n=5) with radiation (n=3), chemotherapy (n=2), chemotherapy and radiation (n=1), no therapy (n=11), and unknown (n=6). Follow-up information was available in 31 patients (mean: 54.2 mo; median: 38.5 mo; range: 2 to 180 mo). Seven patients developed local recurrence. Two patients had systemic metastases and succumbed to disease. Recurrence developed at an average of 40.9 months (median: 24 mo; range: 12 to 100 mo) after resection. Average follow-up in patients without recurrence was 45.2 months (median: 25 mo; range: 2 to 180 mo) (P=0.87). Margin status, size, and grade did not correlate with recurrence (P>0.05). Thus, DDL of the spermatic cord includes a spectrum of morphologic patterns. Complete excision is difficult at first attempt. Local recurrence is common, and relatively few patients develop systemic

Effective apatinib treatment of pleomorphic liposarcoma

PubMed Central

Yan, Peng; Sun, Mei-Li; Sun, Yu-Ping; Liu, Chuan-Yong

2017-01-01

Abstract Rationale: Pleomorphic liposarcoma (PLS) is a rare and aggressive malignant tumor, and both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. Patient Concerns: We presented an 81-year-old Chinese woman with advanced PLS who received apatinib after failure chemotherapy. Diagnoses: The patient was diagnosed as having PLS by biopsy. Interventions: After a failed chemotherapy, apatinib started to be taken orally 425 mg per day. Outcomes: This patient achieved 3-month progression-free survival (PFS) and a higher quality of life. Meanwhile, this patient suffered grade 2 hypertension and grade 3 hand–foot syndrome (HFS). Lessons: In this case, apatinib presented good efficacy and safety to treat PLS. Randomized clinical studies are required to confirm the efficacy and safety of apatinib in the treatment of PLS. PMID:28816958

Histological and immunohistochemical features of histiocytic sarcoma in four domestic ferrets (Mustela putorius furo).

PubMed

Thongtharb, Atigan; Uchida, Kazuyuki; Chambers, James K; Miwa, Yasutsugu; Murata, Yousuke; Nakayama, Hiroyuki

2016-03-01

Four cases of histiocytic sarcoma in domestic ferrets (Mustela putorius furo) are described in the present study. Tumor samples obtained from the abdominal viscera, including the spleen, were submitted for histologic examination. Microscopically, poorly demarcated masses contained numerous round- to pleomorphic-shaped cells with coarsely vacuolated and eosinophilic cytoplasm. Bizarre, binucleated tumor cells and multinucleated giant tumor cells with low phagocytic activity were commonly observed. Immunohistochemically, tumor cells in all of the cases were positive for vimentin, human leukocyte antigen-DR, ionized calcium-binding adapter molecule-1, and lysozyme, but some of them lacked cluster of differentiation (CD)163 or CD208 expression. The survival time after surgical resection was 9 days to 5 months. Histiocytic sarcoma in the ferret is a rare, but highly aggressive, tumor commonly found in the spleen. © 2016 The Author(s).

Primary undifferentiated sarcoma of the meninges: A case report and comprehensive review of the literature.

PubMed

Wapshott, Taylor; Schammel, Christine M G; Schammel, David P; Rezeanu, Luminita; Lynn, Michael

2018-05-21

Sarcomas make up 1% of all cases of adult cancer, with 5-10% of those classified as undifferentiated pleomorphic sarcomas (UPS/PUS) and 0.1-4.3% primary intracranial sarcomas. Intracranial undifferentiated sarcoma is characterized by an earlier age of onset and generally poorer prognosis compared to extracranial undifferentiated sarcomas. Current therapies involve surgical excision with wide margins and radiotherapy, with minimal data available regarding the efficacy of chemotherapy. A 79-year-old man with a history of remote superficial bladder cancer presented with a large frontal scalp lesion. A biopsy was initially attempted by a dermatologist in the outpatient setting, but a follow-up CT scan revealed a skull-eroding, enhancing soft tissue lesion. Neurosurgical treatment revealed an undifferentiated sarcoma. The patient underwent adjuvant radiation therapy of 59.4 Gy fractionated over 45 days following surgery. Follow-up brain MRIs at 1-, 6-, 9-, 12-, 15-, 21-, and 27 months after surgery have not shown any indications of local recurrence or tumor metastasis. Despite the high propensity that undifferentiated sarcomas have for recurrence and metastasis and the patient's advanced age, this patient remains uniquely disease-free. We provide a description of an unusual case and comprehensive literature review of UPS to clarify the hallmarks of the disease, identify the difficulties in diagnosis, and provide a summary of therapies employed in the literature with their corresponding patient outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Principles of treatment for soft tissue sarcoma.

PubMed

Dernell, W S; Withrow, S J; Kuntz, C A; Powers, B E

1998-02-01

Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue elements and are grouped together based on a common biologic behavior. The most common histologic types include malignant peripheral nerve sheath tumors (schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and malignant fibrous histiocytoma. These tumors are relatively slow growing yet locally invasive with a high rate of recurrence following conservative management. Appropriate preoperative planning and aggressive surgical resection often result in long-term remission or cure. Identification and evaluation of resection margins are paramount in appropriate case management. The addition of radiotherapy after surgical resection can aid in remission for incompletely resected masses. Systemic chemotherapy for STS should be considered for high-grade tumors with a moderate metastatic potential. Potential prognostic factors include grade, resection margins, size, location, histologic type, and previous treatment, with grade and margins being the most important. Tumor types classified as STS that differ slightly in their presentation or treatment, including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine-associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating disease to treat, but adherence to solid surgical oncology principles can greatly increase the odds of good disease control.

Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serizawa, Itsuko, E-mail: s_itsuko@nirs.go.j; Kagei, Kenji; Kamada, Tadashi

2009-11-15

Purpose: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. Methods and Materials: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologicmore » grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm{sup 3} and 1,194 cm{sup 3} (median 525 cm{sup 3}). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. Results: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. Conclusions: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.« less

[Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors].

PubMed

Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

2012-09-01

The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

PubMed

Chowdhary, Mudit; Sen, Neilayan; Jeans, Elizabeth B; Miller, Luke; Batus, Marta; Gitelis, Steven; Wang, Dian; Abrams, Ross A

2018-05-18

Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure.

Epidemiology and therapies for metastatic sarcoma

PubMed Central

Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

2013-01-01

Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

[Histopathological diagnostic concordance in bone and soft tissue sarcomas between two comprehensive cancer centers from eastern and western Europe: a collaborative experience].

PubMed

Somcutian, Oana; Buiga, Rares; Galatir, Mihaela; Tudor Eniu, Dan; Rachieru, Claudiu; Coza, Daniela; Terrier, Philippe

2015-01-01

This study aims to assess the degree of concordance of histological diagnosis of bone and soft tissue sarcomas between a Comprehensive Cancer Center (CCC) of Eastern Europe - not specialized in this area of pathology - and an important CCC of Western Europe, which is one of the coordinators of a clinical reference network in sarcoma pathology. The goal is to have an overview of the sarcomatous pathology in a region of Eastern Europe and to discover diagnostic discrepancies between the two centers, while determining their cause. The initial diagnosis was compared with the revised diagnosis on 110 specimens from 88 patients with bone or soft tissue sarcomas from East-European CCC, in a one-year period of time. Complete diagnostic agreement was observed in 55 cases (62.5%), a partial agreement in 23 cases (26.1%) and a major disagreement in 10 cases (11.4%). Major discrepancies of the histological type was observed in only 3 cases (3.4%): one case of discordance benign/malignant and 2 cases of discordance mesenchymal/non mesenchymal. Minor histological discrepancies - not affecting the management of the patient - were observed in 18 cases (20.4%). A major discordance in grading - potentially changing the management of the patient - was noted in 7 cases (7.9%), and a minor discrepancy in 5 cases (5.7%). Some histological types were clearly overdiagnosed, like "adult fibrosarcomas" and "malignant peripheral nerve sheet tumors" (MPNST), mostly converted after the audit into "undifferentiated spindle cell sarcomas" or other types of sarcomas. Some "unclassified" sarcomas and "undifferentiated pleomorphic sarcomas" could be re-classified with the aid of an extensive panel of antibodies. Overall, immunohistochemistry was responsible, but not in exclusivity, for half of the minor discrepancies, and for 2 out of 3 cases of major histological discrepancies. Otherwise, the main cause of discrepancies was the difficulties in the interpretation of the morphology. Molecular

EF5 to Evaluate Tumor Hypoxia in Patients With High-Grade Soft Tissue Sarcoma or Mouth Cancer

ClinicalTrials.gov

2013-01-15

Stage I Adult Soft Tissue Sarcoma; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Adult Soft Tissue Sarcoma; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Adult Soft Tissue Sarcoma; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity

Primary cardiac sarcoma complicated with cerebral infarction and brain metastasis: A case report and literature review.

PubMed

Sun, Yun-Peng; Wang, Xuan; Gao, Yong-Sheng; Zhao, Song; Bai, Yang

2017-12-12

In large autopsy series, the estimated frequency of primary tumors of the heart ranges from 0.0017% to 0.33%. Approximately 25% of primary cardiac tumors are malignant, and nearly 20% of these are sarcomas. To date, a completely feasible surgical resection remains the major treatment measure of cardiac sarcoma, especially for recurrent focal cardiac sarcoma and the recurrence of a restrictive metastasis. Although characteristically medical treatments are recommended, there is no consistent opinion for adjuvant radiotherapy and chemotherapy following an operation. Since these tumors usually undergo extensive spread by the time that the diagnosis is established, the prognosis of cardiac sarcoma remains poor. In this report, we described a case who underwent initial cardiac tumor resection, and was confirmed to be a pleomorphic undifferentiated sarcoma based on pathological findings. However, the patient complicated with cerebral infarction and subsequent brain metastasis sarcoma after the initial surgery, which was confirmed by brain tissue pathology. During the course of therapy, the patient underwent three surgical operations and refused to accept any chemotherapy and radiotherapy intervention. To the best of our knowledge, this is the first case report describing a primary cardiac sarcoma complicated with cerebral infarction and brain metastasis. The management of primary cardiac sarcoma is also discussed.

Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514.

PubMed

Kraybill, William G; Harris, Jonathan; Spiro, Ira J; Ettinger, David S; DeLaney, Thomas F; Blum, Ronald H; Lucas, David R; Harmon, David C; Letson, G Douglas; Eisenberg, Burton

2010-10-01

The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (≥5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. Patients with high-grade soft tissue sarcoma≥8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). Sixty-four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety-seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow-up of 7.7 years in surviving patients, the 5-year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8-32.6) and 28.1% (95% CI, 17.0-39.2). The most common site of metastasis was lung. Estimated 5-year rates of disease-free survival, distant disease-free survival, and overall survival were 56.1% (95% CI, 43.9-68.3), 64.1% (95% CI, 52.3-75.8), and 71.2% (95% CI, 60.0-82.5), respectively. Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long-term outcome was better than might be expected in such high-risk tumors. Copyright © 2010 American Cancer Society.

Establishment and proteomic characterization of a novel cell line, NCC-UPS2-C1, derived from a patient with undifferentiated pleomorphic sarcoma.

PubMed

Oyama, Rieko; Kito, Fusako; Sakumoto, Marimu; Shiozawa, Kumiko; Toki, Shunichi; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2018-03-01

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal malignancy requiring novel therapeutic approaches to improve clinical outcome. Patient-derived cancer cell lines are an essential tool for investigating molecular mechanisms underlying cancer initiation and development; however, there is a lack of patient-derived cell lines of UPS available for research. The objective of this study was to develop a patient-derived cell model of UPS. A cell line designated NCC-UPS2-C1 was established from the primary tumor tissue of an 84-yr-old female patient with UPS. The short tandem repeat pattern of NCC-UPS2-C1 cells was identical to that of the original tumor and distinct from that of any other cell lines deposited in public cell banks. NCC-UPS2-C1 cells were maintained as a monolayer culture for over 80 passages during 30 mo and exhibited spindle-like morphology, continuous growth, and ability for spheroid formation and invasion. Proteomic profiling using mass spectrometry and functional treemap analysis revealed that the original tumor and the derived NCC-UPS2-C1 cells had similar but distinct protein expression patterns. Our results indicate that a novel UPS cell line was successfully established and could be used to study UPS development and effects of anti-cancer drugs. However, the revealed difference between proteomes of the original tumor and NCC-UPS2-C1 cells should be further investigated to determine the appropriate applications of this cell line in UPS research.

Head and Neck Sarcomas: The UCLA Experience

PubMed Central

Tajudeen, Bobby A.; Fuller, Jennifer; Lai, Chi; Grogan, Tristan; Elashoff, David; Abemayor, Elliot; St. John, Maie

2014-01-01

Purpose To profile the clinical presentation, subtype distribution, and treatment results of sarcomas of the head and neck at a single tertiary academic center over an 11-year period. Materials and Methods A retrospective review was performed by examining the records and reviewing the pathology of 186 patients with head and neck sarcomas treated at UCLA Medical Center from 2000 to 2011. Results The mean age of the study population was 49 +/− 22 years. 58% of the patients were male and 42% were female. Median duration of follow-up for the entire group was 18.5 months. The most common presenting symptom was a mass lesion in 59.9% of patients. The nasal cavity/sinus was the most common presenting site seen in 22% of patients. Solitary fibrous tumor/hemangiopericytoma was the most common subtype. 15% of patients had evidence of prior radiation exposure. 26.3% of tumors were greater than 5cm and 35.5% were high-grade. Margins were positive in 31.2% of patients. Lymph node metastasis was rare at 6.5%. Perineural invasion was identified in 6.5%. Among all subtypes, 5-yr recurrence-free survival and overall survival were 50% and 49%, respectively. Multivariate analysis demonstrated that grade and margin status were predictors of recurrence-free survival while grade and age affected overall survival. Conclusions Head and neck sarcomas are a rare entity frequently presenting as a mass lesion. In our series, lesions tended to be high-grade with a significant portion of surgical specimens having positive margins. Grade and margin status were the most important predictors of survival. PMID:24721744

Detection of high-grade atypia nuclei in breast cancer imaging

NASA Astrophysics Data System (ADS)

Noël, Henri; Roux, Ludovic; Lu, Shijian; Boudier, Thomas

2015-03-01

Along with mitotic count, nuclear pleomorphism or nuclear atypia is an important criterion for the grading of breast cancer in histopathology. Though some works have been done in mitosis detection (ICPR 2012,1 MICCAI 2013,2 and ICPR 2014), not much work has been dedicated to automated nuclear atypia grading, especially the most difficult task of detection of grade 3 nuclei. We propose the use of Convolutional Neural Networks for the automated detection of cell nuclei, using images from the three grades of breast cancer for training. The images were obtained from ICPR contests. Additional manual annotation was performed to classify pixels into five classes: stroma, nuclei, lymphocytes, mitosis and fat. At total of 3,000 thumbnail images of 101 × 101 pixels were used for training. By dividing this training set in an 80/20 ratio we could obtain good training results (around 90%). We tested our CNN on images of the three grades which were not in the training set. High grades nuclei were correctly classified. We then thresholded the classification map and performed basic analysis to keep only rounded objects. Our results show that mostly all atypical nuclei were correctly detected.

Comprehensive Surgical Treatment as the Mainstay of Management in Retroperitoneal Sarcomas: Retrospective Study from Two Non-sarcoma Specialist Centers.

PubMed

Petrou, Athanasios; Constantinidou, Anastasia; Kontos, Michael; Papalampros, Alexandros; Moris, Demetrios; Bakoyiannis, Chris; Neofytou, Kyriakos; Kourounis, George; Felekouras, Evangelos

2017-04-01

Complete resection, surgical expertise and individualization of patient management in comprehensive oncology centres result in better clinical outcomes in patients presenting with retroperitoneal sarcomas. Clinical outcomes of primary and recurrent retroperitoneal sarcoma resections performed between January 2002 and December 2016 in two large surgical oncology, but non-sarcoma specialist centers, were reviewed to determine the efficacy of complete surgical resection as the principle instrument for treatment. The histological type, tumor size and grade, as well as organ resection, were recorded and subsequently reviewed. Our study included 108 cases of sarcoma resection (60 first-time, 38 second-time and 10 third-time laparotomies) in 60 patients (35 males and 25 females). Most patients had complete resection: 57 had a macroscopically complete (R0/R1) resection and three had R2 resection. The 90-day mortality rate was zero and morbidity was minimal. Five- and 10-year overall survival (OS) rates were 88% and 79%, respectively, whereas the corresponding disease-free survival (DFS) rates were 65% and 59%, respectively. High-grade tumors were associated with decreased DFS (hazard ratio(HR)=3.35; 95% confidence interval(CI)=1.23-9.10; p=0.018) and decreased OS (HR=7.18; 95% CI=1.50-34.22; p=0.013). Complete surgical resection of retroperitoneal sarcomas combined with individualized patient management when offered by experienced surgical oncology teams, adhering to international guidelines, can succeed in providing patients with good long-term outcomes, comparable to those achieved at sarcoma-specialist centers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effective apatinib treatment of pleomorphic liposarcoma: A case report.

PubMed

Yan, Peng; Sun, Mei-Li; Sun, Yu-Ping; Liu, Chuan-Yong

2017-08-01

Pleomorphic liposarcoma (PLS) is a rare and aggressive malignant tumor, and both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. We presented an 81-year-old Chinese woman with advanced PLS who received apatinib after failure chemotherapy. The patient was diagnosed as having PLS by biopsy. After a failed chemotherapy, apatinib started to be taken orally 425 mg per day. This patient achieved 3-month progression-free survival (PFS) and a higher quality of life. Meanwhile, this patient suffered grade 2 hypertension and grade 3 hand-foot syndrome (HFS). In this case, apatinib presented good efficacy and safety to treat PLS. Randomized clinical studies are required to confirm the efficacy and safety of apatinib in the treatment of PLS.

Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study.

PubMed

Olmos, David; Postel-Vinay, Sophie; Molife, L Rhoda; Okuno, Scott H; Schuetze, Scott M; Paccagnella, M Luisa; Batzel, Gretchen N; Yin, Donghua; Pritchard-Jones, Kathryn; Judson, Ian; Worden, Francis P; Gualberto, Antonio; Scurr, Michelle; de Bono, Johann S; Haluska, Paul

2010-02-01

Figitumumab is a fully human IgG2 monoclonal antibody targeting the insulin-like growth-factor-1 receptor (IGF-1R). Preclinical data suggest a dependence on insulin-like growth-factor signalling for sarcoma subtypes, including Ewing's sarcoma, and early reports show antitumour activity of IGF-1R-targeting drugs in these diseases. Between January, 2006, and August, 2008, patients with refractory, advanced sarcomas received figitumumab (20 mg/kg) in two single-stage expansion cohorts within a solid-tumour phase 1 trial. The first cohort (n=15) included patients with multiple sarcoma subtypes, age 18 years or older, and the second cohort (n=14) consisted of patients with refractory Ewing's sarcoma, age 9 years or older. The primary endpoint was to assess the safety and tolerability of figitumumab. Secondary endpoints included pharmacokinetic profiling and preliminary antitumour activity (best response by Response Evaluation Criteria in Solid Tumours [RECIST]) in evaluable patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov, number NCT00474760. 29 patients, 16 of whom had Ewing's sarcoma, were enrolled and received a total of 177 cycles of treatment (median 2, mean 6.1, range 1-24). Grade 3 deep venous thrombosis, grade 3 back pain, and grade 3 vomiting were each noted once in individual patients; one patient had grade 3 increases in aspartate aminotransferase and gammaglutamyltransferase concentrations. This patient also had grade 4 increases in alanine aminotransferase concentrations. The only other grade 4 adverse event was raised concentrations of uric acid, noted in one patient. Pharmacokinetics were comparable between patients with sarcoma and those with other solid tumours. 28 patients were assessed for response; two patients, both with Ewing's sarcoma, had objective responses (one complete response and one partial response) and eight patients had disease stabilisation (six with Ewing's sarcoma, one with

Socioeconomic factors and the risk for sarcoma.

PubMed

Hampras, Shalaka S; Moysich, Kirsten B; Marimuthu, Sathiya P; Ravi, Vinod; Jayaprakash, Vijayvel

2014-11-01

Sarcomas are a heterogeneous group of rare malignancies arising from mesenchymal tissue. Although several occupational exposures have been evaluated in association with sarcoma, little is known about the role of socioeconomic indicators such as education. Socioeconomic status has been found to be associated with risk of development of several types of cancers, primarily lung, gastric, and cervical cancers. We conducted a hospital-based case-control study to evaluate the association of socioeconomic level with the risk for sarcoma. A total of 371 incident cases of sarcoma were matched in terms of age, sex, and year of enrollment in the study with 742 cancer-free controls. Education and income levels were evaluated as the indicators of socioeconomic status. Higher education (college level) was associated with a significantly lower risk for sarcoma [odds ratio (OR)=0.48, 95% confidence interval (CI)=0.29-0.80], even after adjusting for important confounders. After stratifying by sex, significantly lower risk for sarcoma was observed among men who had college level education compared with men with a level of education of eighth grade or lower (OR=0.38, 95% CI=0.19-0.74). A significant association between education and the risk for sarcoma remained after stratifying by income (OR=0.49, 95% CI=0.28-0.86, among the low income group). When analyzed as a composite exposure, individuals with high education and high income status had significantly lower risk for sarcoma compared with those with low income and low education status (OR=0.41, 95% CI=0.23-0.71). Thus, socioeconomic factors may play a significant role in determining the risk for sarcoma and should be explored further to elucidate the underlying factors that may explain these sociodemographic inequalities related to sarcoma.

High-dose ifosfamide by infusion with Mesna in advanced refractory sarcomas.

PubMed

Güllü, I; Yalçin, S; Tekuzman, G; Barişta, I; Alkiş, N; Celik, I; Zengin, N; Güler, N; Kars, A; Baltali, E

1996-01-01

Twenty patients with advanced sarcomas entered a pilot study with ifosfamide (IF) and mercaptoethane sulfonate sodium (Mesna) as a second-line treatment for six planned cycles. All patients had received prior doxorubicin- and cyclophosphamide-based chemotherapies. IF was administered at a dose of 3 g/m2 given as continuous intravenous infusion for 24 hr on day 1-5 with Mesna. In the absence of disease progression, chemotherapy was planned to be repeated every 4 weeks for six consecutive cycles. Following chemotherapy, only 2 patients (11%) achieved partial response with response durations of 6 and 9 months. There was no complete response. When considered for only high-grade tumors, the response rate reached up to 22%. Toxicity was reported for 48 cycles and the dose-limiting toxicities were myelosuppression (22%) and encephalopathy (17%). Chemotherapy protocol was changed after two or three courses in 16 patients with stable or progressive disease. IF/Mesna chemotherapy at this dose and schedule was not found to be very promising in refractory sarcomas as a second-line chemotherapy.

Dedifferentiated liposarcoma of the spermatic cord with a hemangioendothelioma-like component: a case report and review of the literature.

PubMed

Okano, Shinji; Yamamoto, Hidetaka; Kono, Shinji; Fujii, Hiroshi; Shirabe, Ken; Maehara, Yoshihiko; Oda, Yoshinao

2013-09-01

Atypical lipomatous tumor or well-differentiated liposarcoma/dedifferentiated liposarcoma (DDLPS) is the most frequent subtype of malignant adipocytic tumor. This tumor typically presents in late adult life, most commonly in the retroperitoneum, extremities, or spermatic cord. It has been reported that the dedifferentiated component consists mainly of high-grade sarcoma, including undifferentiated pleomorphic sarcoma, fibrosarcoma, and myxofibrosarcoma, and it has been recently reported that the dedifferentiated component can be also made up of a low-grade sarcomatous component. Therefore, the dedifferentiated areas exhibit a wide morphological spectrum that commonly includes fibroblastic/myofibroblastic and fibrohistiocytic tumors but very rarely includes vascular tumors. We present here the first reported case of DDLPS with a hemangioendothelioma-like component in the spermatic cord. Copyright © 2013 Elsevier GmbH. All rights reserved.

Vaccine-associated sarcomas in cats: a unique cancer model.

PubMed

McNiel, E A

2001-01-01

Epidemiologic evidence supports a relationship between vaccination of cats for rabies and feline leukemia virus with the development of soft tissue sarcomas at the site of administration. These tumors are locally invasive and histologically aggressive. As with high-grade soft tissue sarcoma in humans, combination treatment with radiation therapy and surgery provides for optimum tumor control. Feline vaccine-associated sarcoma has become a difficult issue for the veterinary profession for legal, ethical, and clinical reasons. Although most research efforts have focused on therapeutic intervention, this tumor has great potential to provide an informative model for carcinogenesis and genetic susceptibility applicable to cancer in all species, including humans.

A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma.

PubMed

Sugita, Shintaro; Arai, Yasuhito; Tonooka, Akiko; Hama, Natsuko; Totoki, Yasushi; Fujii, Tomoki; Aoyama, Tomoyuki; Asanuma, Hiroko; Tsukahara, Tomohide; Kaya, Mitsunori; Shibata, Tatsuhiro; Hasegawa, Tadashi

2014-11-01

Differential diagnosis of small round cell sarcomas (SRCSs) grouped under the Ewing sarcoma family of tumors (ESFT) can be a challenging situation for pathologists. Recent studies have revealed that some groups of Ewing-like sarcoma show typical ESFT morphology but lack any EWSR1-ETS gene fusions. Here we identified a novel gene fusion, CIC-FOXO4, in a case of Ewing-like sarcoma with a t(X;19)(q13;q13.3) translocation. The patient was a 63-year-old man who had an asymptomatic, 30-mm, well-demarcated, intramuscular mass in his right posterior neck, and imaging findings suggested a diagnosis of high-grade sarcoma. He was treated with complete resection and subsequent radiotherapy and chemotherapy. He was alive without local recurrence or distant metastasis 6 months after the operation. Histologic examination revealed SRCS with abundant desmoplastic fibrous stroma suggesting a desmoplastic small round cell tumor. Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively. High-throughput transcriptome sequencing revealed a gene fusion, and the genomic rearrangement between the CIC and FOXO4 genes was identified by fluorescence in situ hybridization. Aside from the desmoplastic stroma, the CIC-FOXO4 fusion sarcoma showed morphologic and immunohistochemical similarity to ESFT and Ewing-like sarcomas, including the recently described CIC-DUX4 fusion sarcoma. Although clinicopathologic analysis with additional cases is necessary, we conclude that CIC-FOXO4 fusion sarcoma is a new type of Ewing-like sarcoma that has a specific genetic signature. These findings have important implications for the differential diagnosis of SRCS.

"Atypical" Pleomorphic Lipomatous Tumor: A Clinicopathologic, Immunohistochemical and Molecular Study of 21 Cases, Emphasizing its Relationship to Atypical Spindle Cell Lipomatous Tumor and Suggesting a Morphologic Spectrum (Atypical Spindle Cell/Pleomorphic Lipomatous Tumor).

PubMed

Creytens, David; Mentzel, Thomas; Ferdinande, Liesbeth; Lecoutere, Evelyne; van Gorp, Joost; Atanesyan, Lilit; de Groot, Karel; Savola, Suvi; Van Roy, Nadine; Van Dorpe, Jo; Flucke, Uta

2017-11-01

The classification of the until recently poorly explored group of atypical adipocytic neoplasms with spindle cell features, for which recently the term atypical spindle cell lipomatous tumor (ASLT) has been proposed, remains challenging. Recent studies have proposed ASLT as a unique entity with (in at least a significant subset of cases) a specific genetic background, namely deletions/losses of 13q14, including RB1 and its flanking genes RCBTB2, DLEU1, and ITM2B. Similar genetic aberrations have been reported in pleomorphic liposarcomas (PLSs). This prompted us to investigate a series of 21 low-grade adipocytic neoplasms with a pleomorphic lipoma-like appearance, but with atypical morphologic features (including atypical spindle cells, pleomorphic [multinucleated] cells, pleomorphic lipoblasts and poor circumscription), for which we propose the term "atypical" pleomorphic lipomatous tumor (APLT). Five cases of PLS were also included in this study. We used multiplex ligation-dependent probe amplification to evaluate genetic changes of 13q14. In addition, array-based comparative genomic hybridization was performed on 4 APLTs and all PLSs. Multiplex ligation-dependent probe amplification showed consistent loss of RB1 and its flanking gene RCBTB2 in all cases of APLT. This genetic alteration was also present in all PLSs, suggesting genetic overlap, in addition to morphologic overlap, with APLTs. However, array-based comparative genomic hybridization demonstrated more complex genetic alterations with more losses and gains in PLSs compared with APLTs. APLTs arose in the subcutis (67%) more frequently than in the deep (subfascial) soft tissues (33%). With a median follow-up of 42 months, recurrences were documented in 2 of 12 APLTs for which a long follow-up was available. Herein, we also demonstrate that APLTs share obvious overlapping morphologic, immunohistochemical, genetic and clinical characteristics with the recently defined ASLT, suggesting that they are related

Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report of a case and review of the literature.

PubMed

Tajima, Shogo; Koda, Kenji

2017-06-01

Paratesticular sarcoma is rare, but liposarcoma is its most common type. Paratesticular liposarcoma sometimes presents as dedifferentiated liposarcoma. Both high-grade and low-grade dedifferentiation have been reported. Herein, we presented a unique case of a 64-year-old man with low-grade dedifferentiated liposarcoma with prominent myxoid stroma. Well-differentiated liposarcoma components extended along the spermatic cord. The constituent cells of the dedifferentiated component were peculiar in that, they were relatively uniform cells with atypia and did not have pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. These two markers were also expressed in the well-differentiated component. It could therefore be confirmed that this sarcoma is dedifferentiated liposarcoma but is not mixed-type liposarcoma comprising well-differentiated liposarcoma and myxoid liposarcoma.

Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

PubMed Central

2014-01-01

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma.

PubMed

Guttmann, David M; Frick, Melissa A; Carmona, Ruben; Deville, Curtiland; Levin, William P; Berman, Abigail T; Chinniah, Chidambaram; Hahn, Stephen M; Plastaras, John P; Simone, Charles B

2017-08-01

Proton reirradiation for sarcoma has not been previously described. We hypothesized that this strategy would provide favorable toxicity and survival outcomes. Patients with soft tissue sarcoma in a previously-irradiated field were enrolled on a prospective trial of proton reirradiation. The primary endpoint was provider-reported acute toxicity. Secondary endpoints included late toxicities, local control, and overall survival. 23 patients underwent proton reirradiation. Median time between radiation courses was 40.7months (range 10-272). No grade 4-5 toxicities were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade 2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence (13%). There were two grade 3 late wound infections (10%) and one grade 3 late wound complication (5%). Grade 2 late complications included lymphedema (10%), fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year cumulative incidence of local failure was 41% (95% CI [20-63%]). Median overall survival and progression-free survival were 44 and 29months, respectively. In extremity patients, amputation was spared in 7/10 (70%). Proton reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated. While longer follow-up is needed, early survival outcomes in this high-risk population are encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

Pleomorphic adenoma of the palate in a child.

PubMed

Bovino, Brian F; Sohn, Andy; Winston, Daniel

2013-01-01

Presented is a pleomorphic adenoma of the palate in a 12-year-old boy. Pleomorphic adenoma is usually found in adults and is rarely found in patients under 20 years of age. We present initial exam, diagnosis, treatment and a review of literature.

Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.

PubMed

Tanaka, Miwa; Yamazaki, Yukari; Kanno, Yohei; Igarashi, Katsuhide; Aisaki, Ken-ichi; Kanno, Jun; Nakamura, Takuro

2014-07-01

Ewing's sarcoma is a highly malignant bone tumor found in children and adolescents, and the origin of this malignancy is not well understood. Here, we introduced a Ewing's sarcoma-associated genetic fusion of the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ) of long bones collected from late gestational murine embryos. EWS-ETS fusions efficiently induced Ewing's sarcoma-like small round cell sarcoma formation by these cells. Analysis of the eSZ revealed a fraction of a precursor cells that express growth/differentiation factor 5 (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS-ETS-dependent tumor induction. Genes downstream of the EWS-ETS fusion protein were quite transcriptionally active in eSZ cells, especially in regions in which the chromatin structure of the ETS-responsive locus was open. Inhibition of β-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewing's sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewing's sarcoma and provide clues to the histogenesis of Ewing's sarcoma in bone.

High-grade malignant transformation of a radiation-naïve nasopharyngeal angiofibroma.

PubMed

Allensworth, Jordan J; Troob, Scott H; Lanciault, Christian; Andersen, Peter E

2016-04-01

Nasopharyngeal angiofibromas are typically considered benign vascular neoplasms, with descriptions of high-grade sarcomatous change found only in lesions with prior radiotherapy. We describe the first reported case of high-grade malignant change in a nasopharyngeal angiofibroma naive to radiation. A 45-year-old man presented with left-sided nasal congestion and fullness and was found to have a left-sided nasopharyngeal mass with intracranial extension on CT scan. A biopsy of the mass revealed nasopharyngeal angiofibroma. The patient opted for MRI surveillance, which revealed interval growth 3 years later. Decompression surgery revealed only angiofibroma, but resection 9 months later demonstrated high-grade sarcoma and concomitant angiofibroma. The patient had residual disease which progressed through chemoradiation, and is now pursuing clinical trial enrollment. Malignant transformation of nasopharyngeal angiofibroma is extremely rare. As highlighted by this report, high-grade undifferentiated lesions may arise in tumors without previous radiation. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2425-E2427, 2016. © 2016 Wiley Periodicals, Inc.

Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy.

PubMed

Della Badia, Carl; Karini, Homa

2010-01-01

Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Pleomorphic lipoma: A gentle giant of pathology

PubMed Central

Sakhadeo, Uma; Mundhe, Rajesh; DeSouza, Maria A; Chinoy, Roshan F

2015-01-01

Pleomorphic lipoma is a relatively rare adipocytic neoplasm, occurring predominantly in elderly males in the subcutaneous tissues of the neck or shoulder. To the best of our knowledge, only five cases have been reported in which the lesion was intramuscular. We hereby report a case of a 60-year-old female patient, presenting with an intramuscular, posterior shoulder mass. The aspirate showed a giant cell-rich lesion, admixed with short, plump-looking, spindly cells. There was no overt evidence of malignancy; however, the cell cytology was sufficiently atypical to warrant concern. Subsequent excision revealed a classical pleomorphic lipoma on histology with no evidence of malignancy. CD34 staining by immunohistochemistry further supported the diagnosis. Differential diagnosis and the cytological diagnostic pitfalls of pleomorphic lipomas have been discussed with a review of the literature. PMID:26729985

Pleomorphic lipoma: A gentle giant of pathology.

PubMed

Sakhadeo, Uma; Mundhe, Rajesh; DeSouza, Maria A; Chinoy, Roshan F

2015-01-01

Pleomorphic lipoma is a relatively rare adipocytic neoplasm, occurring predominantly in elderly males in the subcutaneous tissues of the neck or shoulder. To the best of our knowledge, only five cases have been reported in which the lesion was intramuscular. We hereby report a case of a 60-year-old female patient, presenting with an intramuscular, posterior shoulder mass. The aspirate showed a giant cell-rich lesion, admixed with short, plump-looking, spindly cells. There was no overt evidence of malignancy; however, the cell cytology was sufficiently atypical to warrant concern. Subsequent excision revealed a classical pleomorphic lipoma on histology with no evidence of malignancy. CD34 staining by immunohistochemistry further supported the diagnosis. Differential diagnosis and the cytological diagnostic pitfalls of pleomorphic lipomas have been discussed with a review of the literature.

PD-L1 (CD274) copy number gain, expression, and immune cell infiltration as candidate predictors for response to immune checkpoint inhibitors in soft-tissue sarcoma

PubMed Central

Budczies, Jan; Mechtersheimer, Gunhild; Denkert, Carsten; Klauschen, Frederick; Jöhrens, Korinna; Endris, Volker; Lier, Amelie; Lasitschka, Felix; Penzel, Roland; Dietel, Manfred; Brors, Benedikt; Gröschel, Stefan; Glimm, Hanno; Schirmacher, Peter; Renner, Marcus; Fröhling, Stefan; Stenzinger, Albrecht

2017-01-01

ABSTRACT Soft-tissue sarcomas (STS) are rare malignancies that account for 1% of adult cancers and comprise more than 50 entities. Current therapeutic options for advanced-stage STS are limited. Immune checkpoint inhibitors targeting the PD-1/PD-L1 signaling axis are being explored as new treatment modality in STS; however, the determinants of response to these agents are largely unknown. Using the sarcoma data set of The Cancer Genome Altas (TCGA) and an independent cohort of untreated high-grade STS, we analyzed DNA copy number status and mRNA expression of PD-L1 in a total of 335 STS cases. Copy number gains (CNG) were detected in 54 TCGA cases (21.1%), of which 21 (8.2%) harbored focal PD-L1 CNG and that were most prevalent in myxofibrosarcoma (35%) and undifferentiated pleomorphic sarcoma (34%). In the untreated high-grade STS cohort, we detected CNG in six cases (7.6%). Analysis of co-amplified genes identified a 5.6-Mb core region comprising 27 genes, including JAK2. Patients with PD-L1 CNG had higher PD-L1 expression compared with STS without CNG (fold change, 1.8; p = 0.02), an effect that was most pronounced in the setting of focal PD-L1 CNG (fold change, 3.0; p = 0.0027). STS with PD-L1 CNG showed a significantly higher mutational load compared with tumors with a diploid PD-L1 locus (median number of mutated genes; 58 vs. 40; p = 3.6E-06), and PD-L1 CNG were associated with inferior survival (HR = 1.82; p = 0.025). In contrast, T-cell infiltrates quantified by mRNA expression of CD3Z were associated with improved survival (HR = 0.88; p = 0.024) and consequently influenced the prognostic power of PD-L1 CNG, with low CD3Z levels conferring poor survival in cases with PD-L1 CNG (HR = 1.8; p = 0.049). These data demonstrate that PD-L1 GNG and elevated expression of PD-L1 occur in a substantial proportion of STS, have prognostic impact that is modulated by T-cell infiltrates, and thus warrant investigation as response predictors for immune checkpoint

PD-L1 (CD274) copy number gain, expression, and immune cell infiltration as candidate predictors for response to immune checkpoint inhibitors in soft-tissue sarcoma.

PubMed

Budczies, Jan; Mechtersheimer, Gunhild; Denkert, Carsten; Klauschen, Frederick; Mughal, Sadaf S; Chudasama, Priya; Bockmayr, Michael; Jöhrens, Korinna; Endris, Volker; Lier, Amelie; Lasitschka, Felix; Penzel, Roland; Dietel, Manfred; Brors, Benedikt; Gröschel, Stefan; Glimm, Hanno; Schirmacher, Peter; Renner, Marcus; Fröhling, Stefan; Stenzinger, Albrecht

2017-01-01

Soft-tissue sarcomas (STS) are rare malignancies that account for 1% of adult cancers and comprise more than 50 entities. Current therapeutic options for advanced-stage STS are limited. Immune checkpoint inhibitors targeting the PD-1/PD-L1 signaling axis are being explored as new treatment modality in STS; however, the determinants of response to these agents are largely unknown. Using the sarcoma data set of The Cancer Genome Altas (TCGA) and an independent cohort of untreated high-grade STS, we analyzed DNA copy number status and mRNA expression of PD-L1 in a total of 335 STS cases. Copy number gains (CNG) were detected in 54 TCGA cases (21.1%), of which 21 (8.2%) harbored focal PD-L1 CNG and that were most prevalent in myxofibrosarcoma (35%) and undifferentiated pleomorphic sarcoma (34%). In the untreated high-grade STS cohort, we detected CNG in six cases (7.6%). Analysis of co-amplified genes identified a 5.6-Mb core region comprising 27 genes, including JAK2 . Patients with PD-L1 CNG had higher PD-L1 expression compared with STS without CNG (fold change, 1.8; p = 0.02), an effect that was most pronounced in the setting of focal PD-L1 CNG (fold change, 3.0; p = 0.0027). STS with PD-L1 CNG showed a significantly higher mutational load compared with tumors with a diploid PD-L1 locus (median number of mutated genes; 58 vs. 40; p = 3.6E-06), and PD-L1 CNG were associated with inferior survival (HR = 1.82; p = 0.025). In contrast, T-cell infiltrates quantified by mRNA expression of CD3Z were associated with improved survival (HR = 0.88; p = 0.024) and consequently influenced the prognostic power of PD-L1 CNG, with low CD3Z levels conferring poor survival in cases with PD-L1 CNG (HR = 1.8; p = 0.049). These data demonstrate that PD-L1 GNG and elevated expression of PD-L1 occur in a substantial proportion of STS, have prognostic impact that is modulated by T-cell infiltrates, and thus warrant investigation as response predictors for immune checkpoint inhibition.

Dedifferentiated liposarcoma of thigh with chondrosarcomatous dedifferentiated component.

PubMed

Yoon, Richard S; Benevenia, Joseph; Beebe, Kathleen S; Hameed, Meera

2010-11-01

Liposarcomas are common soft-issue sarcomas arising predominantly in deep soft tissue and the retroperitoneum with varied mortality and recurrence rates, largely dependent on histologic type. Thought to arise de novo, liposarcomas typically are classified into 5 types based on strict morphologic characteristics: well-differentiated, dedifferentiated, myxoid, round cell, and pleomorphic. More specifically, dedifferentiated liposarcoma, a common type most prevalent in the retroperitoneum, often has 2 distinct components, a well-differentiated lipomatous component and a dedifferentiated nonlipomatous component composed of sarcomas, such as myxofibrosarcomas or other spindle-cell sarcomas. Morphology typically ranges from low- to high-grade components, most commonly exhibiting myxofibrosarcoma and malignant fibrous histiocytoma components. However, the case reported in this article is unique-the dedifferentiated component exhibited only chondrosarcomatous differentiation-and it is, to our knowledge, the first such case to be described.

[Principles of surgery for retroperitoneal sarcoma].

