DOCSLIB.ORG

Desmoplastic Small Round Cell Tumor: a Review of Main Molecular Abnormalities and Emerging Therapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Desmoplastic Small Round Cell Tumor: a Review of Main Molecular Abnormalities and Emerging Therapy cancers Review Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy Celso Abdon Mello 1,*, Fernando Augusto Batista Campos 1 , Tiago Goss Santos 2,3 , Maria Leticia Gobo Silva 4 , Giovana Tardin Torrezan 3,5 , Felipe D’Almeida Costa 6, Maria Nirvana Formiga 1, Ulisses Nicolau 1, Antonio Geraldo Nascimento 6, Cassia Silva 1, Maria Paula Curado 7 , Suely Akiko Nakagawa 8 , Ademar Lopes 8 and Samuel Aguiar Jr. 8 1 Department of Medical Oncology, A.C.Camargo Cancer Center, Sao Paulo 01509-010, Brazil; [email protected] (F.A.B.C.); [email protected] (M.N.F.); [email protected] (U.N.); [email protected] (C.S.) 2 Laboratory of Tumor Biology and Biomarkers, International Center of Research CIPE, A.C.Camargo Cancer Center, Sao Paulo 01509-010, Brazil; [email protected] 3 National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, Sao Paulo 05403-010, Brazil; [email protected] 4 Department of Radiation Oncology, A.C.Camargo Cancer Center, Sao Paulo 01509-010, Brazil; [email protected] 5 Genomics and Molecular Biology Group, International Center of Research CIPE, A.C.Camargo Cancer Center, Sao Paulo 01508-010, Brazil 6 Department of Pathology, A.C.Camargo Cancer Center, Sao Paulo 01509-010, Brazil; [email protected] (F.D.C.); [email protected] (A.G.N.) 7 Department of Epidemiology, A.C.Camargo Cancer Center, Sao Paulo 01508-010, Brazil; [email protected] 8 Department of Surgery, A.C.Camargo Cancer Center, Sao Paulo 01509-010, Brazil; [email protected] (S.A.N.); [email protected] (A.L.); Citation: Mello, C.A.; Campos, [email protected] (S.A.J.) F.A.B.; Santos, T.G.; Silva, M.L.G.; * Correspondence: [email protected]; Tel.: +55-11-2189-2779 Torrezan, G.T.; Costa, F.DA.; Formiga, M.N.; Nicolau, U.; Nascimento, A.G.; Simple Summary: Desmoplastic small round cell tumor is a rare neoplasm with extremely aggressive Silva, C.; et al. Desmoplastic Small behavior. Despite the multimodal treatment for newly diagnosed patients with chemotherapy, Round Cell Tumor: A Review of Main cytoreductive surgery and radiation, the cure rate is still low. For relapsed or progressive disease, Molecular Abnormalities and there is limited data regarding second and third-line therapies. Novel agents have shown only modest Emerging Therapy. Cancers 2021, 13, activity. Recent molecular changes have been identified in this disease and this opens opportunities 498. https://doi.org/10.3390/ to be explored in future clinical trials. cancers13030498 Abstract: Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma Received: 10 December 2020 Accepted: 20 January 2021 affecting adolescents and young adults with male predominance. Generally, it originates from Published: 28 January 2021 the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1– WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other Publisher’s Note: MDPI stays neutral proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a with regard to jurisdictional claims in combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal published maps and institutional affil- hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain iations. poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular Copyright: © 2021 by the authors. profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the Licensee MDPI, Basel, Switzerland. current studies conducted to better understand DSRCT biology and to explore the new therapeutic This article is an open access article strategies under investigation in preclinical models and in early phase clinical trials. distributed under the terms and conditions of the Creative Commons Keywords: desmoplastic small round cell tumor; treatment; prognosis; surgery; radiotherapy; Attribution (CC BY) license (https:// chemotherapy; tyrosine kinase receptor; target therapy; rare disease creativecommons.org/licenses/by/ 4.0/). Cancers 2021, 13, 498. https://doi.org/10.3390/cancers13030498 https://www.mdpi.com/journal/cancers Cancers 2021, 13, x 2 of 24 Cancers 2021, 13, 498 2 of 22 1.1. IntroductionIntroduction DesmoplasticDesmoplastic smallsmall roundround