PubMed

Hohenberger, P; Dinter, D; Stroebel, P; Kasper, B; Wenz, F

2014-12-01

The successful treatment of retroperitoneal soft tissue sarcomas requires an experienced team consisting of not only surgeons but also pathologists and radiologists with a high case load in these tumours. The decisive step in the preoperative work-up of these, often late detected, tumours is their reliable grading as well as, if necessary, recognition of the sarcoma subtype as a basis for determining the direction of treatment. Imaging methods provide essential information with regard to the detection of infiltration of neighbouring structures and organs. Magnetic resonance imaging (MRI) is the most suitable method for this purpose. Punch needle biopsy is to be preferred over fine-needle biopsy in all cases for histological confirmation. The surgical standard procedure for the majority of the patients comprises multivisceral resection as principle, with additional colon resection, nephrectomy, and resection of abdominal wall musculature or, respectively, the psoas muscle in order to achieve an R0 resection of the retroperitoneal compartment. If only small margins of clearance are to be expected, a preoperative (neoadjuvant) treatment with radiation and/or chemotherapy even in combination with deep wave hyperthermia for high grade sarcomas should be strongly considered. Adjuvant postoperative radiation therapy often cannot be adequately applied due to the occupation of the former tumour bed by abdominal organs that were displaced by the mass effect, especially the radiation-sensitive small bowel. The optimal treatment strategy for these patients must be discussed in a multidisciplinary tumour board prior to any diagnostic or therapeutic procedure. Georg Thieme Verlag KG Stuttgart · New York.

Assessing the reading level of online sarcoma patient education materials.

PubMed

Patel, Shaan S; Sheppard, Evan D; Siegel, Herrick J; Ponce, Brent A

2015-01-01

Cancer patients rely on patient education materials (PEMs) to gather information regarding their disease. Patients who are better informed about their illness have better health outcomes. The National Institutes of Health (NIH) recommends that PEMs be written at a sixth- to seventh-grade reading level. The purpose of this study was to evaluate the readability of online PEMs of bone and soft-tissue sarcomas and related conditions. We identified relevant online PEMs from the following websites: American Academy of Orthopaedic Surgeons, academic training centers, sarcoma specialists, Google search hits, Bonetumor.org, Sarcoma Alliance, Sarcoma Foundation of America, and Medscape. We used 10 different readability instruments to evaluate the reading level of each website's PEMs. In assessing 72 websites and 774 articles, we found that none of the websites had a mean readability score at or below 7 (seventh grade). Collectively, all websites had a mean readability score of 11.4, and the range of scores was grade level 8.9 to 15.5. None of the PEMs in this study of bone and soft-tissue sarcomas and related conditions met the NIH recommendation for PEM reading levels. Concerted efforts to improve the reading level of orthopedic oncologic PEMs are necessary.

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

PubMed

Kawai, Akira; Umeda, Toru; Wada, Takuro; Ihara, Koichiro; Isu, Kazuo; Abe, Satoshi; Ishii, Takeshi; Sugiura, Hideshi; Araki, Nobuhito; Ozaki, Toshifumi; Yabe, Hiroo; Hasegawa, Tadashi; Tsugane, Shoichiro; Beppu, Yasuo

2005-05-01

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Effectiveness of Radiotherapy in Myxoid Sarcomas Is Associated With a Dense Vascular Pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vreeze, Ronald S.A. de; Jong, Daphne de; Haas, Rick L.

2008-12-01

Purpose: Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularizationmore » pattern of MLS. Methods and Materials: Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. Results: Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all 'pure' MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. Conclusions: Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.« less

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

ClinicalTrials.gov

2013-02-06

AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small

Primary dedifferentiated liposarcoma of the axilla arising in a mixed, well-differentiated and myxoid liposarcoma.

PubMed

Campbell, Garth S; Lawrence, Thomas J; Porter, Scott E; Rezeanu, Luminita

2012-01-01

We describe a case of mixed liposarcoma of the axilla presenting as a high grade undifferentiated sarcoma with areas of well-differentiated and myxoid liposarcoma. MRI demonstrated a lobulated, septated intermuscular mass with marked heterogeneous gadolinium enhancement. A small focus of the tumor demonstrated fat suppressed signal more characteristic of well-differentiated liposarcoma. Pathologic analysis following wide local excision revealed a large, high grade sarcomatous component with highly pleomorphic cells with a thin rim of well-differentiated and myxoid liposarcoma on histologic examination. Dedifferentiated liposarcomas arising outside of the retroperitoneum are very rare, as are dedifferentiated liposarcomas arising from a histologically mixed liposarcoma. In this regard, this case illustrates an unusual combination of tumor location and histology which, to our knowledge, has not previously been reported.

Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms

PubMed Central

Herranen, Anni; Schwarzbach, Armin; Gilbert, Leona

2015-01-01

The spirochaete bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, the most common tick-borne infection in the northern hemisphere. There is a long-standing debate regarding the role of pleomorphic forms in Lyme disease pathogenesis, while very little is known about the characteristics of these morphological variants. Here, we present a comprehensive analysis of B. burgdorferi pleomorphic formation in different culturing conditions at physiological temperature. Interestingly, human serum induced the bacterium to change its morphology to round bodies (RBs). In addition, biofilm-like colonies in suspension were found to be part of B. burgdorferi’s normal in vitro growth. Further studies provided evidence that spherical RBs had an intact and flexible cell envelope, demonstrating that they are not cell wall deficient, or degenerative as previously implied. However, the RBs displayed lower metabolic activity compared with spirochaetes. Furthermore, our results indicated that the different pleomorphic variants were distinguishable by having unique biochemical signatures. Consequently, pleomorphic B. burgdorferi should be taken into consideration as being clinically relevant and influence the development of novel diagnostics and treatment protocols. PMID:25564498

Low-grade myofibroblastic sarcoma of the orbit

PubMed Central

Zhang, Shikun; Ma, Ying; Ma, Tie; Wang, Zhiming

2017-01-01

Abstract Rationale: Low-grade myofibroblastic sarcoma (LGMS) is a malignant lesion composed of myofibroblasts. It is an uncommon tumor of unknown etiology that mainly develops in the bone or soft tissue and is most often reported in the head and neck, particularly in the tongue and oral cavity. Patient concerns: A 2-year-old girl, previously well and with no significant medical history or family history of other diseases, presented with a 2-week painless swelling of the right orbit. Diagnoses: Preoperative computed tomography (CT) revealed a large homogeneous enhanced mass, 21 × 13 mm in size, located on lateral wall of the right orbit with bone absorption. The mass was resected and histopathological examination revealed LGMS of the orbit. Interventions: On May 2016, she underwent surgery without the additional postoperative treatment. Outcomes: The patient's postoperative course was uneventful, and was discharged on the 6th day after surgery. During a year follow-up period, there was no recurrence of the postoperative CT. The patient and her family were satisfied with the result of the surgery. Lessons: Based on clinical characteristics and postoperative CT, we considered the mass may be a benign tumor. We completely resected along the capsule without an extensive surgical margin. However, postoperative histopathology diagnose LGMS, which shows a strong potential for local recurrence and vascular invasion. So we should close observation of the patient's symptoms and sign. If the tumor has invaded adjacent tissues, we will use adjuvant chemotherapy or radiotherapy. PMID:29390454

Sarcoma of the thyroid region mimicking Riedel's thyroiditis

PubMed Central

Torres-Montaner, A; Beltran, M; d Romero; Oliva, H

2001-01-01

Because sarcomas of the anterior lower neck region occur so infrequently, they are not usually considered in the differential diagnosis of Riedel's thyroiditis. Riedel's thyroiditis itself may be confused on clinical grounds alone with malignant neoplasms because of its invasive features. Sarcomatoid carcinoma is the main entity to be discarded in this regard. This is accomplished through histological examination by the finding of carcinomatous areas and/or reactivity with epithelial markers. These features also set apart sarcomatoid carcinoma from true sarcomas. This report concerns a patient with a sarcoma of the anterior lower neck region which was initially suspected to be Riedel's thyroiditis or sarcomatoid carcinoma on clinical and radiological grounds. A peroperative biopsy was interpreted by two independent pathologists as consistent with Riedel's thyroiditis. The subsequent clinical course and postmortem examination demonstrated a high grade sarcoma with metastasis to both lungs and the pleura, and invasion of adjacent neck structures. Nevertheless, some areas of the postmortem material showed a microscopic pattern similar to mediastinal fibrosis, raising the possibility of the malignant transformation of a fibrosclerotic lesion. Key Words: Riedel's thyroiditis • sarcomatoid carcinoma • fibrous histiocytoma • differential diagnosis PMID:11429435

Neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide, and dacarbazine (MAID) regimen for adult high-grade non-small round cell soft tissue sarcomas.

PubMed

Ogura, Koichi; Goto, Takahiro; Imanishi, Jungo; Shinoda, Yusuke; Okuma, Tomotake; Tsuda, Yusuke; Kobayashi, Hiroshi; Akiyama, Toru; Hirata, Makoto; Yamamoto, Aiichiro; Kawano, Hirotaka

2013-02-01

Good local control of high-grade non-small round cell soft tissue sarcomas (NSRCSTSs) has been achieved with significant advances in surgical techniques and radiotherapy. However, the role of chemotherapy remains controversial. Our aim was to investigate the efficacy, feasibility and adverse effects of neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide and dacarbazine (MAID) regimen for NSRCSTSs. We conducted a retrospective review of 40 consecutive patients (29 men, 11 women; median age 47 years) with high-grade NSRCSTSs treated in two referral centers between 2004 and 2009 (median follow-up 38.5 months). Patients with distant or nodal metastases at diagnosis were excluded. The regimen consisted of ifosfamide 2,500 mg/m(2)/6 h (days 1-3), mesna 2,500 mg/m(2)/6 h (days 1-3), tetrahydropyranyl adriamycin 20 mg/m(2)/0.5 h (days 1-3), and dacarbazine 300 mg/m(2)/1 h (days 1-3). Among the 26 evaluable patients, there were 8 with a partial response, 15 with stable disease, and 3 with progressive disease. Two- and 5-year overall survival rates were 92 and 86%, respectively, and corresponding disease-free survival rates were 80 and 77%. All relapses were metastases without local recurrence. Grade 3-4 neutropenia, anemia and thrombocytopenia were observed in 38, 18, and 21 patients, respectively. No serious infectious complications occurred due to the administration of granulocyte colony-stimulating factor and prophylactic antibiotics. No other life-threatening serious adverse events were observed. The modified MAID regimen achieved a better outcome with less serious adverse events than previously reported and is a potential option in the management of NSRCSTSs. Further evaluation with long-term follow-up is required.

Low-fat and fat-free pleomorphic lipomas: a diagnostic challenge.

PubMed

Sachdeva, Mandi P; Goldblum, John R; Rubin, Brian P; Billings, Steven D

2009-07-01

Pleomorphic lipomas are benign tumors that most commonly present as subcutaneous masses in the head and neck, shoulder, or back region of middle-aged to elderly men. They are related to spindle cell lipomas based on shared cytogenetic aberrations and histologic features. When little or no fat is present, the diagnosis can be challenging. A review of 38 pleomorphic lipomas seen in consultation revealed 7 cases in which fat was present in reduced (<5%) amounts (n = 5) or absent (n = 2). Six of 7 cases were from men with a mean age of 59 years. Excluding 1 case where the site was not specified, they all presented as solitary well-circumscribed subcutaneous masses in the head and neck (n = 3) or shoulder (n = 2) region. The seventh case was an intradermal tumor from the nose of a 48-year-old woman. All displayed pleomorphic and multinucleated floret cells interspersed among bland spindle cells and ropey collagen. They were diffusely immunoreactive for CD34. Referring diagnoses, when provided, included myxofibrosarcoma, giant cell fibroblastoma, and granulomatous rosacea for the tumor from the nose; none considered pleomorphic lipomas. When fat is absent or present in reduced amounts, clinical context and identification of classic nonlipogenic components are essential for the diagnosis of pleomorphic lipomas.

Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature.

PubMed

Vallejo-Benítez, Ana; Rodríguez-Zarco, Enrique; Carrasco, Sara Pabón; Pereira-Gallardo, Sofia; Brugal Molina, Javier; García-Escudero, Antonio; Robles Frías, Antonio; Marcilla, David; González-Cámpora, Ricardo

2017-10-01

DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10-30%) and of varying intensity (1+ to 2+). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT).

PubMed

Scalici Gesolfo, Cristina; Serretta, Vincenzo; Di Maida, Fabrizio; Giannone, Giulio; Barresi, Elisabetta; Franco, Vito; Montironi, Rodolfo

2017-02-01

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due to the clinical behavior of this tumor, in spite of its benign nature, review of the surgical margins and close follow up after partial nephrectomy are mandatory. Copyright © 2016. Published by Elsevier GmbH.

The Neurological Compromised Spine Due to Ewing Sarcoma. What First: Surgery or Chemotherapy? Therapy, Survival, and Neurological Outcome of 15 Cases With Primary Ewing Sarcoma of the Vertebral Column.

PubMed

Mirzaei, Lida; Kaal, Suzanne E J; Schreuder, Hendrik W B; Bartels, Ronald H M A

2015-11-01

The vertebral column is an infrequent site of primary involvement in Ewing sarcoma. Yet when Ewing sarcoma is found in the spine, the urge for decompression is high because of the often symptomatic compression of neural structures. It is unclear in alleviating a neurological deficit whether chemotherapy is preferred over decompressive laminectomy. To underline, in this case series, the efficiency of initial chemotherapy before upfront surgery in the setting of high-grade spinal cord or cauda equina compression of primary Ewing sarcoma. Fifteen patients with Ewing sarcoma primarily located in the spine were treated at our institution between 1983 and 2015. Localization, neurological deficit expressed as Frankel grade, and outcome expressed as Rankin scale before and after initial chemotherapy, the recurrence rate, and overall survival were evaluated. The multidisciplinary approach of 1 case will be discussed in detail. Nine patients (60%) were female. The age at presentation was 15.0 ± 5.5 years (range: 0.9-22.8 years). Ten patients (67%) were initially treated with chemotherapy, and 1 patient (7%) was treated primarily with radiotherapy followed by chemotherapy. The remaining 4 patients (27%) were initially treated with decompressive surgery. All patients treated primarily nonsurgically improved neurologically at follow-up, showing the importance of chemotherapy as an effective initial treatment option. Adequate and quick decompression of neural structures with similar results can be achieved by chemotherapy and radiotherapy, avoiding the local spill of malignant cells.

Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

PubMed

Chiosea, Simion I; Thompson, Lester D R; Weinreb, Ilan; Bauman, Julie E; Mahaffey, Alyssa M; Miller, Caitlyn; Ferris, Robert L; Gooding, William E

2016-10-15

The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society. �

Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, A.E.; Steinberg, S.M.; Culnane, M.

1989-09-01

We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured bymore » a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone.« less

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas.

PubMed

Hélias-Rodzewicz, Zofia; Pérot, Gaëlle; Chibon, Frédéric; Ferreira, Céline; Lagarde, Pauline; Terrier, Philippe; Coindre, Jean-Michel; Aurias, Alain

2010-12-01

In a series of 404 adult soft tissue sarcomas, analyzed by array-CGH, we have observed in approximately 10% of them a genomic amplification of either chromosome bands 11q22 or 3p12. These two amplicons likely target the YAP1 and VGLL3 genes, respectively. Both genes encode proteins that are cofactors of the TEAD family of transcription factors. Very good correlations between amplification and expression levels were observed. Welch test analyses of transcriptome data demonstrate that tumors with amplicons share a large set of upregulated and downregulated genes. Inhibition of YAP1 and VGLL3 in cell lines with these amplifications/overexpressions leads to similar phenotypes: decrease of proliferation rate, and to a lesser extent decrease of migration properties. These data, and the fact that these amplicons are observed either in de-differentiated liposarcomas or in undifferentiated pleomorphic sarcomas, suggest that these genetics events could be involved in oncogenesis and progression of soft tissue sarcomas. © 2010 Wiley-Liss, Inc.

A randomized phase II/III trial of perioperative chemotherapy with adriamycin plus ifosfamide versus gemcitabine plus docetaxel for high-grade soft tissue sarcoma: Japan Clinical Oncology Group Study JCOG1306.

PubMed

Kataoka, Kozo; Tanaka, Kazuhiro; Mizusawa, Junki; Kimura, Aya; Hiraga, Hiroaki; Kawai, Akira; Matsunobu, Tomoya; Matsumine, Akihiko; Araki, Nobuhito; Oda, Yoshinao; Fukuda, Haruhiko; Iwamoto, Yukihide

2014-08-01

A randomized Phase II/III trial was planned to commence in March 2014. Perioperative chemotherapy with adriamycin plus ifosfamide is the current standard treatment for T2bN0M0 high-grade non-round cell soft tissue sarcoma. The purpose of this study is to confirm the non-inferiority of perioperative chemotherapy with gemcitabine and docetaxel to adriamycin plus ifosfamide for patients with T2bN0M0 or any TN1M0 non-round cell soft tissue sarcoma in the extremities and body wall. A total of 140 patients will be accrued from 28 Japanese institutions over 6 years. The primary endpoint in the Phase II part is the proportion of completion of pre-operative chemotherapy without progressive disease and overall survival in the Phase III part. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, pathological response rate, proportion of preservation of diseased limbs, disease control rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000013175 [http://www.umin.ac.jp/ctr/index.htm]. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas.

PubMed

Feng, Qi; Guo, Peng; Wang, Jin; Zhang, Xiaoyu; Yang, Hui-Chai; Feng, Jian-Gang

2018-03-01

Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes the growth and metastasis of solid tumors. The aim of the present study was to examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to determine their expression is correlated with unfavorable outcomes. Levels of SDF-1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using immunohistochemical and immunofluorescence staining. Potential associations between the expression of SDF-1 and VEGF and various clinical parameters were analyzed using Pearson's χ 2 test and the Spearman-rho test. Additionally, univariate and multivariate Cox regression analyses were used to identify potential prognostic factors, and the Kaplan-Meier method was used to analyze the overall survival rates of patients. Low SDF-1 and VEGF expression was detected in 20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients, respectively. Levels of SDF-1 and VEGF proteins were significantly associated with histological grade (P<0.05), metastasis (P<0.05) and American Joint Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF expression were positively correlated with each other (P<0.001). Univariate analysis also indicated that VEGF expression was associated with shorter overall survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1 expression was associated with shorter patient survival rates (P<0.05). Finally, both SDF-1 and VEGF expression were associated with various characteristics of synovial sarcoma. Therefore, SDF-1 expression may be a potential independent prognostic indicator in patients with synovial sarcomas.

Pitfalls in soft tissue sarcoma imaging: chronic expanding hematomas.

PubMed

Jahed, Kiarash; Khazai, Behnaz; Umpierrez, Monica; Subhawong, Ty K; Singer, Adam D

2018-01-01

Solid or nodular enhancement is typical of soft tissue sarcomas although high grade soft tissue sarcomas and those with internal hemorrhage often appear heterogeneous with areas of nonenhancement and solid or nodular enhancement. These MRI findings often prompt an orthopedic oncology referral, a biopsy or surgery. However, not all masses with these imaging findings are malignant. We report the multimodality imaging findings of two surgically proven chronic expanding hematomas (CEH) with imaging features that mimicked sarcomas. A third case of nonenhancing CEH of the lower extremity is also presented as a comparison. It is important that in the correct clinical scenario with typical imaging findings, the differential diagnosis of a chronic expanding hematoma be included in the workup of these patients. An image-guided biopsy of nodular tissue within such masses that proves to be negative for malignancy should not necessarily be considered discordant. A correct diagnosis may prevent a morbid unnecessary surgery and may indicate the need for a conservative noninvasive follow-up with imaging.

Immunohistochemichal Assessment of the CrkII Proto-oncogene Expression in Common Malignant Salivary Gland Tumors and Pleomorphic Adenoma.

PubMed

Askari, Mitra; Darabi, Masoud; Jahanzad, Esa; Mostakhdemian Hosseini, Zahra; Musavi Chavoshi, Marjan; Darabi, Maryam

2015-01-01

Background and aims. Various morphologies are seen in different salivary gland tumorsor within an individual tumor, and the lesions show divers biological behaviors. Experimental results support the hypothesis that increased CrkII proto-oncogene is associated with cytokine-induced tumor initiation and progression by altering cell motility signaling pathway. The aim of this study was to assess the CrkII expression in common malignant salivary gland tumors and pleomorphic ade-noma. Materials and methods. Immunohistochemical analysis of CrkII expression was performed on paraffin blocks of 64 car-cinomas of salivary glands, 10 pleomorphic adenomas, and 10 normal salivary glands. Biopsies were subjected to immu-nostaining with EnVision detection system using monoclonal anti-CrkII. Evaluation of immunoreactivity of CrkII was based on the immunoreaction intensity and percentage of stained tumor cells which were scored semi-quantitatively on a scale with four grades 0 to 3. Kruskal-wallis test and additional Mann-Whitney statistical test were used for analysis of CrkII expression levels. Results. Increased expression of CrkII was seen (P=0.005) in malignant tumors including: mucoepidermoid carcinoma, adenoid cystic carcinoma, and carcinoma ex pleomorphic adenoma, but CrkII expression in acinic cell carcinoma was weak. CrkII expression in pleomorphic adenoma was weak or negative. A weak staining was sparsely seen in normal acinar serous cell. Conclusion. Increased expression of CrkII and its higher intensity of staining in tumors with more aggressive biologic behavior in carcinomas of salivary gland is consistent with a role for this proto-oncogene in salivary gland tumorigenesis and cancer progression.

Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas.

PubMed

Venigalla, Sriram; Nead, Kevin T; Sebro, Ronnie; Guttmann, David M; Sharma, Sonam; Simone, Charles B; Levin, William P; Wilson, Robert J; Weber, Kristy L; Shabason, Jacob E

2018-03-15

Soft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS). Patients aged ≥18 years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis. Of 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS. In this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to

Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft tissue sarcomas.

PubMed

Le Guellec, S; Lesluyes, T; Sarot, E; Valle, C; Filleron, T; Rochaix, P; Valentin, T; Pérot, G; Coindre, J-M; Chibon, F

2018-05-31

Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management. A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated. CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared to FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI 1.25-15.72). CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with

Primary Dedifferentiated Liposarcoma of the Axilla Arising in a Mixed, Well-differentiated and Myxoid Liposarcoma

PubMed Central

Campbell, Garth S.; Lawrence, Thomas J.; Porter, Scott E.; Rezeanu, Luminita

2012-01-01

We describe a case of mixed liposarcoma of the axilla presenting as a high grade undifferentiated sarcoma with areas of well-differentiated and myxoid liposarcoma. MRI demonstrated a lobulated, septated intermuscular mass with marked heterogeneous gadolinium enhancement. A small focus of the tumor demonstrated fat suppressed signal more characteristic of well-differentiated liposarcoma. Pathologic analysis following wide local excision revealed a large, high grade sarcomatous component with highly pleomorphic cells with a thin rim of well-differentiated and myxoid liposarcoma on histologic examination. Dedifferentiated liposarcomas arising outside of the retroperitoneum are very rare, as are dedifferentiated liposarcomas arising from a histologically mixed liposarcoma. In this regard, this case illustrates an unusual combination of tumor location and histology which, to our knowledge, has not previously been reported. PMID:22690275

Ewing’s sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors

PubMed Central

Tanaka, Miwa; Yamazaki, Yukari; Kanno, Yohei; Igarashi, Katsuhide; Aisaki, Ken-ichi; Kanno, Jun; Nakamura, Takuro

2014-01-01

Ewing’s sarcoma is a highly malignant bone tumor found in children and adolescents, and the origin of this malignancy is not well understood. Here, we introduced a Ewing’s sarcoma–associated genetic fusion of the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ) of long bones collected from late gestational murine embryos. EWS-ETS fusions efficiently induced Ewing’s sarcoma–like small round cell sarcoma formation by these cells. Analysis of the eSZ revealed a fraction of a precursor cells that express growth/differentiation factor 5 (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS-ETS–dependent tumor induction. Genes downstream of the EWS-ETS fusion protein were quite transcriptionally active in eSZ cells, especially in regions in which the chromatin structure of the ETS-responsive locus was open. Inhibition of β-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewing’s sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewing’s sarcoma and provide clues to the histogenesis of Ewing’s sarcoma in bone. PMID:24911143

Gynecological sarcomas: what's new in 2018, a brief review of published literature.

PubMed

Gantzer, Justine; Ray-Coquard, Isabelle

2018-05-26

In this article, we focus on recent published data (2017) on the management of gynecologic sarcomas. The most significant data published in 2017 develop definition of a new molecular subtype of high grade endometrial stromal sarcoma (ESS) using molecular technics added to histological analysis. The identification of a new translocation on presumed uterine leiomyosarcoma (LMS) points to refinement of nosological classification, with fragmentation of even rare tumors into distinct molecular entities: gynecologic sarcomas are now distinguished into distinct entities from a heterogeneous group of tumors. Other articles have discussed the real incidence of unsuspected sarcomas after fibroid mini-invasive surgery and evaluate the risk of relapse and dissemination after morcellation. Among several criteria, preoperative imagery could become a useful tool. For systemic treatment, no clinical trials changing practices were published, only one positive nonrandomized phase II with carboplatin and pegylated liposomal doxorubicin (PLD) in the treatment of uterine sarcomas after the conventional first line, especially in LMSs and ESSs. Many articles were published on this confidential domain in oncology demonstrating interests on rare sarcomas. All specialties were represented in the literature, even though we are still waiting for urgent improvements in early diagnosis and therapeutic strategies to transform the poor prognostic of these tumors.

NKX2.2 is a useful immunohistochemical marker for Ewing sarcoma.

PubMed

Yoshida, Akihiko; Sekine, Shigeki; Tsuta, Koji; Fukayama, Masashi; Furuta, Koh; Tsuda, Hitoshi

2012-07-01

Ewing sarcoma is a high-grade round cell sarcoma that affects bones and soft tissues in children and young adults. Its diagnosis can be challenging, and the differential diagnoses include a wide variety of small round cell tumors. CD99 and FLI-1 are the currently accepted immunohistochemical markers for Ewing sarcoma, but their accuracy has been controversial. NKX2.2 is a homeodomain-containing transcription factor that plays a critical role in neuroendocrine/glial differentiation. The NKX2.2 gene was recently identified as a target of EWS-FLI-1, the fusion protein specific to Ewing sarcoma, and was shown to be differentially upregulated in Ewing sarcoma on the basis of array-based gene expression analysis. However, the immunohistochemical diagnostic potential of this marker has not been tested. We immunostained representative sections of 30 genetically confirmed Ewing sarcomas and 130 non-Ewing small round cell tumors by using an antibody to NKX2.2. Nuclear staining in at least 5% of the cells was deemed positive. Twenty-eight (93%) of the 30 Ewing sarcomas were positive for NKX2.2. The staining was diffuse (>50%) in all the positive cases and was moderate or strong in intensity for most cases (25 of 28). NKX2.2 was also positive in 14 non-Ewing tumors, including all the olfactory neuroblastomas and a minor subset of small cell carcinomas, synovial sarcomas, mesenchymal chondrosarcomas, and malignant melanomas. All the other non-Ewing tumors tested were negative for this marker. NKX2.2 is a valuable marker for Ewing sarcoma, with a sensitivity of 93% and a specificity of 89%, and aids in the differential diagnosis of small round cell tumors.

Pneumothorax as adverse event in patients with lung metastases of soft tissue sarcoma treated with pazopanib: a single reference centre case series.

PubMed

Verschoor, Arie J; Gelderblom, Hans

2014-01-01

Recently, the phase III PALETTE study introduced pazopanib (Votrient®) as treatment for adult patients with locally advanced or metastatic non-liposarcoma soft tissue sarcoma after prior treatment with doxorubicin and/or ifosfamide. Pneumothorax was reported as adverse event in 8 of 246 treated patients (3.3%) in that study. This case series presents the incidence and clinic of this complication in the Leiden University Medical Centre. Forty-three patients were treated with pazopanib of which six patients (14.0%) developed a pneumothorax. These six patients were treated for malignant peripheral nerve sheath tumour, angiosarcoma, synovial sarcoma, fibromyxomatoid sarcoma, pleomorphic sarcoma and endometrial stromal sarcoma. All six patients had subpleural pulmonary or pleural metastases at the start of pazopanib and the pneumothorax developed during or shortly after treatment with pazopanib and was difficult to treat. The incidence reported by us is higher than the incidence in the PALETTE study. Trials with pazopanib in renal cell carcinoma, urothelial carcinoma and cervix carcinoma did not report pneumothorax as an adverse event, suggesting pneumothorax as a specific adverse event in soft tissue sarcoma patients treated with pazopanib. This may be related to the fact that there is often pleural metastatic involvement and cystic degeneration due to pazopanib treatment may add to the risk. The risk of an, often difficult to treat, pneumothorax during pazopanib therapy should be discussed with the patient before initiation of treatment for a pulmonary metastasized sarcoma and physicians should be alert to the occurrence of such an event.

The role of radiology in paediatric soft tissue sarcomas

PubMed Central

van Rijn, R.; McHugh, K.

2008-01-01

Abstract Paediatric soft tissue sarcomas (STS) are a group of malignant tumours that originate from primitive mesenchymal tissue and account for 7% of all childhood tumours. Rhabdomyosarcomas (RMS) and undifferentiated sarcomas account for approximately 50% of soft tissue sarcomas in children and non-rhabdomyomatous soft tissue sarcomas (NRSTS) the remainder. The prognosis and biology of STS tumours vary greatly depending on the age of the patient, the primary site, tumour size, tumour invasiveness, histologic grade, depth of invasion, and extent of disease at diagnosis. Over recent years, there has been a marked improvement in survival rates in children and adolescents with soft tissue sarcoma and ongoing international studies continue to aim to improve these survival rates whilst attempting to reduce the morbidity associated with treatment. Radiology plays a crucial role in the initial diagnosis and staging of STS, in the long term follow-up and in the assessment of many treatment related complications. We review the epidemiology, histology, clinical presentation, staging and prognosis of soft tissue sarcomas and discuss the role of radiology in their management. PMID:18442956

Pleomorphic Structures in Human Blood Are Red Blood Cell-Derived Microparticles, Not Bacteria.

PubMed

Mitchell, Adam J; Gray, Warren D; Schroeder, Max; Yi, Hong; Taylor, Jeannette V; Dillard, Rebecca S; Ke, Zunlong; Wright, Elizabeth R; Stephens, David; Roback, John D; Searles, Charles D

2016-01-01

Red blood cell (RBC) transfusions are a common, life-saving therapy for many patients, but they have also been associated with poor clinical outcomes. We identified unusual, pleomorphic structures in human RBC transfusion units by negative-stain electron microscopy that appeared identical to those previously reported to be bacteria in healthy human blood samples. The presence of viable, replicating bacteria in stored blood could explain poor outcomes in transfusion recipients and have major implications for transfusion medicine. Here, we investigated the possibility that these structures were bacteria. Flow cytometry, miRNA analysis, protein analysis, and additional electron microscopy studies strongly indicated that the pleomorphic structures in the supernatant of stored RBCs were RBC-derived microparticles (RMPs). Bacterial 16S rDNA PCR amplified from these samples were sequenced and was found to be highly similar to species that are known to commonly contaminate laboratory reagents. These studies suggest that pleomorphic structures identified in human blood are RMPs and not bacteria, and they provide an example in which laboratory contaminants may can mislead investigators.

Bone Sarcoma Pathology: Diagnostic Approach for Optimal Therapy.

PubMed

Rosenberg, Andrew E

2017-01-01

The pathologic interpretation of malignant bone tumors is one of the more challenging areas in surgical pathology. This is based on the reality that primary bone sarcomas are uncommon, demonstrate significant morphologic heterogeneity, and have a broad spectrum of biology. Accordingly, it is difficult for pathologists to acquire the necessary experience to confidently and accurately diagnose bone sarcomas. The task is further complicated by the fact that it requires the integration of clinical and radiologic information into the diagnostic process. Lastly, molecular aberrations in sarcomas are being newly discovered and their identification is often critical to make specific diagnoses. The pathologist's role in guiding optimal treatment in biopsy specimens is to make an accurate diagnosis and provide the grade and molecular aberrations when appropriate. The pathology report of resected tumors must confirm this information and assess the surgical resection margins and the percentage of necrosis if the sarcoma has been treated with neoadjuvant systemic therapy.

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

PubMed Central

Kalinich, John F.; Emond, Christy A.; Dalton, Thomas K.; Mog, Steven R.; Coleman, Gary D.; Kordell, Jessica E.; Miller, Alexandra C.; McClain, David E.

2005-01-01

Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys. PMID:15929896

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas

PubMed Central

Huang, Xin; Park, Haein; Greene, Joseph; Zhou, Sophia X.; Albert, Catherine M.; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V.; Loeb, David M.; Cairo, Mitchell S.; Zhou, Xianzheng

2015-01-01

Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients. PMID:26173023

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.

PubMed

Huang, Xin; Park, Haein; Greene, Joseph; Pao, James; Mulvey, Erin; Zhou, Sophia X; Albert, Catherine M; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V; Loeb, David M; Cairo, Mitchell S; Zhou, Xianzheng

2015-01-01

Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.

[Grading of gynecological tumors : Current aspects].

PubMed

Horn, L-C; Mayr, D; Brambs, C E; Einenkel, J; Sändig, I; Schierle, K

2016-07-01

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3‑tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.

Atypical pleomorphic neoplasms of the pineal gland: Case report and review of the literature.

PubMed

Praver, M; D'Amico, R; Arraez, C; Zacharia, B E; Varma, H; Goldman, J E; Bruce, J N; Canoll, P

2015-01-01

Pineal region tumors are rare and diverse. Among them exist reports of pleomorphic xanthroastrocytoma (PXA) and pleomorphic granular cell astrocytoma (PGCA) of the pineal gland. These related tumors are remarkably similar sharing pleomorphic histologic features with only minor immunohistochemical and ultrastructural differences. We present a case of a 42-year old right-handed woman presented with a longstanding history of migraine headaches which had worsened over the two months leading up to her hospitalization. MRI revealed a 1.7 × 1.3 × 1.6 cm intensely enhancing lesion originating in the pineal gland. The tumor closely resembled PGCA but did not strictly fit the diagnostic requirements of either PGCA or PXA. The present case highlights the exotic nature of pineal region tumors with pleomorphic cell histology. Given the diverse range of tumors encountered in the pineal region, pathological confirmation is mandatory. Favorable clinical outcomes demonstrate that surgical resection alone can yield excellent long-term results for tumors falling within the spectrum of pleomorphic lesions of the pineal gland.

Aggressive behavior and anaplasia in pleomorphic xanthoastrocytoma: a plea for a revision of the current WHO classification.

PubMed

Kahramancetin, Nesibe; Tihan, Tarik

2013-11-01

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm that commonly affects children and young adults, and presents with seizures. PXA is typically supratentorial with a predilection to the temporal lobe, and often involves the cortex and the meninges. PXAs have a favorable prognosis with a 10-year survival probability of >70%, and are WHO grade II neoplasms. Recent observations and studies demonstrate that PXAs are clinically, histologically and genetically distinct. Some PXAs recur and exhibit aggressive clinical behavior. In such cases, certain histological and clinical factors could account for the aggressive behavior. However, the histological features that predict adverse outcome are poorly defined. In the current WHO classification of CNS tumors, there is no option for a high-grade PXA, even if the tumor had numerous recurrences and poor outcome. In this review, we focus on aggressive clinical behavior and anaplasia in PXA, and discuss how our current experience suggests modifications in the current WHO classification. We also review recent discoveries on the molecular characteristics of PXA that could help us better understand their biological behavior.

Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demizu, Yusuke, E-mail: y_demizu@nifty.com; Jin, Dongcun; Sulaiman, Nor Shazrina

Purpose: To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials: From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results: The median patient age was 67 years (range 18-87). The median planning targetmore » volume (PTV) was 455 cm{sup 3} (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm{sup 3} were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm{sup 3} were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). Conclusions: Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic

Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis.

PubMed

Demizu, Yusuke; Jin, Dongcun; Sulaiman, Nor Shazrina; Nagano, Fumiko; Terashima, Kazuki; Tokumaru, Sunao; Akagi, Takashi; Fujii, Osamu; Daimon, Takashi; Sasaki, Ryohei; Fuwa, Nobukazu; Okimoto, Tomoaki

2017-06-01

To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm 3 (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm 3 were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm 3 were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a longer follow-up period is needed to confirm these results

The Successful Treatment of Pulmonary Pleomorphic Carcinoma with Pembrolizumab: A Case Report

PubMed Central

Matsumoto, Yoko; Miura, Tamaki; Horiuchi, Hajime; Usui, Kazuhiro

2017-01-01

Pulmonary pleomorphic carcinomas are rare malignant tumors, and no standard treatments have been established. We herein report the successful treatment of a patient with pulmonary pleomorphic carcinoma with pembrolizumab. A 51-year-old man who was a current smoker presented to our hospital due to dyspnea and hemosputum. Chest X-ray showed right-sided pneumothorax with pleural effusion; chest tube drainage was therefore performed. Computed tomography after chest tube drainage showed a cavitary nodule in the right upper lobe and right hilar and bilateral mediastinal lymphadenopathy. Surgery was performed for the diagnosis and treatment. He was eventually diagnosed with pulmonary pleomorphic carcinoma corresponding to clinical stage IVB (cT2aN2M1c [PLE, ADR, HEP]). The giant cells strongly expressed programmed death ligand-1, and the tumor proportion score was more than 50%. Therefore, pembrolizumab was introduced as the first-line therapy. After 3 cycles of pembrolizumab, his right hilar and bilateral mediastinal lymphadenopathy and pleural dissemination notably decreased. Pembrolizumab might be an effective therapy for pulmonary pleomorphic carcinoma. PMID:28878661

Sarcoma of the prostate: a single institutional review.

PubMed

Janet, Nguyen L; May, Abdel-Wahab; Akins, Robin S

2009-02-01

We report the management and outcome of prostate sarcoma at 1 institution and analyze factors that may determine prognosis. The medical records of 10 patients with prostate sarcoma were reviewed to identify symptoms at presentation, diagnostic procedures, and staging methods. Histology, grade, tumor size, stage, and treatment modality were analyzed. Overall survival was assessed. Five patients had rhabdomyosarcoma (RMS) and five had other subtypes, including two with carcinosarcoma, two with high-grade sarcoma not-otherwise-specified, and one with leiyomyosarcoma. Eight patients presented with locally advanced disease and two with metastatic disease.The two metastatic patients received chemotherapy, and one also had hormonal ablation therapy. Of the eight with local disease, two had neoadjuvant chemotherapy and surgery, one had surgery alone, one had surgery and postoperative radiation, one had radiation alone, and three had chemoradiation.Chemotherapy consisted of vincristine, adriamycin, and cyclophosphomide for rhabdomyosarcoma and of cisplatin, adriamycin, and ifosphamide for the other subtypes. Radiation dose ranged from 40 Gy to 55.8 Gy.The median survival follow-up of the study is 46.5 months. The median survival for the rhabdomyosarcoma subgroup and nonrhabdomyosarcoma subroup is 142 months and 24 months, respectively. There were three deaths, of which two had metastatic disease at presentation and one later developed distant metastases after having surgery alone. One patient developed a local recurrence 47 months after chemoradiation and was successfully salvaged with surgery. In terms of tumor-related factors, the histologic subtype of prostate sarcoma appears to have prognostic significance. The overall survival for adults with non-RMS histologies is poor with a median survival of only 2 years. Pediatric patients with RMS faired much better with a median survival of over 10 years. We did not find any difference in outcome with regard to grade or tumor

Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bahig, Houda; Roberge, David, E-mail: david.roberge.chum@ssss.gouv.qc.ca; Bosch, Walter

Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a singlemore » observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm{sup 3} (7-413 cm{sup 3}), 280 cm{sup 3} and 360 cm{sup 3}. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm{sup 3} (24-565 cm{sup 3}) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm{sup 3} (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm{sup 3}, respectively. There were 3 large tumors with >30 cm{sup 3} of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant

Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity.

PubMed

Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; Delaney, Thomas F; Abrams, Ross A; Indelicato, Danny J; Baldini, Elizabeth H; Hitchcock, Ying; Kirsch, David G; Kozak, Kevin R; Wolfson, Aaron; Wang, Dian

2013-06-01

Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm(3) (7-413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm(3) (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. Copyright © 2013 Elsevier Inc. All rights

Electrical stimulation treatment for facial palsy after revision pleomorphic adenoma surgery

PubMed Central

Goldie, Simon; Sandeman, Jack; Cole, Richard; Dennis, Simon; Swain, Ian

2016-01-01

Surgery for pleomorphic adenoma recurrence presents a significant risk of facial nerve damage that can result in facial weakness effecting patients’ ability to communicate, mental health and self-image. We report two case studies that had marked facial weakness after resection of recurrent pleomorphic adenoma and their progress with electrical stimulation. Subjects received electrical stimulation twice daily for 24 weeks during which photographs of expressions, facial measurements and Sunnybrook scores were recorded. Both subjects recovered good facial function demonstrating Sunnybrook scores of 54 and 64 that improved to 88 and 96, respectively. Neither subjects demonstrated adverse effects of treatment. We conclude that electrical stimulation is a safe treatment and may improve facial palsy in patients after resection of recurrent pleomorphic adenoma. Larger studies would be difficult to pursue due to the low incidence of cases. PMID:27106613

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma.

PubMed

Ballo, Matthew T; Zagars, Gunar K; Cormier, Janice N; Hunt, Kelly K; Feig, Barry W; Patel, Shreyaskumar R; Pisters, Peter W T

2004-04-01

To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.

Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

PubMed

Ohashi, R; Matsubara, M; Watarai, Y; Yanagihara, K; Yamashita, K; Tsuchiya, S-I; Takei, H; Naito, Z

2017-04-01

Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples. © 2016 John Wiley & Sons Ltd.

Electrical stimulation treatment for facial palsy after revision pleomorphic adenoma surgery.

PubMed

Goldie, Simon; Sandeman, Jack; Cole, Richard; Dennis, Simon; Swain, Ian

2016-04-22

Surgery for pleomorphic adenoma recurrence presents a significant risk of facial nerve damage that can result in facial weakness effecting patients' ability to communicate, mental health and self-image. We report two case studies that had marked facial weakness after resection of recurrent pleomorphic adenoma and their progress with electrical stimulation. Subjects received electrical stimulation twice daily for 24 weeks during which photographs of expressions, facial measurements and Sunnybrook scores were recorded. Both subjects recovered good facial function demonstrating Sunnybrook scores of 54 and 64 that improved to 88 and 96, respectively. Neither subjects demonstrated adverse effects of treatment. We conclude that electrical stimulation is a safe treatment and may improve facial palsy in patients after resection of recurrent pleomorphic adenoma. Larger studies would be difficult to pursue due to the low incidence of cases. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

Intraosseous pleomorphic adenoma: case report and review of the literature.

PubMed

Aver-De-Araujo, L M; Chaves-Tarquinio, S B; Neuzling-Gomes, A P; Etges, A

2002-01-01

Pleomorphic adenoma is the most common neoplasm of the salivary glands, affecting mainly the parotid gland. The preferential intraoral site of this tumor is the palate. A case of a 31-year-old woman with an intraosseous pleomorphic adenoma located in the maxilla (left paramedian region), showing an approximate evolution of one year is reported. The present intraosseous case represents a rare location, with the tumor probably originating from glandular epithelial remnants captured during embryogenesis. In a review of the literature of 142 cases of intragnathic localization (24% in the maxilla) are identified. A slight predominance of women was observed (56%), with 55% of the patients being affected during the 5th to 7th decade of life. The tumors were malignant in 94% of the cases, with special predominance of mucoepidermoid carcinoma (65%). Intraosseous pleomorphic adenomas are rare, with the present patient being the 6th case reported in the literature and the second found in the maxilla. Mean age of the 5 previously reported cases was 58.8 years.

Dedifferentiated liposarcoma with lipoma-like well-differentiated liposarcoma: clinicopathological study of 30 cases, with particular attention to the comingling pattern of well- and dedifferentiated components: a proposal for regrouping of the present subclassification of well-differentiated liposarcoma and dedifferentiated liposarcoma.

PubMed

Iwasa, Yoko; Nakashima, Yasuaki

2013-02-01

Dedifferentiated liposarcoma (DDL) is defined as nonlipogenic sarcoma, with an abrupt transition from coexisting well-differentiated liposarcoma (WDL). However, intermingled transition in a mosaic pattern between WDL and DDL is not infrequently encountered. Here, the authors review clinicopathological features of 30 cases of DDL associated with lipoma-like WDL. Histological examination revealed 20 tumors that showed an abrupt transition between WDL and DDL. Among these, 13 tumors showed high-grade spindle-cell sarcoma having histological features of unclassified malignant fibrous histiocytoma (MFH)-like sarcoma (high-grade DDL [HDDL]). The remaining 7 tumors showed moderate cellular spindle-cell proliferation with mild nuclear atypia and scant mitotic figures (low-grade DDL [LDDL]). The other 10 tumors showed intermingled transition between WDL and DDL. The interface between these 2 components overlapped, resulting in frequent occurrence of a lipogenic spindle-cell component (comingling DDL). Based on the cellularity and nuclear atypia of the spindle-cell components, there were 7 comingling HDDLs and 3 comingling LDDLs. The histology of comingling LDDL simulated an admixture of spindle-cell liposarcoma and LDDL, and distinction from each other was practically difficult. The histology of comingling HDDL simulated pleomorphic liposarcoma. Follow-up data, available for 23 patients (median, 39 months), showed that 2 patients died of tumor (both had HDDL), and 1 patient died of unrelated disease; 8 patients were alive with recurrent or metastatic diseases (3 HDDLs, 3 LDDLs, and 2 comingling HDDLs). Statistical analysis by Fisher's exact test showed no correlation between histological subtypes (HDDL and LDDL, and typical DDL and comingling DDL).

Anthracycline-induced cardiotoxicity in patients with paediatric bone sarcoma and soft tissue sarcoma.

PubMed

Bini, Ilaria; Asaftei, Sebastian D; Riggi, Chiara; Tirtei, Elisa; Manicone, Rosaria; Biasin, Eleonora; Basso, Maria Eleonora; Agnoletti, Gabriella; Fagioli, Franca

2017-11-01

Anthracycline cardiotoxicity is an important side-effect in long-term childhood cancer survivors. We evaluated the incidence of and factors associated with anthracycline cardiotoxicity in a population of patients diagnosed with bone or soft tissue sarcoma. Materials and methods We retrospectively enrolled patients diagnosed with bone or soft tissue sarcoma, from 1995 to 2011, treated with anthracycline chemotherapy at our Centre and with a follow-up echocardiography carried out ⩾3 years from cardiotoxic therapy completion. Cardiac toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0. A total of 82 patients were eligible. The median age at treatment was 11.9 years (1.44-18). We evaluated the median cumulative anthracycline dose, age at treatment, sex, thoracic radiotherapy, hematopoietic stem cell transplantation, and high-dose cyclophosphamide treatment as possible risk factors for cardiotoxicity. The median cumulative anthracycline dose was 390.75 mg/m2 (80-580). Of the 82 patients, 12 (14.6%) developed cardiotoxicity with grade ⩾2 ejection fraction decline: four patients were asymptomatic and did not receive any treatment; six patients were treated with pharmacological heart failure therapy; one patient with severe cardiomyopathy underwent heart transplantation and did not need any further treatment; and one patient died while waiting for heart transplantation. The median time at cardiac toxicity, from the end of anthracycline frontline chemotherapy, was 4.2 years (0.05-9.6). Cumulative anthracycline dose ⩾300 mg/m2 (p 0.04) was the only risk factor for cardiotoxicity on statistical analyses. In our population, the cumulative incidence of cardiotoxicity is comparable to rates in the literature. This underlines the need for primary prevention and lifelong cardiac toxicity surveillance programmes in long-term childhood cancer survivors.

Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

PubMed Central

2012-01-01

Abstract Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2315906377648045. PMID:23134683

Durable clinical activity of single-agent bevacizumab in a nonagenarian patient with metastatic alveolar soft part sarcoma.

PubMed

Mir, Olivier; Boudou-Rouquette, Pascaline; Larousserie, Frédérique; Blanchet, Benoit; Babinet, Antoine; Anract, Philippe; Goldwasser, François

2012-08-01

Alveolar soft part sarcoma is a rare malignancy usually considered resistant to conventional chemotherapy, but recent data suggest that the multikinase inhibitors sunitinib and cediranib could be active in this setting. A 90-year-old lady with alveolar soft part sarcoma of the leg and lung metastases was started on sunitinib 37.5 mg daily. The treatment was poorly tolerated with grade 3 hypertension and grade 3 thrombocytopenia, which persisted after dose reduction to 25 mg daily. The patient was subsequently started on bevacizumab 10 mg/kg every 2 weeks, resulting in a marked improvement in pain and a partial response on lung metastases for 16 months and ongoing. Agents targeting the vascular endothelial growth factor-signalling pathway seem to exert clinically relevant and prolonged activity against alveolar soft part sarcoma and deserve further evaluation in the treatment of this rare soft tissue sarcoma.

Primary synovial sarcoma of the thyroid with locally repeated relapses in short periods: A case report

PubMed Central

SHI, RONG-LIANG; QU, NING; GAO, LI-LI; LU, ZHONG-WU; SUN, GUO-HUA; JI, QING-HAI

2016-01-01

The primary occurrence of synovial sarcoma (SS) in the thyroid is quite rare. As other SS arise from the head and neck structure, it tends to present poor biological behaviors and is generally treated as a high-grade sarcoma. The present study reports the case of a 31-year-old male who presented a neck mass, involving the thyroid, as shown by ultrasonography. The tumor was resected by total thyroidectomy and diagnosed as SS by histopathology. However, the initial surgery was considered as incomplete (R2) and no adjuvant protocol was followed. At the follow-up, neck recurrences within local lymph nodes were found repeatedly. The tumor grade increased for the metastatic lesions, indicating poorer differentiations with repeated relapses. The accurate evaluations of the primary tumor facilitated it to tailor the initial treatments, otherwise, the prognosis may be deteriorated by inappropriate management. PMID:27330751

Adult Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult soft tissue sarcoma (STS) treatment is determined by the tumor grade and may include surgery, radiation therapy, and/or chemotherapy. Get comprehensive information for newly diagnosed and recurrent STS and treatment in this summary for clinicians.

[Pleomorphic carcinoma of the lung with high serum granulocyte colony stimulating factor, suggested of pulmonary abscess by preoperative radiology; report of a case].

PubMed

Mizuno, Mikoto; Miyoshi, Tatsu; Nabeshima, Kazuki; Iwasaki, Akinori; Shirakusa, Takaho

2006-08-01

A 52-year-old man with a history of heavy smoking was hospitalized for evaluation of fever. Pulmonary abscess was initially suspected by computed tomography (CT) showing an ovoid, well-demarcated nodule of 61 mm in diameter with coarse calcification in S2a of the right lung. The patient was treated with antibiotics, but no improvement was seen in inflammatory reactions or lesion size. Marked leukocytosis and high level of granulocyte colony stimulating factor (G-CSF) was shown by laboratory examination. To improve patient condition and ensure correct diagnosis, right upper lobectomy of the lung was performed. Pleomorphic carcinoma of the lung was subsequently diagnosed. G-CSF producing tumor was suspected, since the normalization of serum G-CSF level followed by the improvement of both fever and inflammatory reaction was observed postoperatively. We also present herein a review of 22 Japanese cases of pleomorphic carcinoma producing G-CSF of the lung, characterized by leukocytosis.

Pleomorphic xanthoastrocytoma with anaplastic features: A rare case report and review of literature with reference to current management

PubMed Central

Patibandla, M. R.; Nayak, Madhukar; Purohit, A. K.; Thotakura, Amit Kumar; Uppin, Megha; Challa, Sundaram

2016-01-01

Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor constitutes less than 1% of all astrocytic glial neoplasms was first reported in 1979. PXA commonly occurs in young patients and manifests itself first as seizures followed by focal neurological deficits. The role of radiotherapy or chemotherapy has not yet been established because of the relative infrequency of this disease. PXA is classified as grade II tumor in the WHO classification of tumors of the CNS. In literature 9 to 20 % PXA may undergo malignant change at recurrence or may display at the time of initial presentation. Malignant transformation is mainly associated with high mitotic activity and necrosis. The criteria for PXA with anaplastic features was five or more mitotic activity per 10 high power fields, necrosis, microvascular proliferation, marked cellular anaplasia, and high Ki-67 labeling indices. PXA with anaplastic features management is highly controversial as very sparse literature is available. We are reporting a case of PXA with anaplastic features with atypical radiology and tried to review the up to date literature regarding this rare tumor. PMID:27366280

Pleomorphic Malignant Mesothelioma in a Broiler Breeder Infected with Avian Leucosis Virus Subgroup J.

PubMed

Murakami, T; Sassa, Y

2018-04-01

Avian leucosis virus (ALV) is an oncogenic retrovirus that induces tumours including lymphoid leucosis and myeloid leucosis. Pleomorphic malignant mesothelioma and myelocytoma, which were thought to be induced by ALV subgroup J (ALV-J) infection, were identified in a 432-day-old broiler breeder. The bird showed no clinical signs; however, at necropsy examination there were multiple nodules in the alimentary tract. Microscopical analysis showed that these consisted of pleomorphic cells and myelocyte-like cells. Immunohistochemistry revealed that the pleomorphic cells were atypical and expressed cytokeratin, vimentin, c-kit, calretinin and ALV. The myelocyte-like cells were also positive for ALV. Retroviral type C particles were observed by electron microscopy. ALV-E and ALV-J nucleotide sequences were detected in DNA extracted from formalin-fixed and paraffin wax-embedded small intestinal tissue. Based on these results, the tumours were diagnosed as pleomorphic malignant mesothelioma and myelocytoma and were thought to have been induced by ALV-J infection. This is the first report of malignant mesothelioma associated with naturally acquired ALV-J infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prospective evaluation of Ki-67 system in histological grading of soft tissue sarcomas in the Japan Clinical Oncology Group Study JCOG0304.

PubMed

Tanaka, Kazuhiro; Hasegawa, Tadashi; Nojima, Takayuki; Oda, Yoshinao; Mizusawa, Junki; Fukuda, Haruhiko; Iwamoto, Yukihide

2016-04-18

The correct clinical staging of soft tissue sarcomas (STS) is critical for the selection of treatments. The staging system consists of histological grade of the tumors and French Federation of Cancer Center (FNCLCC) system based on mitotic count is widely used for the grading. In this study, we compared the validity and usefulness of Ki-67 grading system with FNCLCC system in JCOG0304 trial which investigated the efficacy and safety of perioperative chemotherapy with doxorubicin and ifosfamide for STS. All 70 eligible patients with STS in the extremities treated by perioperative chemotherapy in JCOG0304 were analyzed. Univariate and multivariate Cox regression analyses were conducted to investigate an influence on overall survival. The reproducibility of Ki-67 grading system in the histological grading of STS was higher than FNCLCC system (κ = 0.54 [95 % CI 0.39-0.71], and 0.46 [0.32-0.62], respectively). Although FNCLCC grade was not associated with overall survival (OS) in univariate analysis (HR 2.80 [0.74-10.55], p = 0.13), Ki-67 grading system had a tendency to associate with OS in univariate analysis (HR 4.12 [0.89-19.09], p = 0.07) and multivariate analysis with backward elimination (HR 3.51 [0.75-16.36], p = 0.11). This is the first report demonstrating the efficacy of Ki-67 grading system for the patients with STS in the prospective trial. The results indicate that Ki-67 grading system might be useful for the evaluation of histological grade of STS.

Pleomorphic liposarcoma following radiotherapy for breast carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arbabi, L.; Warhol, M.J.

1982-03-01

A pleomorphic liposarcoma arising in a site previously irradiated as a treatment for breast carcinoma is described. This case fulfills the criteria for a tumor to be radiation-induced. The tumor is localized with an irradiated area, there is a clear histologic distinction between the previous and current tumor, and there is a long latent interval.

[Pleomorphic rhabdomyosarcoma of the larynx--a case report and literature review].

PubMed

Prgomet, Drago; Males, Josip; Manojlović, Spomenka; Bumber, Zeljko

2006-06-01

Rhabdomyosarcoma is a very rare malignant tumor of the larynx which can present in a number of histologic variants. The pleomorphic variant of the tumor has been described in 16 patients to date. Being a rarity, rhabdomyosarcoma is as a rule managed according to the principle of treatment for malignant mesenchymal tumors of the head and neck, and includes radical surgery with postoperative radiotherapy and/or chemotherapy. A case is presented of a pleomorphic rhabdomyosarcoma of the vocal cord. Successfully treated by endoscopic CO2 laser cordectomy with adjuvant chemotherapy and 6-year uneventful follow up.

Biologic Activity of Autologous, Granulocyte-Macrophage Colony Stimulating Factor Secreting Alveolar Soft Parts Sarcoma and Clear Cell Sarcoma Vaccines

PubMed Central

Goldberg, John; Fisher, David E.; Demetri, George D.; Neuberg, Donna; Allsop, Stephen A.; Fonseca, Catia; Nakazaki, Yukoh; Nemer, David; Raut, Chandrajit P.; George, Suzanne; Morgan, Jeffrey A.; Wagner, Andrew J.; Freeman, Gordon J.; Ritz, Jerome; Lezcano, Cecilia; Mihm, Martin; Canning, Christine; Hodi, F. Stephen; Dranoff, Glenn

2015-01-01

Purpose Alveolar soft parts sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Experimental Design Metastatic tumors from ASPS and CCS patients were resected, processed to single cell suspensions, transduced with a replication defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly times three and then every other week. Results Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from 3 to 13 immunizations. Toxicities were restricted to grade 1–2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell mediated delayed type-hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1) positive CD8+ T cells in association with PD ligand-1 (PD-L1) expressing sarcoma cells. No tumor regressions were observed. Conclusions Vaccination with irradiated, GM-CSF secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1 negative regulatory pathway might intensify immune-mediated tumor destruction. PMID:25805798

Genetic susceptibility to bone and soft tissue sarcomas: a field synopsis and meta-analysis.

PubMed

Benna, Clara; Simioni, Andrea; Pasquali, Sandro; De Boni, Davide; Rajendran, Senthilkumar; Spiro, Giovanna; Colombo, Chiara; Virgone, Calogero; DuBois, Steven G; Gronchi, Alessandro; Rossi, Carlo Riccardo; Mocellin, Simone

2018-04-06

The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases. To evaluate result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Integrative analysis of genetic and eQTL (expression quantitative trait locus) data was coupled with network and pathway analysis to explore the hypothesis that specific cell functions are involved in sarcoma predisposition. We retrieved 90 eligible studies comprising 47,796 subjects (cases: 14,358, 30%) and investigating 1,126 polymorphisms involving 320 distinct genes. Meta-analysis identified 55 single nucleotide polymorphisms (SNPs) significantly associated with disease risk with a high (N=9), moderate (N=38) and low (N=8) level of evidence, findings being classified as noteworthy basically only when the level of evidence was high. The estimated joint population attributable risk for three independent SNPs (rs11599754 of ZNF365/EGR2 , rs231775 of CTLA4 , and rs454006 of PRKCG ) was 37.2%. We also identified 53 SNPs significantly associated with sarcoma risk based on single studies.Pathway analysis enabled us to propose that sarcoma predisposition might be linked especially to germline variation of genes whose products are involved in the function of the DNA repair machinery. We built the first knowledgebase on the evidence linking DNA variation to sarcomas susceptibility, which can be used to generate mechanistic hypotheses and inform future studies in this field of oncology.

Genetic susceptibility to bone and soft tissue sarcomas: a field synopsis and meta-analysis

PubMed Central

Benna, Clara; Simioni, Andrea; Pasquali, Sandro; De Boni, Davide; Rajendran, Senthilkumar; Spiro, Giovanna; Colombo, Chiara; Virgone, Calogero; DuBois, Steven G.; Gronchi, Alessandro; Rossi, Carlo Riccardo; Mocellin, Simone

2018-01-01

Background The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. Methods We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases. To evaluate result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Integrative analysis of genetic and eQTL (expression quantitative trait locus) data was coupled with network and pathway analysis to explore the hypothesis that specific cell functions are involved in sarcoma predisposition. Results We retrieved 90 eligible studies comprising 47,796 subjects (cases: 14,358, 30%) and investigating 1,126 polymorphisms involving 320 distinct genes. Meta-analysis identified 55 single nucleotide polymorphisms (SNPs) significantly associated with disease risk with a high (N=9), moderate (N=38) and low (N=8) level of evidence, findings being classified as noteworthy basically only when the level of evidence was high. The estimated joint population attributable risk for three independent SNPs (rs11599754 of ZNF365/EGR2, rs231775 of CTLA4, and rs454006 of PRKCG) was 37.2%. We also identified 53 SNPs significantly associated with sarcoma risk based on single studies. Pathway analysis enabled us to propose that sarcoma predisposition might be linked especially to germline variation of genes whose products are involved in the function of the DNA repair machinery. Conclusions We built the first knowledgebase on the evidence linking DNA variation to sarcomas susceptibility, which can be used to generate mechanistic hypotheses and inform future studies in this field of oncology. PMID:29719630

Pleomorphic adenoma of minor salivary gland with therapeutic misadventure: a rare case report.

PubMed

Thakur, Jagdeep S; Mohindroo, Narinder K; Mohindroo, Shobha; Sharma, Dev R; Thakur, Anamika

2010-01-08

The benign tumors of nasopharynx are least encountered tumors in otolaryngology, as nasopharynx is considered one of notorious anatomical site for the malignant tumors. Pleomorphic adenoma of the minor salivary gland of nasopharynx and parapharyngeal space is rare. We present a pleomorphic adenoma of minor salivary gland which was mismanaged. An adult male presented with left nostril obstruction for five months. The examination found big mass extending from nasopharynx to oropharynx. On CT scan, this tumor was quite big and extending to the parapharyngeal space. The FNAB found it a carcinoma but it did not respond to radiotherapy. The excision biopsy of tumor revealed it as pleomorphic adenoma. We found only five published reports on this tumor arising from nasopharynx. Although, in this case report exact origin of the tumor could not be ascertained as it also appeared to be a parapharyngeal tumor but we kept the possibility of a nasopharyngeal tumor on the basis of clinical features. The pleomorphic adenoma of nasopharynx is rare. It can be misdiagnosed as malignant epithelial tumor on histopathology. The differentiation from its malignant variant is also difficult. A possibility of benign tumor should always be kept in nasopharyngeal growth with no evidence of metastasis, and histopathological diagnosis of growth should be available before any definitive treatment.

Adult Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Soft tissue sarcomas (STS) arise in any of the extremities, trunk, retroperitoneum, or head and neck. Treatment is determined by the tumor grade and options include surgery, radiation therapy, and chemotherapy. Get comprehensive information for STS and treatment in this clinician summary.

[Sonoelastography, B-mode sonography, and color Doppler sonography findings of pleomorphic adenomas and Warthin tumors of parotid gland].

PubMed

Yerli, Hasan; Eşki, Erkan

2015-01-01

This study aims to investigate the sonoelastography (SE), B-mode sonography, and color Doppler sonography findings of the pleomorphic adenomas and Warthin tumors of the parotid gland. A total of 84 parotid masses (23 pleomorphic adenomas, 25 Warthin tumors) in 72 patients (37 males, 35 females; mean age 59 years; range 30 to 79 years) were retrospectively analyzed. For each lesion, B-mode sonography, color Doppler sonography, and SE images were evaluated. Vascularity and elasticity scores of the tumors during color Doppler sonography and SE examinations were calculated by 4-scoring method. Lobulated contour and cystic areas were more common in the pleomorphic adenomas and Warthin tumors during the B-mode sonography examination (p<0.05). Peripheral vascularity was common in more than half of the pleomorphic adenoma patients, whereas central or mixed vascularity was seen in a large group of the Warthin tumor patients (p<0.05). The mean scores on color Doppler sonography examination were 1.13±0.81 for pleomorphic adenomas and 1.96±0.97 for Warthin tumors (p<0.05). The mean scores on SE examination were 2.69±0.70 for pleomorphic adenomas and 1.83±0.63 for Warthin tumors (p<0.05). Score 1 on SE examination was found in three of five Warthin tumor patients with peripheral vascularity on color Doppler sonography. B-mode, color Doppler and elastography examinations by sonography provide some helpful findings in the differentiation of pleomorphic adenomas and Warthin tumors.

Usefulness of a Novel Ultrasonographic Classification Based on Anechoic Area Patterns for Differentiating Warthin Tumors from Pleomorphic Adenomas of the Parotid Gland

PubMed Central

Matsuda, Eriko; Fukuhara, Takahiro; Donishi, Ryohei; Kawamoto, Katsuyuki; Hirooka, Yasuaki; Takeuchi, Hiromi

2018-01-01

Background Ultrasonographic homogeneity is an important differential finding between Warthin tumor and pleomorphic adenoma, two types of benign parotid gland tumors, with the former likely to be heterogeneous and the latter homogeneous. However, differences in the performance of ultrasound machines or the homogeneity cut-off level affect the judgment of ultrasonographic homogeneity. Therefore, in this study, we adopted a novel system for classifying the composition of tumors via ultrasonography, using anechoic area as a substitute for differences in homogeneity to differentiate between Warthin tumors and pleomorphic adenomas. Methods We evaluated 68 tumors that were histopathologically diagnosed as Warthin tumor or pleomorphic adenoma between July 2009 and November 2015. Ultrasonographic images of the tumors were evaluated on the basis of key differentiating features, including features on B-mode imaging and color Doppler imaging. Additionally, the tumors were classified into four groups based on anechoic area, and findings were compared between Warthin tumors and pleomorphic adenomas. Results While 38 of the tumors were pleomorphic adenomas, 30 were Warthin tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of Warthin tumors using our novel classification system were 73.3%, 76.3%, 71.0%, 78.4% and 75.0%, respectively. Compared to pleomorphic adenomas, Warthin tumors showed large or sponge-like anechoic areas, rich vascularization and an oval shape even at large tumor sizes, and the difference was significant. On defining Warthin tumor as a tumor demonstrating two or more of the findings noted above, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for its detection were 73.3%, 84.2%, 78.6%, 80.0% and 79.4%, respectively. Conclusion Our novel classification system based on anechoic area patterns demonstrated by the tumors had high

Usefulness of a Novel Ultrasonographic Classification Based on Anechoic Area Patterns for Differentiating Warthin Tumors from Pleomorphic Adenomas of the Parotid Gland.

PubMed

Matsuda, Eriko; Fukuhara, Takahiro; Donishi, Ryohei; Kawamoto, Katsuyuki; Hirooka, Yasuaki; Takeuchi, Hiromi

2017-12-01

Ultrasonographic homogeneity is an important differential finding between Warthin tumor and pleomorphic adenoma, two types of benign parotid gland tumors, with the former likely to be heterogeneous and the latter homogeneous. However, differences in the performance of ultrasound machines or the homogeneity cut-off level affect the judgment of ultrasonographic homogeneity. Therefore, in this study, we adopted a novel system for classifying the composition of tumors via ultrasonography, using anechoic area as a substitute for differences in homogeneity to differentiate between Warthin tumors and pleomorphic adenomas. We evaluated 68 tumors that were histopathologically diagnosed as Warthin tumor or pleomorphic adenoma between July 2009 and November 2015. Ultrasonographic images of the tumors were evaluated on the basis of key differentiating features, including features on B-mode imaging and color Doppler imaging. Additionally, the tumors were classified into four groups based on anechoic area, and findings were compared between Warthin tumors and pleomorphic adenomas. While 38 of the tumors were pleomorphic adenomas, 30 were Warthin tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of Warthin tumors using our novel classification system were 73.3%, 76.3%, 71.0%, 78.4% and 75.0%, respectively. Compared to pleomorphic adenomas, Warthin tumors showed large or sponge-like anechoic areas, rich vascularization and an oval shape even at large tumor sizes, and the difference was significant. On defining Warthin tumor as a tumor demonstrating two or more of the findings noted above, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for its detection were 73.3%, 84.2%, 78.6%, 80.0% and 79.4%, respectively. Our novel classification system based on anechoic area patterns demonstrated by the tumors had high sensitivity, specificity and

Alternative lengthening of telomeres and loss of ATRX are frequent events in pleomorphic and dedifferentiated liposarcomas.

PubMed

Lee, Jen-Chieh; Jeng, Yung-Ming; Liau, Jau-Yu; Tsai, Jia-Huei; Hsu, Hung-Han; Yang, Ching-Yao

2015-08-01

Telomerase activation and alternative lengthening of telomeres are two major mechanisms of telomere length maintenance. Soft tissue sarcomas appear to use the alternative lengthening of telomeres more frequently. Loss of α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated protein 6 (DAXX) expression has been implicated in the pathogenesis of alternative telomere lengthening in pancreatic endocrine neoplasm and glioma. The mechanism leading to the alternative lengthening of telomeres in liposarcoma remains unknown. Whereas alternative telomere lengthening was determined to be an indicator of poor prognosis in liposarcomas as a whole, its prognostic power has not been verified in any subtype of liposarcoma. In this study, we characterized the status of alternative telomere lengthening and expression of ATRX and DAXX in 111 liposarcomas (28 well-differentiated, 52 dedifferentiated, 20 myxoid or round cell, and 11 pleomorphic liposarcomas) by telomere fluorescence in situ hybridization and immunohistochemistry, respectively. Alternative lengthening of telomere was observed in 0% (0/16) of well-differentiated, 30% (14/46) of dedifferentiated, 5% (1/19) of myxoid or round cell, and 80% (8/10) of pleomorphic liposarcomas. Eighteen (16%) and one (1%) tumors were negative for ATRX and DAXX immunostaining, respectively. Remarkably, all cases with loss of either ATRX or DAXX expression had alternative lengthening of telomeres, and 83% (19/23) of tumors that had alternative lengthening of telomeres showed loss of either protein. The correlation between loss of either ATRX or DAXX and alternative telomere lengthening was 100% in dedifferentiated liposarcoma. The presence of alternative telomere lengthening in dedifferentiated liposarcoma suggested poor overall survival (hazard ratio=1.954, P=0.077) and was the most significant indicator of short progression-free survival (hazard ratio=3.119, P=0.003). In conclusion, we found that ATRX loss was

A case report of CIC-rearranged undifferentiated small round cell sarcoma in the cerebrum.

PubMed

Ito, Mayumi; Ishikawa, Misawo; Kitajima, Masateru; Narita, Jun; Hattori, Shinya; Endo, Otone; Goto, Keisuke

2016-10-01

CIC-rearranged undifferentiated small round cell sarcoma (CIC-rearranged USRCS) is a recently established type of Ewing-like small round cell sarcomas, characterized by CIC gene rearrangement, most commonly CIC-DUX4 fusion. This report presents the second case of CIC-rearranged USRCS arising primarily in the cerebrum. A 64-year-old otherwise healthy woman presented with a 1 × 1 cm sized hemorrhagic subcortical tumor in the left temporo-parietal lobe. The tumor repeatedly recurred, and the patient underwent three surgeries, chemotherapy with doxorubicin and ifosfamide, and radiotherapy, as well as gamma knife surgery. Systemic examination revealed no other extracranial masses. Imprint cytology revealed small to moderate-sized round-to-ovoid tumor cells with mild pleomorphism and variations in size and shape. The nuclei contained finely granular chromatin, and some had easily-recognizable nucleoli. The tumor exhibited a mainly cytoplasmic pattern of CD99 immunostaining, rather than a diffuse membranous pattern. The tumor also exhibited diffuse positivity for calretinin and p16, as well as partial positivity for WT1 (nuclear and cytoplasmic staining pattern) and D2-40. FISH assessment showed CIC split signals. In conclusion, CIC-rearranged USRCSs can occur primarily in the cerebrum. It would be impossible to diagnose them through cytology alone, but cytology would be useful to rule out other small round cell brain tumors including gliomas, lymphomas, carcinomas, and germinoma. Immunohistochemical analysis including tests for CD99, calretinin, and WT1 would help to suggest CIC-rearranged USRCSs and distinguish them from Ewing sarcomas. Additionally, immunohistochemistry for p16 might be useful in the diagnosis. Diagn. Cytopathol. 2016;44:828-832. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Apatinib for advanced sarcoma: results from multiple institutions' off-label use in China.

PubMed

Xie, Lu; Guo, Wei; Wang, Ye; Yan, Taiqiang; Ji, Tao; Xu, Jie

2018-04-06

Anti-angiogenesis Tyrosine kinase inhibitors (TKIs) have been proved to show promising effects on prolonging progression-free survival (PFS) for advanced sarcoma after failure of standard multimodal Therapy. Methylsulfonic apatinib is one of those TKIs which specifically inhibits VEGFR-2. This paper summarizes the experience of three Peking University affiliated hospitals in off-label use of apatinib in the treatment of extensively pre-treated sarcoma. We retrospectively analysed files of patients with advanced sarcoma not amenable to curative treatment, who were receiving an apatinib-containing regimen between June 1, 2015 and December 1, 2016. Fifty-six patients were included: 22 osteosarcoma, 10 Ewing's sarcoma, 3 chondrosarcoma and 21 soft tissue sarcoma. With median follow-up time of 6 months (range, 0.7-18.0 m), thirty-five (62.5%) patients had partial response, and disease was stable in 11 (19.6%). The 4-month and 6-month progression-free survival rates were 46.3 and 36.5%, respectively. The median duration of response was 3.8 months (95% CI 1.9-5.6 m), with much variability among disease subtypes. The median overall survival was 9.9 months (95% CI 7.6-12.2 m). Grade 3 and 4 toxicities were observed in 8 (14.3%) patients, the most common being hypertension, pneumothorax, wound-healing problems, anorexia, and rash or desquamation. Apatinib might be effective, with a high objective response rate, in an off-label study of sarcoma patients with advanced, previously treated disease. The duration of response was consistent with reports in different subtypes of sarcomas. Prospective trials of apatinib in the treatment of selected subtypes of sarcomas are needed. Retrospectively registered in the Medical Ethics Committee of Peking University People's Hospital, Peking University Shougang Hospital and Peking University International Hospital. The trial registration number is 2017PHB176-03 and the date of registration is January 20th 2017.

Radiation-induced sarcoma of the thyroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griem, K.L.; Robb, P.K.; Caldarelli, D.D.

1989-08-01

A 23-year-old white man presented with a thyroid mass 12 years after receiving high-dose radiotherapy for a T2 and N1 lymphoepithelioma of the nasopharynx. Following subtotal thyroidectomy, a histopathologic examination revealed liposarcoma of the thyroid gland. The relationship between sarcomas and irradiation is described and Cahan and colleagues' criteria for radiation-induced sarcomas are reviewed. To our knowledge, we are presenting the first such case of a radiation-induced sarcoma of the thyroid gland.

Efficacy and safety of Apatinib in stage IV sarcomas: experience of a major sarcoma center in China.

PubMed

Li, Feng; Liao, Zhichao; Zhao, Jun; Zhao, Gang; Li, Xubin; Du, Xiaoling; Yang, Yun; Yang, Jilong

2017-09-08

This study was conducted to review the efficacy and safety of Apatinib in stage IV sarcoma patients who failed previous chemotherapy. The clinical information on 16 patients with stage IV sarcomas who failed in prior chemotherapy and subsequently received Apatinib treatment was collected. Apatinib was given 500mg/daily and 4 weeks as a cycle. All patients had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1.0 criteria. Progression free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse effects (AEs) were reviewed and evaluated. Patients was administered Apatinib for 0 to 9 cycles with the median of 3.2 cycles. Median follow-up time was 8.4 months (1 to 12 months). Ten of 16 patients received at least 1 complete cycle of Apatinib treatment were eligible for the efficacy analysis. The median PFS was 8.84 months. Two patients achieved partial response (PR) and 6 patients achieved stable disease (SD). Two patients were evaluated as progression disease (PD) and one patient died of disease progression. The ORR was 20.0% (2/10) and the DCR was 80.0% (8/10). The most common grade 3/4 treatment-related AEs were hypertension (18.7%), hand-foot syndrome (12.5%) and proteinuria (6.3%). No drug-related severe AEs occurred. CApatinib treatment in this exploratory study exhibited objective efficacy and manageable toxicity in stage IV sarcoma patients who failed in chemotherapy. This result supports future random controlled trial to further define Apatinib activity in stage IV sarcomas.

[Extraskeletal Ewing's sarcoma].

PubMed

Baram, J; Tichler, T; Nass, D; Brenner, H J

1992-01-01

5 patients diagnosed as having extraskeletal Ewing's sarcoma have been referred to our adult oncology unit since 1980. All were men, ranging in age from 18-57 (mean 32 years). The primary tumor was located on the trunk in 4 and in an extremity in 1. Wide tumor excision was feasible in only 2. 3 died within 27 months and 2 are alive, 13 and 67 months, respectively, following diagnosis. This study demonstrates the highly aggressive nature of extraskeletal Ewing's sarcoma and the need for early diagnosis and efficient chemotherapy.

Cell Pleomorphism and Cytoskeleton Disorganization in Human Liver Cancer.

PubMed

Cheng, Chiung-Chi; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Chao, Wei-Ting; Tseng, Yu-Hui; Hsu, Yung-Hsiang; Chen, You-Yin; Liu, Yi-Hsiang

Nucleoskeleton maintains the framework of a cell nucleus that is required for a variety of nuclear functions. However, the nature of nucleoskeleton structure has not been yet clearly elucidated due to microscopy visualization limitations. Plectin, a nuclear pore-permeable component of cytoskeleton, exhibits a role of cross-linking between cytoplasmic intermediate filaments and nuclear lamins. Presumably, plectin is also a part of nucleoskeleton. Previously, we demonstrated that pleomorphism of hepatoma cells is the consequence of cytoskeletal changes mediated by plectin deficiency. In this study, we applied a variety of technologies to detect the cytoskeletons in liver cells. The images of confocal microscopy did not show the existence of plectin, intermediate filaments, microfilaments and microtubules in hepatic nuclei. However, in the isolated nuclear preparation, immunohistochemical staining revealed positive results for plectin and cytoskeletal proteins that may contribute to the contamination derived from cytoplasmic residues. Therefore, confocal microscopy provides a simple and effective technology to observe the framework of nucleoskeleton. Accordingly, we verified that cytoskeletons are not found in hepatic cell nuclei. Furthermore, the siRNA-mediated knockdown of plectin in liver cells leads to collapsed cytoskeleton, cell transformation and pleomorphic nuclei. Plectin and cytoskeletons were not detected in the nuclei of liver cells compared to the results of confocal microscopy. Despite the absence of nuclear plectin and cytoskeletal filaments, the evidence provided support that nuclear pleomorphism of cancer cells is correlated with the cytoplasmic disorganization of cytoskeleton. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Promiscuous partnerships in Ewing's sarcoma.

PubMed

Sankar, Savita; Lessnick, Stephen L

2011-07-01

Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing's sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing's sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing's sarcoma. However, in recent years there have been reports of rare fusions in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing's sarcoma and Ewing's-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

Histopathologic grading of anaplasia in retinoblastoma.

PubMed

Mendoza, Pia R; Specht, Charles S; Hubbard, G Baker; Wells, Jill R; Lynn, Michael J; Zhang, Qing; Kong, Jun; Grossniklaus, Hans E

2015-04-01

To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Retrospective clinicopathologic study. The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Increasing grade of anaplasia was associated with decreased overall survival (P = .003) and increased risk of metastasis (P = .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P < .0001), choroidal invasion (P < .0001), and anterior segment invasion (P = .04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P = .01 for metastasis, P = .03 for death) but anaplasia was not (P = .63 for metastasis, P = .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P = .0004) and death (P = .01). Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Retroperitoneal sarcoma (RPS) high risk gross tumor volume boost (HR GTV boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists.

PubMed

Baldini, Elizabeth H; Bosch, Walter; Kane, John M; Abrams, Ross A; Salerno, Kilian E; Deville, Curtiland; Raut, Chandrajit P; Petersen, Ivy A; Chen, Yen-Lin; Mullen, John T; Millikan, Keith W; Karakousis, Giorgos; Kendrick, Michael L; DeLaney, Thomas F; Wang, Dian

2015-09-01

Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.

Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.

PubMed

Rao, Donald D; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

2016-08-01

The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.

Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma

PubMed Central

Rao, Donald D.; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

2016-01-01

The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85–92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing. PMID:27166877

Ewing Sarcoma Treatment (PDQ®)—Patient Version

Cancer.gov

Ewing sarcoma treatment usually begins with chemotherapy and/or radiation followed by surgery to remove any remaining cancer. Treatment options for recurrent sarcoma include targeted therapy and high-dose chemotherapy with stem cell transplant. Learn more in this expert-reviewed summary.

Ewing sarcoma

MedlinePlus

Bone cancer - Ewing sarcoma; Ewing family of tumors; Primitive neuroectodermal tumors (PNET); Bone neoplasm - Ewing sarcoma ... adulthood. But it usually develops during puberty, when bones are growing rapidly. It is more common in ...

A Scary Onset of a Rare and Aggressive Type of Primary Breast Sarcoma: A Case Report.

PubMed

Ramalho, Inês; Campos, Sara; Rebelo, Teresa; Figueiredo Dias, Margarida

2016-01-01

Primary breast sarcoma, arising from connective tissue within the breast, is extremely rare, accounting for less than 1% of all primary breast malignancies and no more than 5% of all sarcomas. The rarity of this pathology limits most studies to case reports and small retrospective studies, which has led to a lack of consensus on the clinical management. We report a clinical case of a 52-year-old woman, perimenopausal, previously healthy, with regular breast surveillance, who presented with a large (>20 cm) and rapidly expanding hypervascularized tumor of the left breast developed over 10 days, with a very thin preulcerative skin over the last 4 days. There was no systemic dissemination. The patient was submitted to total mastectomy and excision of axillary adenopathy. The tumor was diagnosed histologically as malignant phyllodes tumor associated with areas of high-grade sarcoma. Due to rapid growth and aggressive histological characteristics, adjuvant chemotherapy and radiotherapy were performed. There is a lot of evidence that tumors larger than 5 cm are associated with a poor prognosis. Despite the poor prognosis associated with this aggressive entity, the patient had no recurrence during 5 years of follow-up. We review the relevant literature about primary breast sarcomas.

A Scary Onset of a Rare and Aggressive Type of Primary Breast Sarcoma: A Case Report

PubMed Central

Ramalho, Inês; Campos, Sara; Rebelo, Teresa; Figueiredo Dias, Margarida

2016-01-01

Primary breast sarcoma, arising from connective tissue within the breast, is extremely rare, accounting for less than 1% of all primary breast malignancies and no more than 5% of all sarcomas. The rarity of this pathology limits most studies to case reports and small retrospective studies, which has led to a lack of consensus on the clinical management. We report a clinical case of a 52-year-old woman, perimenopausal, previously healthy, with regular breast surveillance, who presented with a large (>20 cm) and rapidly expanding hypervascularized tumor of the left breast developed over 10 days, with a very thin preulcerative skin over the last 4 days. There was no systemic dissemination. The patient was submitted to total mastectomy and excision of axillary adenopathy. The tumor was diagnosed histologically as malignant phyllodes tumor associated with areas of high-grade sarcoma. Due to rapid growth and aggressive histological characteristics, adjuvant chemotherapy and radiotherapy were performed. There is a lot of evidence that tumors larger than 5 cm are associated with a poor prognosis. Despite the poor prognosis associated with this aggressive entity, the patient had no recurrence during 5 years of follow-up. We review the relevant literature about primary breast sarcomas. PMID:28101028

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest.

PubMed

Francis, Ashleigh M; Alexander, Angela; Liu, Yanna; Vijayaraghavan, Smruthi; Low, Kwang Hui; Yang, Dong; Bui, Tuyen; Somaiah, Neeta; Ravi, Vinod; Keyomarsi, Khandan; Hunt, Kelly K

2017-09-01

Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow. Here we describe the development of a synergistic combination treatment strategy that may be applicable in both soft tissue sarcomas as well as sarcomas of bone that takes advantage of targeting the cell cycle. We show that Rb-positive cell lines treated with the CDK4/6 inhibitor palbociclib reversibly arrest in the G 1 phase of the cell cycle, and upon drug removal cells progress through the cell cycle as expected within 6-24 hours. Using a long-term high-throughput assay that allows us to examine drugs in different sequences or concurrently, we found that palbociclib-induced cell-cycle arrest poises Rb-positive sarcoma cells (SK-LMS1 and HT-1080) to be more sensitive to agents that work preferentially in S-G 2 phase such as doxorubicin and Wee1 kinase inhibitors (AZD1775). The synergy between palbociclib and AZD1775 was also validated in vivo using SK-LMS1 xenografts as well as Rb-positive patient-derived xenografts (PDX) developed from leiomyosarcoma patients. This work provides the necessary preclinical data in support of a clinical trial utilizing this treatment strategy. Mol Cancer Ther; 16(9); 1751-64. ©2017 AACR . ©2017 American Association for Cancer Research.