cellcell tumortumor (DSRCT)(DSRCT) isis anan extremelyextremely rare,rare, aggressiveaggressive sar-sar- coma.coma. It affectsaffects mainlymainly adolescentsadolescents andand youngyoung adultsadults andand originatesoriginates inin andand primarilyprimarily involvesinvolves thethe serosalserosal surfacessurfaces ofof thethe abdominalabdominal cavity.cavity. ItIt waswas firstfirst describeddescribed by by GeraldGerald and and RosaiRosai inin 1989 1989 as as a a newly newly characterized characterized clinicopathologic clinicopathologic entity entity [1]. [1]. Current Current management management of theof the disease disease includes includes a combination a combination of chemotherapy,of chemotherapy, radiation, radiation, and and aggressive aggressive surgical surgi- resectioncal resection [2,3 ][2,3] as summarized as summarized in Figure in Figure1. Despite 1. Despite advances advances in multimodal in multimodal therapy, therapy, the outcomethe outcome remains remains poor poor since since the majority the majority of patients of patients develop develop high rates high of rates disease of disease recur- rencerecurrence or die or within die within three three years years [4,5]. [4,5]. Due toDu thee to dismal the dismal survival, survival, DSRCT DSRCT has anhas urgent an ur- unmetgent unmet need forneed more for more effective effective and innovative and innovative therapeutic therapeutic options. options. FigureFigure 1.1. TherapeuticTherapeutic optionsoptions forfor desmoplasticdesmoplastic smallsmall roundround cellcell tumortumor (DSRCT).(DSRCT). BasedBased on on multiplemultiple retrospectivesretrospectives andand few prospective studies, studies, the the benefit benefit was was observed observed for for therapies therapies in ingreen, green, low low evidenceevidence ofof the the benefit benefit for for therapies therapies in in blue. blue. For For relapsed relapsed or or progressive progressive disease, disease, strategies strategies in in yellow yel- hadlow beenhad been used used and inand white in white are perspectives. are perspectiv HIPECes. HIPEC (hyperthermic (hyperthermic intraperitoneal intraperitoneal chemotherapy), chemo- RTKitherapy), (Receptor RTKi Tyrosine(Receptor Kinase Tyrosine inhibition), Kinase inhibiti ARi (Androgenon), ARi (Androgen Receptor inhibition),Receptor inhibition), VEGFi (Vascular VEGFi (Vascular Endothelial Growth Factor inhibition), IO (immune check point inhibition), IGFi (Insulin Endothelial Growth Factor inhibition), IO (immune check point inhibition), IGFi (Insulin Growth Growth Factor inhibiotion), mTORi (mammalian Target of Rapamycin inhibition), ABMT (autol- Factor inhibiotion), mTORi (mammalian Target of Rapamycin inhibition), ABMT (autologous bone ogous bone marrow transplant). marrow transplant). 1.1.1.1. DemographicsDemographics ofof DSRCTDSRCT DesmoplasticDesmoplastic smallsmall roundround cellcell tumortumor isis aa veryvery rareraresubtype subtypeof ofsarcoma. sarcoma. ForFor researchresearch purposes,purposes, DSRCTDSRCT casescases cancan bebe searchedsearched usingusing thethe histologyhistology andand behaviorbehavior (malignant)(malignant) classificationclassification codecode 8806/3.8806/3. Ther Theree is no uniformuniform definitiondefinition ofof rarerare sarcoma,sarcoma, however,however, thethe burdenburden of of rare rare cancer cancer in in our our current current days days is great.is great. The The US OrphanUS Orphan Drug Drug Act ofAct 1983 of 1983 defined de- rarefined diseases rare diseases as those as affectingthose affecting less than less 200,000 than 200,000 people people in the Unitedin the United States States [6]. In [6]. 2010, In Greenlee2010, Greenlee et al. [7 et] describedal. [7] describe the USd the burden US burden of rare cancersof rare cancers according according to the National to the National Cancer InstituteCancer Institute definition definition as those as cancers those withcancers fewer with than fewer 15 cases than per15 cases 100,000 per people 100,000 per people year. Moreper year. recently, More a recently, consortium a consortium from the European from the Union,European Surveillance Union, Surveillance of Rare Cancer of Rare in EuropeCancer (RARECARE)in Europe (RARECARE) [8], described [8], a newdescribed definition a new of raredefinition cancer of in rare Europe cancer as those in Europe with feweras those than with 6 cases fewer per than 100,000 6 cases people per 100,000 per year. people per year. InIn aa studystudy publishedpublished inin 20142014 [[9],9], aa totaltotal ofof 192192 casescases ofof DSRCTDSRCT werewere identifiedidentified inin thethe SEERSEER databasedatabase between between 1973 1973 to 2007.to 2007. The age-adjustedThe
Load more

Recommended publications
  • Soft Tissue Cytopathology: a Practical Approach Liron Pantanowitz, MD
    4/1/2020 Soft Tissue Cytopathology: A Practical Approach Liron Pantanowitz, MD Department of Pathology University of Pittsburgh Medical Center [email protected] What does the clinician want to know? • Is the lesion of mesenchymal origin or not? • Is it begin or malignant? • If it is malignant: – Is it a small round cell tumor & if so what type? – Is this soft tissue neoplasm of low or high‐grade? Practical diagnostic categories used in soft tissue cytopathology 1 4/1/2020 Practical approach to interpret FNA of soft tissue lesions involves: 1. Predominant cell type present 2. Background pattern recognition Cell Type Stroma • Lipomatous • Myxoid • Spindle cells • Other • Giant cells • Round cells • Epithelioid • Pleomorphic Lipomatous Spindle cell Small round cell Fibrolipoma Leiomyosarcoma Ewing sarcoma Myxoid Epithelioid Pleomorphic Myxoid sarcoma Clear cell sarcoma Pleomorphic sarcoma 2 4/1/2020 CASE #1 • 45yr Man • Thigh mass (fatty) • CNB with TP (DQ stain) DQ Mag 20x ALT –Floret cells 3 4/1/2020 Adipocytic Lesions • Lipoma ‐ most common soft tissue neoplasm • Liposarcoma ‐ most common adult soft tissue sarcoma • Benign features: – Large, univacuolated adipocytes of uniform size – Small, bland nuclei without atypia • Malignant features: – Lipoblasts, pleomorphic giant cells or round cells – Vascular myxoid stroma • Pitfalls: Lipophages & pseudo‐lipoblasts • Fat easily destroyed (oil globules) & lost with preparation Lipoma & Variants . Angiolipoma (prominent vessels) . Myolipoma (smooth muscle) . Angiomyolipoma (vessels + smooth muscle) . Myelolipoma (hematopoietic elements) . Chondroid lipoma (chondromyxoid matrix) . Spindle cell lipoma (CD34+ spindle cells) . Pleomorphic lipoma . Intramuscular lipoma Lipoma 4 4/1/2020 Angiolipoma Myelolipoma Lipoblasts • Typically multivacuolated • Can be monovacuolated • Hyperchromatic nuclei • Irregular (scalloped) nuclei • Nucleoli not typically seen 5 4/1/2020 WD liposarcoma Layfield et al.
    [Show full text]
  • Well-Differentiated Spindle Cell Liposarcoma
    Modern Pathology (2010) 23, 729–736 & 2010 USCAP, Inc. All rights reserved 0893-3952/10 $32.00 729 Well-differentiated spindle cell liposarcoma (‘atypical spindle cell lipomatous tumor’) does not belong to the spectrum of atypical lipomatous tumor but has a close relationship to spindle cell lipoma: clinicopathologic, immunohistochemical, and molecular analysis of six cases Thomas Mentzel1, Gabriele Palmedo1 and Cornelius Kuhnen2 1Dermatopathologie, Friedrichshafen, Germany and 2Institute of Pathology, Medical Center, Mu¨nster, Germany Well-differentiated spindle cell liposarcoma represents a rare atypical/low-grade malignant lipogenic neoplasm that has been regarded as a variant of atypical lipomatous tumor. However, well-differentiated spindle cell liposarcoma tends to occur in subcutaneous tissue of the extremities, the trunk, and the head and neck region, contains slightly atypical spindled tumor cells often staining positively for CD34, and lacks an amplification of MDM2 and/or CDK4 in most of the cases analyzed. We studied a series of well-differentiated spindle cell liposarcomas arising in two female and four male patients (age of the patients ranged from 59 to 85 years). The neoplasms arose on the shoulder, the chest wall, the thigh, the lower leg, the back of the hand, and in paratesticular location. The size of the neoplasms ranged from 1.5 to 10 cm (mean: 6.0 cm). All neoplasms were completely excised. The neoplasms were confined to the subcutis in three cases, and in three cases, an infiltration of skeletal muscle was seen. Histologically, the variably cellular neoplasms were composed of atypical lipogenic cells showing variations in size and shape, and spindled tumor cells with slightly enlarged, often hyperchromatic nuclei.