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baldini, Elizabeth H., E-mail: ebaldini@partners.org; Abrams, Ross A.; Bosch, Walter

Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneousmore » truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.« less

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

PubMed Central

Baldini, Elizabeth H.; Abrams, Ross A.; Bosch, Walter; Roberge, David; Haas, Rick L.M.; Catton, Charles N.; Indelicato, Daniel J.; Olsen, Jeffrey R.; Deville, Curtiland; Chen, Yen-Lin; Finkelstein, Steven E.; DeLaney, Thomas F.; Wang, Dian

2015-01-01

Purpose The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed. PMID:26194680

Variation in the Gross Tumor Volume and Clinical Target Volume for Preoperative Radiotherapy of Primary Large High-Grade Soft Tissue Sarcoma of the Extremity Among RTOG Sarcoma Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Dian, E-mail: dwang@mcw.edu; Bosch, Walter; Kirsch, David G.

Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) weremore » 674, 798, 752 {+-} 35 for the lower extremity case and 383, 543, 447 {+-} 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 {+-} 211 for the lower extremity case and 637, 1246, 1006 {+-} 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]). Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI.« less

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

DOE PAGES

Benz, Matthias R.; Czernin, Johannes; Tap, William D.; ...

2010-01-01

Purpose . Tmore » he aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods . Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results . Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders ( 64 ± 19 % versus 29 ± 30 %, resp.; P = .03 ). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion . These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.« less

A Case Report of Rare Carcinoma Ex Pleomorphic Adenoma of Submandibular Gland and its Detailed Description

PubMed Central

Deshmukh, Ajinkya Amritrao; Deshmukh, Atul A.

2017-01-01

A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy. PMID:28658924

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.

PubMed

Drozdzik, Agnieszka; Kowalczyk, Robert; Lipski, Mariusz; Łapczuk, Joanna; Urasinska, Elzbieta; Kurzawski, Mateusz

2016-01-01

Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma. Copyright © 2015. Published by Elsevier Ltd.

Dynamic pion irradiation of unresectable soft tissue sarcomas.

PubMed

Greiner, R H; Blattmann, H J; Thum, P; Coray, A; Crawford, J F; Kann, R H; Munkel, G; Pedroni, E; von Essen, C F; Zimmermann, A

1989-11-01

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN, now Paul Scherrer Institute, PSI) a dynamic, 3-dimensional spot scan treatment technique has been in use. To exploit this technique a special optimization treatment planning system has been designed. Of a total of 331 patients treated with pions from November 1981-December 1987, 35 were irradiated for unresectable soft tissue sarcomas. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. Twenty-nine tumors had a maximum diameter of greater than 10 cm, 18 tumors of greater than 15 cm; 30 tumors had grade 2/3 and 32 Stage III B/IV A/IV B. Eight of 35 patients received a low pion total dose, 7-27 Gy. Twenty-seven patients received a total dose of 30-36 Gy, fraction size 150-170 cGy (90%-isodose), 20 fractions, 4 times per week. Of these 27 patients, severe late reactions appeared in five: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer used). Seven of 27 patients had metastases at the beginning of irradiation. Three of 27 were treated with excisional biopsy, 9 with incisional biopsy or partial resection and in 15 patients biopsies were performed for histology only. The median follow-up of these 27 patients was 17 months (5-66). There was no progression in eight extremity/groin tumors but in 4 of 19 retroperitoneal/pelvic tumors. Three of these were marginal progressions. The actuarial 5-year rate of local tumor control is 64%; the actuarial 5-year survival rate of patients without metastases at the beginning of treatment is 58%. Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study.

PubMed

Zhu, Baorang; Li, Jing; Xie, Qiaosheng; Diao, Liyan; Gai, Lvhua; Yang, Wuwei

2018-03-04

Sarcomas are rare but malignant tumors with high risks of local recurrence and distant metastasis. Anti-angiogenic therapy is a potential strategy against un-controlled and not-organized tumor angiogenesis. We aimed to assess the safety and efficacy of apatinib, an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, in patients with advanced sarcoma. Thirty-one patients who received initial apatinib between September 2015 and August 2016 were retrospectively reviewed. Among them, 19 (61.3%) patients were heavily pretreated with two or more lines of cytotoxic chemotherapy. Apatinib was given at a start-dose of 425 mg qd. During therapy, 9 (29.0%) patients required dose interruption and 7 (22.6%) needed dose reduction, and the mean dosage of apatinib was 372.9 ± 68.4 mg/day. In the study cohort, one patient was treated as adjunctive therapy and 6 patients stopped treatment before radiographic response assessment. Thus, 24 patients were eligible for tumor response evaluation. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The progression free survival was 4.25 (95% confidence interval [CI], 2.22-5.11) months, whereas the overall survival was 9.43 (95% CI, 6.64-18.72) months. Compared with other histological subtypes, leiomyosarcoma did not show significant survival benefits. Most of the adverse events (AEs) were at grade 1 or 2. The main grade 3 AEs were hypertension (6.5%), hand foot skin reaction (6.5%), and diarrhea (3.2%). In conclusion, apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent sarcoma, giving rationale clinical evidence to conduct clinical trials.

Promiscuous Partnerships in Ewing’s Sarcoma

PubMed Central

Sankar, Savita; Lessnick, Stephen L.

2011-01-01

Ewing’s sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing’s sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing’s sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing’s sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing’s sarcoma. However, in recent years there have been reports of rare fusions in “Ewing’s-like tumors” that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing’s sarcoma and Ewing’s-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing’s sarcoma is strictly a “TET/ETS” fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor. PMID:21872822

Histopathologic Grading of Anaplasia in Retinoblastoma

PubMed Central

Mendoza, Pia R.; Specht, Charles S.; Hubbard, G. Baker; Wells, Jill R.; Lynn, Michael J.; Zhang, Qing; Kong, Jun; Grossniklaus, Hans E.

2014-01-01

Purpose To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Design Retrospective clinicopathologic study. Methods The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher's exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Results Increasing grade of anaplasia was associated with decreased overall survival (p=0.003) and increased risk of metastasis (p=0.0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (p<0.0001), choroidal invasion (p=<0.0001), and anterior segment invasion (p=0.04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (p=0.01 for metastasis, p=0.03 for death) but anaplasia was not (p=0.63 for metastasis, p=0.30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (p=0.0004) and death (p=0.01). Conclusion Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy. PMID:25528954

F-18-FDG PET-CT in children and young adults with Ewing sarcoma diagnosed in Norway during 2005-2012: a national population-based study.

PubMed

Johnsen, Boel; Boye, Kjetil; Rosendahl, Karen; Biermann, Martin; Trovik, Clement; Aukland, Stein Magnus

2016-11-01

To examine national imaging strategies regarding the use of F-18-FDG PET-CT in patients with Ewing sarcoma and study factors that might influence the use of PET-CT, such as tumour biology (Picci grade of operation specimen), clinical disease stage and age. We examined the medical records including pathology and imaging of all patients below 30 years diagnosed with Ewing sarcoma in Norway in 2005-2012. Of 61 patients treated at one of the two national sarcoma treatment service centres (Oslo: 35, Bergen: 26), 29 patients had localized disease, 8 had tumour extending to organs nearby and 24 had metastases. Among 35 operated patients with neoadjuvant chemotherapy, 15 had Picci grades II and III (good responders) and 20 grade I (poor responders). We found a significant difference in the use of PET-CT (Oslo/Bergen 0·9 versus 2·0 scans per patient, P = 0·010) and in the use of MRI (Oslo/Bergen: eight versus 13, P = 0·006). No differences were proven for ultrasound, radiography, CT or skeletal scintigraphy. The number of PET-CTs was associated with clinical disease stage at diagnosis (P = 0·041) but not with Picci grade or age. The number of PET studies was not correlated to the number of MR studies. The use of PET-CT in children and young adults diagnosed with Ewing sarcoma in Norway during 2005-2012 at the two national sarcoma treatment service centres differed significantly. The use of PET-CT imaging was related to the clinical disease stage at diagnosis but unrelated to patient age and tumour biology (Picci grade). © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Paratesticular dedifferentiated liposarcoma with leiomyosarcomatous differentiation: a case report with a review of literature.

PubMed

Hatanaka, Kazuhito; Yoshioka, Takako; Tasaki, Takashi; Tanimoto, Akihide

2013-08-23

Paratesticular liposarcoma is a rare neoplasm, described in single case studies or components of larger studies, as histologically well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DL). However, leiomyosarcomatous differentiation is an extremely rare occurrence in WDL and DL. We report a case of leiomyosarcomatous differentiation in a 77-year-old man. The patient presented with a painless right scrotal mass. Magnetic resonance imaging showed a large mass along the right spermatic cord. The resected mass, measuring 17.5 × 12 × 5 cm, was composed of a high-grade pleomorphic undifferentiated sarcomatous component with necrosis. Atypical smooth muscle differentiation was also detected. Additional tumor sampling revealed the presence of a WDL component. Immunohistochemical analysis of the pleomorphic sarcomatous component showed positive staining for MDM2 and CDK4, and negative staining for alpha smooth muscle actin (αSMA) and desmin. The smooth muscle component was positive for αSMA and desmin, and negative for MDM2 and CDK4. Extension from primary retroperitoneal sarcoma was not proved. We diagnosed of DL with leiomyosarcomatous differentiation. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1484291498104021.

Paratesticular dedifferentiated liposarcoma with leiomyosarcomatous differentiation: a case report with a review of literature

PubMed Central

2013-01-01

Abstract Paratesticular liposarcoma is a rare neoplasm, described in single case studies or components of larger studies, as histologically well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DL). However, leiomyosarcomatous differentiation is an extremely rare occurrence in WDL and DL. We report a case of leiomyosarcomatous differentiation in a 77-year-old man. The patient presented with a painless right scrotal mass. Magnetic resonance imaging showed a large mass along the right spermatic cord. The resected mass, measuring 17.5 × 12 × 5 cm, was composed of a high-grade pleomorphic undifferentiated sarcomatous component with necrosis. Atypical smooth muscle differentiation was also detected. Additional tumor sampling revealed the presence of a WDL component. Immunohistochemical analysis of the pleomorphic sarcomatous component showed positive staining for MDM2 and CDK4, and negative staining for alpha smooth muscle actin (αSMA) and desmin. The smooth muscle component was positive for αSMA and desmin, and negative for MDM2 and CDK4. Extension from primary retroperitoneal sarcoma was not proved. We diagnosed of DL with leiomyosarcomatous differentiation. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1484291498104021. PMID:23971887

Pleomorphic adenoma of a deep orbital ectopic lacrimal gland.

PubMed

Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti

2016-10-01

Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.

Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)

ClinicalTrials.gov

2014-04-01

Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Is There a Predisposition Gene for Ewing's Sarcoma?

PubMed Central

Randall, R. L.; Lessnick, S. L.; Jones, K. B.; Gouw, L. G.; Cummings, J. E.; Cannon-Albright, L.; Schiffman, J. D.

2010-01-01

Ewing's sarcoma is a highly malignant tumor of children and young adults. The molecular mechanisms that underlie Ewing's Sarcoma development are beginning to be understood. For example, most cases of this disease harbor somatic chromosomal translocations that fuse the EWSR1 gene on chromosome 22 with members of the ETS family. While some cooperative genetic events have been identified, such as mutations in TP53 or deletions of the CDKN2A locus, these appear to be absent in the vast majority of cases. It is therefore uncertain whether EWS/ETS translocations are the only consistently present alteration in this tumor, or whether there are other recurrent abnormalities yet to be discovered. One method to discover such mutations is to identify familial cases of Ewing's sarcoma and to then map the susceptibility locus using traditional genetic mapping techniques. Although cases of sibling pairs with Ewing's sarcoma exist, familial cases of Ewing's sarcoma have not been reported. While Ewing's sarcoma has been reported as a 2nd malignancy after retinoblastoma, significant associations of Ewing's sarcoma with classic tumor susceptibility syndromes have not been identified. We will review the current evidence, or lack thereof, regarding the potential of a heritable condition predisposing to Ewing's sarcoma. PMID:20300555

Ewing Sarcoma of the External Ear Canal

PubMed Central

Kecelioglu Binnetoglu, Kiymet; Gerin, Fatma; Sari, Murat

2016-01-01

Background. Ewing sarcoma (ES) is a high-grade malignant tumor that has skeletal and extraskeletal forms and consists of small round cells. In the head and neck region, reported localization of extraskeletal ES includes the larynx, thyroid gland, submandibular gland, nasal fossa, pharynx, skin, and parotid gland, but not the external ear canal. Methods. We present the unique case of a 2-year-old boy with extraskeletal ES arising from the external ear canal, mimicking auricular hematoma. Results. Surgery was performed and a VAC/IE (vincristine, adriamycin, cyclophosphamide alternating with ifosfamide, and etoposide) regimen was used for adjuvant chemotherapy for 12 months. Conclusion. The clinician should consider extraskeletal ES when diagnosing tumors localized in the head and neck region because it may be manifested by a nonspecific clinical picture mimicking common otorhinolaryngologic disorders. PMID:27313930

Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

PubMed

Murray, Jeffrey C; Donahue, David J; Malik, Saleem I; Dzurik, Yvette B; Braly, Emily Z; Dougherty, Margaret J; Eaton, Katherine W; Biegel, Jaclyn A

2011-05-01

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

PubMed Central

2016-01-01

Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high-risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3-year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high-risk or recurrent bone and soft tissue sarcomas. PMID:27366002

The epidemiology of classic, African, and immunosuppressed Kaposi's sarcoma.

PubMed

Wahman, A; Melnick, S L; Rhame, F S; Potter, J D

1991-01-01

The etiology of Kaposi's sarcoma remains somewhat obscure. While lesions of classic Kaposi's sarcoma, African Kaposi's sarcoma, and immunosuppressed Kaposi's sarcoma have been found to be indistinguishable from one another, the reasons for the variations in type and severity have not been established. The origin of the spindle cell is yet to be agreed on. Geographic variation does not seem as important as ethnic variation. The very young and the very old, perhaps two ages of weakened immunity, tend to have a higher incidence of Kaposi's sarcoma. Children and AIDS patients tend to develop more virulent disease. Males tend to get Kaposi's sarcoma at higher rates than do females. Jewish and Mediterranean males have the highest incidence of classic Kaposi's sarcoma, and African Bantu have the highest incidence of African Kaposi's sarcoma, classifications which do not apply to the Kaposi's sarcoma population in the United States. Male homosexuals have much higher incidence of Kaposi's sarcoma than do male heterosexuals, but since the early 1980s, its incidence as the presenting manifestation of AIDS has decreased dramatically. There is no unequivocal association with HLA haplotype (though DR5 carriers may be at especially high risk) or evidence of family clustering. There is an impressive but not always consistent association between Kaposi's sarcoma development and immunodeficiency. Environmental factors, such as nitrite use, immunosuppression, and repeated cytomegalovirus infection, are associated with Kaposi's sarcoma, but the exact mechanism is unclear and the associations remain inconsistent. Finally, it is still unclear if there is a causative infectious agent for Kaposi's sarcoma. While cytomegalovirus has been linked to Kaposi's sarcoma, there are weaknesses in its hypothetical role as an etiologic agent as is the case for HIV itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.

PubMed

2017-11-02

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities.

PubMed

Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei; Jungbluth, Achim A; Huang, Shih-Chiang; Argani, Pedram; Agaram, Narasimhan P; Zin, Angelica; Alaggio, Rita; Antonescu, Cristina R

2016-12-01

With the advent of next-generation sequencing, an increasing number of novel gene fusions and other abnormalities have emerged recently in the spectrum of EWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of SBRCTs harboring either BCOR gene fusions (BCOR-CCNB3, BCOR-MAML3), BCOR internal tandem duplications (ITD), or YWHAE-NUTM2B share a transcriptional signature including high BCOR mRNA expression, as well as similar histologic features. Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and primitive myxoid mesenchymal tumor of infancy also demonstrate BCOR ITDs and high BCOR gene expression. The molecular diagnosis of these various BCOR genetic alterations requires an elaborate methodology including custom BAC fluorescence in situ hybridization (FISH) probes and reverse transcription polymerase chain reaction assays. As these tumors show high level of BCOR overexpression regardless of the genetic mechanism involved, either conventional gene fusion or ITD, we sought to investigate the performance of an anti-BCOR monoclonal antibody clone C-10 (sc-514576) as an immunohistochemical marker for sarcomas with BCOR gene abnormalities. Thus we assessed the BCOR expression in a pathologically and genetically well-characterized cohort of 25 SBRCTs, spanning various BCOR-related fusions and ITDs and YWHAE-NUTM2B fusion. In addition, we included related pathologic entities such as 8 CCSKs and other sarcomas with BCOR gene fusions. As a control group we included 20 SBRCTs with various (non-BCOR) genetic abnormalities, 10 fusion-negative SBRCTs, 74 synovial sarcomas, 29 rhabdomyosarcomas, and other sarcoma types. In addition, we evaluated the same study group for SATB2 immunoreactivity, as these tumors also showed SATB2 mRNA upregulation. All SBRCTs with BCOR-MAML3 and BCOR-CCNB3 fusions, as well as most with BCOR ITD (93%), and all CCSKs showed strong and diffuse nuclear BCOR immunoreactivity. Furthermore, all SBRCTs with

Does surgery or radiation provide the best overall survival in Ewing's sarcoma? A review of the National Cancer Data Base.

PubMed

Miller, Benjamin J; Gao, Yubo; Duchman, Kyle R

2017-09-01

There is continuing debate regarding the ideal modality for local control of the primary tumor for patients with Ewing's sarcoma. The primary aim of this study is to investigate the impact of the method of local control on overall survival in patients with Ewing's sarcoma. The National Cancer Data Base was used to identify patients <40 years of age with high-grade Ewing's sarcoma of bone. A Kaplan-Meier survival analysis was performed at 2, 5, and 10 years. Factors with a level of significance of P < 0.1 at the 5-year time point were included in a multivariate Cox proportional hazards model. Diminished 5-year survival was noted for patients with metastatic disease, local control with radiation alone, age ≥18 years, tumor size >8 cm, and male sex while controlling for tumor site. Surgery alone was consistently the method of local control that resulted in the highest overall survival. Surgery alone resulted in the best overall survival for patients with Ewing's sarcoma of bone. The results of this investigation provide support to the approach of surgical resection with negative margins when possible. © 2017 Wiley Periodicals, Inc.

Outcomes in a series of 103 retroperitoneal sarcomas.

PubMed

Pierie, J-P E N; Betensky, R A; Choudry, U; Willett, C G; Souba, W W; Ott, M J

2006-12-01

To report the effect on outcome of selection in patients receiving intra-operative electron beam radiation (IOERT) and external beam radiation therapy (EBRT). One hundred and three patients treated for primary RS were studied. Median follow-up was 27 months. Clinical presentation, tumor characteristics, and treatment methods were analyzed to determine impact on survival and recurrence and if selection was occurring. Mean age was 55+/-17 years. Mean tumor size was 15+/-6cm and 88 were high-grade. Complete gross tumor resection (CR) occurred in 62 patients and improved survival vs. both debulking (p=0.0005) and biopsy (p<0.0001). The 5- and 10-year survival rates were 62% and 52% for those with CR vs. 29% and 20% after incomplete resection. Among the 62 CR patients, there was selection to receive additional EBRT+/-IOERT in patients with high-grade tumors (p=0.005) and/or microscopically positive margins (p=0.011). In these high-risk patients there was a trend for IOERT to further augment survival vs. EBRT alone and to increase the time to both local and distant recurrences (p=0.036). Complete gross resection is the primary form of curative treatment for retroperitoneal sarcomas. Selection led to patients with high-risk tumors receiving additional radiation therapy. There appears to be a beneficial effect of IOERT plus EBRT in these high-risk patients after complete tumor resection.

Malignant bone tumors (other than Ewing's): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS).

PubMed

Redondo, Andrés; Bagué, Silvia; Bernabeu, Daniel; Ortiz-Cruz, Eduardo; Valverde, Claudia; Alvarez, Rosa; Martinez-Trufero, Javier; Lopez-Martin, Jose A; Correa, Raquel; Cruz, Josefina; Lopez-Pousa, Antonio; Santos, Aurelio; García Del Muro, Xavier; Martin-Broto, Javier

2017-12-01

Primary malignant bone tumors are uncommon and heterogeneous malignancies. This document is a guideline developed by the Spanish Group for Research on Sarcoma with the participation of different specialists involved in the diagnosis and treatment of bone sarcomas. The aim is to provide practical recommendations with the intention of helping in the clinical decision-making process. The diagnosis and treatment of bone tumors requires a multidisciplinary approach, involving as a minimum pathologists, radiologists, surgeons, and radiation and medical oncologists. Early referral to a specialist center could improve patients' survival. The multidisciplinary management of osteosarcoma, chondrosarcoma, chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this guideline. Ewing's sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the available data. Surgical excision is the mainstay of treatment of a localized bone tumor, with various techniques available depending on the histologic type, grade and location of the tumor. Chemotherapy plays an important role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other subtypes, historically considered chemoresistant (such as chordoma or giant cell tumor of bone), new targeted therapies have emerged recently, with a very significant efficacy in the case of denosumab. Radiation therapy is usually necessary in the treatment of chordoma and sometimes of other bone tumors.

A comparative study using WHO and binary oral epithelial dysplasia grading systems in actinic cheilitis.

PubMed

Câmara, P R; Dutra, S N; Takahama Júnior, A; Fontes, Kbfc; Azevedo, R S

2016-09-01

To evaluate comparatively the influence of histopathological features on epithelial dysplasia (ED) and the effectiveness in usage of WHO and binary grading systems in actinic cheilitis (AC). Cytological and architectural alterations established by WHO for ED were evaluated in 107 cases of AC. Epithelial dysplasia was graded using WHO and binary systems. The comparisons were performed using kappa, chi-square, and phi coefficient tests (P < 0.05). Most cases were classified as mild ED (44.5%) in the WHO system and as low risk for malignant transformation (64.5%) in the binary system. There was a positive correlation between WHO and binary systems (k = 0.33; P < 0.0002). Loss of basal cell polarity (P < 0.001) was associated with severity of ED grade in the WHO system. Anisonucleosis (P < 0.0001), nuclear pleomorphism (P < 0.0001), anisocytosis (P = 0.03), cell pleomorphism (P = 0.002) increased nuclear/cytoplasm ratio (P < 0.0001), increased nuclear size (P < 0.0001), increased number of mitotic figures (P = 0.0006), and dyskeratosis (P = 0.008) were associated with severity of ED grade in the binary system. It seems that usage of binary ED grading system in AC may be more precise because there is correlation between many of cytological and some of architectural microscopic alterations with increased grade of ED. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sonographic findings of high-grade and non-high-grade ductal carcinoma in situ of the breast.

PubMed

Park, Ji-Sung; Park, Young-Mi; Kim, Eun-Kyung; Kim, Suk-Jung; Han, Sang-Suk; Lee, Sun-Joo; In, Hyun-Sin; Ryu, Ji-Hwa

2010-12-01

The purpose of this study was to differentiate between high-grade and non-high-grade ductal carcinoma in situ (DCIS) of the breast on sonography. From October 2003 to August 2009, 76 DCIS lesions in 73 women who underwent sonography and mammography were included in this study. Lesions were confirmed by mastectomy, breast-conserving surgery, or surgical biopsy. Images were analyzed by 2 radiologists with consensus and were correlated with histologic grades. Of the 76 lesions, 44 were classified as high--grade and 32 as non-high-grade DCIS. Fifty-seven lesions (75.0%) were identified on sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal changes in 4, and architectural distortion in 3. All cases with false-negative findings on sonography (n = 19) showed microcalcifications on mammography. On sonography, masses were more frequently found in non-high-grade (62.5%) than high-grade DCIS (22.7%; P < .01). No significant difference was seen in the sonographic features of masses between high-grade and non-high-grade DCIS. Microcalcifications were more common in high-grade (43.2%) than non-high-grade (3.1%) DCIS (P = .02). Most sonographically visible microcalcifications had associated findings such as ductal changes (n = 11), a mass (n = 7), or a hypoechoic area (n = 5). The detection rate of microcalcifications on sonography was higher in high-grade (62.9%) than non-high-grade DCIS (25.0%; P = .023). Microcalcifications with associated ductal changes (11 of 31 [35.5%]) were the most common sonographic findings in high-grade DCIS. An irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26 [50.0%]) was the most frequent finding in non-high-grade DCIS.

Patient, tumour and treatment factors affect complication rates in soft tissue sarcoma flap reconstruction in a synergistic manner.

PubMed

Slump, J; Ferguson, P C; Wunder, J S; Griffin, A M; Hoekstra, H J; Liu, X; Hofer, S O P; O'Neill, A C

2017-06-01

Flap reconstruction plays an essential role in the management of soft tissue sarcoma, facilitating wide resection while maximizing preservation of function. The addition of reconstruction increases the complexity of the surgery and identification of patients who are at high risk for post-operative complications is an important part of the preoperative assessment. This study examines predictors of complications in these patients. 294 patients undergoing flap reconstruction following sarcoma resection were evaluated. Data on patient, tumour and treatment variables as well as post-operative complications were collected. Bivariate and multivariate regression analysis was performed to identify independent predictors of complications. Analysis of synergistic interaction between key patient and tumour risk factors was subsequently performed. A history of cerebrovascular events or cardiac disease were found to be the strongest independent predictors of post-operative complications (OR 14.84, p = 0.003 and OR 5.71, p = 0.001, respectively). Further strong independent tumour and treatment-related predictors were high grade tumours (OR 1.91, p = 0.038) and the need for additional reconstructive procedures (OR 2.78, p = 0.001). Obesity had significant synergistic interaction with tumour resection diameter (RERI 1.1, SI 1.99, p = 0.02) and high tumour grade (RERI 0.86, SI 1.5, p = 0.01). Comorbidities showed significant synergistic interaction with large tumour resections (RERI 0.91, SI 1.83, p = 0.02). Patient, tumour and treatment-related variables contribute to complications following flap reconstruction of sarcoma defects. This study highlights the importance of considering the combined effect of multiple risk factors when evaluating and counselling patients as significant synergistic interaction between variables can further increase the risk of complications. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society

MRI differentiation of low-grade from high-grade appendicular chondrosarcoma.

PubMed

Douis, Hassan; Singh, Leanne; Saifuddin, Asif

2014-01-01

To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. • Accurate differentiation of low-grade from high-grade chondrosarcomas is essential before surgery • MRI can reliably differentiate high-grade from low-grade chondrosarcomas of long bone • Differentiating features are bone expansion, periostitis, soft tissue mass and tumour length • Presence of these four MRI features demonstrated a diagnostic accuracy (AUC) of 95.6 % • The findings

Soft Tissue Sarcoma

MedlinePlus

... begins in the lining of blood vessels, while liposarcoma arises from fat cells. Some types of soft ... sarcoma Gastrointestinal stromal tumor (GIST) Kaposi's sarcoma Leiomyosarcoma Liposarcoma Malignant peripheral nerve sheath tumor Myxofibrosarcoma Rhabdomyosarcoma Solitary ...

[The WHO/ISUP grading system for renal carcinoma].

PubMed

Moch, H

2016-07-01

Histological tumor grading is an accepted prognostic parameter of renal cell carcinoma (RCC). In 2012, the International Society of Urologic Pathologists (ISUP) proposed a novel grading system for RCC, mainly based on the evaluation of nucleoli: grade 1 tumors have nucleoli that are inconspicuous and basophilic at ×400 magnification; grade 2 tumors have nucleoli that are clearly visible at ×400 magnification and eosinophilic; grade 3 tumors have clearly visible nucleoli at ×100 magnification; and grade 4 tumors have extreme pleomorphism or rhabdoid and/or sarcomatoid morphology. This grading system was validated for clear cell renal cell carcinoma and papillary renal cell carcinoma. At the same time, the ISUP proposed not grading chromophobe renal cell carcinomas according to this system. At a consensus conference in Zurich the World Health Organization (WHO) recommended the ISUP grading system; thus, the WHO/ISUP grading system is now going to be implemented internationally. The ISUP/WHO grading system has not been validated as a prognostic parameter for other tumor subtypes, but can be used for descriptive purposes.

68Ga-DOTA-TOC Uptake in Pleomorphic Adenoma.

PubMed

Laurens, S Tom; Netea-Maier, Romana T; Aarntzen, Erik J H G

2018-07-01

A 56-year-old man who was recently diagnosed with a carcinoid tumor of the os petrosum was referred for a Ga-DOTA-TOC PET/CT scan. Besides the moderately increased Ga-DOTA-TOC accumulation in the carcinoid tumor, the scan showed strongly increased and focal Ga-DOTA-TOC uptake in an additional lesion in the right parotid gland. The markedly different Ga-DOTA-TOC avidity suggested a different etiology, and histological examination demonstrated a pleomorphic adenoma.

Outcomes and Toxicity for Hypofractionated and Single-Fraction Image-Guided Stereotactic Radiosurgery for Sarcomas Metastasizing to the Spine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Folkert, Michael R.; Bilsky, Mark H.; Tom, Ashlyn K.

2014-04-01

Purpose: Conventional radiation treatment (20-40 Gy in 5-20 fractions, 2-5 Gy per fraction) for sarcoma metastatic to the spine provides subtherapeutic doses, resulting in poor durable local control (LC) (50%-77% at 1 year). Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) may provide a more effective means of managing these lesions. Methods and Materials: Patients with pathologically proven high-grade sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. LC and overall survival (OS) were analyzed by the use of Kaplan-Meier statistics. Univariate and multivariate analyses were performed by the use of Cox regression with competing-risksmore » analysis; all confidence intervals are 95%. Toxicities were assessed according to Common Terminology Criteria for Adverse Events, version 4.0. Results: From May 2005 to November 11, 2012, 88 patients with 120 discrete metastases received HF (3-6 fractions; median dose, 28.5 Gy; n=52, 43.3%) or SF IG-SRS (median dose, 24 Gy; n=68, 56.7%). The median follow-up time was 12.3 months. At 12 months, LC was 87.9% (confidence interval [CI], 81.3%-94.5%), OS was 60.6% (CI, 49.6%-71.6%), and median survival was 16.9 months. SF IG-SRS demonstrated superior LC to HF IG-SRS (12-month LC of 90.8% [CI, 83%-98.6%] vs 84.1% [CI, 72.9%-95.3%] P=.007) and retained significance on multivariate analysis (P=.030, hazard ratio 0.345; CI, 0.132-0.901]. Treatment was well tolerated, with 1% acute grade 3 toxicity, 4.5% chronic grade 3 toxicity, and no grade >3 toxicities. Conclusions: In the largest series of metastatic sarcoma to the spine to date, IG-SRS provides excellent LC in the setting of an aggressive disease with low radiation sensitivity and poor prognosis. Single-fraction IG-SRS is associated with the highest rates of LC with minimal toxicity.« less

Primary low-grade fibromyxoid sarcoma of breast: A rare case report with immunohistochemical and fluorescence in situ hybridization detection.

PubMed

Master, Yutao Zhang; Master, Dan Wan; Master, Fuping Gao

2018-02-24

Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a bland histological appearance but malignant biological behavior. Primary LGFMS of breast has not been described in the English-language literature. Here, we report a 58-year-old Chinese female patient who presented with a painless mass in the right breast for more than 30 years. The tumor consists of spindle cells resembling fibroblasts and includes two kinds of morphological change, which are alternating collagenized hypocellular zone and cell-rich myxoid area. There are more arcades of curvilinear blood vessels. The spindle cells are not heteromorphic and mitotic figures are scarce. Immunostaining shows tumor cells are positive for vimentin, mucin4, CD99 and Bcl-2, but negative for SMA, desmin, S100, CD34, ALK and myogenin. FUS gene rearrangement is positively detected by FISH. The patient has been followed up for 59 months and is in a favorable condition. This rare location of LGFMS should be noted. Copyright © 2018. Published by Elsevier Inc.

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

PubMed

Shim, Jenny; Staruch, Robert M; Koral, Korgun; Xie, Xian-Jin; Chopra, Rajiv; Laetsch, Theodore W

2016-10-01

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors. © 2016 Wiley Periodicals, Inc.

Long-term recurrence rate of pleomorphic adenoma and postoperative facial nerve paresis (in parotid surgery).

PubMed

Zernial, Oliver; Springer, Ingo N; Warnke, Patrick; Härle, Franz; Risick, Christian; Wiltfang, Jörg

2007-04-01

The purpose of this study was to evaluate recurrence rates and comorbidity in patients with pleomorphic adenomas of patients after superficial and total conservative parotidectomy. Localization of pleomorphic adenomas, age, sex distribution and facial nerve function of 73 patients were examined in this retrospective study. The recurrence rate could be determined in 43 of these patients. The interval between surgery and last recall varied between 2 and 20 years (median: 8.1 years). Most of the patients were female (67%) with a parotid pleomorphic adenoma. No recurrence was found regard less of whether a superficial or total conservative parotidectomy had been performed. Our data did show that the total conservative parotidectomy is associated with a higher incidence of temporary impaired facial nerve function, which was seen in 42% of this group. Temporary decreased nerve function after superficial parotidectomy was rare being apparent in only 16% of this group. A more radical procedure does not significantly lower the recurrence rate. We suggest that the indication for a total conservative parotidectomy in cases of superficial adenomas should be considered carefully.

Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA.

PubMed

Hayashi, Masanori; Chu, David; Meyer, Christian F; Llosa, Nicolas J; McCarty, Gregory; Morris, Carol D; Levin, Adam S; Wolinsky, Jean-Paul; Albert, Catherine M; Steppan, Diana A; Park, Ben Ho; Loeb, David M

2016-10-01

Even though virtually all patients with Ewing sarcoma achieve a radiographic complete response, up to 30% of patients who present with localized disease and up to 90% of those who present with metastases experience a metastatic disease recurrence, highlighting the inability to identify patients with residual disease at the end of therapy. Up to 95% of Ewing sarcomas carry a driving EWS-ETS translocation that has an intronic breakpoint that is specific to each tumor, and the authors developed a system to quantitatively detect the specific breakpoint DNA fragment in patient plasma. The authors used a long-range multiplex polymerase chain reaction (PCR) technique to identify tumor-specific EWS-ETS breakpoints in Ewing sarcoma cell lines, patient-derived xenografts, and patient tumors, and this sequence was used to design tumor-specific primer sets to detect plasma tumor DNA (ptDNA) by droplet digital PCR in xenograft-bearing mice and patients. Tumor-specific breakpoint DNA fragments were detected in the plasma of xenograft-bearing mice, and the signal correlated with tumor burden during primary tumor growth, after surgical resection, and at the time of metastatic disease recurrence. Furthermore, the authors were able to detect the specific breakpoint in plasma DNA obtained from 3 patients with Ewing sarcoma and in 2 patients the authors were able to detect ptDNA when there was radiographically undetectable disease present. The use of droplet digital PCR to detect tumor-specific EWS-ETS fusion gene breakpoint ptDNA fragments can be developed into a highly personalized biomarker of disease recurrence that can be optimized in animal studies for ultimate use in patients. Cancer 2016;122:3015-3023. © 2016 American Cancer Society. © 2016 American Cancer Society.

Neurotensin receptors in human neoplasms: high incidence in Ewing's sarcomas.

PubMed

Reubi, J C; Waser, B; Schaer, J C; Laissue, J A

1999-07-19

Receptors for regulatory peptides, such as somatostatin or vasoactive intestinal peptide (VIP), expressed at high density by neoplastic cells, can be instrumental for tumor diagnosis and therapy. Little is known about the expression of neurotensin receptors in human tumors. In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand. Neurotensin receptors were identified and localized in tumor cells of 11/17 Ewing's sarcomas, 21/40 meningiomas, 10/23 astrocytomas, 5/13 medulloblastomas, 7/24 medullary thyroid cancers and 2/8 small cell lung cancers. They were rarely found in non-small cell lung cancers and breast carcinomas; they were absent in prostate, ovarian, renal cell and hepatocellular carcinomas, neuroendocrine gut tumors, pituitary adenomas, schwannomas, neuroblastomas and lymphomas. When present, the receptors bound with nanomolar affinity neurotensin and acetyl-neurotensin-(8-13), with lower affinity neuromedin N, diethylenetriamine penta-acetic acidneurotensin-(8-13) and SR 48692, but not neurotensin-(1-11). They were all of the NT1 type, without high affinity for levocabastine. Further, in 2 receptor-positive Ewing's sarcomas, neurotensin mRNA was detected by in situ hybridization techniques. Since neurotensin is known to stimulate cell proliferation, the presence of neurotensin receptors in human neoplasia may be of biological relevance, possibly as an integrative part of an autocrine feedback mechanism of tumor growth stimulation.

Advances in sarcoma genomics and new therapeutic targets

PubMed Central

Taylor, Barry S.; Barretina, Jordi; Maki, Robert G.; Antonescu, Cristina R.; Singer, Samuel; Ladanyi, Marc

2012-01-01

Preface Increasingly, human mesenchymal malignancies are classified by the abnormalities that drive their pathogenesis. While many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities and in many cases are resistant to adjuvant therapies. In this Review, we discuss the core molecular determinants of sarcomagenesis and emphasize the emerging genomic and functional genetic approaches that, coupled to novel therapeutic strategies, have the potential to transform the care of patients with sarcoma. PMID:21753790

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

PubMed Central

Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

2011-01-01

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

Variations of Surveillance Practice for Patients with Bone Sarcoma: A Survey of Australian Sarcoma Clinicians

PubMed Central

Thompson, Kate; Bae, Susie; Desai, Jayesh; Strong, Robyn; Caruso, Denise; Howell, Deborah; Herschtal, Alan; Sullivan, Michael; Orme, Lisa

2017-01-01

Introduction. After treatment, bone sarcoma patients carry a high chance of relapse and late effects from multimodal therapy. We hypothesize that significant variation in surveillance practice exists between pediatric medical oncology (PO) and nonpediatric medical oncology (NP) sarcoma disciplines. Methods. Australian sarcoma clinicians were approached to do a web based survey that assessed radiologic surveillance (RS) strategies, late toxicity assessment, and posttreatment psychosocial interventions. Results. In total, 51 clinicians responded. No differences were identified in local disease RS. In metastatic disease response assessment, 100% of POs (23/23) and 93% of NPs (24/26) conducted CT chest. However, this was more likely to occur for NPs in the context of a CT chest/abdomen/pelvis (NP: 10/26; PO: 1/23; p = 0.006). POs were more likely to use CXR for RS (p = 0.006). POs showed more prescriptive intensity in assessment of heart function (p = 0.001), hearing (p < 0.001), and fertility (p = 0.02). POs were more likely to deliver written information for health maintenance/treatment summary (p = 0.04). The majority of respondents described enquiring about psychosocial aspects of health (n = 33/37, 89%), but a routine formal psychosocial screen was only used by 23% (n = 6/26). Conclusion. There is high variability in bone sarcoma surveillance between PO and NP clinicians. Efforts to harmonize approaches would allow early and late effects recognition/intervention and facilitate improved patient care/transition and research. PMID:28348507

PHASE II STUDY OF HIGH DOSE PHOTON/PROTON RADIOTHERAPY IN THE MANAGEMENT OF SPINE SARCOMAS

PubMed Central

DeLaney, Thomas F.; Liebsch, Norbert J.; Pedlow, Francis X.; Adams, Judith; Dean, Susan; Yeap, Beow Y.; McManus, Patricia; Rosenberg, Andrew E.; Nielsen, G. Petur; Harmon, David C.; Spiro, Ira J.; Raskin, Kevin A.; Suit, Herman D.; Yoon, Sam S.; Hornicek, Francis J.

2009-01-01

Purpose Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of ≥ 66 Gy are recommended. A Phase II clinical trial evaluated high dose photon/proton XRT for spine sarcomas. Materials/Methods Eligible patients had non-metastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or post-op photon/proton XRT +/- radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (GyRBE) to subclinical disease, 70.2 GyRBE to microscopic disease in the tumor bed, and 77.4 GyRBE to gross disease at 1.8 GyRBE q.d. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 GyRBE to surface/center. Intra-operative boost doses of 7.5-10 Gy could be given by dural plaque. Results 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n=25) or subtotal (n=12) resection or biopsy (n=13). With 48 month median follow-up, five-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence, p<0.001. Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared following 77.12-77.4 GyRBE. Conclusions Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 GyRBE are at risk for late toxicity. PMID:19095372

Phase II Study of High-Dose Photon/Proton Radiotherapy in the Management of Spine Sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeLaney, Thomas F.; Liebsch, Norbert J.; Pedlow, Francis X.

Purpose: Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of {>=}66 Gy are recommended. A Phase II clinical trial evaluated high-dose photon/proton XRT for spine sarcomas. Methods and Materials: Eligible patients had nonmetastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or postoperative photon/proton XRT with or without radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (Gy RBE) to subclinical disease, 70.2 Gy RBE to microscopic disease in the tumor bed, and 77.4 Gy RBE to grossmore » disease at 1.8 Gy RBE qd. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 Gy RBE to surface/center. Intraoperative boost doses of 7.5 to 10 Gy could be given by dural plaque. Results: A total of 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). With 48 month median follow-up, 5-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence (p < 0.001). Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared after 77.12 to 77.4 Gy RBE. Conclusions: Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 Gy RBE are at risk for late toxicity.« less

Vinorelbine Tartrate and Cyclophosphamide in Combination With Bevacizumab or Temsirolimus in Treating Patients With Recurrent or Refractory Rhabdomyosarcoma

ClinicalTrials.gov

2017-03-24

Adult Rhabdomyosarcoma; Childhood Alveolar Rhabdomyosarcoma; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma

Pleomorphic Rhabdomyosarcoma Arising from True Vocal Fold of Larynx: Report of a Rare Case and Literature Review.

PubMed

Mungan, Sevdegül; Arslan, Selçuk; Küçüktülü, Eda; Ersöz, Şafak; Çobanoğlu, Bengü

2016-01-01

We present an extremely rare case of a pleomorphic rhabdomyosarcoma of the true vocal fold. The histopathological diagnosis was confirmed by immunohistochemistry. The patient was treated with radical surgery including total laryngectomy and radical neck dissection followed by postoperative radiotherapy. The clinicopathologic features of this rare malignancy are discussed together with a review of the literature. This case report and literature review highlights the more favorable prognosis of pleomorphic rhabdomyosarcoma in the larynx than in other locations.

[Immunohistochemistry in the diagnosis of sarcomas].