    [Show full text]
  • The Health-Related Quality of Life of Sarcoma Patients and Survivors In
    Cancers 2020, 12 S1 of S7 Supplementary Materials The Health-Related Quality of Life of Sarcoma Patients and Survivors in Germany—Cross-Sectional Results of A Nationwide Observational Study (PROSa) Martin Eichler, Leopold Hentschel, Stephan Richter, Peter Hohenberger, Bernd Kasper, Dimosthenis Andreou, Daniel Pink, Jens Jakob, Susanne Singer, Robert Grützmann, Stephen Fung, Eva Wardelmann, Karin Arndt, Vitali Heidt, Christine Hofbauer, Marius Fried, Verena I. Gaidzik, Karl Verpoort, Marit Ahrens, Jürgen Weitz, Klaus-Dieter Schaser, Martin Bornhäuser, Jochen Schmitt, Markus K. Schuler and the PROSa study group Includes Entities We included sarcomas according to the following WHO classification. - Fletcher CDM, World Health Organization, International Agency for Research on Cancer, editors. WHO classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013. 468 p. (World Health Organization classification of tumours). - Kurman RJ, International Agency for Research on Cancer, World Health Organization, editors. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: International Agency for Research on Cancer; 2014. 307 p. (World Health Organization classification of tumours). - Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul;70(1):106–19. - World Health Organization, Swerdlow SH, International Agency for Research on Cancer, editors. WHO classification of tumours of haematopoietic and lymphoid tissues: [... reflects the views of a working group that convened for an Editorial and Consensus Conference at the International Agency for Research on Cancer (IARC), Lyon, October 25 - 27, 2007]. 4. ed.
    [Show full text]
  • TERT Promoter Mutations Occur Frequently in Gliomas and a Subset of Tumors Derived from Cells with Low Rates of Self-Renewal
    TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal Patrick J. Killelaa,1, Zachary J. Reitmana,1, Yuchen Jiaob,1, Chetan Bettegowdab,c,1, Nishant Agrawalb,d, Luis A. Diaz, Jr.b, Allan H. Friedmana, Henry Friedmana, Gary L. Galliac,d, Beppino C. Giovanellae, Arthur P. Grollmanf, Tong-Chuan Heg, Yiping Hea, Ralph H. Hrubanh, George I. Jalloc, Nils Mandahli, Alan K. Meekerh,m, Fredrik Mertensi, George J. Nettoh,l, B. Ahmed Rasheeda, Gregory J. Rigginsc, Thomas A. Rosenquistf, Mark Schiffmanj, Ie-Ming Shihh, Dan Theodorescuk, Michael S. Torbensonh, Victor E. Velculescub, Tian-Li Wangh, Nicolas Wentzensenj, Laura D. Woodh, Ming Zhangb, Roger E. McLendona, Darell D. Bignera, Kenneth W. Kinzlerb, Bert Vogelsteinb,2, Nickolas Papadopoulosb, and Hai Yana,2 aThe Preston Robert Tisch Brain Tumor Center at Duke, Pediatric Brain Tumor Foundation Institute at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC 27710; bLudwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231; Departments of cNeurosurgery, dOtolaryngology—Head and Neck Surgery, hPathology, lUrology, and mOncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231; eChristus Stehlin Foundation for Cancer Research, Houston, TX 77025; fDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794; gMolecular Oncology Laboratory, Department of Orthopaedic
    [Show full text]
  • Spindle Cell Liposarcoma with a TRIO-TERT Fusion Transcript
    Virchows Archiv (2019) 475:391–394 https://doi.org/10.1007/s00428-019-02545-5 BRIEF REPORTS Spindle cell liposarcoma with a TRIO-TERT fusion transcript David I. Suster1 & Vikram Deshpande1 & Ivan Chebib1 & Martin S. Taylor1 & John Mullen2 & Miriam A. Bredella3 & G. Petur Nielsen1 Received: 7 January 2019 /Revised: 8 February 2019 /Accepted: 11 February 2019 /Published online: 22 February 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Conventional well-differentiated, dedifferentiated, and myxoid liposarcomas have long been known to harbor numerous typical genetic alterations that allow for diagnosis of these tumors. These include MDM2 and CDK4 amplification in well-differentiated and dedifferentiated liposarcomas as well as FUS-DDIT3 rearrangements in myxoid liposarcoma. More recently, in-frame TRIO- TERT fusion genes have been described in a subset of non-translocation-related sarcomas including myxofibrosarcoma, dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, pleomorphic rhabdomyosarcoma, and leiomyosarcoma. These genetic rearrangements lead to TERT mRNA expression levels hundreds of times higher than normal, causing increased telomerase activation in these tumors. Herein, we describe an unusual case of a liposarcoma with spindle cell features and a TRIO-TERT fusion transcript identified through next-generation sequencing. Keywords Liposarcoma . TRIO-TERT . Fusion transcript The current classification of spindle cell lipomatous neoplasms Recently, a novel in-frame TRIO-TERT fusion has been is still evolving. In the literature, the term Bspindle cell identified in some non-translocation-related sarcomas [6]. liposarcoma^ has been used to describe many tumors including TRIO plays an important role in cell adhesion and nuclear spindled variants of well-differentiated liposarcoma and signaling pathways and is part of a family of Rho GTPases myxoid liposarcoma, as well as spindle cell lipomas with that act as guanine nucleotide exchange factors [7].
    [Show full text]
  • Pleural Mesothelioma Dilated and the Pulmonary Trunk Was Occluded by a Large Embolus
    Thorax 1993;48:409-410 409 lungs showed fibrosis, subpleural honeycomb Liposarcomatous changes, chronic bronchitis, and foci of bron- chopneumonia. The heart was slightly differentiation in diffuse enlarged (weight 430 g, right ventricle 120 g, left ventricle 230 g). The right side was Thorax: first published as 10.1136/thx.48.4.409 on 1 April 1993. Downloaded from pleural mesothelioma dilated and the pulmonary trunk was occluded by a large embolus. The left atrium J Krishna, M T Haqqani was occupied by a large myxoid tumour mass measuring 15 x 6 cm attached to a blood clot which extended into the pulmonary veins. The rest of the organs showed no abnor- Abstract malities. A case history is presented of a woman who died eight hours after hospital MICROSCOPICAL APPEARANCES admission with severe breathlessness. At The right pleura was diffusely infiltrated by necropsy the right lung was encased in a the tumour, which showed a sarcomatous thickened pleura with a large tumour. pattern with myxoid change and abundant Histological examination of the tumour typical lipoblasts containing sharply defined showed pleural mesothelioma with cytoplasmic vacuoles indenting hyperchro- liposarcomatous differentiation. The matic nuclei in the right upper lobe. This was lungs showed changes of asbestosis and confirmed on the electron microscope after the asbestos fibre count was significandy the tissue was post fixed in osmium tetraoxide raised. Liposarcomatous differentiation (fig 1). The right upper lobe also showed an in pleural mesothelioma has not been adjacent mesothelioma with an epithelial reported previously. glandular component (fig 2), uniformly nega- tive for carcinoembryonic antigen but (Thorax 1993;48:409-410) strongly positive for epithelial membrane antigen and cytokeratin.
    [Show full text]
  • Soft Tissue Sarcoma Classifications
    Soft Tissue Sarcoma Classifications Contents: 1. Introduction 2. Summary of SSCRG’s decisions 3. Issue by issue summary of discussions A: List of codes to be included as Soft Tissue Sarcomas B: Full list of codes discussed with decisions C: Sarcomas of neither bone nor soft tissue D: Classifications by other organisations 1. Introduction We live in an age when it is increasingly important to have ‘key facts’ and ‘headline messages’. The national registry for bone and soft tissue sarcoma want to be able to produce high level factsheets for the general public with statements such as ‘There are 2000 soft tissue sarcomas annually in England’ or ‘Survival for soft tissue sarcomas is (eg) 75%’ It is not possible to write factsheets and data briefings like this, without a shared understanding from the SSCRG about which sarcomas we wish to include in our headline statistics. The registry accepts that soft tissue sarcomas are a very complex and heterogeneous group of cancers which do not easily reduce to headline figures. We will still strive to collect all data from cancer registries about anything that is ‘like a sarcoma’. We will also produce focussed data briefings on sites such as dermatofibrosarcomas and Kaposi’s sarcomas – the aim is not to forget any sites we exclude! The majority of soft tissue sarcomas have proved fairly uncontroversial in discussions with individual members of the SSCRG, but there were 7 particular issues it was necessary to make a group decision on. This paper records the decisions made and the rationale behind these decisions. 2. Summary of SSCRG’s decisions: Include all tumours with morphology codes as listed in Appendix A for any cancer site except C40 and C41 (bone).