PubMed

Decouvelaere, Anne-Valérie

2015-01-01

Immunohistochemistry (IHC) is essential in the diagnosis of soft tissue tumor and must rely on good quality technic. Among useful antibodies, it is important to distinguish those with a poor specificity required in order to establish the broad lineage, from those with high specificity, which may lead straightforward towards the entity. Diagnostically useful antibodies such as myogenin, ALK1 and DOG1 have been recently completed by MUC4 and STAT6 which show good sensitivity and specificity in the diagnosis of low-grade fibromyxoid sarcoma and solitary fibrous tumor respectively. ERG is also an interesting antibody. However, it is not completely specific of vascular tumors. Moreover, available material is often limited because of the increase of microbiopsy specimens. Therefore, it is mandatory to optimize this precious tissue by using these new antibodies, especially because molecular technics are increasingly performed in addition to IHC. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Fractal analysis for assessing tumour grade in microscopic images of breast tissue

NASA Astrophysics Data System (ADS)

Tambasco, Mauro; Costello, Meghan; Newcomb, Chris; Magliocco, Anthony M.

2007-03-01

In 2006, breast cancer is expected to continue as the leading form of cancer diagnosed in women, and the second leading cause of cancer mortality in this group. A method that has proven useful for guiding the choice of treatment strategy is the assessment of histological tumor grade. The grading is based upon the mitosis count, nuclear pleomorphism, and tubular formation, and is known to be subject to inter-observer variability. Since cancer grade is one of the most significant predictors of prognosis, errors in grading can affect patient management and outcome. Hence, there is a need to develop a breast cancer-grading tool that is minimally operator dependent to reduce variability associated with the current grading system, and thereby reduce uncertainty that may impact patient outcome. In this work, we explored the potential of a computer-based approach using fractal analysis as a quantitative measure of cancer grade for breast specimens. More specifically, we developed and optimized computational tools to compute the fractal dimension of low- versus high-grade breast sections and found them to be significantly different, 1.3+/-0.10 versus 1.49+/-0.10, respectively (Kolmogorov-Smirnov test, p<0.001). These results indicate that fractal dimension (a measure of morphologic complexity) may be a useful tool for demarcating low- versus high-grade cancer specimens, and has potential as an objective measure of breast cancer grade. Such prognostic value could provide more sensitive and specific information that would reduce inter-observer variability by aiding the pathologist in grading cancers.

Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion.

PubMed

Mok, Yingting; Pang, Yin Huei; Sanjeev, Jain Sudhanshi; Kuick, Chik Hong; Chang, Kenneth Tou-En

2018-01-01

Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features of both entities are considered hybrid LGFMS-SEF lesions. While the majority of LGFMS cases are characterized by FUS-CREB3L2 gene fusions, most cases of pure SEF show EWSR1 gene rearrangements. In the largest study of hybrid LGFMS-SEF tumors to date, all cases exhibited FUS rearrangements, a similar genetic profile to LGFMS. We herein describe the clinicopathological features and genetic findings of a case of primary renal hybrid LGFMS-SEF occurring in a 10-year-old child, with disseminated metastases. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was performed on both the primary renal tumor that showed the morphology of a LGFMS, and a cervical metastasis that showed the morphology of SEF. An EWSR1-CREB3L1 gene fusion occurring between exon 11 of EWSR1 and exon 6 of CREB3L1 was present in both the LGFMS and SEF components. This unusual case provides evidence that a subset of hybrid LGFMS-SEF harbor EWSR1-CREB3L1 gene fusions. In this case, these features were associated with an aggressive clinical course, with disease-associated mortality occurring within 12 months of diagnosis.

[Demographic Analysis of Patients with Osteosarcoma, Chonddrosarcoma, Ewing's Sarcoma from one Sarcoma Center in Switzerland].

PubMed

Hodel, Sandro; Seeli, Franziska; Fuchs, Bruno

2015-06-17

Retrospective analysis of presentation, diagnosis and outcome of patients with osteosarcoma, chondrosarcoma and Ewing's sarcoma was performed for a single Sarcoma Center in Zurich at the University Hospital Balgrist. 201 patients were included. Overall survival at five and ten years were 74 ± 6%, 69 ± 7% for osteosarcoma (n = 85, since 2000), 85 ± 7%, 80 ± 9% for Ewing's sarcoma (n = 43, since 1990) and 86 ± 5%, 78 ± 9% for chondrosarcoma (n = 73, since 2000). The here presented overall survival rates from a single Sarcoma Center in Switzerland appear to be equivalent to other large international monocenter studies. The presentation and epidemiology of these patients are in accordance with large multicenter epidemiological studies. A nationwide sarcoma database (SwissSARCOS; www.sarcoma.ch) seems indispensable for more detailed analysis and quality management in such rare diseases.

Vascular Pattern Analysis on Microvascular Sonography for Differentiation of Pleomorphic Adenomas and Warthin Tumors of Salivary Glands.

PubMed

Ryoo, Inseon; Suh, Sangil; Lee, Young Hen; Seo, Hyung Suk; Seol, Hae Young; Woo, Jeong-Soo; Kim, Soo Chin

2018-03-01

Pleomorphic adenomas and Warthin tumors are the most common salivary gland tumors. It is important to differentiate between them because at least a partial parotidectomy is necessary for pleomorphic adenomas, whereas enucleation is sufficient for Warthin tumors. This study aimed to evaluate the usefulness of vascular pattern analysis using microvascular sonography to differentiate between the tumors. Sixty-two patients with pathologically proven pleomorphic adenomas (n = 38) and Warthin tumors (n = 24) were included. For all tumors, grayscale, power Doppler, and microvascular sonographic examinations were performed. Differences in vascular patterns (vascular distribution and internal vascularity) on power Doppler and microvascular sonography as well as grayscale sonographic features (size, shape, border, echogenicity, heterogeneity, and cystic change) between pleomorphic adenomas and Warthin tumors were evaluated. A comparison of diagnostic performances of grayscale sonography with power Doppler sonography and grayscale sonography with microvascular sonography was performed. The level of interobserver agreement between 2 reviewers in diagnosing tumors was evaluated. No grayscale sonographic features showed a significant difference between the tumors. Vascular distributions and internal vascularity on power Doppler sonography (P = .01 and .002) and microvascular sonography (both P < .001) were all significantly different. The diagnostic accuracy of grayscale sonography with microvascular sonography (79.0%) was higher than that of grayscale sonography with power Doppler sonography (72.6%). This difference was significant according to the McNemar test (P = .004). Interobserver agreement was excellent in diagnosing tumors on both grayscale sonography with power Doppler sonography (κ = 0.83) and grayscale sonography with microvascular sonography (κ = 0.94). Vascular pattern analysis using microvascular sonography with other sonographic

Morphological and immunohistochemical diversity of endometrial stromal sarcoma in rats.

PubMed

Kumabe, Shino; Sato, Junko; Tomonari, Yuki; Takahashi, Miwa; Inoue, Kaoru; Yoshida, Midori; Doi, Takuya; Wako, Yumi; Tsuchitani, Minoru

2018-04-01

To clarify the histopathological characteristics of rat endometrial stromal sarcoma (ESS), we morphologically reviewed 12 malignant uterine tumors protruding into the lumen in previous rat carcinogenicity studies. The 12 cases were classified into the following 6 types based on their morphological features: spindle cell and collagen rich type, pleomorphic/spindle cell and compact type, decidual alteration type, histiocytic and multinucleated giant cell mixture type, Antoni A-type schwannoma type, and Antoni B-type schwannoma type. Immunohistochemically, tumor cells in all cases exhibited focal or diffuse positive reactions for vimentin, and 11 of the 12 cases were positive for S-100. Interestingly, 9 cases were positive for desmin or αSMA, indicating tumor cells expressing smooth muscle properties. Both Antoni A- and B-type schwannoma types showed low reactions for both muscle markers. Positive results for estrogen receptor α in the 11 cases suggested that they were derived from endometrial stromal cells. On the basis of their immunohistochemical profiles, they were considered to be derived from endometrial stromal cells while they showed morphological variation. The detection of a basement membrane surrounding tumor cells might not be a definitive indicator for differential diagnosis of ESS from malignant schwannoma. In conclusion, ESS could exhibit wide morphological and immunohistochemical variation including features of schwannoma or smooth muscle tumor.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.

Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportionalmore » hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.« less

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

PubMed

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Imaging and Outcomes for a New Entity: Low-Grade Sinonasal Sarcoma with Neural and Myogenic Features.

PubMed

Cannon, Richard B; Wiggins, Richard H; Witt, Benjamin L; Dundar, Yusuf; Johnston, Tawni M; Hunt, Jason P

2017-01-01

Objectives  Low-grade sinonasal sarcoma with neural and myogenic features (LGSSNMF) is a new, rare tumor. Our goal is to describe the imaging characteristics and surgical outcomes of this unique skull base malignancy. Design  Retrospective case series. Setting  Academic medical center. Participants  There were three patients who met inclusion criteria with a confirmed LGSSNMF. Main Outcome Measures  Imaging and histopathological characteristics, treatments, survival and recurrence outcomes, complications, morbidity, and mortality. Results  Patients presented with diplopia, facial discomfort, a supraorbital mass, and nasal obstruction. Magnetic resonance imaging and computed tomography imaging in all cases showed an enhancing sinonasal mass with associated hyperostotic bone formation that involved the frontal sinus, invaded the lamina papyracea and anterior skull base, and had intracranial extension. One patient underwent a purely endoscopic surgical resection and the second underwent a craniofacial resection, while the last is pending treatment. All patients recovered well, without morbidity or long-term complications, and are currently without evidence of disease (mean follow-up of 2.1 years). One patient recurred after 17 months and underwent a repeat endoscopic skull base and dural resection. Conclusions  The surgical outcomes and imaging of this unique, locally aggressive skull base tumor are characterized.

Trial of Dasatinib in Advanced Sarcomas

ClinicalTrials.gov

2017-03-20

Rhabdomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Chondrosarcoma; Sarcoma, Ewing's; Sarcoma, Alveolar Soft Part; Chordoma; Epithelioid Sarcoma; Giant Cell Tumor of Bone; Hemangiopericytoma; Gastrointestinal Stromal Tumor (GIST)

Carcinoma ex pleomorphic adenoma, with particular emphasis on early lesions.

PubMed

Di Palma, Silvana

2013-07-01

Carcinoma ex pleomorphic adenoma (CXPA) is a broad category of carcinomas of the salivary glands which includes at least 2 clinically relevant categories; one is referred here as early CXPA (ECXPA), the other as widely invasive CXPA. The former includes several histological patterns ranging from non-invasive/in situ/intraductal/intratubular, early invasive/extratubular/intracapsular and extracapsular (up to 6 mm). The latter includes any CXPA with invasion of >6 mm. The clinical behaviour of ECXPA is not aggressive and tends to overlap that of a pleomorphic adenoma (PA) which makes the histological report of carcinoma contradictory. These early malignant changes in PA are known since the 1970s but it has been the use of immunohistochemical and molecular genetic analysis for HER-2 and TP53 gene in the last decade that has clarified the genuine malignant nature of the cells. HER-2 and TP53 gene and protein are involved in the early stages of malignant transformation of PA. Moreover the immunohistochemical over-expression HER-2, p53 protein and Mib-1 proliferation marker may be useful markers to identify malignant areas in PA.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

PubMed

Ilic, Ivan R; Djordjevic, Nebojsa P; Randjelovic, Pavle J; Stojanovic, Nikola M; Radulovic, Niko S; Ilic, Ratko S

2016-01-01

The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

Sarcomas of nasal cavity and paranasal sinuses: chondrosarcoma, osteosarcoma and fibrosarcoma.

PubMed

Koka, V; Vericel, R; Lartigau, E; Lusinchi, A; Schwaab, G

1994-11-01

Forty-two patients were treated for sarcoma of the nasal cavity and paranasal sinuses at the Institut Gustave Roussy, Paris, between 1960 and 1993. Twelve patients had chondrosarcoma (CS), 14 had osteosarcoma (OS) and 16 had fibrosarcoma (FS). Ten patients had grade I, six grade II and 26 grade III tumours. All but 10 patients had surgery for the primary tumour. A significantly increased risk of local failure was associated with the male sex (p < 0.01), grade III tumours (p < 0.02) and patients excluded from surgery (p < 0.04). The overall incidence of local and distant failure was 76 and 12 per cent respectively. Overall survival was 28 per cent at three years and 23 per cent at five years. Eight patients (20 per cent) were alive more than 10 years later. The factors significantly influencing survival were sex (p < 0.01), grade (p < 0.05) and local failure (p < 0.01).

Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.

PubMed

Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T W; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S; Raman, Pichai; Waanders, Angela J; Resnick, Adam C; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascale; Jones, Chris

2018-05-14

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8 + tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term "HGG" in the pediatric population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG).

PubMed

2018-04-01

Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%-0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

PubMed

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Sam S., E-mail: syoon@partners.org; Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA; Duda, Dan G.

Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with {>=}5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor sizemore » of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in {>=}80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen

Patients with Advanced, Rare Sarcoma Respond to Cediranib | Center for Cancer Research

Cancer.gov

Alveolar soft part sarcomas (ASPS) are highly vascular tumors that usually affect adolescents and young adults. Comprising less than one percent of soft tissue sarcomas, ASPS can be cured with surgery. However, its tendency to metastasize and its lack of response to standard soft tissue sarcoma chemotherapy regimens makes ASPS a particularly lethal cancer with a five-year

A rare case of dedifferentiated liposarcoma of the sinonasal cavity: A case report.

PubMed

Miyazaki, Masaru; Aoki, Mikiko; Oba, Satoru; Sakata, Toshifumi; Nakagawa, Takashi; Nabeshima, Kazuki

2017-10-01

Sarcoma is an uncommon histopathological presentation of sinonasal tumors, comprising ~15% of all cases; liposarcoma is particularly uncommon. An analysis of the available medical literature revealed no prior reports of dedifferentiated liposarcoma (DDLPS) of the sinonasal cavity. This case report presents a rare case of DDLPS of the sinonasal cavity. A 40-year old six-week pregnant female was admitted with a left nasal obstruction. Endoscopic evaluation of the left nasal cavity revealed a polypoid lesion. A computed tomography scan indicated a mass invading the left nasal cavity, maxillary sinus and anterior ethmoid sinus with focal destruction of the surrounding bone. A biopsy of the tumor was performed and hematoxylin and eosin staining of the tissue sections revealed proliferation of atypical and pleomorphic spindle cells with enlarged or elongated hyperchromatic nuclei and occasional vacuolated cytoplasm arranged in short interlacing fascicles or storiform structures, accompanied by tumor necrosis. These findings were consistent with undifferentiated pleomorphic sarcoma. Immunohistochemically, the tumor cells were positive for cyclin dependent kinase 4, mouse double minute 2 homolog (MDM2) and adipophilin. Fluorescence in situ hybridization (FISH) analysis revealed amplification of the MDM2 gene. Recently, undifferentiated pleomorphic sarcoma without areas of well-differentiated liposarcoma but with MDM2 amplification is regarded as conventional DDLPS. In the present case, the tumor was diagnosed as a DDLPS due to the results of histopathological, immunohistochemical and FISH analysis.

Stages of Ewing Sarcoma

MedlinePlus

... for Ewing sarcoma have an increased risk of acute myeloid leukemia and myelodysplastic syndrome . There is also an increased risk of sarcoma in the area treated with radiation therapy . Some late effects may be treated or ...

CIC-DUX4 Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma.

PubMed

Yoshimoto, Toyoki; Tanaka, Miwa; Homme, Mizuki; Yamazaki, Yukari; Takazawa, Yutaka; Antonescu, Cristina R; Nakamura, Takuro

2017-06-01

CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). However, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here, we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA. Recipient mice transplanted with eMC-expressing CIC-DUX4 rapidly developed an aggressive, undifferentiated sarcoma composed of small round to short spindle cells. Gene-expression profiles of CDS and eMC revealed upregulation of CIC-DUX4 downstream genes such as PEA3 family genes, Ccnd2, Crh , and Zic1 IHC analyses for both mouse and human tumors showed that CCND2 and MUC5AC are reliable biomarkers to distinguish CDS from ES. Gene silencing of CIC-DUX4 as well as Ccnd2, Ret , and Bcl2 effectively inhibited CDS tumor growth in vitro The CDK4/6 inhibitor palbociclib and the soft tissue sarcoma drug trabectedin also blocked the growth of mouse CDS. In summary, our mouse model provides important biological information about CDS and provides a useful platform to explore biomarkers and therapeutic agents for CDS. Cancer Res; 77(11); 2927-37. ©2017 AACR . ©2017 American Association for Cancer Research.

AIDS associated Kaposi's sarcoma.

PubMed

Thomas, Sumi; Sindhu, C B; Sreekumar, S; Sasidharan, P K

2011-06-01

Epidemic Kaposi's sarcoma (KS) is the most common malignant neoplasm occuring in HIV patients. Although the prevalence of HIV infection is high in Asian countries, KS is rarely reported. We report a case of fatal KS involving the skin and mucous membranes in a homosexual male.

Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

PubMed

Nannini, Nazarena; Rebusso, Alessandro; Lunardi, Francesca; Loy, Monica; Calabrese, Francesca; Battistella, Lucia; Schiavon, Marco; Rea, Federico; Calabrese, Fiorella

2017-08-01

Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

[Update on soft tissue sarcomas].

PubMed

Bui, Binh Nguyen; Tabrizi, Reza; Dagada, Corinne; Trufflandier, Nathalie; St ckle, Eberhard; Coindre, Jean-Michel

2002-01-01

Important refinements have taken place in the diagnosis of soft tissue sarcoma with extensive use of immuno-histochemistry. New entities have been described, while malignant histiocytofibroma, the most diagnosed sarcoma type during the last two decades, has been dismembered. As for prognosis, the new UICC classification is effectively more discriminating in the definition of prognostic groups; but the usefullness of new biological or genetic markers remains to be assessed. Several breakthrough have taken place in the last years in the treatment of soft tissue sarcoma. Isolated limb perfusion with TNF, hyperthermia and melphalan have proven its efficacy, and is now an alternative to preoperative chemotherapy and/or radiotherapy for limb sparing treatment of the primary tumor site or to amputation. For systemic treatments, novel cytostatic drugs have been shown to be active in sarcomas, including ecteinascidine (ET743) and Glivec (STI571). This last drug has been shown to be remarkably active in c-kit+ stromal sarcoma of the gastro-intestinal tract. It can hopefully regarded as an example for targeted therapies, which may come with a better understanding of the molecular mechanisms triggered by the fundamental, specific genetic alterations shown in sarcoma.

Intraoperative extracorporeal autogenous irradiated tendon grafts for functional limb salvage surgery of soft tissue sarcomas of the wrist and hand.

PubMed

Omori, Shinsuke; Hamada, Kenichiro; Outani, Hidetatsu; Oshima, Kazuya; Joyama, Susumu; Tomita, Yasuhiko; Naka, Norifumi; Araki, Nobuhito; Yoshikawa, Hideki

2015-05-12

In patients with soft tissue sarcoma of the wrist and hand, limb salvage operation is extremely challenging for surgeons in attempting a complete tumor resection with negative surgical margins. In this study, we report four patients with soft tissue sarcoma of the wrist and hand treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts. The patients were all male, and the mean age at the time of surgery was 45 years. Histological diagnoses included clear cell sarcoma in two patients, synovial sarcoma in one, and angiosarcoma in one. All four patients had high grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage III disease and one with AJCC stage IV disease. The tumors were resected en bloc with involved tendons. The tendons were isolated from the resected tissues, irradiated ex vivo, and re-implanted into the host tendons. In one patient, the bone was resected additionally because of tumor invasion to the bone. Hand function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system. Of the four patients, three died of distant metastatic disease. The remaining patient lives and remains disease-free. The mean follow-up period was 33 months. One patient had local recurrence outside the irradiated graft at 20 months after surgery. The functional rating was 22. Lower scores were seen in patients with reconstruction of flexor tendons than extensor tendons. Limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts is an acceptable method in selected patients with soft tissue sarcoma of the wrist and hand.

State of the art in myeloid sarcoma.

PubMed

Klco, J M; Welch, J S; Nguyen, T T; Hurley, M Y; Kreisel, F H; Hassan, A; Lind, A C; Frater, J L

2011-12-01

Myeloid sarcomas are extramedullary lesions composed of myeloid lineage blasts that typically form tumorous masses and may precede, follow, or occur in the absence of systemic acute myeloid leukemia. They most commonly involve the skin and soft tissues, lymph nodes, and gastrointestinal tract and are particularly challenging to diagnose in patients without an antecedent history of acute myeloid leukemia. We conducted a search of the English language medical literature for recent studies of interest to individuals involved in the diagnosis of myeloid sarcoma. The differential diagnosis includes non-Hodgkin lymphoma, blastic plasmacytoid dendritic cell neoplasm, histiocytic sarcoma, melanoma, carcinoma, and (in children) small round blue cell tumors. The sensitivity and specificity of immunohistochemical markers must be considered when evaluating a suspected case of myeloid sarcoma. A high percentage of tested cases have cytogenetic abnormalities. A minimal panel of immunohistochemical markers should include anti-CD43 or anti-lysozyme as a lack of immunoreactivity for either of these sensitive markers would be inconsistent with a diagnosis of myeloid sarcoma. Use of more specific markers of myeloid disease, such as CD33, myeloperoxidase, CD34 and CD117 is necessary to establish the diagnosis. Other antibodies may be added depending on the differential diagnosis. Identification of acute myeloid leukemia-associated genetic lesions may be helpful in arriving at the correct diagnosis. © 2011 Blackwell Publishing Ltd.

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.

PubMed

Pinheiro, Céline; Penna, Valter; Morais-Santos, Filipa; Abrahão-Machado, Lucas F; Ribeiro, Guilherme; Curcelli, Emílio C; Olivieri, Marcus V; Morini, Sandra; Valença, Isabel; Ribeiro, Daniela; Schmitt, Fernando C; Reis, Rui M; Baltazar, Fátima

2014-05-09

Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters. MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.

MET exon 14 skipping mutation in triple-negative pulmonary adenocarcinomas and pleomorphic carcinomas: An analysis of intratumoral MET status heterogeneity and clinicopathological characteristics.

PubMed

Kwon, Dohee; Koh, Jaemoon; Kim, Sehui; Go, Heounjeong; Kim, Young A; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Jeon, Yoon Kyung; Chung, Doo Hyun

2017-04-01

MET mutations leading to exon 14 skipping rarely occur in non-small cell lung cancer (NSCLC). Recently, small molecule inhibitors targeting MET mutations showed clinical benefit. However, the clinicopathological characteristics of NSCLC harboring MET mutations, and the correlation among mutations, protein expression, and gene copy number of MET in NSCLC remain unclear. Therefore, we address these issues. MET exon 14 skipping mutations were evaluated using real-time quantitative reverse-transcription-PCR (qRT-PCR) in 102 triple-negative (i.e., EGFR mutation (-)/ALK translocation (-)/KRAS mutation (-)) pulmonary adenocarcinomas, and 45 pleomorphic carcinomas. MET mutation and gene copy were also examined in microdissected tissues obtained from tumor areas with heterogeneous MET immunohistochemical expression. MET mutations were detected in 8.8% (9/102) of triple-negative adenocarcinomas and 20% (9/45) of pleomorphic carcinomas of the lung. Patients with MET-mutated adenocarcinomas was significantly older than those without MET mutations (P=0.015). The male to female and ever-to never-smoker ratios were 3:6 and 2:7, respectively, among patients with MET-mutated adenocarcinomas. All (9/9) of the MET-mutated adenocarcinomas showed acinar predominant histology with associated lepidic patterns. In contrast, the male to female and ever- to never-smoker ratios were 8:1 and 7:1, respectively, among patients with MET-mutated pleomorphic carcinomas. The carcinoma component of MET-mutated pleomorphic carcinomas was mostly adenocarcinoma of acinar pattern (8/9). MET mutation was detected by qRT-PCR in all samples with heterogeneous MET expression microdissected from five cases with MET-mutated adenocarcinoma, while MET gene amplification was detected in tumor areas expressing high MET protein levels among MET-mutated adenocarcinomas. MET-mutated NSCLC is characterized by older age in patients with adenocarcinoma and by an acinar histology and variable MET expression in patients

Proximal-type epithelioid sarcoma - Case report*

PubMed Central

dos Santos, Luciana Mendes; Nogueira, Lisiane; Matsuo, Christiane Yuri; Talhari, Carolina; Santos, Mônica

2013-01-01

Epithelioid sarcoma, first described by Enzinger in 1970, is a rare soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in distal portions of the extremities of adolescents and young adults. In 1997, Guillou et al. described a different type of epithelioid sarcoma, called proximal-type epithelioid sarcoma, which is found mostly in the pelvic and perineal regions and genital tracts of young to middle-aged adults. It is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. In this paper we present a case of proximal-type epithelioid sarcoma with an aggressive clinical course, including distant metastasis and death nine months after diagnosis. PMID:23793215

Thermal Dose is Related to Duration of Local Control in Canine Sarcomas Undergoing Thermoradiotherapy

PubMed Central

Thrall, Donald E.; LaRue, Susan M.; Yu, Daohai; Samulski, Thaddeus; Sanders, Linda; Case, Beth; Rosner, Gary; Azuma, Chieko; Poulson, Jeannie; Pruitt, Amy F.; Stanley, Wilma; Hauck, Marlene L.; Williams, Laurel; Hess, Paul; Dewhirst, Mark W.

2009-01-01

Purpose To test that prospective delivery of higher thermal dose is associated with longer tumor control duration. Experimental Design 122 dogs with a heatable soft tissue sarcoma were randomized to receive a low (2–5 CEM43°CT90) or high (20–50 CEM43°CT90) thermal dose in combination with radiotherapy. Most dogs (90%) received 4–6 hyperthermia treatments over 5 weeks. Results In the primary analysis, median (95% CI) duration of local control in the low dose group was 1.2 (0.7–2.1) years versus 1.9 (1.4–3.2) years in the high dose group (logrank p=0.28). The probability (95% CI) of tumor control at one year in the low vs. high dose groups was 0.57 (0.43–0.70) vs. 0.74 (0.62–0.86), respectively. Using multivariable procedure, thermal dose group (p=0.023), total duration of heating (p=0.008), tumor volume (p=0.041) and tumor grade (p=0.027) were significantly related to duration of local tumor control. When correcting for volume, grade and duration of heating, dogs in the low dose group were 2.3 times as likely to experience local failure. Conclusions Thermal dose is directly related to local control duration in irradiated canine sarcomas. Longer heating being associated with shorter local tumor control was unexpected. However, the effect of thermal dose on tumor control was stronger than for heating duration. The heating duration effect is possibly mediated through deleterious effects on tumor oxygenation. These results are the first to show the value of prospectively controlled thermal dose in achieving local tumor control with thermoradiotherapy, and they establish a paradigm for prescribing thermoradiotherapy and writing a thermal prescription. PMID:16033838

The financial burden of reexcising incompletely excised soft tissue sarcomas: a cost analysis.

PubMed

Alamanda, Vignesh K; Delisca, Gadini O; Mathis, Shannon L; Archer, Kristin R; Ehrenfeld, Jesse M; Miller, Mark W; Homlar, Kelly C; Halpern, Jennifer L; Schwartz, Herbert S; Holt, Ginger E

2013-09-01

Although survival outcomes have been evaluated between those undergoing a planned primary excision and those undergoing a reexcision following an unplanned resection, the financial implications associated with a reexcision have yet to be elucidated. A query for financial data (professional, technical, indirect charges) for soft tissue sarcoma excisions from 2005 to 2008 was performed. A total of 304 patients (200 primary excisions and 104 reexcisions) were identified. Wilcoxon rank sum tests and χ2 or Fisher's exact tests were used to compare differences in demographics and tumor characteristics. Multivariable linear regression analyses were performed with bootstrapping techniques. The average professional charge for a primary excision was $9,694 and $12,896 for a reexcision (p<.001). After adjusting for tumor size, American Society of Anesthesiologists status, grade, and site, patients undergoing reexcision saw an increase of $3,699 in professional charges more than those with a primary excision (p<.001). Although every 1-cm increase in size of the tumor results in an increase of $148 for a primary excision (p=.006), size was not an independent factor in affecting reexcision charges. The grade of the tumor was positively associated with professional charges of both groups such that higher-grade tumors resulted in higher charges compared to lower-grade tumors (p<.05). Reexcision of an incompletely excised sarcoma results in significantly higher professional charges when compared to a single, planned complete excision. Additionally, when the cost of the primary unplanned surgery is considered, the financial burden nearly doubles.

Epithelioid sarcoma: a diagnostic challenge.

PubMed

Pai, Kanthilatha K; Pai, Sathish B; Sripathi, H; Rao, Purnima

2006-01-01

Epithelioid sarcoma is an uncommon slow-growing soft tissue malignancy, associated with a high incidence of local recurrence and metastasis. We report a 26-year-old male with epithelioid sarcoma on the right palm with a long history of over seven years, which was initially misdiagnosed as cutaneous tuberculosis and epithelioid hemangioendothelioma, as a result of which the treatment was delayed. No metastasis was found in our patient. The patient was referred to the oncology centre where he underwent wide excision of the lesion followed by radiotherapy. The review of the literature including clinical and histological differential diagnosis is presented as it mimics inflammatory, benign tumors as well as other malignant conditions.

Pleomorphic Xanthoastrocytoma: Natural History and Long-Term Follow-Up.

PubMed

Ida, Cristiane M; Rodriguez, Fausto J; Burger, Peter C; Caron, Alissa A; Jenkins, Sarah M; Spears, Grant M; Aranguren, Dawn L; Lachance, Daniel H; Giannini, Caterina

2015-09-01

Prognostic significance of histological anaplasia and BRAF V600E mutation were retrospectively evaluated in 74 patients with pleomorphic xanthoastrocytoma (PXA). Median age at diagnosis was 21.5 years (31 pediatric, 43 adult) and median follow-up 7.6 years. Anaplasia (PXA-AF), defined as mitotic index ≥ 5/10 HPF and/or presence of necrosis, was present in 33 cases. BRAF V600E mutation was detected in 39 (of 60) cases by immunohistochemical and/or molecular analysis, all negative for IDH1 (R132H). Mitotic index ≥ 5/10 HPF and necrosis were associated with decreased overall survival (OS; P = 0.0005 and P = 0.0002, respectively). In all cases except two, necrosis was associated with mitotic index ≥ 5/10 HPF. Patients with BRAF V600E mutant tumors had significantly longer OS compared with those without BRAF V600E mutation (P = 0.02). PXA-AF patients, regardless of age, had significantly shorter OS compared with those without (P = 0.0003). Recurrence-free survival was significantly shorter for adult PXA-AF patients (P = 0.047) only. Patients who either recurred or died ≤ 3 years from diagnosis were more likely to have had either PXA-AF at first diagnosis (P = 0.008) or undergone a non-gross total resection procedure (P = 0.004) as compared with patients who did not. This study provides further evidence that PXA-AF behaves more aggressively than PXA and may qualify for WHO grade III "anaplastic" designation. © 2014 International Society of Neuropathology.

Pleomorphic Xanthoastrocytoma: Natural History and Long-Term Follow-Up

PubMed Central

Ida, Cristiane M.; Rodriguez, Fausto J.; Burger, Peter C.; Caron, Alissa A.; Jenkins, Sarah M.; Spears, Grant M.; Aranguren, Dawn L.; Lachance, Daniel H.; Giannini, Caterina

2015-01-01

Prognostic significance of histological anaplasia and BRAF V600E mutation were retrospectively evaluated in 74 patients with pleomorphic xanthoastrocytoma (PXA). Median age at diagnosis was 21.5 years (31 pediatric, 43 adult) and median follow-up 7.6 years. Anaplasia (PXA-AF), defined as mitotic index ≥ 5/10HPF and/or presence of necrosis, was present in 33 cases. BRAF V600E mutation was detected in 39 (of 60) cases by immunohistochemical and/or molecular analysis, all negative for IDH1 (R132H). Mitotic index ≥ 5/ 10HPF and necrosis were associated with decreased overall survival (OS; P = 0.0005 and P = 0.0002, respectively). In all cases except two, necrosis was associated with mitotic index ≥ 5/10HPF. Patients with BRAF V600E mutant tumors had significantly longer OS compared with those without BRAF V600E mutation (P = 0.02). PXA-AF patients, regardless of age, had significantly shorter OS compared with those without (P = 0.0003). Recurrence-free survival was significantly shorter for adult PXA-AF patients (P = 0.047) only. Patients who either recurred or died ≤3 years from diagnosis were more likely to have had either PXA-AF at first diagnosis (P = 0.008) or undergone a non-gross total resection procedure (P = 0.004) as compared with patients who did not. This study provides further evidence that PXA-AF behaves more aggressively than PXA and may qualify for WHO grade III “anaplastic” designation. PMID:25318587

Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pixberg, Caroline; Koch, Raphael; Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de

Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Asmore » of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior

Fine-needle aspiration biopsy of large-cell undifferentiated carcinoma of the salivary glands: presentation of two cases, literature review, and differential cytodiagnosis of high-grade salivary gland malignancies.

PubMed

Moore, J G; Bocklage, T

1998-07-01

Primary undifferentiated carcinoma of the salivary glands is a rare, high-grade neoplasm which accounts for a very small number (1-5.5%) of malignant salivary gland tumors. The large-cell variant (LCU) is less well-characterized than the small-cell form. We report on the fine-needle aspiration (FNA) biopsy findings of 2 cases of LCU, one arising in the parotid gland, and the other in a buccal mucosa accessory salivary gland. The 2 cases were similar in composition: isolated and loosely cohesive large cells with abundant cytoplasm, and variability pleomorphic nuclei with prominent nucleoli. One case also featured multinucleated tumor giant cells and macrophage polykaryons; the latter has not previously been described in FNA biopsies of LCU. There was no evidence of squamous, myoepithelial, or widespread mucinous differentiation by morphological, cytochemical, or immunohistochemical analyses (focal rare mucin production identified on special stains in one case). The differential diagnosis is lengthy and consists of other high-grade primary salivary gland malignancies as well as metastatic lesions, including melanoma. The pattern of immunohistochemical reactivity (positive keratin, negative S-100, and HMB-45 antigens), and lack of conspicuous mucin production of significant lymphoidinfiltrate, were useful in establishing the correct diagnosis.

Primary osteogenic sarcoma of the breast

PubMed Central

Ogundiran, Temidayo O; Ademola, Samuel A; Oluwatosin, Odunayo M; Akang, Effiong E; Adebamowo, Clement A

2006-01-01

Background Primary extra-osseous osteogenic sarcomas have been reported in many tissues of the body but their occurrence in the breast is extremely rare. It can arise as a result of osseous metaplasia in a pre-existing benign or malignant neoplasm of the breast or as non-phylloides sarcoma from the soft tissue of a previously normal breast. Case presentation A 40 year-old Nigerian woman was clinically diagnosed to have carcinoma of the left breast. The histology report of core-needle biopsy of the mass showed a malignant neoplasm comprising islands of chondroblastic and osteoblastic stromal cells. This report changed the diagnosis from carcinoma to osteogenic sarcoma of the breast. She had a left modified radical mastectomy, however there was significant post surgery skin deficit. A latissimus dorsi musculocutaneous flap was used to cover the anterior chest wall defect. Sections from the mastectomy specimen confirmed the diagnosis of osteogenic sarcoma. She died six months after mastectomy. Conclusion A diagnosis of osteogenic sarcoma of the breast was made based on histology report and after excluding an osteogenic sarcoma arising from underlying ribs and sternum. This is the second documented case of primary osteogenic sarcoma of the breast coming from Nigeria PMID:17156481

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1-Common Sarcomas: From the Radiologic Pathology Archives.

PubMed

Levy, Angela D; Manning, Maria A; Al-Refaie, Waddah B; Miettinen, Markku M

2017-01-01

Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis.

Histomolecular interpretation of pleomorphic adenomas of the salivary gland by matrix-assisted laser desorption ionization imaging and spatial segmentation.

PubMed

Ernst, Günther; Guntinas-Lichius, Orlando; Hauberg-Lotte, Lena; Trede, Dennis; Becker, Michael; Alexandrov, Theodore; von Eggeling, Ferdinand

2015-07-01

Despite efforts in localization of key proteins using immunohistochemistry, the complex proteomic composition of pleomorphic adenomas has not yet been characterized. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI imaging) allows label-free and spatially resolved detection of hundreds of proteins directly from tissue sections and of histomorphological regions by finding colocalized molecular signals. Spatial segmentation of MALDI imaging data is an algorithmic method for finding regions of similar proteomic composition as functionally similar regions. We investigated 2 pleomorphic adenomas by applying spatial segmentation to the MALDI imaging data of tissue sections. The spatial segmentation subdivided the tissue in a good accordance with the tissue histology. Numerous molecular signals colocalized with histologically defined tissue regions were found. Our study highlights the cellular transdifferentiation within the pleomorphic adenoma. It could be shown that spatial segmentation of MALDI imaging data is a promising approach in the emerging field of digital histological analysis and characterization of tumors. © 2014 Wiley Periodicals, Inc.

External-beam radiation therapy combined with limb-sparing surgery in elderly patients (>70 years) with primary soft tissue sarcomas of the extremities : A retrospective analysis.

PubMed

Andrä, Claudia; Klein, Alexander; Dürr, Hans Roland; Rauch, Josefine; Lindner, Lars Hartwin; Knoesel, Thomas; Angele, Martin; Baur-Melnyk, Andrea; Belka, Claus; Roeder, Falk

2017-08-01

To report our experience with EBRT combined with limb-sparing surgery in elderly patients (>70 years) with primary extremity soft tissue sarcomas (STS). Retrospectively analyzed were 35 patients (m:f 18:17, median 78 years) who all presented in primary situation without nodal/distant metastases (Charlson score 0/1 in 18 patients; ≥2 in 17 patients). Median tumor size was 10 cm, mainly located in lower limb (83%). Stage at presentation (UICC7th) was Ib:3%, 2a:20%, 2b:20%, and 3:57%. Most lesions were high grade (97%), predominantly leiomyosarcoma (26%) and undifferentiated pleomorphic/malignant fibrous histiocytoma (23%). Limb-sparing surgery was preceded (median 50 Gy) or followed (median 66 Gy) by EBRT. Median follow-up was 37 months (range 1-128 months). Margins were free in 26 patients (74%) and microscopically positive in 9 (26%). Actuarial 3‑ and 5‑year local control rates were 88 and 81% (4 local recurrences). Corresponding rates for distant control, disease-specific survival, and overall survival were 57/52%, 76/60%, and 72/41%. The 30-day mortality was 0%. Severe postoperative complications were scored in 8 patients (23%). Severe acute radiation-related toxicity was observed in 2 patients (6%). Patients with Charlson score ≥2 had a significantly increased risk for severe postoperative complications and acute radiation-related side effects. Severe late toxicities were found in 7 patients (20%), including fractures in 3 (8.6%). Final limb preservation rate was 97%. Combination of EBRT and limb-sparing surgery is feasible in elderly patients with acceptable toxicities and encouraging but slightly inferior outcome compared to younger patients. Comorbidity correlated with postoperative complications and acute toxicities. Late fracture risk seems slightly increased.

Cytogenetically confirmed primary Ewing's sarcoma of the pancreas.

PubMed

Golhar, Ankush; Ray, Samrat; Haugk, Beate; Singhvi, Suresh Kumar

2017-05-04

Ewing's sarcoma is a highly aggressive malignant tumour most commonly affecting long bones in children and adolescents. It is part of the Ewing's sarcoma family of tumours (ESFTs) that also include peripheral primitive neuroectodermal tumour and Askin's tumours. ESFTs share common cytogenetic aberrations, antigenic profiles and proto-oncogene expression with an overall similar clinical course. In 99% of ESFTs, genetic translocation with molecular fusion involves the EWSR1 gene on 22q12. Approximately 30% of ESFTs are extraosseous, most commonly occurring in the soft tissues of extremities, pelvis, retroperitoneum and chest wall. Primary presentation in solid organs is very rare but has been described in multiple sites including the pancreas. Accurate diagnosis of a Ewing's sarcoma in a solid organ is critical in facilitating correct treatment. We report the case of a 17-year-old girl with cytogenetically confirmed primary pancreatic Ewing's sarcoma and provide a brief review of the published literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

PubMed

Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

2010-08-18

Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma

ClinicalTrials.gov

2014-05-07

Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Leiomyosarcoma; Adult Malignant Fibrous Histiocytoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

Patients with Advanced, Rare Sarcoma Respond to Cediranib | Center for Cancer Research

Cancer.gov

Alveolar soft part sarcomas (ASPS) are highly vascular tumors that usually affect adolescents and young adults. Comprising less than one percent of soft tissue sarcomas, ASPS can be cured with surgery. However, its tendency to metastasize and its lack of response to standard soft tissue sarcoma chemotherapy regimens makes ASPS a particularly lethal cancer with a five-year survival rate of 20 percent in patients with metastatic disease who are not candidates for surgery.

Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waxweiler, Timothy V., E-mail: timothy.waxweiler@ucdenver.edu; Rusthoven, Chad G.; Proper, Michelle S.

Purpose: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those <20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics. Methods and Materials: From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex,more » year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk. Results: A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P<.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P<.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P<.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P<.001). Conclusions: The current COG risk

General Information about Ewing Sarcoma

MedlinePlus

... Research Ewing Sarcoma Treatment (PDQ®)–Patient Version General Information About Ewing Sarcoma Go to Health Professional Version ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information about Kaposi Sarcoma

MedlinePlus

... Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information About Uterine Sarcoma

MedlinePlus

... Research Uterine Sarcoma Treatment (PDQ®)–Patient Version General Information About Uterine Sarcoma Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Treatment Option Overview (Ewing Sarcoma)

MedlinePlus

... for Ewing sarcoma have an increased risk of acute myeloid leukemia and myelodysplastic syndrome . There is also an increased risk of sarcoma in the area treated with radiation therapy . Some late effects may be treated or ...

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1—Common Sarcomas: From the Radiologic Pathology Archives

PubMed Central

Manning, Maria A.; Al-Refaie, Waddah B.; Miettinen, Markku M.

2017-01-01

Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis. PMID:28287938

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

PubMed Central

2014-01-01

Background Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). Methods Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients’ clinical-pathological parameters. Results MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. Conclusions The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients’ prognosis, while nuclear expression is associated with better prognosis. PMID:24885736

A novel method for morphological pleomorphism and heterogeneity quantitative measurement: Named cell feature level co-occurrence matrix.

PubMed

Saito, Akira; Numata, Yasushi; Hamada, Takuya; Horisawa, Tomoyoshi; Cosatto, Eric; Graf, Hans-Peter; Kuroda, Masahiko; Yamamoto, Yoichiro

2016-01-01

Recent developments in molecular pathology and genetic/epigenetic analysis of cancer tissue have resulted in a marked increase in objective and measurable data. In comparison, the traditional morphological analysis approach to pathology diagnosis, which can connect these molecular data and clinical diagnosis, is still mostly subjective. Even though the advent and popularization of digital pathology has provided a boost to computer-aided diagnosis, some important pathological concepts still remain largely non-quantitative and their associated data measurements depend on the pathologist's sense and experience. Such features include pleomorphism and heterogeneity. In this paper, we propose a method for the objective measurement of pleomorphism and heterogeneity, using the cell-level co-occurrence matrix. Our method is based on the widely used Gray-level co-occurrence matrix (GLCM), where relations between neighboring pixel intensity levels are captured into a co-occurrence matrix, followed by the application of analysis functions such as Haralick features. In the pathological tissue image, through image processing techniques, each nucleus can be measured and each nucleus has its own measureable features like nucleus size, roundness, contour length, intra-nucleus texture data (GLCM is one of the methods). In GLCM each nucleus in the tissue image corresponds to one pixel. In this approach the most important point is how to define the neighborhood of each nucleus. We define three types of neighborhoods of a nucleus, then create the co-occurrence matrix and apply Haralick feature functions. In each image pleomorphism and heterogeneity are then determined quantitatively. For our method, one pixel corresponds to one nucleus feature, and we therefore named our method Cell Feature Level Co-occurrence Matrix (CFLCM). We tested this method for several nucleus features. CFLCM is showed as a useful quantitative method for pleomorphism and heterogeneity on histopathological image

Blue Cell Tumour at Unusual Site: Retropritoneal Ewings Sarcoma.

PubMed

Javalgi, Anita P; Karigoudar, Mahesh H; Palur, Katyayani

2016-04-01

Ewing's sarcoma is a highly malignant tumour of osseous or non-osseous origin, tremed as extra-skeletal Ewings sarcoma if arising from soft tissue. It is rare occurrence tumor most commonly occurring in paravertebral area, chest wall, head & neck and retroperitoneum. Reporting an interesting case of retroperitoneal Ewing's sarcoma in 39 years old female. Patient had complains of abdominal discomfort & vague pain since 2 months, following weakness in lower limb and loss of weight. On detail history and examination she was further referred to detail pathological and radiological investigations. Haematological profile, renal function test and liver function test were in normal limits. USG abdomen was normal, MRI showed a mass in pelvis retroperitoneum measuring 10x10cms, bilateral ovaries and tubes were normal. Because of retroperitoneal nature of tumor and suspicion of uterine sarcoma, laparotomy was performed. The large retroperitoneal mass adherent to posterior of uterus was excised and send for histopathological diagnosis. On gross and microscopy examination the diagnosis of blue cell tumor with PAS positivity, possibility of extraskeletal Ewing's sarcoma/primitive neuro-ectodermal tumor was made which was further confirmed by immunohistochemistry, positive for S100, Vementin and CD99 and negative for desmin and CK. Confirmed diagnosis help in accurate management and improves survival rate.

The role of postoperative radiation therapy in carcinoma ex pleomorphic adenoma of the parotid gland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M.; Garcia, Joaquin; Bucci, M. Kara

2007-01-01

Purpose: To evaluate the impact of postoperative radiation therapy on the clinical course of patients with carcinoma ex pleomorphic adenoma of the parotid gland. Methods and Materials: Between 1960 and 2004, 63 patients were treated with definitive surgery for carcinoma ex pleomorphic adenoma of the parotid gland. Forty patients (63%) received postoperative radiation therapy to a median dose of 60 Gy (range, 45-71 Gy). Adenocarcinoma (29 patients), salivary duct carcinoma (16 patients), and adenoid cystic carcinoma (9 patients) were the most common malignant subtypes. Pathologic T -stage was: 16% T1, 33% T2, 32% T3, and 19% T4. Twenty-one patients (33%)more » had microscopically positive margins and 39 (62%) had perineural invasion. Median follow-up was 50 months (range, 2-96 months). Results: The use of postoperative therapy significantly improved 5-year local control from 49% to 75% (p = 0.005) and was associated with an improvement in survival among patients without evidence of cervical lymph node metastasis (p = 0.01). A Cox proportional hazard model identified pathologic involvement of cervical lymph nodes as an independent predictor of overall survival. Overall survival was 16% for patients with pathologic N-positive disease compared with 67% for those whose lymph node status was negative or unknown (p = 0.001). Conclusion: Surgery followed by postoperative radiation should be considered the standard of care for patients with carcinoma ex pleomorphic adenoma.« less

Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets

PubMed Central

Marchetto, Aruna; Gerke, Julia S.; Rubio, Rebeca Alba; Kiran, Merve M.; Musa, Julian; Knott, Maximilian M. L.; Ohmura, Shunya; Li, Jing; Akpolat, Nusret; Akatli, Ayse N.; Özen, Özlem; Dirksen, Uta; Hartmann, Wolfgang; de Alava, Enrique; Baumhoer, Daniel; Sannino, Giuseppina; Kirchner, Thomas; Grünewald, Thomas G. P.

2018-01-01

Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4-, BCOR-CCNB3-, EWSR1-NFATc2-, and EWSR1-ETS-translocated sarcomas are distinct entities, and revealed that ATP1A1, BCL11B, and GLG1 constitute specific markers for Ewing sarcoma. Their high expression was validated by immunohistochemistry and proved to depend on EWSR1-FLI1-binding to highly active proximal super-enhancers. Automated cut-off-finding and combination-testing in a tissue-microarray comprising 174 samples demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined strong BCL11B- and GLG1-immunoreactivity. Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple, and cost-efficient way to diagnose Ewing sarcoma by immunohistochemistry. These markers may significantly reduce the number of misdiagnosed patients, and thus improve patient care. PMID:29416716

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

PubMed

Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

2014-06-01

To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

Ewing's Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies.

PubMed

Wolpert, Fabian; Grotzer, Michael A; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth; Bode-Lesniewska, Beata

2016-01-01

Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing's sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing's sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing's sarcoma is summarized and possible pathogenic mechanisms are critically discussed.

Genomic and Expression Profiling of Benign & Malignant Nerve Sheath Tumors in Neurofibromatosis Patients

DTIC Science & Technology

2006-05-01

high grade chondrosarcoma (1/8), Ewing sarcoma (1/13 cases), MPNST (4/88), gastrointestinal stromal tumor (1/34) and leiomyosarcoma (1/41) were...Alveolar rhabdomyosarcoma; ASPS: Alveolar soft parts sarcoma; BS Benign schwannoma; CCS: Clear cell sarcoma; CSa: Chondrosarcoma ; DFSP...0 1 2 4 1 14 Clear Cell Sarcoma 7 1 0 1 5 1 14 Chondrosarcoma , high grade 8 0 1 0 7 1 13 Ewing Sarcoma 13 1 0 1 11 1 8 GIST 35 0 2 7 26 2 6

Chronic administration of phenytoin and pleomorphic adenoma: A case report and review of literature.

PubMed

Maharshi, Vikas; Nagar, Pravesh

2017-01-01

Adverse drug effects that are uncommon or appear only on chronic administration of a drug may not be detected in clinical trials. This explains the need of strict post-marketing vigilance on drug use. Phenytoin administration has been shown in the literature to be associated with development of neoplasia (benign/malignant). In our knowledge current work represents the first case of pleomorphic-adenoma of sub-mandibular salivary gland developed following chronic phenytoin use. A 40 year old male having a history of head trauma twenty years back, had been on tablet phenytoin 100 mg thrice daily since then. One year back he noticed a small swelling in left sub-mandibular region and gradually increasing in size. FNAC and CECT revealed the diagnosis of pleomorphic-adenoma of sub-mandibular salivary gland. Other causes were ruled out. Surgical excision was performed successfully and continuing follow-up with no recurrence at the end of 6 months. Histo-pathogical examination of the tissue did not show any malignant changes.

Anaplastic sarcoma of the kidney.

PubMed

Labanaris, Apostolos; Zugor, Vahudin; Smiszek, Robert; Nützel, Reinhold; Kühn, Reinhard

2009-02-15

Wilms tumor can appear with a wide spectrum of morphologic features and can sometimes cover or delay the recognition of other clinicopathologic entities of the kidney. We present a case of a new tumor entity of the kidney, namely the anaplastic sarcoma of the kidney, a tumor of high malignancy.

Adrenal Ewing's Sarcoma in an Elderly Man.

PubMed

Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

2018-02-15

Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

Adoptive cell therapy for sarcoma

PubMed Central

Mata, Melinda; Gottschalk, Stephen

2015-01-01

Current therapy for sarcomas, though effective in treating local disease, is often ineffective for patients with recurrent or metastatic disease. To improve outcomes, novel approaches are needed and cell therapy has the potential to meet this need since it does not rely on the cytotoxic mechanisms of conventional therapies. The recent successes of T-cell therapies for hematological malignancies have led to renewed interest in exploring cell therapies for solid tumors such as sarcomas. In this review, we will discuss current cell therapies for sarcoma with special emphasis on genetic approaches to improve the effector function of adoptively transferred cells. PMID:25572477

Current state of pediatric sarcoma biology and opportunities for future discovery: A report from the sarcoma translational research workshop.

PubMed

Hingorani, Pooja; Janeway, Katherine; Crompton, Brian D; Kadoch, Cigall; Mackall, Crystal L; Khan, Javed; Shern, Jack F; Schiffman, Joshua; Mirabello, Lisa; Savage, Sharon A; Ladanyi, Marc; Meltzer, Paul; Bult, Carol J; Adamson, Peter C; Lupo, Philip J; Mody, Rajen; DuBois, Steven G; Parsons, D Williams; Khanna, Chand; Lau, Ching; Hawkins, Douglas S; Randall, R Lor; Smith, Malcolm; Sorensen, Poul H; Plon, Sharon E; Skapek, Stephen X; Lessnick, Stephen; Gorlick, Richard; Reed, Damon R

2016-05-01

Sarcomas are a rare subgroup of pediatric cancers comprised of a variety of bone and soft-tissue tumors. While significant advances have been made in improving outcomes of patients with localized pediatric sarcomas since the addition of systemic chemotherapy to local control many decades ago, outcomes for patients with metastatic and relapsed sarcoma remain poor with few novel therapeutics identified to date. With the advent of new technologies to study cancer genomes, transcriptomes and epigenomes, our understanding of sarcoma biology has improved tremendously in a relatively short period of time. However, much remains to be accomplished in this arena especially with regard to translating all of this new knowledge to the bedside. To this end, a meeting was convened in Philadelphia, PA, on April 18, 2015 sponsored by the QuadW foundation, Children's Oncology Group and CureSearch for Children's Cancer that brought together sarcoma clinicians and scientists from North America to review the current state of pediatric sarcoma biology and ongoing/planned genomics based clinical trials in an effort to identify and bridge knowledge gaps that continue to exist at present. At the conclusion of the workshop, three key objectives that would significantly further our understanding of sarcoma were identified and a proposal was put forward to develop an all-encompassing pediatric sarcoma biology protocol that would address these specific needs. This review summarizes the proceedings of the workshop. Copyright © 2016. Published by Elsevier Inc.

Whole-Body Radiation Therapy, Systemic Chemotherapy, and High-Dose Chemotherapy Followed By Stem Cell Rescue in Treating Patients With Poor-Risk Ewing Sarcoma

ClinicalTrials.gov

2015-01-07

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Sarcoma-The standard-bearer in cancer discovery.

PubMed

Potter, Jared W; Jones, Kevin B; Barrott, Jared J

2018-06-01

Sarcoma is a rare tumor type that occurs most frequently in connective tissue. Despite its uncommon occurrence, sarcoma research has provided the means for groundbreaking research that has advanced our understanding of general cancer mechanisms. It is through sarcoma research that the pioneering efforts of cancer immunotherapy were explored, that we understand the inherent genetic nature of cancer mutations, and that we appreciate the subclassification of general cancer types to make more accurate prognoses. This review explores the brief history of sarcoma research and what sarcomas can still teach us about the future of cancer research, especially in regard to novel immunotherapy targets, the role of epigenetics in disease progression and chemoresistance, and the benefits of more focused clinical trials. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Intra- and inter-observer agreement in histological assessment of canine soft tissue sarcoma.

PubMed

Yap, F W; Rasotto, R; Priestnall, S L; Parsons, K J; Stewart, J

2017-12-01

The diagnosis of canine soft tissue sarcoma (STS) is based on histological assessment. Assessment of criteria such as, degree of differentiation, necrosis score and mitotic score, gives rise to a final tumour grade, which is important in the recommendation of treatment and prognosis of patients. Previously diagnosed cases of STS were independently assessed by three board-certified veterinary pathologists. Participating pathologists were blinded to the original results. For the intra-observer study, the cases were assessed by a single pathologist six months apart and slides were randomized between readings. For the inter-observer study, the whole case series was assessed by a single pathologist before being passed onto the next pathologist. Intraclass correlation coefficient (ICC) and Fleiss's Kappa (ƙ) for the intra- (single observer) and inter-observer agreement. Strong agreement was observed for the intra-observer assessment in necrosis score, mitotic score, total score and tumour grading (ICC between 0.78 to 0.91). The intra-observer agreement for differentiation score was rated perfect (ICC 1.00). The agreement between pathologists for the diagnosis and grading of canine STS was moderate (ƙ = 0.60 and 0.43 respectively). Histological assessment of canine STS had high reproducibility by an individual pathologist. The agreement of diagnosis and grading of canine STS was moderate between pathologists. Future studies are required to investigate further assessment criteria to improve the specificity of STS diagnosis and the accuracy of the STS grading in dogs. © 2017 John Wiley & Sons Ltd.

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.

PubMed

Grignani, Giovanni; Palmerini, Emanuela; Ferraresi, Virginia; D'Ambrosio, Lorenzo; Bertulli, Rossella; Asaftei, Sebastian Dorin; Tamburini, Angela; Pignochino, Ymera; Sangiolo, Dario; Marchesi, Emanuela; Capozzi, Federica; Biagini, Roberto; Gambarotti, Marco; Fagioli, Franca; Casali, Paolo Giovanni; Picci, Piero; Ferrari, Stefano; Aglietta, Massimo

2015-01-01

Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment. We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01804374. We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28-61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths. Although the combination of sorafenib and everolimus showed activity as a further-line treatment

Ewing's sarcoma of the patella.

PubMed

Gorelik, Natalia; Dickson, Brendan C; Wunder, Jay S; Bleakney, Robert

2013-05-01

Ewing's sarcoma is a relatively rare malignancy, occurring mainly between 4 and 25 years of age. It usually arises from the pelvis, followed by the femur, tibia, and remainder of both the long bones of the extremities and flat bones of the axial skeleton. To the best of our knowledge, Ewing's sarcoma of the patella has never been reported previously. Patellar tumors occur infrequently and represent an uncommon etiology of anterior knee pain. We describe the rare case of a 41-year-old man who presented with a 3-4 month history of escalating right anterior knee pain and swelling. Imaging demonstrated an aggressive patellar tumor with an adjacent soft tissue mass. The diagnosis of Ewing's sarcoma was confirmed by pathology. Physicians should be aware of atypical locations for Ewing's sarcoma and, conversely, of rare tumors arising in the patella and accounting for anterior knee pain. Early recognition of such malignancies allows prompt initiation of treatment, hence improving prognosis.

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

PubMed

Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case report.

PubMed

Grifasi, Carlo; Calogero, Armando; Carlomagno, Nicola; Campione, Severo; D'Armiento, Francesco Paolo; Renda, Andrea

2013-11-26

Liposarcoma is the most common type of soft tissue sarcoma (STS). It is divided into five groups according to histological pattern: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while an intraperitoneal location is extremely rare. Only seven cases have been reported in literature. Many pathologists recognize that a large number of intra-abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We report a case initially diagnosed as undifferentiated sarcoma that was reclassified as intraperitoneal dedifferentiated liposarcoma showing an amplification of the MDM2 gene. A 59-year-old woman with abdominal pain and constipation was referred to the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy, in November 2012. On physical examination, a very large firm mass was palpable in the meso-hypogastrium. Computed tomography (CT) scan showed a heterogeneous density mass (measuring 10 × 19 cm) that was contiguous with the mesentery and compressed the third part of the duodenum and jejunum.At laparotomy, a large mass occupying the entire abdomen was found, adhering to the first jejunal loop and involving the mesentery. Surgical removal of the tumor along with a jejunal resection was performed because the first jejunal loop was firmly attached to the tumor.Macroscopic examination showed a solid, whitish, cerebroid, and myxoid mass, with variable hemorrhage and cystic degeneration, measuring 26 × 19 × 5 cm. Microscopic examination revealed two main different morphologic patterns: areas with spindle cells in a myxoid matrix and areas with pleomorphic cells. The case was initially diagnosed as undifferentiated pleomorphic sarcoma. Histological review showed areas of well-differentiated liposarcoma. Fluorescence in situ hybridization (FISH) analysis was performed and demonstrated an amplification of the MDM2 gene

Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case report

PubMed Central

2013-01-01

Background Liposarcoma is the most common type of soft tissue sarcoma (STS). It is divided into five groups according to histological pattern: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while an intraperitoneal location is extremely rare. Only seven cases have been reported in literature. Many pathologists recognize that a large number of intra-abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We report a case initially diagnosed as undifferentiated sarcoma that was reclassified as intraperitoneal dedifferentiated liposarcoma showing an amplification of the MDM2 gene. Case presentation A 59-year-old woman with abdominal pain and constipation was referred to the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy, in November 2012. On physical examination, a very large firm mass was palpable in the meso-hypogastrium. Computed tomography (CT) scan showed a heterogeneous density mass (measuring 10 × 19 cm) that was contiguous with the mesentery and compressed the third part of the duodenum and jejunum. At laparotomy, a large mass occupying the entire abdomen was found, adhering to the first jejunal loop and involving the mesentery. Surgical removal of the tumor along with a jejunal resection was performed because the first jejunal loop was firmly attached to the tumor. Macroscopic examination showed a solid, whitish, cerebroid, and myxoid mass, with variable hemorrhage and cystic degeneration, measuring 26 × 19 × 5 cm. Microscopic examination revealed two main different morphologic patterns: areas with spindle cells in a myxoid matrix and areas with pleomorphic cells. The case was initially diagnosed as undifferentiated pleomorphic sarcoma. Histological review showed areas of well-differentiated liposarcoma. Fluorescence in situ hybridization (FISH) analysis was performed and

Double-Pedicled Free Deep Inferior Epigastric Perforator Flap for the Coverage of Thigh Soft-Tissue Defect.

PubMed

Bota, Olimpiu; Spindler, Nick; Sauber, Jeannine; Aydogan, Emrah; Langer, Stefan

2017-08-01

Soft-tissue defects caused by radiation injury are a challenging task for the reconstructive surgeon, due to the extent of the soft-tissue damage and the associated injuries of the local blood vessels and bone tissue. We present the application of the versatile deep inferior epigastric perforator (DIEP) flap for the coverage of an extended lateral thigh soft-tissue defect after the surgical resection of an undifferentiated pleomorphic high-grade sarcoma, neoadjuvant chemotherapy, and adjuvant chemo- and radiotherapy. A double-pedicled free DIEP flap (756 cm 2 ) was harvested and anastomosed to the transverse branch of the lateral femoral circumflex artery and a lateral branch of the popliteal artery (P1). The flap survived completely without serious complications, and the patient was able to walk with crutches 3 months postoperatively. This is the first case report of a free bipedicled DIEP flap for the coverage of a thigh defect in a male patient.

Double-Pedicled Free Deep Inferior Epigastric Perforator Flap for the Coverage of Thigh Soft-Tissue Defect

PubMed Central

Spindler, Nick; Sauber, Jeannine; Aydogan, Emrah; Langer, Stefan

2017-01-01

Summary: Soft-tissue defects caused by radiation injury are a challenging task for the reconstructive surgeon, due to the extent of the soft-tissue damage and the associated injuries of the local blood vessels and bone tissue. We present the application of the versatile deep inferior epigastric perforator (DIEP) flap for the coverage of an extended lateral thigh soft-tissue defect after the surgical resection of an undifferentiated pleomorphic high-grade sarcoma, neoadjuvant chemotherapy, and adjuvant chemo- and radiotherapy. A double-pedicled free DIEP flap (756 cm2) was harvested and anastomosed to the transverse branch of the lateral femoral circumflex artery and a lateral branch of the popliteal artery (P1). The flap survived completely without serious complications, and the patient was able to walk with crutches 3 months postoperatively. This is the first case report of a free bipedicled DIEP flap for the coverage of a thigh defect in a male patient. PMID:28894652

Ewing sarcoma: a chronicle of molecular pathogenesis.

PubMed

Kim, Sang Kyum; Park, Yong-Koo

2016-09-01

Sarcomas have traditionally been classified according to their chromosomal alterations regardless of whether they accompany simple or complex genetic changes. Ewing sarcoma, a classic small round cell bone tumor, is a well-known mesenchymal malignancy that results from simple sarcoma-specific genetic alterations. The genetic alterations are translocations between genes of the TET/FET family (TLS/FUS, EWSR1, and TAF15) and genes of the E26 transformation-specific (ETS) family. In this review, we intend to summarize a chronicle of molecular findings of Ewing sarcoma including recent advances and explain resultant molecular pathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.

PubMed

Yang, Li-Peng; Sun, He-Fen; Zhao, Yang; Chen, Meng-Ting; Zhang, Nong; Jin, Wei

2017-12-01

The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Testicular myeloid sarcoma: case report.

PubMed

Zago, Luzia Beatriz Ribeiro; Ladeia, Antônio Alexandre Lisbôa; Etchebehere, Renata Margarida; de Oliveira, Leonardo Rodrigues

2013-01-01

Myeloid sarcomas are extramedullary solid tumors composed of immature granulocytic precursor cells. In association with acute myeloid leukemia and other myeloproliferative disorders, they may arise concurrently with compromised bone marrow related to acute myeloid leukemia, as a relapsed presentation, or occur as the first manifestation. The testicles are considered to be an uncommon site for myeloid sarcomas. No therapeutic strategy has been defined as best but may include chemotherapy, radiotherapy and/or hematopoietic stem cell transplantation. This study reports the evolution of a patient with testicular myeloid sarcoma as the first manifestation of acute myeloid leukemia. The patient initially refused medical treatment and died five months after the clinical condition started.

Preclinical Evaluation of Vemurafenib as Therapy for BRAFV600E Mutated Sarcomas.

PubMed

Gouravan, Sarina; Meza-Zepeda, Leonardo A; Myklebost, Ola; Stratford, Eva W; Munthe, Else

2018-03-23

The BRAF V600E mutation, which in melanoma is targetable with vemurafenib, is also found in sarcomas and we here evaluate the therapeutic potential in sarcoma cell lines. Four sarcoma cell lines harboring the BRAFV600E mutation, representing liposarcomas (SA-4 and SW872), Ewing sarcoma (A673) and atypical synovial sarcoma (SW982), were treated with vemurafenib and the effects on cell growth, apoptosis, cell cycle progression and cell signaling were determined. Vemurafenib induced a strong cytostatic effect in SA-4 cells, mainly due to cell cycle arrest, whereas only moderate levels of apoptosis were observed. However, a high dose was required compared to BRAF V600E mutated melanoma cells, and removal of vemurafenib demonstrated that the continuous presence of drug was required for sustained growth inhibition. A limited growth inhibition was observed in the other three cell lines. Protein analyses demonstrated reduced phosphorylation of ERK during treatment with vemurafenib in all the four sarcoma cell lines confirming that the MAPK pathway is active in these cell lines, and that the pathway can be inhibited by vemurafenib, but also that these cells can proliferate despite this. These findings indicate that vemurafenib alone would not be an efficient therapy against BRAF V600E mutated sarcomas. However, further investigations of combination with other drugs are warranted.

[KAPOSI'S SARCOMA OF THE VULVA].

PubMed

Chokoeva, Aa; Tchernev, G; Wollina, U

2015-01-01

Kaposi's sarcoma represents multiple idiopathic hemorrhagic sarcoma--a mesenchymal tumor that affects the blood and lymph vessels. Its performance is associated with an infection with human herpes virus type 8--the so called KSHV (Kaposi's sarcoma -associated virus), and with the human immunodeficiency virus. Kaposi's sarcoma is considered as a typical clinical manifestation in male homosexuals suffering from acquired immune deficiency syndrome (AIDS), while his performance in HIV-positive women is unusual, with a ratio of men to women--10-15: 1. Vulvar localization is much rarer. It is up to 5 times more frequent in HIV- positive patients. It is clinically represented in most of the cases by the clinical picture of nonspecific tumor mass. Biopsy and further virological testing for establishing KSHV in lesional tissue is essential for confirming the diagnosis. Serological testing for HIV/AIDS in affected patients is required. Local treatment includes surgical excision of solitary lesions, cryotherapy as well as radiotherapy. The use of interferon alpha resulted in complete remission in approximately 40% of the affected patients. New trends in treatment tend to be pathogenetically directed as in the process of studies to date are inhibitors of angiogenesis. Due to the rarity of the occurrence, non-specific clinical picture and histological findings, Kaposi's sarcoma should be considered in the differential diagnosis of tumor masses with vulvar localization, especially in HIV-positive patients.

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity.

PubMed

Alektiar, Kaled M; Brennan, Murray F; Singer, Samuel

2005-09-01

The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95

Synovial sarcoma: a rare presentation of parapharyngeal mass.

PubMed

Shaariyah, Mohd Mokhtar; Mazita, Ami; Masaany, Mansor; Razif, Mohd Yunus; Isa, Mohamed Rose; Asma, Abdullah

2010-06-01

Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and received adjuvant radiotherapy.

Ewing's Sarcoma of the Adrenal Gland.

PubMed

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Pleomorphic Adenoma of Base of Tongue: Is Midline Mandibulotomy Necessary for Approaching Benign Base Tongue Lesions?

PubMed Central

Bansal, Sandeep; Kalsotra, Gopika; Mohammed, Abdul Wadood; Bahl, Amanjit; Gupta, Ashok K.

2012-01-01

Objective. To report a rare presentation of pleomorphic adenoma, at base tongue, excised surgically by a transoral midline glossotomy technique without mandibulotomy. Case Report. Pleomorphic adenoma is a benign tumor of the salivary gland found rarely in the base of tongue. Surgery is the definitive treatment for this tumor, and different approaches have been mentioned in the literature. In our case we surgically excised the tumor by a transoral midline glossotomy technique without mandibulotomy where we combined the cosmetic advantage of transoral technique and the exposure advantage of a glossotomy technique. Discussion. We discuss the different approaches to oropharynx, their advantages and disadvantages. Primary transoral approach provides better cosmesis but less exposure whereas median labiomandibuloglossotomy approach provides more exposure but is cosmetically unacceptable. Conclusion. A transoral midline glossotomy approach without mandibulotomy provides wide exposure with acceptable cosmesis. PMID:22953125

Effectiveness of Vascular Markers (Immunohistochemical Stains) in Soft Tissue Sarcomas.

PubMed

Naeem, Namra; Mushtaq, Sajid; Akhter, Noreen; Hussain, Mudassar; Hassan, Usman

2018-05-01

To ascertain the effectiveness of IHC markers of vascular origin like CD31, CD34, FLI1 and ERG in vascular soft tissue sarcomas including angiosarcomas, Kaposi sarcomas, epithelioid hemangioendothelioma and a non-vascular soft tissue sarcoma (Epithelioid sarcoma). Descriptive study. Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2011 to 2017. Diagnosed cases of angiosarcomas (n=48), epithelioid hemangioendothelioma (n=9), Kaposi sarcoma (n=9) and epithelioid sarcoma (n=20) were selected. Immunohistochemical staining as performed on formalin fixed paraffin embedded sections. The sections were stained for the following markers: CD34 (VENTANA clone Q Bend 10), CD31 (Leica clone 1 A 10), FLI1 (CELL MARQUE clone MRQ-1) and ERG (CELL MARQUE clone EP111). A complete panel of CD34, CD31 and ERG was applied on 8/48 cases of angiosarcomas with triple positivity in 6 cases. Eight cases showed positivity for only CD31 and ERG and 2 cases showed positivity for only ERG. A complete panel of CD34, CD31 and ERG was applied on 3/9 cases of epithelioid hemangioendothelioma with positivity for all markers in 2 cases. Combined positivity for ERG and CD34 was seen in 2 cases and on 4 cases only CD31 immunohistochemical was solely applied with 100% positivity. FLI1 was not applied on any case. Among 9 cases of Kaposi sarcoma, ERG, CD34 and CD31 in combination were applied on only 1 case with triple positivity. Remaining cases show positivity for either CD34, CD31 or FLI1. Majority of cases of epithelioid sarcomas were diagnosed on the basis of cytokeratin and CD34 positivity with loss of INI1. The other vascular markers showed negativity in all cases. Among these four markers, ERG immunohistochemical stain is highly effective for endothelial differentiation due to its specific nuclear staining pattern in normal blood vessel endothelial cells (internal control) as well as neoplastic cells of vascular tumors and lack of background staining.

[Primitive cutaneous Ewing's sarcoma: a diagnostic and therapeutic dilemma].

PubMed

Delaplace, M; Mélard, P; Perrinaud, A; Goré, C; Vergier, B; Machet, L

2011-05-01

Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman. A 21-year-old woman presented with a scapular lesion that had been slowly developing for one year. The 1-cm lesion was removed and histological examination showed proliferation of small round cells in the dermis. Immunostaining revealed cytoplasmic membrane expression of CD99 and a negative immunoprofile for other small round-cell tumors. Ewing's sarcoma fusion gene transcripts were detected using fluorescence in situ hybridization (FISH). A staging examination revealed no other abnormalities. It was decided to treat the lesion as for osseous Ewing's sarcoma with wide resection followed by systemic adjuvant chemotherapy. Cutaneous Ewing's sarcoma raises concerns about diagnosis and treatment. Owing to the non-specificity of its clinical presentation, histology and immunoprofile, diagnosis of superficial Ewing's sarcoma is difficult and numerous differential diagnoses must be considered. When dealing with a surface tumour, the diagnosis of cutaneous Ewing's sarcoma must be considered. CD99 immunostaining and molecular testing for evidence of EWSR1 rearrangement are useful investigations to confirm the diagnosis. Furthermore, modalities of treatment must be carefully discussed. Cutaneous Ewing's sarcoma is currently treated in the same way as osseous Ewing's sarcoma (wide surgical excision, adjuvant radiotherapy when surgical margins are unsatisfactory, systemic adjuvant chemotherapy, and, in some cases, bone marrow transplant). However, some studies show a more favourable prognosis for cutaneous Ewing's sarcoma than for osseous Ewing's sarcoma. We may thus ask whether such aggressive multimodal treatment is needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Metastatic synovial sarcoma of the scalp: Case report.

PubMed

Lippert, Dylan C; Britt, Christopher J; Pflum, Zachary E; Rush, Patrick S; Hartig, Gregory K

2016-02-01

Synovial sarcoma is a malignant tumor of soft tissue that is rarely found in the head and neck. Even less common are metastasis within the head and neck. We describe a case of a delayed metastatic synovial sarcoma to the scalp. A man who had been diagnosed and treated 16 years previously for monophasic synovial sarcoma of the groin, presented with a new scalp lesion confirmed to be metastatic monophasic synovial sarcoma. Wide local excision and sentinel lymph node biopsy (SLNB) were performed and adjuvant radiation therapy was deferred. A positron emission tomography (PET)/CT was obtained 3 months after surgery and showed no evidence of local recurrence or metastatic disease. This case report describes a rare case of synovial sarcoma metastasizing to the scalp. The genetic, histopathologic, and clinical features of synovial sarcoma are reviewed with a focus on their manifestation and management within the head and neck. © 2015 Wiley Periodicals, Inc.

Synovial sarcoma of the temporomandibular joint and infratemporal fossa.

PubMed

Nomura, Fuminori; Kishimoto, Seiji

2014-12-01

Synovial sarcoma in the head and neck region is rare, and is difficult to resect with adequate safety margins because of its anatomical complexity. We herein report our experiences with synovial sarcoma in this region, and review the literature regarding the management of such cases. We retrospectively examined four cases of synovial sarcoma arising from the temporomandibular joint (TMJ) area and infratemporal fossa. Only one patient remains alive without disease, while the other three patients have died. The local control of these tumors has improved because of the progress in the surgical operation methods, while it is expected that there is still a high rate of deaths due to distant metastasis increase. The development of strong chemotherapy is needed for the use after the initial treatment and surgery. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

High-Grading Lunar Samples

NASA Technical Reports Server (NTRS)

Allen, Carlton; Sellar, Glenn; Nunez, Jorge; Mosie, Andrea; Schwarz, Carol; Parker, Terry; Winterhalter, Daniel; Farmer, Jack

2009-01-01

Astronauts on long-duration lunar missions will need the capability to high-grade their samples to select the highest value samples for transport to Earth and to leave others on the Moon. We are supporting studies to define the necessary and sufficient measurements and techniques for high-grading samples at a lunar outpost. A glovebox, dedicated to testing instruments and techniques for high-grading samples, is in operation at the JSC Lunar Experiment Laboratory. A reference suite of lunar rocks and soils, spanning the full compositional range found in the Apollo collection, is available for testing in this laboratory. Thin sections of these samples are available for direct comparison. The Lunar Sample Compendium, on-line at http://www-curator.jsc.nasa.gov/lunar/compendium.cfm, summarizes previous analyses of these samples. The laboratory, sample suite, and Compendium are available to the lunar research and exploration community. In the first test of possible instruments for lunar sample high-grading, we imaged 18 lunar rocks and four soils from the reference suite using the Multispectral Microscopic Imager (MMI) developed by Arizona State University and JPL (see Farmer et. al. abstract). The MMI is a fixed-focus digital imaging system with a resolution of 62.5 microns/pixel, a field size of 40 x 32 mm, and a depth-of-field of approximately 5 mm. Samples are illuminated sequentially by 21 light emitting diodes in discrete wavelengths spanning the visible to shortwave infrared. Measurements of reflectance standards and background allow calibration to absolute reflectance. ENVI-based software is used to produce spectra for specific minerals as well as multi-spectral images of rock textures.

Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

ClinicalTrials.gov

2017-05-18

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

AIDS-related Kaposi sarcoma: findings on thallium-201 scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, V.W.; Rosen, M.P.; Baum, A.

1988-12-01

No simple, noninvasive method is available for evaluating extracutaneous Kaposi sarcoma in AIDS patients or for following the tumor's response to treatment. We report our preliminary experience with thallium-201 scintigraphy in nine AIDS patients with proved Kaposi sarcoma. Eight of the nine had abnormal uptake of the radionuclide in skin, lymph nodes, oral cavity, vagina, and lungs. Only four of the nine had cutaneous Kaposi sarcoma at the time of scanning. All cutaneous and mucosal lesions were thallium avid. Two of the six patients with thallium-avid nodes underwent nodal biopsy. Both biopsies confirmed the diagnosis of Kaposi sarcoma. Cutaneous Kaposimore » sarcoma developed later in one of these patients, showing the efficacy of thallium scintigraphy for the early detection of extracutaneous lesions. These preliminary results show thallium avidity in Kaposi sarcoma involving the skin and various extracutaneous sites (lymph nodes, lung, mucosa, and vagina). Thallium scintigraphy is a potentially useful procedure for detecting extracutaneous Kaposi sarcoma in AIDS patients.« less

Gastric myeloid sarcoma without acute myeloblastic leukemia

PubMed Central

Huang, Xiao-Li; Tao, Jin; Li, Jian-Zhong; Chen, Xiao-Liang; Chen, Jian-Ning; Shao, Chun-Kui; Wu, Bin

2015-01-01

Myeloid sarcomas (MS) involve extramedullary blast proliferation from one or more myeloid lineages that replace the original tissue architecture, and these neoplasias are called granulocytic sarcomas, chloromas or extramedullary myeloid tumors. Such tumors develop in lymphoid organs, bones (e.g., skulls and orbits), skin, soft tissue, various mucosae, organs, and the central nervous system. Gastrointestinal (GI) involvement is rare, while the occurrence of myeloid sarcomas in patients without leukemia is even rare. Here, we report a case of a 38-year-old man who presented with epigastric pain and progressive jaundice. An upper GI endoscopy had shown extensive multifocal hyperemic fold thickening and the spread of nodular lesions in the body of the stomach. Biopsies from the gastric lesions indicated myeloid sarcoma of the stomach. However, concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia. For diagnosis, the immunohistochemical markers must be checked when evaluating a suspected myeloid sarcoma case. Accurate MS diagnosis determines the appropriate therapy and prognosis. PMID:25717265

Uterine sarcoma

MedlinePlus

... Churchill Livingstone; 2014:chap 88. Crum CP, Laury AR, Hirsch MS, Quick CM, Peters WA. Undifferentiated uterine sarcoma. In: Crum CP, Quick CM, Laury AR, Peters WA, Hirsch MS, eds. Gynecologic and Obstetric ...

Ewing's sarcoma of bone tumor cells produces MCSF that stimulates monocyte proliferation in a novel mouse model of Ewing's sarcoma of bone.

PubMed

Margulies, B S; DeBoyace, S D; Damron, T A; Allen, M J

2015-10-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Ewing's Sarcoma of Bone Tumor Cells Produce MCSF that Stimulates Monocyte Proliferation in a Novel Mouse Model of Ewing's Sarcoma of Bone

PubMed Central

Margulies, BS; DeBoyace, SD; Damron, TA; Allen, MJ

2015-01-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. PMID:26051470

[Clinical and Pathologic Features of Myeloid Sarcoma].

PubMed

Jiang, Ya-Jun; Wang, Hong-Xia; Zhuang, Wan-Chuan; Chen, Hao; Zhang, Chang; Li, Xiu-Mei; Zhu, Gui-Hua; He, Yao

2017-06-01

To explore the clinicopathologic features, differential diagnosis and therapy of myeloid sarcoma. The clinical data including clinical manifestations, laboratorial tests, histopathologicical examination, immunohistochemistry and clinical prognosis of 10 patients with myeloid sarcoma were analyzed retrospectively. Among 10 patients, 5 male and 5 female, aged 23 to 71 years old (median = 36 years). 2 cases of myeloid sarcoma were secondary from chronic myeloid leukemia, and 1 cases of myeloid sarcoma occurred after the allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia, and the others lacked the anamnesis of malignancies. The neoplasms occurred at bone, brain, skin, breast, epididymis, uterine cervix, small intestine, ovary and lymph nodes. Microscopically, the tumor cells were round or oval, which infiltrated diffusely or arranged in single-file. The cytoplasm was scarce and immature eosinophils were scattered. The nuclei were round, oval or focally irregular, and the mitosis was visible. The neoplasms were positive for MPO, CD34, CD43, CD45, CD99 and CD117 by immunohistochemical staining. 4 patients progressed into acute myeloid leukemia from 2 to 10 months after the diagnosis of myeloid sarcoma. All of them achieved complete remission after inductive chemotherapy, but 3 patients relapsed from 3 to 12 months after remission and only survived for 14 to 23 months. 4 patients were treated by using chemotherapy before bone marrow abnormality, and with the disease-free survival for 1 to 48 months. Myeloid sarcoma needs to be distinguished from lymphoblastic lymphoma, Burkitt's lymphoma, blastic plasmacytoid dendritic cell neoplasms and so on. The diagnosis and differential diagnosis of myeloid sarcoma are dependent on the pathological and immunohisto-chemical features. The chemotherapy and allogeneic hematopoietic stem cell transplantation of acute myeloid leukemia are the main methods for treatment of myeloid sarcoma.

Dural metastasis of Ewing's sarcoma.

PubMed

Ben Nsir, Atef; Boughamoura, Mohamed; Maatouk, Mezri; Kilani, Mohamed; Hattab, Nejib

2013-01-01

Metastatic Ewing's sarcoma to the central nervous system is an uncommon condition and debate concerning the true origin of its metastases is still up to date. To the best of our knowledge, only two cases of dural metastatic Ewing's sarcoma have been published in the English medical literature. We present an additional case in a 24-year-old female and discuss the pathogenesis of these unusual tumors with review of the relevant literature concerning their treatment and outcome. A 24-year-old female with previous history of pelvis Ewing's sarcoma and recently discovered lung metastases, presented with moderate headache for the past 2 weeks and weakness in her left leg for the past 2 days. Computed tomography scan and magnetic resonance imaging revealed an extra-axial right frontoparietal mass invading the superior sagittal sinus but with clear delineation with brain parenchyma. Imaging features were suggestive of a meningioma as no abnormalities in the skull abutting to the tumor were noted. The patient underwent surgical removal of her tumor. Near total resection was achieved and histological examination showed evidence of metastatic Ewing's sarcoma. Postoperative adjuvant radiation and chemotherapy were administered. The patient improved well postoperatively with full recovery of her motor weakness. She is symptom free with no signs of progression, at most recent follow-up, 8 months after surgery. Despite its rarity, metastatic Ewing's sarcoma must be considered in the differential diagnosis of extra-axial dural masses particularly meningiomas.

Canine Soft Tissue Sarcomas: Can Being a Dog’s Best Friend Help a Child?

PubMed Central

Séguin, Bernard

2017-01-01

Soft tissue sarcomas (STSs) remain a therapeutic challenge for pediatric and adolescent and young adult (AYA) patients. Still today, surgery, radiation therapy, and chemotherapy remain the mainstay of treatment. Obstacles in developing new treatment approaches to improve the outcome are: few patients to enroll in clinical trials, and the diversity of tumor biology between histologic subtypes. Pet dogs may offer an additional strategy to discover and test new therapeutic avenues. The number of dogs diagnosed with a STS each year in the United States is estimated to be around 27,000 to 95,000. In comparison, approximately 900 children less than 20 years old and 1,500 AYAs between 15 and 29 years old are diagnosed with a STS each year in the United States. The mainstay for treatment of STSs in dogs is also surgery, with radiation therapy and chemotherapy when necessary. Similar to what is seen in humans, grade and stage are prognostic in dogs. In one comparative study of the histology and immunohistochemistry of canine STSs, most tumors were diagnosed as the human equivalent of undifferentiated sarcoma, spindle cell sarcoma, or unclassified spindle cell sarcoma. But much work remains to be done to fully assess the validity of canine STSs as a model. Gene expression analysis has been done in a limited number of canine STSs. Tissue banking, development of cell lines, and the ability to mobilize large-scale clinical trials will become essential in veterinary medicine to benefit both dogs and humans. PMID:29218302

Multimodality therapy for metastatic sarcomas confined to the lung

PubMed Central

GOLLARD, RUSSELL P.; TURNER, J. FRANCIS

2012-01-01

Metastectomy or resection of sarcomas which have metastasized to the lung from other sites has a long and established history. At present, there are more than forty different drugs with activity in soft tissue sarcomas. A number of sarcomas demonstrate differential sensitivities to chemotherapy and targeted agents. Intimate knowledge of the biological behavior of each distinct type of sarcoma should predicate what treatment or protocol is most suitable. Certain patients might benefit from either neoadjuvant or adjuvant therapy following the resection of metastatic lesions. Much remains to be learned about the differential sensitivities of various sarcomas to different treatment regimens. PMID:23205068

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review.

PubMed

García-Castellano, José M; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H

2012-01-01

Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into "good" and "poor" responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

Characterization of a distinct subgroup of high-risk persons with Kaposi's sarcoma and good prognosis who present with normal T4 cell number and T4:T8 ratio and negative HTLV-III/LAV serologic test results.

PubMed

Afrasiabi, R; Mitsuyasu, R T; Nishanian, P; Schwartz, K; Fahey, J L

1986-12-01

Three homosexual male patients with biopsy-proved Kaposi's sarcoma were classified as having the acquired immune deficiency syndrome (AIDS) by Centers for Disease Control criteria when first seen in 1983 and 1984. These patients, however, differed from most patients with AIDS and Kaposi's sarcoma in having normal CD4 cell numbers and normal CD4:CD8 ratio. Furthermore, these immunologic parameters remained normal for eight to 24 months of follow-up, and the disease did not progress. Results of recent testing of serum from these patients were negative for HTLV-III/LAV antibodies. The Kaposi's sarcoma was limited to skin (stage I tumors) and the patients did not have persistent lymphadenopathy, fever, night sweats, or weight loss. In contrast to AIDS, the serum immunoglobulin levels (IgG, IgA, IgM) and number of B cells that were spontaneously forming immunoglobulin were within normal range with no evidence of polyclonal activation. The lymphocyte proliferative responses to phytohemagglutinin and Candida were reduced in two of the three patients, and skin test anergy was observed in the two patients tested. These findings are not frequently encountered in other healthy, homosexually active men or in classic Kaposi's sarcoma. They may be indicative of functional T cell changes (without numerical changes) induced by factors other than HTLV-III/LAV virus, which made these homosexually active men susceptible to development of low-grade Kaposi's sarcoma lesions.

Endometrial stromal sarcoma mimicking submucosal myoma protruding to the vagina: MRI findings.

PubMed

Chien, J C W; Hsieh, S C; Lee, R C; Chen, C Y; Cheng, C J; Chan, W P

2005-01-01

A 46-year-old woman complained of persistent abnormal vaginal bleeding over ten days. Her intrauterine device had been removed two years before. Soon after, she suffered from menorrhagia and metrorrhagia. An incidental finding of severe anemia was also noted. In this admission, our initial T2-weighted magnetic resonance imaging (MRI) revealed a well-demarcated mass predominantly in the uterine cavity. The mass was depicted by an isointense signal relative to the myometrium on T1-weighted images, high signal intensity on T2-weighted images, and slightly heterogeneous enhancement on post-contrast images. The patient refused surgery. After two years, follow-up MRI showed a pedunculated mass protruding into the upper third of the vagina with a stalk connecting to the posterior wall of the uterine cavity, simulating submucosal myoma. Histological diagnosis was compatible with low-grade endometrial stromal sarcoma.

Biological characterization of soft tissue sarcomas.

PubMed

Hayashi, Takuma; Horiuchi, Akiko; Sano, Kenji; Kanai, Yae; Yaegashi, Nobuo; Aburatani, Hiroyuki; Konishi, Ikuo

2015-12-01

Soft tissue sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to mesenchymal transformation and the establishment of new therapies and diagnostic biomarker has been hampered by several critical factors. First, malignant soft tissue sarcomas are rarely observed in the clinic with fewer than 15,000 newly cases diagnosed each year in the United States. Another complicating factor is that soft tissue sarcomas are extremely heterogeneous as they arise in a multitude of tissues from many different cell lineages. The scarcity of clinical materials coupled with its inherent heterogeneity creates a challenging experimental environment for clinicians and scientists. Faced with these challenges, there has been extremely limited advancement in clinical treatment options available to patients as compared to other malignant tumours. In order to glean insight into the pathobiology of soft tissue sarcomas, scientists are now using mouse models whose genomes have been specifically tailored to carry gene deletions, gene amplifications, and somatic mutations commonly observed in human soft tissue sarcomas. The use of these model organisms has been successful in increasing our knowledge and understanding of how alterations in relevant oncogenic and/or tumour suppressive signal cascades, i.e., interferon-γ (IFN-γ), tumour protein 53 (TP53) and/or retinoblastoma (RB) pathway directly impact sarcomagenesis. It is the goal of many in the physiological community that the use of several mouse models will serve as powerful in vivo tools for further understanding of sarcomagenesis and potentially identify new diagnostic biomarker and therapeutic strategies against human soft tissue sarcomas.

Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

ClinicalTrials.gov

2013-06-20

Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Prognostic significance of serum lactate dehydrogenase levels in Ewing's sarcoma: A meta-analysis.

PubMed

Li, Suoyuan; Yang, Qing; Wang, Hongsheng; Wang, Zhuoying; Zuo, Dongqing; Cai, Zhengdong; Hua, Yingqi

2016-12-01

A number of studies have investigated the role of serum lactate dehydrogenase (LDH) levels in patients with Ewing's sarcoma, although these have yielded inconsistent and inconclusive results. Therefore, the present study aimed to systematically review the published studies and conduct a meta-analysis to assess its prognostic value more precisely. Cohort studies assessing the prognostic role of LDH levels in patients with Ewing's sarcoma were included. A pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) or 5-year disease-free survival (DFS) was used to assess the prognostic role of the levels of serum LDH. Nine studies published between 1980 and 2014, with a total of 1,412 patients with Ewing's sarcoma, were included. Six studies, with a total of 644 patients, used OS as the primary endpoint and four studies, with 795 patients, used 5-year DFS. Overall, the pooled HR evaluating high LDH levels was 2.90 (95% CI: 2.09-4.04) for OS and 2.40 (95% CI: 1.93-2.98) for 5-year DFS. This meta-analysis demonstrates that high levels of serum LDH are associated with lower OS and 5-year DFS rates in patients with Ewing's sarcoma. Therefore, serum LDH levels are an effective biomarker of Ewing's sarcoma prognosis.

The progression of CD56+ myeloid sarcoma: A case report and literature review

PubMed Central

WANG, XIN; LI, WEN-SHENG; ZHENG, YAN; YING, ZHAO-XIA; WANG, YONG-XIAN; WANG, YING-MEI; ZHENG, JUN-FENG; XIAO, SHENG-XIANG

2016-01-01

The current study presents a case of cluster of differentiation (CD)56+ myeloid sarcoma in a patient that initially presented with skin lesions, and provides evidence for the clinical and differential diagnosis of myeloid sarcoma. The patient of the present case report was a 65-year-old man who was admitted to hospital with a six-month history of bilateral purple-red papules and nodules, which were present on the upper limbs of the patient and had spread over his whole body one month prior to admission to the hospital. Pathological examination demonstrated a diffuse infusion of primitive round cells at the papillary dermis and subcutaneous tissues. The infiltrated cells were 40–60 µm in diameter and morphologically identical. Immunohistochemical examination revealed that the cells expressed myeloperoxidase, CD56, CD43 and T-cell intracytoplasmic antigen. In addition, several cells expressed CD34, and 90% of the cells expressed Ki67. While the majority of cells in myeloid sarcoma do not express CD56, the present case was a myeloid sarcoma that expressed CD56, which is extremely rare. The sarcoma in the present patient progressed rapidly, and the patient died eight months following the onset of disease. Clinicians should be aware of CD56+ myeloid sarcoma, which is easily misdiagnosed and inappropriately treated. Consequently, myeloid sarcoma may have a high malignancy and poor outcome for patients. PMID:27123069

Feasibility of Preoperative Chemotherapy With or Without Radiation Therapy in Localized Soft Tissue Sarcomas of Limbs and Superficial Trunk in the Italian Sarcoma Group/Grupo Español de Investigación en Sarcomas Randomized Clinical Trial: Three Versus Five Cycles of Full-Dose Epirubicin Plus Ifosfamide.

PubMed

Palassini, Elena; Ferrari, Stefano; Verderio, Paolo; De Paoli, Antonino; Martin Broto, Javier; Quagliuolo, Vittorio; Comandone, Alessandro; Sangalli, Claudia; Palmerini, Emanuela; Lopez-Pousa, Antonio; De Sanctis, Rita; Bottelli, Stefano; Libertini, Michela; Picci, Piero; Casali, Paolo G; Gronchi, Alessandro

2015-11-01

We report on feasibility of preoperative chemotherapy with or without radiation therapy (RT) in the context of a phase III randomized clinical trial involving localized, high-risk, soft tissue sarcomas. Of 321 eligible patients, 161 were randomly assigned to three preoperative cycles of epirubicin 120 mg/m(2) plus ifosfamide 9 g/m(2), and 160 were randomly assigned to three preoperative plus two postoperative cycles. Among them, 303 patients were included in this analysis; 169 were male and 134 were female, with a median age of 48 years (range, 15 to 79 years). One hundred fifty-two patients received concurrent RT preoperatively at a total dose of 44 to 50 Gy. Preoperative chemotherapy-related hematologic toxicity and early postoperative complications were reported. The influence of RT, age, and sex on hematologic grade 3 or 4 toxicities and wound complications was analyzed. Chemotherapeutic dose intensity (DI) was analyzed. Among the patients, 61.4%, 22.4%, and 23.8% experienced, grade 4 leucopenia, grade 3 or 4 anemia, and grade 3 or 4 thrombocytopenia, respectively. Respective rates were 66.4%, 24.3%, and 31.6% when RT was added preoperatively, and 56.3%, 20.5%, and 15.9% when preoperative chemotherapy was administered alone. Patient age affected grade 3 or 4 thrombocytopenia. Grade 4 leucopenia and grade 3 or 4 anemia presented 2.5 times more frequently in female patients than in male patients. Wound complications were observed in 13.5% of patients: 17% with preoperative RT and 10% without. Chemotherapeutic DI was greater than 90%, even in patients receiving preoperative RT and in patients age 65 years or older. This preoperative chemotherapy is feasible and can also be proposed for selected elderly patients. Grade 3 or 4 hematologic toxicity was common, but DI was excellent. Concurrent preoperative RT is safe, although an increased rate of grade 4 thrombocytopenia and limited increase in wound complications may be observed. © 2015 by American Society of

Physiotherapy management of patients with HIV-associated Kaposi's sarcoma.

PubMed

Harris-Love, Michael O; Shrader, Joseph A

2004-01-01

Kaposi's sarcoma is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although Kaposi sarcoma lesions may contribute to significant physical impairments, there is a lack of scientific literature detailing the role of physiotherapy in the treatment of HIV-associated Kaposi's sarcoma. The present Case Report includes two males, aged 36 and 39 years, seropositive for HIV with invasive Kaposi's sarcoma. Patient A was evaluated for bilateral foot pain caused by plantar surface Kaposi s sarcoma lesions that rendered him unable to walk. He progressed to walking 400feet after a treatment regimen of gait training with the use of custom plastazote sandals. Patient B was evaluated for right lower extremity lymphoedema secondary to invasive Kaposi's sarcoma. He experienced an 18% reduction in limb volume, a 38% reduction in pain and a 20 degrees increase in terminal knee flexion after therapeutic exercise and the use of compressive bandaging and garments. This Case Report suggests that physiotherapy interventions may be valuable in the conservative management of patients with HIV-associated Kaposi s sarcoma.

Collecting and Storing Biological Samples From Patients With Ewing Sarcoma

ClinicalTrials.gov

2017-12-11

Askin Tumor; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

[Molecular biology for sarcoma: useful or necessary?].

PubMed

Neuville, Agnès; Coindre, Jean-Michel; Chibon, Frédéric

2015-01-01

Sarcomas are a heterogeneous group of tumors. Their diagnosis is based on morphology and immunohistochemical profile, with categories of tumors according to the type of tissue that they resemble. Nevertheless, for several tumors, cellular origin is unknown. Molecular analysis performed in recent years allowed, combining histophenotype and genomics, better classifying such sarcomas, individualizing new entities and grouping some tumors. Simple and recurrent genetic alterations, such as translocation, mutation, amplification, can be identified in one of two sarcomas and appear as new diagnostic markers. Their identification in specialized laboratories in molecular pathology of sarcomas is often useful and sometimes necessary for a good diagnosis, leading to a heavy and multidisciplinary multi-step treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Reconstruction of the proximal humerus with a composite of extracorporeally irradiated bone and endoprosthesis following excision of high grade primary bone sarcomas.

PubMed

Moran, Matthew; Stalley, Paul D

2009-10-01

Functional reconstruction of the shoulder joint following excision of a malignant proximal humeral tumour is a difficult proposition. Eleven patients with primary osteosarcoma or Ewing's sarcoma underwent reconstruction with a composite of extra-corporeally irradiated autograft with the addition of a long stemmed hemiarthroplasty. At a mean follow-up of 5.8 years two patients had died from disseminated disease and one patient had undergone amputation for local recurrence. The eight patients with a surviving limb were examined clinically and radiographically. The mean Toronto Extremity Salvage Score was 74 and Musculo-Skeletal Tumour Society score 66. Rotation was well preserved but abduction (mean 32 degrees ) and flexion (40 degrees ) were poor. There was a high rate of secondary surgery, with five out of eleven patients requiring re-operation for complications of reconstruction surgery. Radiographic estimate of graft remaining at follow up was 71%. There were no infections, revisions or radiographic failures. Whilst the reconstructions were durable in the medium term, the functional outcome was no better than with other reported reconstructive methods. The composite technique was especially useful in subtotal humeral resections, allowing preservation of the elbow joint even with very distal osteotomy. Bone stock is restored, which may be useful for future revision surgery in this young group of patients.

Diagnostic features of feline restrictive orbital myofibroblastic sarcoma.

PubMed

Bell, C M; Schwarz, T; Dubielzig, R R

2011-05-01

A progressive debilitating disease of the orbit and adjacent connective tissues of cats has historically been called feline orbital pseudotumor. The authors reviewed clinical, histopathologic, and diagnostic imaging features of this disease in 12 cases from the Comparative Ocular Pathology Laboratory of Wisconsin. The cats' ages ranged from 7 to 16 years (mean, 10.8 years). All cats had a history of severely restricted mobility of the globe and eyelids with secondary corneal disease. Eleven cats (92%) had concurrent involvement of the contralateral eye and/or the oral cavity. Diffuse scleral or episcleral thickening was seen with computed tomography in all clinically affected eyes. Histologically, an insidious infiltration of neoplastic spindle cells in the orbit, eyelids, and periorbital skin and soft tissues, with collagen deposition and a few perivascular lymphocytes, led to entrapment and restricted mobility of the eyelids and orbital tissues. The tumor failed to form a discrete mass, and it spread along fascial planes to the contralateral orbit and eyelids and/or the lips and oral cavity. In all tested cases (n = 10), neoplastic cells were immunohistochemically positive for vimentin, S100 protein, and smooth muscle actin. The authors adopted the term feline restrictive orbital myofibroblastic sarcoma to reflect the restricted mobility of the eyelids and globe and the imaging and histologic features of an invasive yet low-grade myofibroblastic sarcoma.

Kaposi Sarcoma

MedlinePlus

Kaposi sarcoma (KS) is a cancer that causes patches of abnormal tissue to grow under the skin, in the lining of ... of cancer cells, blood vessels, and blood cells. KS is caused by infection with human herpesvirus-8 ( ...

Recurrent high-grade glioma.

PubMed

Quant, Eudocia C; Drappatz, Jan; Wen, Patrick Y; Norden, Andrew D

2010-07-01

Opinions vary on the best treatment options for recurrent high-grade glioma. Some argue that bevacizumab should become standard of care for patients with recurrent glioblastoma, especially in light of recent FDA approval for this indication. However, this opinion is not uniformly accepted. Age, performance status, histology, tumor size and location, O6-methylguanine-DNA methyltransferase (MGMT) methylation status for glioblastoma, 1p/19q status for oligodendroglial tumors, and the number and types of prior therapies are important considerations. In addition, recurrent disease must be distinguished from "pseudoprogression" due to treatment effects. Enrollment in a clinical trial is the optimal choice for most patients with recurrent high-grade glioma after failure of radiation therapy and temozolomide. For patients who are ineligible or do not have access to clinical trials, then either bevacizumab monotherapy or bevacizumab in combination with a second agent such as irinotecan is recommended. Involved-field external beam radiation should be considered for patients with anaplastic gliomas who have not received radiation. For patients with anaplastic astrocytoma who progress after radiotherapy, temozolomide may be used. For patients with anaplastic oligodendroglioma who progress after radiotherapy, PCV chemotherapy and temozolomide are options. Oligodendroglial tumors with 1p/19q deletions are more likely to respond to treatment. In the past, carmustine was commonly used to treat recurrent high-grade glioma, but the utility of carmustine in the modern era is unknown because most studies were performed prior to the widespread use of temozolomide. High-precision re-irradiation such as stereotactic radiosurgery is another option in high-grade glioma, especially for patients with poor bone marrow reserve or inability to tolerate chemotherapy, but there is a paucity of studies with adequate controls. Surgery may be useful as adjuvant treatment for patients with symptoms

An unusual case of gastric cancer presenting with breast metastasis with pleomorphic microcalcifications.

PubMed

Luk, Yiu Shiobhon; Ka, Solomon Yig Joon; Lo, Sherwin Shing Wai; Chu, Chi Yeung; Ma, Ming Wai

2012-09-01

Breast metastasis from gastric carcinoma is rare. We present a case of right breast mass with microcalcification in which the diagnosis of poorly differentiated adenocarcinoma from the stomach was made after a biopsy. Pleomorphic microcalcification was noted in the ill-defined breast mass, which is a rare feature in breast metastasis. Since breast metastasis usually signifies advanced metastatic disease, differentiating primary breast cancer from metastasis is important for appropriate treatment.

Does an Algorithmic Approach to Using Brachytherapy and External Beam Radiation Result in Good Function, Local Control Rates, and Low Morbidity in Patients With Extremity Soft Tissue Sarcoma?

PubMed

Klein, Jason; Ghasem, Alex; Huntley, Samuel; Donaldson, Nathan; Keisch, Martin; Conway, Sheila

2018-03-01

High-dose-rate brachytherapy (HDR-BT) and external-beam radiation therapy (EBRT) are two modalities used in the treatment of soft tissue sarcoma. Previous work at our institution showed early complications and outcomes for patients treated with HDR-BT, EBRT, or a combination of both radiation therapy modalities. As the general indications for each of these approaches to radiation therapy differ, it is important to evaluate the use of each in an algorithmic way, reflecting how they are used in contemporary practice at sites that use these treatments. QUESTION/PURPOSES: (1) To determine the proportions of intermediate- and long-term complications associated with the use of brachytherapy in the treatment of primary high-grade extremity soft tissue sarcomas; (2), to characterize the long-term morbidity of the three radiation treatment groups using the Radiation Therapy Oncology Group/ European Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Scheme; (3) to determine whether treatment with HDR-BT, EBRT, and HDR-BT+EBRT therapy, in combination with limb-salvage surgery, results in acceptable local control in this high-risk group of sarcomas. We retrospectively studied data from 171 patients with a diagnosis of high-grade extremity soft tissue sarcoma treated with limb-sparing surgery and radiation therapy between 1990 and 2012 at our institution, with a mean followup of 72 months. Of the 171 patients, 33 (20%) were treated with HDR-BT, 128 (75%) with EBRT, and 10 (6%) with HDR-BT+EBRT. We excluded 265 patients with soft tissue sarcomas owing to axial tumor location, previous radiation to the affected extremity, incomplete patient records, patients receiving primary amputation, recurrent tumors, pediatric patients, low- and intermediate-grade tumors, and rhabdoid histology. Fifteen patients (9%) were lost to followup for any reason including died of disease or other causes during the first 12 months postoperatively. This

Quantitative morphology in canine cutaneous soft tissue sarcomas.

PubMed

Simeonov, R; Ananiev, J; Gulubova, M

2015-12-01

Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and dermal fibrosis (n = 12)] were analysed by computer-assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; µm(2)), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (Dmin; µm) and maximum nuclear diameter (Dmax; µm). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for Dmax) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour-like fibrous lesions in dogs. © 2014 John Wiley & Sons Ltd.

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review

PubMed Central

García-Castellano, José M.; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H.

2012-01-01

Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into “good” and “poor” responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients. PMID:22550418

Treatment of femoral Ewing's sarcoma.

PubMed

Terek, R M; Brien, E W; Marcove, R C; Meyers, P A; Lane, J M; Healey, J H

1996-07-01

The treatment of Ewing's sarcoma consists of chemotherapy for systemic and local disease. However, the role of radiation therapy, and/or surgical resection for definitive local treatment has yet to be determined. A retrospective review of 32 patients (24 males and 8 females) treated for femoral Ewing's sarcoma between 1970 and 1985 was performed. Patients were divided into 3 treatment groups: chemotherapy and radiotherapy (CR) (10); chemotherapy and surgery (CS) (9); and chemotherapy, surgery, and radiotherapy (CSR) (13). Patients in the CR group received a mean of 5320 centigray (cGy) of radiation and patients in the CSR group received a mean of 3590 cGy. Multiagent cyclophosphamide/doxorubicin based chemotherapy was used in all cases. Surgery consisted of wide resection or amputation. Patients in the CR group had a higher risk of local recurrence than patients in the CS and CSR groups (P=0.02, log rank). The combination of local recurrences and treatment complications necessitated surgery for 7 of 10 CR patients, whereas 1 of 9 and 4 of 13 in the CS and CSR groups required additional surgery. The median survival for the entire group was 39 months. Minimum follow-up for surviving patients was 45 months. Five-year survival consisted of 1 of 10 patients in the CR group, 2 of 9 in the CS group, and 7 of 13 in the CSR group. There were no statistically significant differences among the three survival curves. Tumor location within the femur was a significant prognostic variable. Distal femoral location had a survival advantage compared with proximal and mid-femur locations (P = 0.049, log rank). Femoral Ewing's sarcoma remains a disease with a poor prognosis. Radiation alone for local treatment results in a high rate of local recurrence and complications. Our current local treatment strategy for femoral Ewing's sarcoma includes surgery in all and adjuvant radiotherapy in many of the patients.

Intratumoral oxygen gradients mediate sarcoma cell invasion

PubMed Central

Lewis, Daniel M.; Park, Kyung Min; Tang, Vitor; Xu, Yu; Pak, Koreana; Eisinger-Mathason, T. S. Karin; Simon, M. Celeste; Gerecht, Sharon

2016-01-01

Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma cell invasion and migration. O2 gradient measurements showed that large sarcoma mouse tumors (>300 mm3) contain a severely hypoxic core [≤0.1% partial pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients throughout the tumor mass (0.1–6% pO2). To analyze tumor invasion, we used O2-controllable hydrogels to recreate the physiopathological O2 levels in vitro. Small tumor grafts encapsulated in the hydrogels revealed increased invasion that was both faster and extended over a longer distance in the hypoxic hydrogels compared with nonhypoxic hydrogels. To model the effect of the O2 gradient accurately, we examined individual sarcoma cells embedded in the O2-controllable hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and matrix remodeling through hypoxia-inducible factor-1α (HIF-1α) activation. We further found that in the hypoxic gradient, individual cells migrate more quickly, across longer distances, and in the direction of increasing O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma metastasis, abrogated cell migration and matrix remodeling in the hypoxic gradient. Overall, we show that O2 acts as a 3D physicotactic agent during sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive system to study early stages of the metastatic process and therapeutic targets. PMID:27486245

Intratumoral oxygen gradients mediate sarcoma cell invasion.

PubMed

Lewis, Daniel M; Park, Kyung Min; Tang, Vitor; Xu, Yu; Pak, Koreana; Eisinger-Mathason, T S Karin; Simon, M Celeste; Gerecht, Sharon

2016-08-16

Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma cell invasion and migration. O2 gradient measurements showed that large sarcoma mouse tumors (>300 mm(3)) contain a severely hypoxic core [≤0.1% partial pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients throughout the tumor mass (0.1-6% pO2). To analyze tumor invasion, we used O2-controllable hydrogels to recreate the physiopathological O2 levels in vitro. Small tumor grafts encapsulated in the hydrogels revealed increased invasion that was both faster and extended over a longer distance in the hypoxic hydrogels compared with nonhypoxic hydrogels. To model the effect of the O2 gradient accurately, we examined individual sarcoma cells embedded in the O2-controllable hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and matrix remodeling through hypoxia-inducible factor-1α (HIF-1α) activation. We further found that in the hypoxic gradient, individual cells migrate more quickly, across longer distances, and in the direction of increasing O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma metastasis, abrogated cell migration and matrix remodeling in the hypoxic gradient. Overall, we show that O2 acts as a 3D physicotactic agent during sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive system to study early stages of the metastatic process and therapeutic targets.

BCOR-CCNB3 Fusions Are Frequent in Undifferentiated Sarcomas of Male Children

PubMed Central

Peters, Tricia L.; Kumar, Vijetha; Polikepahad, Sumanth; Lin, Frank Y.; Sarabia, Stephen F.; Liang, Yu; Wang, Wei-Lien; Lazar, Alexander J.; Doddapaneni, Harsha Vardhan; Chao, Hsu; Muzny, Donna M.; Wheeler, David A.; Okcu, M. Fatih; Plon, Sharon E.; Hicks, M. John; López-Terrada, Dolores; Parsons, D. Williams; Roy, Angshumoy

2014-01-01

The BCOR-CCNB3 fusion gene, resulting from a chromosome X paracentric inversion, was recently described in translocation-negative ‘Ewing-like’ sarcomas arising in bone and soft tissue. Genetic subclassification of undifferentiated unclassified sarcomas may potentially offer markers for reproducible diagnosis and substrates for therapy. Using whole transcriptome paired end RNA sequencing (RNA-seq) we unexpectedly identified BCOR-CCNB3 fusion transcripts in an undifferentiated spindle cell sarcoma. RNA-seq results were confirmed through direct RT-PCR of tumor RNA and cloning of the genomic breakpoints from tumor DNA. Five additional undifferentiated sarcomas with BCOR-CCNB3 fusions were identified in a series of 42 pediatric and adult unclassified sarcomas. Genomic breakpoint analysis demonstrated unique breakpoint locations in each case at the DNA level even though the resulting fusion mRNA was identical in all cases. All patients with BCOR-CCNB3 sarcoma were males diagnosed in mid-childhood (7-13 years of age). Tumors were equally distributed between axial and extra-axial locations. Five of the six tumors were soft tissue lesions with either predominant spindle cell morphology or spindle cell areas interspersed with ovoid to round cells. CCNB3 immunohistochemistry showed strong nuclear positivity in 5 tumors prior to oncologic therapy, but was patchy to negative in post-treatment tumor samples. An RT-PCR assay developed to detect the fusion transcript in archival formalin-fixed tissue was positive in all 6 cases, with high sensitivity and specificity in both pre- and post-treated samples. This study adds to recent reports on the clinicopathologic spectrum of BCOR-CCNB3 fusion-positive sarcomas, a newly-emerging entity within the undifferentiated unclassified sarcoma category, and describes a simple RT-PCR assay that in conjunction with CCNB3 immunohistochemistry can be useful in diagnosing these tumors. PMID:25360585

Alveolar soft part sarcoma causing perianal abscess.

PubMed

Sullivan, Niall; McCulloch, Tom; Leverton, David

2011-07-01

A 34-year-old woman presented with a perianal abscess that communicated with the vagina. There was a background of a one-year history of a conservatively treated, traumatic, paravaginal haematoma. Histology of the fistula tract showed alveolar soft part sarcoma and subsequent imaging identified a large soft tissue mass in the pelvis with lung metastases. Alveolar soft part sarcoma is a rare soft tissue sarcoma of unknown cellular origin affecting predominantly young women, often in deep soft tissues and lower extremities.

Synovial sarcoma of nerve.

PubMed

Scheithauer, Bernd W; Amrami, Kimberly K; Folpe, Andrew L; Silva, Ana I; Edgar, Mark A; Woodruff, James M; Levi, Allan D; Spinner, Robert J

2011-04-01

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome. Copyright © 2011. Published by Elsevier Inc.

General Information about Childhood Soft Tissue Sarcoma

MedlinePlus

... Soft Tissue Sarcoma Treatment (PDQ®)–Patient Version General Information About Childhood Soft Tissue Sarcoma Go to Health ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information about Adult Soft Tissue Sarcoma

MedlinePlus

... Soft Tissue Sarcoma Treatment (PDQ®)–Patient Version General Information About Adult Soft Tissue Sarcoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Primary dermal pleomorphic liposarcoma: utility of adipophilin and MDM2/CDK4 immunostainings.

PubMed

Ramírez-Bellver, Jose L; López, Joaquín; Macías, Elena; Alegría-Landa, Victoria; Gimeno, Ignacio; Pérez-Plaza, Alejandra; Kutzner, Heinz; Requena, Luis

2017-03-01

Liposarcoma, usually arises in deep soft tissues and pleomorphic liposarcoma (PL), is the rarest histopathologic variant. However, 15 cases of entirely dermal PL have been reported. We describe a case of a 79-year-old man who developed a rapidly growing nodule on his thorax. Excisional biopsy was performed and immunohistochemical studies were carried. The lesion was a well-circumscribed dermal nodule composed of multivacuolated pleomorphic lipoblasts and atypical mitotic figures. Neoplastic cells expressed CD10 and resulted negative S100 protein, Melan-A, MITF-1, AE1/AE3, CD4, CD68 (PGM1), retinoblastoma gene family protein, pericentrine and lysozyme. Adipophilin stain showed the lipid contents in the cytoplasm of the neoplastic cells. MDM2 and CDK4 resulted both negative. A diagnosis of primary dermal PL was made. This case shows the utility of adipophilin immunostaining to prove the lipid contents in neoplastic cells, which has the advantage of using formalin-fixed paraffin-embedded tissue and making needless frozen sections and ultrastructural studies to show these findings. Negative MDM2/CDK4 staining in our case argues against the possibility of dedifferentiated liposarcoma and further supports the diagnosis of true PL. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical Trial Enrollment of Adolescents and Young Adults With Sarcoma

PubMed Central

Davis, Lara E.; Janeway, Katherine A.; Weiss, Aaron R.; Chen, Yen-Lin E.; Scharschmidt, Thomas J.; Krailo, Mark; Glade Bender, Julia L.; Kopp, Lisa M.; Patel, Shreyaskumar R.; Schwartz, Gary K.; Horvath, L. Elise; Hawkins, Douglas S.; Chuk, Meredith K.; Reinke, Denise K.; Gorlick, Richard G.; Randall, R. Lor

2017-01-01

More than half of all sarcomas occur in adolescents and young adults (AYAs) aged 15 to 39 years. After the publication of the AYA series in the April 1, 2016 issue of Cancer, several leaders in the field of sarcoma across disciplines gathered to discuss the status of sarcoma clinical research in AYAs. They determined that a focused effort to include the underrepresented and understudied AYA population in current and future sarcoma clinical trials is overdue. Trial enrichment for AYA-aged sarcoma patients will produce more meaningful results that better represent the disease's biology, epidemiology, and treatment environment. To address the current deficit, this commentary outlines changes believed to be necessary to expediently achieve an increase in the enrollment of AYAs in sarcoma clinical trials. PMID:28493547

Effect of marital status on treatment and survival of extremity soft tissue sarcoma

PubMed Central

Alamanda, V. K.; Song, Y.; Holt, G. E.

2014-01-01

Background Spousal support has been hypothesized as providing important psychosocial support for patients and as such has been noted to provide a survival advantage in a number of chronic diseases and cancers. However, the specific effect of marital status on survival in soft tissue sarcomas (STSs) of the extremity has not been explored in detail. Patients and methods A total of 7384 patients were evaluated for this study using a Surveillance, Epidemiology, and End Results (SEER) registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009. Survival outcomes were analyzed using Gray's test after patients were stratified by marital status. The Fine and Gray model, a multivariable regression model, was used to assess whether marital status was an independent predictor of sarcoma specific death. Statistical significance was maintained at P < 0.05. Results Analysis of the SEER database showed that single patients were more likely to die of their STS and at a faster rate than married patients. No differences were noted in tumor size and tumor site on presentation between married and single patients. However, single patients presented with higher grade tumors more frequently (P = 0.013), received less radiotherapy (P < 0.001), and had less surgery carried out (P < 0.001), compared with their married peers. Regression analysis showed that after accounting for tumor size, grade, site, histology, use of radiotherapy, age, gender, region where the patients were from, and income, being single continued to serve as an independent predictor of sarcoma-specific death; P < 0.0001. Conclusion Overall survival is worse for single patients, when compared with married patients, with STS. Single patients do not undergo surgical resection or receive radiation therapy as frequently as their married counterparts. Social support systems and barriers to care should be evaluated at time of diagnosis and addressed in single patients to potentially improve

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

ClinicalTrials.gov

2018-03-21

Childhood Alveolar Soft Part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Gliosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma; Rhabdomyosarcoma

Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

ClinicalTrials.gov

2018-02-09

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Supratentorial Primitive Neuroectodermal Tumor; Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Peripheral Primitive Neuroectodermal Tumor of the Kidney; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

[Inhibitory effect of taspine on mouse S180 sarcoma and its mechanism].

PubMed

Zhang, Yan-Min; He, Lang-Chong; Wang, Hong-Ying

2007-05-01

To study the inhibition effect of taspine on mouse S180 sarcoma and its mechanism. The mouse S180 sarcoma model was established and used to observe the antitumor activity of taspine. The microvessel density and protein expressing of the VEGF, bFGF, Bcl-2 and Bax in the tumor were measured by immunohistochemistry. Taspine showed antitumor activity on the mouse S180 sarcoma in a good dose-dependent manner. The inhibition rates on tumor of taspine at low, middle and high concentrations were 39.08% , 43.99% and 48.60%, respectively. The microvessel density and protein expressing of the VEGF, bFGF, Bcl-2 and Bax in the tumor were decreased compared with the negative control. The ratio of Bax to Bcl-2 was increased. Taspine has antitumor effect on the S180 sarcoma, and the mechanism may be through the way of decreasing the expressing of the VEGF, bFGF, Bcl-2 and Bax and inducing the vascular endothelial cell apoptosis.

Uterine sarcoma vs adenocarcinoma: can MRI distinguish between them?

PubMed

Hernández Mateo, P; Méndez Fernández, R; Serrano Tamayo, E

2016-01-01

To analyze the MRI characteristics of uterine sarcomas (mainly carcinosarcomas) and to compare them with those of adenocarcinomas to define the findings that would be useful for the differential diagnosis. We retrospectively reviewed the MRI studies of 13 patients with histologically diagnosed uterine sarcoma. We analyzed tumor size, signal in T2-weighted, unenhanced and gadolinium-enhanced T1-weighted, and diffusion-weighted sequences. We compared the data obtained with those of another series of 30 consecutive cases of adenocarcinomas studied with MRI. The sarcomas (> 9cm in 77% of cases) were considerably larger than the adenocarcinomas (p<0.001). There were no differences in FIGO staging by MRI or surgery: both tumor types were diagnosed in early stages. The signal intensity in T2-weighted images differed significantly between the two tumor types: all the sarcomas were heterogeneous and predominantly hyperintense with respect to the myometrium in T2-weighted sequences (p<0.001). In postcontrast studies, all the sarcomas showed enhancement greater than or equal to the myometrium; this finding was significantly different from the adenocarcinomas (p<0.001). In diffusion-weighted sequences, we found no significant differences in ADC values in the areas with greatest restriction, but the ADC map was more heterogeneous in the sarcomas. Uterine sarcomas do not have specific characteristics on MRI, but some findings can indicate the diagnosis. In our study, we found significant differences between sarcomas and adenocarcinomas. Sarcomas were larger, had more hyperintense and heterogeneous signal intensity in T2-weighted sequences, and enhanced more than or at least as much as the myometrium. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Analysis of Gene Expression Profiles of Soft Tissue Sarcoma Using a Combination of Knowledge-Based Filtering with Integration of Multiple Statistics

PubMed Central

Doi, Ayano; Ichinohe, Risa; Ikuyo, Yoriko; Takahashi, Teruyoshi; Marui, Shigetaka; Yasuhara, Koji; Nakamura, Tetsuro; Sugita, Shintaro; Sakamoto, Hiromi; Yoshida, Teruhiko; Hasegawa, Tadashi

2014-01-01

The diagnosis and treatment of soft tissue sarcomas (STS) have been difficult. Of the diverse histological subtypes, undifferentiated pleomorphic sarcoma (UPS) is particularly difficult to diagnose accurately, and its classification per se is still controversial. Recent advances in genomic technologies provide an excellent way to address such problems. However, it is often difficult, if not impossible, to identify definitive disease-associated genes using genome-wide analysis alone, primarily because of multiple testing problems. In the present study, we analyzed microarray data from 88 STS patients using a combination method that used knowledge-based filtering and a simulation based on the integration of multiple statistics to reduce multiple testing problems. We identified 25 genes, including hypoxia-related genes (e.g., MIF, SCD1, P4HA1, ENO1, and STAT1) and cell cycle- and DNA repair-related genes (e.g., TACC3, PRDX1, PRKDC, and H2AFY). These genes showed significant differential expression among histological subtypes, including UPS, and showed associations with overall survival. STAT1 showed a strong association with overall survival in UPS patients (logrank p = 1.84×10−6 and adjusted p value 2.99×10−3 after the permutation test). According to the literature, the 25 genes selected are useful not only as markers of differential diagnosis but also as prognostic/predictive markers and/or therapeutic targets for STS. Our combination method can identify genes that are potential prognostic/predictive factors and/or therapeutic targets in STS and possibly in other cancers. These disease-associated genes deserve further preclinical and clinical validation. PMID:25188299

Histology and imaging of soft tissue sarcomas.

PubMed

Kind, Michèle; Stock, Nathalie; Coindre, Jean Michel

2009-10-01

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Pleomorphic adenoma of the accessory parotid gland: case report and reappraisal of intraoral extracapsular dissection for management.

PubMed

Tsegga, Tibebu M; Britt, Jennifer D; Ellwanger, Aragon R

2015-03-01

Pleomorphic adenoma is the most common tumor of the major and minor salivary glands. Rarely is it found evolving from an ectopic location of major salivary glandular tissue in the mid cheek. A healthy 56-year-old woman presented to our institution with a 20-year duration of a slowly growing right cheek soft tissue mass that was causing facial asymmetry. No significant functional or neurosensory dysfunction was appreciated. Radiologic examination showed a heterogeneous, hyperintense, well-delineated mass within the region of the right buccal fat pad. Fine-needle aspiration biopsy showed benign salivary gland elements consistent with pleomorphic adenoma. The decision was made to perform intraoral extracapsular dissection for removal. Discussion of the clinical assessment and magnetic resonance imaging evaluation with an emphasis on intraoral extracapsular dissection for definitive surgical therapy of longstanding benign salivary gland tumors is emphasized. Published by Elsevier Inc.

Genome Sequence of Rough and Smooth Variants of Pleomorphic Strain Lactobacillus farciminis CNCM-I-3699

PubMed Central

Tareb, R.; Bernardeau, M.

2015-01-01

The probiotic Lactobacillus farciminis CNCM-I-3699 is a pleomorphic strain exhibiting smooth and rough variants. We report their complete genomes consisting of a chromosome of 2, 4 Mb and a plasmid of 6,417 bp. The smooth variant differs by the presence of an additional plasmid of 35,418 bp. PMID:26383668

Apatinib as targeted therapy for sarcoma

PubMed Central

Li, Feng; Liao, Zhichao; Zhang, Chao; Zhao, Jun; Xing, Ruwei; Teng, Sheng; Zhang, Jin; Yang, Yun; Yang, Jilong

2018-01-01

Sarcomas are a group of malignant tumors originating from mesenchymal tissue with a variety of cell subtypes. Despite several major treatment breakthroughs, standard treatment using surgery, radiation, and chemotherapy has failed to improve overall survival. Therefore, there is an urgent need to explore new strategies and innovative therapies to further improve the survival rates of patients with sarcomas. Pathological angiogenesis has an important role in the growth and metastasis of tumors. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) play a central role in tumor angiogenesis and represent potential targets for anticancer therapy. As a novel targeted therapy, especially with regard to angiogenesis, apatinib is a new type of small molecule tyrosine kinase inhibitor that selectively targets VEGFR-2 and has shown encouraging anticancer activity in a wide range of malignancies, including gastric cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma, and sarcomas. In this review, we summarize the preclinical and clinical data for apatinib, focusing primarily on its use in the treatment of sarcomas. PMID:29849960

[Colonic granulocytic sarcoma: a case report].

PubMed

Makni, S; Bahri, I; Ayadi, L; Mseddi, A; Bouaziz, M; Jlidi, R

2002-06-01

Granulocytic sarcoma is a rare tumor composed of immature cells of the granulocytic series which usually occurs as a secondary manifestation of acute leukaemia. We report the case of a 60 years old woman without particular previous pathologies who was hospitalised for chronic diarrhea developed in a context of health impairment state. The blood cell count revealed severe leucopenia and thrombopenia; an emergency right colectomy was accomplished. The histologic examination showed granulocytic sarcoma of the ascending colon. The death occurred rapidly as a consequence of a toxic shock. This observation seems to be the sixth case report of the granulocytic large bowel sarcoma in the literature which likely complicated a pre-existant and unknown myeloid leukaemia.

Kaposi Sarcoma Treatment (PDQ®)—Patient Version

Cancer.gov

Kaposi sarcoma treatment depends upon the type and can include scraping to remove a lesion, radiation therapy, surgery, and sometimes chemotherapy. Learn more about the diagnosis and treatment of newly diagnosed and recurrent Kaposi sarcoma in this expert-reviewed summary.

RUNX3 Facilitates Growth of Ewing Sarcoma Cells

PubMed Central

Bledsoe, Krista L.; McGee-Lawrence, Meghan E.; Camilleri, Emily T.; Wang, Xiaoke; van Wijnen, Andre J.; Oliveira, Andre M.; Westendorf, Jennifer J.

2014-01-01

Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. PMID:24812032

Extraskeletal Ewing's sarcoma.

PubMed

El-Essawy, Manar T

2009-06-01

We report 2 rare cases of extraskeletal Ewing's sarcoma, one is arising primarily from the posterior mediastinum in a middle-aged man (patient 1), and the other one is arising from the left kidney in a young male patient (patient 2). The CT in the first case showed a large mass of heterogeneous texture, with areas of cystic changes in the right side of the posterior mediastinum, no underlying bony changes or intra-spinal extension, and this mass was diagnosed as lymphoma. The second case showed almost complete replacement of the left kidney by a mass with extension through the renal vein and inferior vena cava, and it was diagnosed as renal cell carcinoma. The histological analysis of these lesions revealed extraskeletal Ewing's sarcoma.

Hypoxia-Dependent Modification of Collagen Networks Promotes Sarcoma Metastasis

PubMed Central

Eisinger-Mathason, T.S. Karin; Zhang, Minsi; Qiu, Qiong; Skuli, Nicolas; Nakazawa, Michael S.; Karakasheva, Tatiana; Mucaj, Vera; Shay, Jessica E.S.; Stangenberg, Lars; Sadri, Navid; Puré, Ellen; Yoon, Sam S.; Kirsch, David G.; Simon, M. Celeste

2013-01-01

Intratumoral hypoxia and expression of Hypoxia Inducible Factor 1α (HIF1α) correlate with metastasis and poor survival in sarcoma patients. We demonstrate here that hypoxia controls sarcoma metastasis through a novel mechanism wherein HIF1α enhances expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). We show that loss of HIF1α or PLOD2 expression disrupts collagen modification, cell migration and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSLKrasG12D/+; Trp53fl/fl murine sarcoma models. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF1α-deficient tumors, and analysis of human sarcomas reveal elevated HIF1α and PLOD2 expression in metastatic primary lesions. Pharmacological inhibition of PLOD enzymatic activity suppresses metastases. Collectively, these data indicate that HIF1α controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors. We conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination. PMID:23906982

Clinical trial enrollment of adolescents and young adults with sarcoma.

PubMed

Davis, Lara E; Janeway, Katherine A; Weiss, Aaron R; Chen, Yen-Lin E; Scharschmidt, Thomas J; Krailo, Mark; Glade Bender, Julia L; Kopp, Lisa M; Patel, Shreyaskumar R; Schwartz, Gary K; Horvath, L Elise; Hawkins, Douglas S; Chuk, Meredith K; Reinke, Denise K; Gorlick, Richard G; Randall, R Lor

2017-09-15

More than half of all sarcomas occur in adolescents and young adults (AYAs) aged 15 to 39 years. After the publication of the AYA series in the April 1, 2016 issue of Cancer, several leaders in the field of sarcoma across disciplines gathered to discuss the status of sarcoma clinical research in AYAs. They determined that a focused effort to include the underrepresented and understudied AYA population in current and future sarcoma clinical trials is overdue. Trial enrichment for AYA-aged sarcoma patients will produce more meaningful results that better represent the disease's biology, epidemiology, and treatment environment. To address the current deficit, this commentary outlines changes believed to be necessary to expediently achieve an increase in the enrollment of AYAs in sarcoma clinical trials. Cancer 2017;123:3434-40. © 2017 American Cancer Society. © 2017 American Cancer Society.

Variable Expression of PIK3R3 and PTEN in Ewing Sarcoma Impacts Oncogenic Phenotypes

PubMed Central

Niemeyer, Brian F.; Parrish, Janet K.; Spoelstra, Nicole S.; Joyal, Teresa; Richer, Jennifer K.; Jedlicka, Paul

2015-01-01

Ewing Sarcoma is an aggressive malignancy of bone and soft tissue affecting children and young adults. Ewing Sarcoma is driven by EWS/Ets fusion oncoproteins, which cause widespread alterations in gene expression in the cell. Dysregulation of receptor tyrosine kinase signaling, particularly involving IGF-1R, also plays an important role in Ewing Sarcoma pathogenesis. However, the basis of this dysregulation, including the relative contribution of EWS/Ets-dependent and independent mechanisms, is not well understood. In the present study, we identify variable expression of two modifiers of PI3K signaling activity, PIK3R3 and PTEN, in Ewing Sarcoma, and examine the consequences of this on PI3K pathway regulation and oncogenic phenotypes. Our findings indicate that PIK3R3 plays a growth-promotional role in Ewing Sarcoma, but suggest that this role is not strictly dependent on regulation of PI3K pathway activity. We further show that expression of PTEN, a well-established, potent tumor suppressor, is lost in a subset of Ewing Sarcomas, and that this loss strongly correlates with high baseline PI3K pathway activity in cell lines. In support of functional importance of PTEN loss in Ewing Sarcoma, we show that re-introduction of PTEN into two different PTEN-negative Ewing Sarcoma cell lines results in downregulation of PI3K pathway activity, and sensitization to the IGF-1R small molecule inhibitor OSI-906. Our findings also suggest that PTEN levels may contribute to sensitivity of Ewing Sarcoma cells to the microtubule inhibitor vincristine, a relevant chemotherapeutic agent in this cancer. Our studies thus identify PIK3R3 and PTEN as modifiers of oncogenic phenotypes in Ewing Sarcoma, with potential clinical implications. PMID:25603314

Endometrial stromal sarcoma involving the urinary bladder: a study of 6 cases.

PubMed

Tian, Wei; Latour, Mathieu; Epstein, Jonathan I

2014-07-01

Endometrial stromal sarcoma (ESS) involving the urinary bladder is very rare, with no prior series reported. We identified 6 cases of low-grade ESS involving the bladder at our institution (1998 to 2013), 5 of them consults. The median age at bladder involvement was 60 years (range, 44 to 77 y). One patient presented with bladder involvement at initial diagnosis of ESS. The remaining 5 cases with bladder involvement presented 7 to 30 years (mean 18 y) after a known diagnosis of ESS (n=2) or after a remote history of hysterectomy with an uncertain diagnosis (n=3). The location of bladder involvement included dome (n=1), trigone (n=2), diffuse (n=1), and unknown (n=2). Two cases demonstrated worm-like infiltrating tumor nests classic of low-grade ESS with little stromal reaction with retraction artifact mimicking vascular invasion. One case originating from the ovary showed focal glandular differentiation in the bladder, resembling endometriosis. Two cases had abundant keloidal collagen formation, arranged haphazardly or in a sunburst pattern. One case showed primitive cells infiltrating entirely hyalinized stroma, after chemotherapy given for a misdiagnosis of urothelial carcinoma. CD31 was negative in all cases, except for 1 case with obvious large vessel invasion. The differential diagnosis included a large nested variant of urothelial carcinoma, carcinoid tumor, synovial sarcoma, solitary fibrous tumor, Ewing sarcoma/primitive neuroectodermal tumors, and endometriosis. CD10 was strongly positive in 5 cases, and 1 case had very focal, moderate staining. Estrogen receptor showed strong and diffuse staining in all 6 cases. Progesterone receptor showed moderate to strong staining in 5 cases and focal staining in 1 case. One case showed PAX8 expression, and 2 cases showed p16 nuclear and cytoplasmic expression. CD56 showed weak to strong staining in 4 cases. Two cases had diffuse synaptophysin, and 1 case had focal p63 positivity. GATA-3, CD34, and CD99 were negative

Genome Sequence of Rough and Smooth Variants of Pleomorphic Strain Lactobacillus farciminis CNCM-I-3699.

PubMed

Tareb, R; Bernardeau, M; Vernoux, J P

2015-09-17

The probiotic Lactobacillus farciminis CNCM-I-3699 is a pleomorphic strain exhibiting smooth and rough variants. We report their complete genomes consisting of a chromosome of 2, 4 Mb and a plasmid of 6,417 bp. The smooth variant differs by the presence of an additional plasmid of 35,418 bp. Copyright © 2015 Tareb et al.

Uterine Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Uterine sarcoma treatment is primarily surgery, with or without radiation or chemotherapy. Get detailed information about the treatment options for newly diagnosed or recurrent uterine sarcoma cancer in this summary for clinicians.

Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors

ClinicalTrials.gov

2018-01-31

Ewing Sarcoma; Rhabdomyosarcoma; Wilms Tumor; Osteosarcoma; Non-Rhabdomyosarcoma Soft Tissue Sarcoma, Nos; Renal Tumor; Rhabdoid Tumor; Clear Cell Renal Cell Carcinoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Sarcoma

Immunoexpression of GLUT-1 and angiogenic index in pleomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas of the salivary glands.

PubMed

de Souza, Lélia Batista; de Oliveira, Lucileide Castro; Nonaka, Cassiano Francisco Weege; Lopes, Maria Luiza Diniz de Sousa; Pinto, Leão Pereira; Queiroz, Lélia Maria Guedes

2017-06-01

This study aimed to evaluate and compare the immunoexpression of glucose transporter-1 (GLUT-1) and angiogenic index between pleomorphic adenomas (PAs), adenoid cystic carcinomas (ACCs), and mucoepidermoid carcinomas (MECs) of the salivary glands, and establish associations with the respective subtype/histological grade. Twenty PAs, 20 ACCs, and 10 MECs were submitted to morphological and immunohistochemical analysis. GLUT-1 expression was semi-quantitatively evaluated and angiogenic index was assessed by microvessel counts using anti-CD34 antibody. Higher GLUT-1 immunoexpression was observed in the MECs compared to PAs and ACCs (p = 0.022). Mean number of microvessels was 66.5 in MECs, 40.4 in PAs, and 21.2 in ACCs (p < 0.001). GLUT-1 expression and angiogenic index showed no significant correlation in the tumors studied. Results suggest that differences in biological behavior of the studied tumors are related to GLUT-1. Benign and malignant salivary gland tumors differ in the angiogenic index; however, angiogenesis may be independent of the tumor cell's metabolic demand.

Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma

PubMed Central

Hettmer, Simone; Schinzel, Anna C; Tchessalova, Daria; Schneider, Michaela; Parker, Christina L; Bronson, Roderick T; Richards, Nigel GJ; Hahn, William C; Wagers, Amy J

2015-01-01

Current therapies for sarcomas are often inadequate. This study sought to identify actionable gene targets by selective targeting of the molecular networks that support sarcoma cell proliferation. Silencing of asparagine synthetase (ASNS), an amidotransferase that converts aspartate into asparagine, produced the strongest inhibitory effect on sarcoma growth in a functional genomic screen of mouse sarcomas generated by oncogenic Kras and disruption of Cdkn2a. ASNS silencing in mouse and human sarcoma cell lines reduced the percentage of S phase cells and impeded new polypeptide synthesis. These effects of ASNS silencing were reversed by exogenous supplementation with asparagine. Also, asparagine depletion via the ASNS inhibitor amino sulfoximine 5 (AS5) or asparaginase inhibited mouse and human sarcoma growth in vitro, and genetic silencing of ASNS in mouse sarcoma cells combined with depletion of plasma asparagine inhibited tumor growth in vivo. Asparagine reliance of sarcoma cells may represent a metabolic vulnerability with potential anti-sarcoma therapeutic value. DOI: http://dx.doi.org/10.7554/eLife.09436.001 PMID:26499495

V-ATPase as an effective therapeutic target for sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perut, Francesca, E-mail: francesca.perut@ior.it; Avnet, Sofia; Fotia, Caterina

2014-01-01

Malignant tumors show intense glycolysis and, as a consequence, high lactate production and proton efflux activity. We investigated proton dynamics in osteosarcoma, rhabdomyosarcoma, and chondrosarcoma, and evaluated the effects of esomeprazole as a therapeutic agent interfering with tumor acidic microenvironment. All sarcomas were able to survive in an acidic microenvironment (up to 5.9–6.0 pH) and abundant acidic lysosomes were found in all sarcoma subtypes. V-ATPase, a proton pump that acidifies intracellular compartments and transports protons across the plasma membrane, was detected in all cell types with a histotype-specific expression pattern. Esomeprazole administration interfered with proton compartmentalization in acidic organelles andmore » induced a significant dose-dependent toxicity. Among the different histotypes, rhabdomyosarcoma, expressing the highest levels of V-ATPase and whose lysosomes are most acidic, was mostly susceptible to ESOM treatment. - Highlights: • Osteosarcoma, rhabdomyosarcoma, and chondrosarcoma survive in acidic microenvironment. • At acidic extracellular pH, sarcoma survival is dependent on V-ATPase expression. • Esomeprazole administration induce a significant dose-dependent toxicity.« less

Extraskeletal presentation of Ewing's Sarcoma.

PubMed

Mangual, Danny; Bisbal-Matos, Luis A; Jiménez-Lee, Ricardo; Vélez, Román; Noy, Miguel

2018-03-01

The case of a 27-year-old Hispanic female who presented with an occipito-parietal tumor after suffering trauma to the area. A physical examination revealed no tenderness to palpation and with evidence of healing ulcerations. The biopsy was consistent with a synovial sarcoma. A wide excision of the mass (15cm x 14cm x 6cm) followed by a pericranial flap was performed. A follow-up CT showed recurrence involving the parietal sagittal sinus. After a second biopsy the mass was determined to be a small-cell sarcoma, consistent with Ewing's sarcoma. Chemotherapy included 8 cycles of doxorubicin, vincristine, and cyclophosphamide, with alternating cycles of etoposide and ifosfamide. A year later, a second wide excision of the mass was performed, followed by bilaminate skin substitute and skin graft placement for reconstruction of the soft-tissue defect. After chemotherapy, a follow-up PET scan showed no signs of re-uptake in any soft tissue or skeletal structures. After 2 years, the patient remains in complete remission.

Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas

ClinicalTrials.gov

2016-05-13

Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Chordoma; Desmoid Tumor; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Recurrent Childhood Soft Tissue Sarcoma

Medical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported

The Hippo signal transduction pathway in soft tissue sarcomas.

PubMed

Mohamed, Abdalla D; Tremblay, Annie M; Murray, Graeme I; Wackerhage, Henning

2015-08-01

Sarcomas are rare cancers (≈1% of all solid tumours) usually of mesenchymal origin. Here, we review evidence implicating the Hippo pathway in soft tissue sarcomas. Several transgenic mouse models of Hippo pathway members (Nf2, Mob1, LATS1 and YAP1 mutants) develop various types of sarcoma. Despite that, Hippo member genes are rarely point mutated in human sarcomas. Instead, WWTR1-CAMTA1 and YAP1-TFE3 fusion genes are found in almost all cases of epithelioid haemangioendothelioma. Also copy number gains of YAP1 and other Hippo members occur at low frequencies but the most likely cause of perturbed Hippo signalling in sarcoma is the cross-talk with commonly mutated cancer genes such as KRAS, PIK3CA, CTNNB1 or FBXW7. Current Hippo pathway-targeting drugs include compounds that target the interaction between YAP and TEAD G protein-coupled receptors (GPCR) and the mevalonate pathway (e.g. statins). Given that many Hippo pathway-modulating drugs are already used in patients, this could lead to early clinical trials testing their efficacy in different types of sarcoma. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Histiocyte-like cells expressing factor XIIIa do not belong to the neoplastic cell population in malignant fibrous histiocytoma.

PubMed

Szollosi, Zoltan; Nemeth, Tamas; Egervari, Kristof; Nemes, Zoltan

2005-01-01

The term malignant fibrous histiocytoma (MFH) is widely used for pleomorphic soft tissue sarcomas without a specific line of differentiation. MFH is included in the category of fibrohistiocytic soft tissue tumors. MFH has a broad range of histological appearances, and it has several subtypes. All of these subtypes are composed of spindled fibroblast-like cells, undifferentiated cells, and histiocytic or histiocyte-like cells. A large number of fibroblast-like and pleomorphic cells express factor XIIIa in MFH. The cytological pleomorphism of factor XIIIa cells suggests that these cells may belong to the neoplastic population. It is equally possible that the factor XIIIa-positive cells are only activated stromal cells. The relation of factor XIIIa-positive cells to the neoplastic cell population in MFH is addressed in the present study. A morphometric approach compares the measure of nuclear pleomorphism of the factor XIIIa-positive cells with that of the factor XIIIa-negative tumor cells in high-grade MFH. The immunohistochemical approach compares the factor XIIIa-positive and -negative cell populations with regard to mutations of p53 tumor suppressor gene in p53-positive MFH cases. We selected 58 cases of soft tissue pleomorphic or storiform-pleomorphic MFH on the basis of histopathological examinations. A combination of incident light immunofluorescence for factor XIIIa and transmitted light examination for nuclear staining was used for morphometrical analysis. We found cytoplasmic factor XIIIa positivity in at least 2% of cells in 39 cases; the number of factor XIIIa-positive cells was under 0.5% in two cases, and the number of factor-positive cells ranged between 0.5% and 2% in 13 cases. Eighteen cases were analyzed with nuclear morphometry. We found that mean nuclear area and mean nuclear Ferret diameter in factor XIIIa-positive cells differed significantly from those of the tumor cells in all cases. The mean nuclear roundness factor differed significantly only

Synthesis and surface modification of magnetic nanoparticles for potential applications in sarcomas

NASA Astrophysics Data System (ADS)

Shahbazi, S.; Wang, X.; Yang, J.-L.; Jiang, X. C.; Ryan, R.; Yu, A. B.

2015-06-01

The application of nano-science in cancer therapy has become one of the most attractive tools in scientific research because of its versatility in diagnosis and treatment. Among the different types of nanoparticles, iron oxide nanoparticles (IONPs) are renowned for their low toxicity and suitability for therapeutic and diagnostic, or `theragnostic,' approach against different types of cancers. Research investigating the effect of IONPs with different physiochemical characteristics in sarcoma is limited. In this study, we initially prepared IONPs of different sizes (200, 100, 20, and 10 nm) and modified their surface with different types of coatings (polyethylene glycol, d-glucose, and silica) under mild conditions. Various methods were used to illustrate and quantify cellular uptake of magnetic nanoparticles in sarcoma cell lines. Finally, the safety of the uptaken nanoparticles on diverse human sarcoma cell lines was investigated and found that the readily available IONPs can be taken up by synovial sarcoma and liposarcoma cell lines in the selective histological tumor types; however, they seem highly toxic for fibrous histiocytoma and fibrosarcoma.

Infiltration characteristics and influencing factors of retroperitoneal liposarcoma: Novel evidence for extended surgery and a tumor grading system.

PubMed

Wang, Zhen; Wu, Jianhui; Lv, Ang; Li, Chengpeng; Li, Zhongwu; Zhao, Min; Hao, Chunyi

2018-05-13

This study sought to evaluate the infiltration tendency of retroperitoneal liposarcoma (RPLS) from a new pathological angle by exploring the infiltration characteristics, which could provide helpful information to facilitate surgical decision-making and prognosis prediction. Concurrently, we aim to identify significant indicators of infiltration. A total of 61 consecutive patients with RPLS at our institution were retrospectively analyzed. All patients received extended surgery. The tumor infiltration characteristics and influencing factors were studied based on the pathological diagnosis. Univariate and multivariate analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients, and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%). The percentage of lipoblasts and the rates of necrosis and mitosis were all significantly higher in high-grade tumors (dedifferentiated, round cell, and pleomorphic). A high lipoblast percentage (≥ 20%) was the only independent risk factor for OI. A recurrent tumor and a high-grade tumor were independent risk factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue. Therefore, extended resection of the tumor and the adjacent organs is recommended. The percentage of lipoblasts was associated with the tumor grade and infiltration characteristics; thus, lipoblast percentage may become a new grading factor for RPLS.

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

PubMed

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-06-21

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

Primary extra-skeletal Ewing's sarcoma mimicking a disc protrusion.

PubMed

Ruelle, A; Boccardo, M

1987-07-01

One of the rarest cases of primary epidural neoplasm is a soft tissue sarcoma histologically similar to Ewing's sarcoma of the bone. In the literature only eleven cases of such an extra-skeletal Ewing's sarcoma have been described. The authors report an additional case presenting as a disc protrusion in a young male. The authors include some diagnostic, prognostic and nosologic remarks about this condition.

Extra osseous primary Ewing's sarcoma.

PubMed

Ali, Syed Asad; Muhammad, Agha Taj; Soomro, Abdul Ghani; Siddiqui, Akmal Jamal

2010-01-01

The case of 20 years old boy with an extra osseous Ewing's sarcoma is described. He was initially diagnosed as a case of infiltrative malignant tumour of left suprarenal gland on the basis of preoperative workup but postoperative biopsy of surgically excised specimen confirmed Extra-osseous Ewing's Sarcoma (EES) suprarenal gland with no evidence of malignancy on skeletal scintiscan, bone marrow aspirate and histopathology Suprarenal location of primary EES is unknown and probably has not been reported in literature. We report a unique case of EES.

Extraskeletal Ewing sarcoma of the abdominal wall

PubMed Central

Farhat, L. Ben; Ghariani, B.; Rabeh, A.; Dali, N.; Said, W.; Hendaoui, L.

2008-01-01

Abstract Ewing sarcoma is most commonly a bone tumour which has usually extended into the soft tissues at the time of diagnosis. Exceptionally, this tumour can have an extraskeletal origin. Clinical or imaging findings are non-specific and diagnosis is based on histology. We report a case of an extraskeletal Ewing sarcoma developed in the soft tissues of the abdominal wall in a 35-year-old woman who presented a painful abdominal wall tumefaction. Ultrasongraphy and computed tomography showed a large, well-defined soft tissue mass developed in the left anterolateral muscle group of the abdominal wall. Surgical biopsy was performed and an extraskeletal Ewing sarcoma was identified histologically. PMID:18818133

Results for patients with sarcoma not otherwise specified and other diagnoses than Ewing sarcoma treated according to the Euro-EWING 99 trial.

PubMed

Frank, Judith Amalie; Ranft, Andreas; Paulussen, Michael; Juergens, Heribert; Kruseova, Jarmila; Bauer, Sebastian; Niggli, Felix; Reichardt, Peter; Dirksen, Uta

2017-10-01

Euro-EWING 99 trial of the European Ewing tumor Working Initiative of National Groups (EE99) was an international phase III study in patients with Ewing sarcoma. The German Society of Pediatric Oncology and Hematology (GPOH) data center registered and followed patients with other diagnoses than Ewing sarcoma who were treated according to the EE99 protocol in an additional non-Ewing database. Data of 27 patients with other diagnoses than Ewing sarcoma treated according to the EE99 protocol were analyzed. Patients had miscellaneous histologic diagnoses, the majority were diagnosed with sarcoma not otherwise specified (NOS) arising in bone and soft tissue (63%). The median age at diagnosis was 16.9 years (range 4.5-41.4). Localized disease was diagnosed in 61.5% of the patients and 38.5% had distant metastases at time of primary diagnosis. The median follow-up time was 3.7 years (range 0.5-9.5). Patients with localized disease showed a 3-year event-free survival (EFS) of 68%, compared to 3-year EFS of 20% in patients with metastases (P = 0.042). Three-year EFS for patients with sarcoma NOS was 52%, patients with localized and metastatic disease showed 3-year EFS of 66 and 20%, respectively. EFS in patients with other diagnoses than Ewing sarcoma treated according to EE99 was significantly higher in patients with localized than metastatic disease. Sarcomas of soft tissue and bone that cannot be classified to current diagnostic categories constitute a therapeutic challenge. © 2017 Wiley Periodicals, Inc.

Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model

PubMed Central

Gieger, Tracy L.; Karakashian, Alexander A.; Nikolova-Karakashian, Mariana N.; Posner, Lysa P.; Roback, Donald M.; Rivera, Judith N.; Chang, Sha

2017-01-01

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID (P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic

Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

ClinicalTrials.gov

2018-02-27

Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

Ewing Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Ewing sarcoma is derived from a primordial bone marrow–derived mesenchymal stem cell. Get comprehensive information about the presentation, genomics, diagnostic evaluation, prognosis, and treatment of newly diagnosed and recurrent Ewing sarcoma in this summary for clinicians.

Custom-made endoprostheses for the femoral amputation stump: an alternative to hip disarticulation in tumour surgery.

PubMed

Kalson, N S; Gikas, P D; Aston, W; Miles, J; Blunn, G; Pollock, R; Skinner, J; Briggs, T W R; Cannon, S R

2010-08-01

Disarticulation of the hip in patients with high-grade tumours in the upper thigh results in significant morbidity. In patients with no disease of the proximal soft tissue a femoral stump may be preserved, leaving a fulcrum for movement and weight-bearing. We reviewed nine patients in whom the oncological decision would normally be to disarticulate, but who were treated by implantation of an endoprosthesis in order to create a functioning femoral stump. The surgery was undertaken for chondrosarcoma in four patients, pleomorphic sarcoma in three, osteosarcoma in one and fibrous dysplasia in one. At follow-up at a mean of 80 months (34 to 132), seven patients were alive and free from disease, one had died from lung metastases and another from a myocardial infarction. The mean functional outcome assessment was 50 (musculoskeletal tumor society), 50 and 60 (physical and mental Short-form 36 scores). Implantation of an endoprosthesis into the stump in carefully selected patients allows fitting of an above-knee prosthesis and improves wellbeing and the functional outcome.

Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

ClinicalTrials.gov

2017-09-07

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Major vascular resections in retroperitoneal sarcoma.

PubMed

Tzanis, Dimitri; Bouhadiba, Toufik; Gaignard, Elodie; Bonvalot, Sylvie

2018-01-01

Retroperitoneal sarcomas (RPS) frequently involve major vessels, which either originate from them or secondarily encase or invade them. In this field, major vascular resections result in increased morbidity. However, survival does not seem to be affected by the need for vascular resection or by this higher morbidity. This paper aims to provide descriptions of the surgical strategy and outcomes for retroperitoneal sarcomas involving major vessels. © 2017 Wiley Periodicals, Inc.

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

PubMed Central

Lin, Patrick P.; Wang, Yongxing; Lozano, Guillermina

2011-01-01

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further. PMID:20953407

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum

PubMed Central

Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-01-01

Abstract Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor. PMID:26886614

Primary Intimal Sarcoma of Thoracic Aorta Presenting as Hypertensive Crisis.

PubMed

Lin, Shu-I; Su, Min-I; Tsai, Cheng-Ting

2015-11-01

We report a 45-year-old woman who presented to our facility in a hypertensive crisis. Computed tomography (CT) revealed a thoracic aortic tumor, and tissues obtained via endovascular biopsy revealed undifferentiated sarcoma. A final diagnosis of intimal sarcoma was made by intra-operative pathological examination. Despite undergoing surgical resection followed by adjuvant chemotherapy, the patient died from progressive multiple metastasis and severe sepsis. Although aortic sarcoma is rarely diagnosed, it should be considered a possible etiology of hypertensive crisis. Aortic tumor; Endovascular biopsy; Hypertension crisis; Intimal sarcoma.

Molecular profiling of sarcomas: new vistas for precision medicine.

PubMed

Al-Zaid, Tariq; Wang, Wei-Lien; Somaiah, Neeta; Lazar, Alexander J

2017-08-01

Sarcoma is a large and heterogeneous group of malignant mesenchymal neoplasms with significant histological overlap. Accurate diagnosis can be challenging yet important for selecting the appropriate treatment approach and prognosis. The currently torrid pace of new genomic discoveries aids our classification and diagnosis of sarcomas, understanding of pathogenesis, development of new medications, and identification of alterations that predict prognosis and response to therapy. Unfortunately, demonstrating effective targets for precision oncology has been elusive in most sarcoma types. The list of potential targets greatly outnumbers the list of available inhibitors at the present time. This review will discuss the role of molecular profiling in sarcomas in general with emphasis on selected entities with particular clinical relevance.

Kaposi Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Kaposi sarcoma treatment depends upon the type and can include curettage and desiccation, radiation therapy, surgery, and sometimes chemotherapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent Kaposi sarcoma in this summary for clinicians.

[Kaposi's sarcoma of the penis in a HIV-seronegative patient].

PubMed

Touzani, Mohammed Alae; Yddoussalah, Othmane

2017-01-01

Sarcomas of the penis account for less than 5% of all tumors of the penis. They are dominated by Kaposi's sarcoma that mainly affects HIV-positive patients. However, recent studies have shown a relationship between Kaposi's sarcoma and HHV-8 infection (Human herpes virus-8), which explains why this sarcoma occurs in non-immunocompromised and HIV-seronegative patients. We here report the case of a 72-year old patient, with no previous medical history, reporting of gradual onset of tumor-like granulation tissue of 3 years duration at the level of the gland, without secondary location. Given the patient's clinical condition, epidermoid carcinoma or sarcomatoid carcinoma of the penis were suspected. Initial biopsy was negative, the second was in favor of Kaposi's sarcoma, confirmed by immunohistochemistry. The patient underwent chemotherapy.

Advances in sarcoma diagnostics and treatment

PubMed Central

Dancsok, Amanda R; Asleh-Aburaya, Karama; Nielsen, Torsten O

2017-01-01

The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed. Transcriptome sequencing techniques have brought forward new diagnostic tools for identifying fusions and/or characterizing unclassified entities. Next-generation sequencing and advanced molecular techniques were also applied to identify potential targets for directed and epigenetic therapy, where preclinical studies reported results for agents active within the receptor tyrosine kinase, mTOR, Notch, Wnt, Hedgehog, Hsp90, and MDM2 signaling networks. At the level of clinical practice, modest developments were seen for some sarcoma subtypes in conventional chemotherapy and in therapies targeting the pathways activated by various receptor tyrosine kinases. In the burgeoning field of immune therapy, sarcoma work is in its infancy; however, elaborate protocols for immune stimulation are being explored, and checkpoint blockade agents advance from preclinical models to clinical studies. PMID:27732970

Advanced and amplified BOLD fluctuations in high-grade gliomas.

PubMed

Gupta, Lalit; Gupta, Rakesh K; Postma, Alida A; Sahoo, Prativa; Gupta, Pradeep K; Patir, Rana; Ahlawat, Sunita; Saha, Indrajit; Backes, Walter H

2018-06-01

Glioma grade along with patient's age and general health are used for treatment planning and prognosis. To characterize and quantify the spontaneous blood oxygen level-dependent (BOLD) fluctuations in gliomas using measures based on T2*-weighted signal time-series and to distinguish between high- and low-grade gliomas. Retrospective. Twenty-one patients with high-grade and 13 patients with low-grade gliomas confirmed on histology were investigated. Dynamic T2*-weighted (multislice single-shot echo-planar-imaging) magnetic resonance imaging (MRI) was performed on a 3T system with an 8-element receive-only head coil to measure the BOLD fluctuations. In addition, a dynamic T 1 -weighted (3D fast field echo) dynamic contrast-enhanced (DCE) perfusion scan was performed. Three BOLD measures were determined: the temporal shift (TS), amplitude of low frequency fluctuations (ALFF), and regional homogeneity (ReHo). DCE perfusion-based cerebral blood volume (CBV) and time-to-peak (TTP) maps were concurrently evaluated for comparison. An analysis-of-variance test was first used. When the test appeared significant, post-hoc analysis was performed using analysis-of-covariance with age as covariate. Logistic regression and receiver-operator characteristic curve analysis were also performed. TS was significantly advanced in high-grade gliomas compared to the contralateral cortex (P = 0.01) and low-grade gliomas (P = 0.009). In high-grade gliomas, ALFF and CBV were significantly higher than the contralateral cortex (P = 0.041 and P = 0.008, respectively) and low-grade gliomas (P = 0.036 and P = 0.01, respectively). ReHo and TTP did not show significant differences between high- and low-grade gliomas (P = 0.46 and P = 0.42, respectively). The area-under-curve was above 0.7 only for the TS, ALFF, and CBV measures. Advanced and amplified hemodynamic fluctuations manifest in high-grade gliomas, but not in low-grade gliomas, and can be assessed using BOLD

Principles of treatment for vaccine-associated sarcomas.

PubMed

Novosad, C Andrew

2003-05-01

In the last decade, there has been a great deal of information surrounding the etiology, diagnosis, and treatment of feline vaccine-associated sarcomas. The presence of a mass in areas used for subcutaneous or intramuscular injections should alert the clinician to the possibility of a vaccine-associated sarcoma. Early detection and subsequent treatment is paramount to limit local invasion and distant metastasis. The current data are suggesting that a team approach with multi-modality therapy is the appropriate way to address this disease. In the following article, we will discuss the history/incidence, pathology, diagnosis, and current treatment options, which include a combination of surgery, radiation, and chemotherapy for vaccine-associated sarcomas.

Assessing the risk of laparoscopic morcellation of occult uterine sarcomas during hysterectomy and myomectomy: Literature review and the ISGE recommendations.

PubMed

Sizzi, Ornella; Manganaro, Lucia; Rossetti, Alfonso; Saldari, Matteo; Florio, Giuseppe; Loddo, Alessandro; Zurawin, Robert; van Herendael, Bruno; Djokovic, Dusan

2018-01-01

This project of the International Society for Gynecologic Endoscopy (ISGE) had the objective to review the literature and provide recommendations on the occult sarcoma risk assessment in patients who are candidates for minimally invasive gynecological surgery involving intra-abdominal electromechanical tissue morcellation. The ISGE Task Force for Estimation of the Risk in Endoscopic Morcellation initially defined key topics and clinical questions which may guide a comprehensive preoperative patient assessment. A literature search within the Medline/PubMed and Cochrane Database was carried out using keywords "morcellation", "uterine fibroids", "uterine sarcoma", "myomectomy" and "hysterectomy". Relevant publications (original studies, meta-analyses and previous reviews), written in English and published until May 30th, 2017, were selected and analyzed. Previously emitted statements of 12 recognized professional societies or government institutions and their supporting literature were also studied. For each topic/clinical question, the available information was graded by the level of evidence. The ISGE recommendations were established in accordance with the evidence quality. In the light of available information, 9 recommendations on preoperative clinical, laboratorial and imaging evaluation of the candidates for intracorporeal uterus/leiomyoma morcellation were formulated, mainly based on consensus and expert opinions. There is a lack of high-quality evidence, which does not allow the establishment of strong recommendations. Electromechanical tissue morcellation may be used in gynecological patients who are considered "low risk" upon appropriate preoperative evaluation; however, further studies and prospective data collection are greatly needed to improve sarcoma risk assessment in women with presumed uterine leiomyomas. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

PubMed

Schwartz, Boris; Benadjaoud, Mohamed Amine; Cléro, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cécile; Oberlin, Odile; Veres, Cristina; Pacquement, Hélène; Munzer, Martine; N'guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Hawkins, Mike; Winter, David; Lefkopoulos, Dimitri; Chavaudra, Jean; Rubino, Carole; Diallo, Ibrahima; Bénichou, Jacques; de Vathaire, Florent

2014-05-01

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.

Granulocytic sarcoma.

PubMed

Hutchison, R E; Kurec, A S; Davey, F R

1990-12-01

Granulocytic sarcoma is a variant presentation of acute myeloblastic leukemia, occurring in extramedullary locations. It is uncommon, but it may occur at any site and at any age, which necessitates its inclusion in the differential diagnosis of all undifferentiated tumors. Histology, touch-imprint cytology, cytochemistry, immunocytochemistry, electron microscopy, and molecular studies all contribute to the diagnosis.

Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma.

PubMed

Ghisoli, Maurizio; Barve, Minal; Mennel, Robert; Lenarsky, Carl; Horvath, Staci; Wallraven, Gladice; Pappen, Beena O; Whiting, Sam; Rao, Donald; Senzer, Neil; Nemunaitis, John

2016-08-01

Ewing's sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG (Vigil) vaccine, in which 12 advanced stage Ewing's patients were safely treated and went on to achieve a predicted immune response (IFNγ ELISPOT). We describe follow-up through year 3 of a prospective, nonrandomized study comparing an expanded group of Vigil-treated advanced disease Ewing's sarcoma patients (n = 16) with a contemporaneous group of Ewing's sarcoma patients (n = 14) not treated with Vigil. Long-term follow-up results show a survival benefit without evidence of significant toxicity (no ≥ grade 3) to Vigil when administered once monthly by intradermal injection (1 × 10e(6) cells/injection to 1 × 10e(7) cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil-treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2-month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing's sarcoma.

Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

PubMed

Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

2011-01-01

Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

Ewing Sarcoma Cells Secrete EWS/Fli-1 Fusion mRNA via Microvesicles

PubMed Central

Tsugita, Masanori; Yamada, Nami; Noguchi, Shunsuke; Yamada, Kazunari; Moritake, Hiroshi; Shimizu, Katsuji; Akao, Yukihiro; Ohno, Takatoshi

2013-01-01

Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients. Recently, it was validated that cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids, and that these MVs contain a selected set of tumor-related proteins and high levels of mRNAs and miRNAs. In this present study, we detected the Ewing sarcoma-specific EWS/Fli-1 mRNA in MVs from the culture medium of ES cell lines carrying t(11;22) (q24; 12). Also, we detected this fusion gene in approximately 40% of the blood samples from mice inoculated with xenografts of TC135 or A673 cells. These findings indicate the EWS/Fli-1 mRNA in MVs might be a new non-invasive diagnostic marker for specific cases of Ewing sarcoma. PMID:24124617

High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

PubMed

Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

2015-01-01

Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

PubMed

Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

2014-01-01

Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

BCOR-CCNB3-positive soft tissue sarcoma with round-cell and spindle-cell histology: a series of four cases highlighting the pitfall of mimicking poorly differentiated synovial sarcoma.

PubMed

Li, Wan-Shan; Liao, I-Chuang; Wen, Mei-Chin; Lan, Howard Haw-Chang; Yu, Shih-Chen; Huang, Hsuan-Ying

2016-11-01

BCOR-CCNB3 sarcoma is a genetically defined undifferentiated malignancy with Ewing sarcoma (ES)-like round cells, and preferentially affects the bones of male adolescents. Sarcomas harbouring BCOR-CCNB3 rarely arise from soft tissues; therefore, we aimed to report four cases to expand the clinicopathological spectrum. By reverse transcription polymerase chain reaction and confirmatory sequencing, we detected a BCOR-CCNB3 transcript in primary undifferentiated sarcomas of the deep musculature of four male patients, comprising two teenagers (aged 14 and 17 years) and two adults (aged 34 and 44 years). The tumours originated in the back (n = 2), pelvis (n = 1), and thigh (n = 1), and were 70-140 mm in size (mean, 107 mm). All tumours showed sheets of primitive round or ovoid cells with vesicular nuclei, active mitosis (28-41/10 high-power fields), variably prominent nucleoli, and geographical necrosis. This major component transformed into fascicles of elongated spindle cells with staghorn vessels and a myxoid reticular stroma, accounting for 10-50% of areas. All cases were positive for CD99, three were positive for TLE1, and one was positive for EMA, indicating poorly differentiated synovial sarcomas (PDSSs). Nuclear cyclin B3 reactivity was present in all cases, but not in molecularly confirmed atypical ESs and PDSSs. At the last follow-up (median, 13.5 months), one patient had died of lung metastasis, two were alive with tumours, and one was tumour-free. BCOR-CCNB3-positive sarcomas may primarily occur in soft tissues of adults and show PDSS-mimicking round-cell and spindle-cell histology with aggressive behaviour. Cyclin B3 is useful for selecting candidates for BCOR-CCNB3 molecular testing. © 2016 John Wiley & Sons Ltd.

Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma.

PubMed

Yamaguchi, Munekage; Erdenebaatar, Chimeddulam; Saito, Fumitaka; Motohara, Takeshi; Miyahara, Yo; Tashiro, Hironori; Katabuchi, Hidetaka

2015-11-01

There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.

Molecular Approaches to Sarcoma Therapy

PubMed Central

Olsen, R. J.; Tarantolo, S. R.

2002-01-01

Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed. PMID:18521343

A single institution experience of combined modality management of extra skeletal Ewings sarcoma.

PubMed

Venkitaraman, Ramachandran; George, Mathew K; Ramanan, S Ganapathy; Sagar, T G

2007-01-11

Extraskeletal Ewings sarcoma are rare tumors for which there is no consensus on optimal management. A retrospective review of the clinical features, treatment and outcome of patients with extraskeletal Ewings sarcoma who reported to a single institution between January 1992-December 2003 is reported. A total of 19 patients with extraskeletal Ewings sarcoma were identified. Of these, 4 patients had metastatic disease at presentation and 15 patients with non-metastatic disease received combined modality treatment with primary combination chemotherapy followed by local treatment with radiotherapy or surgery. Disease free survival and overall survival for patients with non metastatic disease after combined modality treatment were 60% and 30% respectively. The significant predictors for prolonged disease free survival and overall survival were high haemoglobin (p = 0.002), low lactate dehydrogenase (p = 0.028), chemotherapy with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide and Etoposide regime (p = 0.008) and complete response to chemotherapy (p = 0.001). Aggressive combination chemotherapy followed by complete surgery or radiotherapy to a dose of more than 50 Gy is essential to confer optimal outcome for patients with extraskeletal Ewings sarcoma.

Primary Occipital Ewing's Sarcoma with Subsequent Spinal Seeding.

PubMed

Alqahtani, Ali; Amer, Roaa; Bakhsh, Eman

2017-01-01

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

PubMed

Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

2015-07-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Terahertz reflectometry imaging for low and high grade gliomas

NASA Astrophysics Data System (ADS)

Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

2016-10-01

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

Gemcitabine Hydrochloride, Docetaxel, and Radiation Therapy in Treating Patients With Uterine Sarcoma That Has Been Removed By Surgery

ClinicalTrials.gov

2015-01-16

Stage IA Uterine Sarcoma; Stage IB Uterine Sarcoma; Stage IC Uterine Sarcoma; Stage IIA Uterine Sarcoma; Stage IIB Uterine Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma

Proliferating Myositis: An Inflammatory Lesion often Misdiagnosed as A Malignant Tumor.

PubMed

Binesh, Fariba; Sobhanardekani, Mohammad; Zabihi, Somayeh; Behniafard, Nasim

2016-12-01

Proliferative myositis (PM) is a rare inflammatory disease. Most commonly, the lesion occurs in the extremities. Regarding its fast growth and bizarre shape of the cellular components this entity commonly misdiagnosed and the patients undergo improper therapeutic approaches. In other words, it is often misdiagnosed as sarcoma. The diagnosis can only be made by the microscopic examination, so biopsy is mandatory. Here the authors report a patient with PM who was initially misdiagnosed as pleomorphic sarcoma of the lower extremity and explain this rare entity. Proliferative myositis should be taken into account if a fast growing, intramuscular mass occurs in the extremities.

Serum vascular endothelial growth factor in dogs with soft tissue sarcomas.