    [Show full text]
  • Transcriptional Regulation of IGF-I Receptor Gene Expression by Novel Isoforms of the EWS-WT1 Fusion Protein
    Oncogene (2002) 21, 1890 ± 1898 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS-WT1 fusion protein Ina Finkeltov1, Scott Kuhn3,4, Tova Glaser1, Gila Idelman1, John J Wright2, Charles T Roberts Jr3 and Haim Werner*,1 1Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, 69978 Israel; 2Medicine Branch, Division of Clinical Science, National Cancer Institute, NIH, Bethesda, Maryland MD 20889, USA; 3Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon OR 97201, USA The EWS family of genes is involved in numerous Werner et al., 1994a). In addition to its central role in chromosomal translocations that are characteristic of a normal growth processes, the IGF-I-R plays a pivotal variety of sarcomas. A recently described member of this role in malignant transformation (Baserga et al., 1994; group is desmoplastic small round cell tumor (DSRCT), Grimberg and Cohen, 2000; Werner and LeRoith, which is characterized by a recurrent t(11;22)(p13;q12) 1996). The IGF-I-R is highly expressed in most tumors translocation that fuses the 5' exons of the EWS gene to and cancer cell lines, where it functions as a potent the 3' exons of the WT1 gene. The originally described antiapoptotic agent, conferring enhanced survival to chimera comprises exons 1 ± 7 of EWS and exons 8 ± 10 malignant cells (Resnico et al., 1995; Werner and of WT1. We have previously reported that the WT1 LeRoith, 1997). Transcription of the IGF-I-R gene is protein represses the expression of the IGF-I receptor negatively regulated by a number of tumor suppres- gene, whereas the EWS(1 ± 7)-WT1(8 ± 10) fusion protein sors, including p53, BRCA1 and WT1 (Maor et al., activates IGF-I receptor gene expression.
    [Show full text]
  • About Soft Tissue Sarcoma Overview and Types
    cancer.org | 1.800.227.2345 About Soft Tissue Sarcoma Overview and Types If you've been diagnosed with soft tissue sarcoma or are worried about it, you likely have a lot of questions. Learning some basics is a good place to start. ● What Is a Soft Tissue Sarcoma? Research and Statistics See the latest estimates for new cases of soft tissue sarcoma and deaths in the US and what research is currently being done. ● Key Statistics for Soft Tissue Sarcomas ● What's New in Soft Tissue Sarcoma Research? What Is a Soft Tissue Sarcoma? Cancer starts when cells start to grow out of control. Cells in nearly any part of the body can become cancer and can spread to other areas. To learn more about how cancers start and spread, see What Is Cancer?1 There are many types of soft tissue tumors, and not all of them are cancerous. Many benign tumors are found in soft tissues. The word benign means they're not cancer. These tumors can't spread to other parts of the body. Some soft tissue tumors behave 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 in ways between a cancer and a non-cancer. These are called intermediate soft tissue tumors. When the word sarcoma is part of the name of a disease, it means the tumor is malignant (cancer).A sarcoma is a type of cancer that starts in tissues like bone or muscle. Bone and soft tissue sarcomas are the main types of sarcoma. Soft tissue sarcomas can develop in soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.
    [Show full text]
  • Mesenchymal) Tissues E
    Bull. Org. mond. San 11974,) 50, 101-110 Bull. Wid Hith Org.j VIII. Tumours of the soft (mesenchymal) tissues E. WEISS 1 This is a classification oftumours offibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours offibrous tissue are divided into fibroma, fibrosarcoma (including " canine haemangiopericytoma "), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tamours is described and illustrated with photographs. For the purpose of this classification " soft tis- autonomic nervous system, the paraganglionic struc- sues" are defined as including all nonepithelial tures, and the mesothelial and synovial tissues. extraskeletal tissues of the body with the exception of This classification was developed together with the haematopoietic and lymphoid tissues, the glia, that of the skin (Part VII, page 79), and in describing the neuroectodermal tissues of the peripheral and some of the tumours reference is made to the skin. HISTOLOGICAL CLASSIFICATION AND NOMENCLATURE OF TUMOURS OF THE SOFT (MESENCHYMAL) TISSUES I. TUMOURS OF FIBROUS TISSUE C. RHABDOMYOMA A. FIBROMA D. RHABDOMYOSARCOMA 1. Fibroma durum IV. TUMOURS OF BLOOD AND 2. Fibroma molle LYMPH VESSELS 3. Myxoma (myxofibroma) A. CAVERNOUS HAEMANGIOMA B. FIBROSARCOMA B. MALIGNANT HAEMANGIOENDOTHELIOMA (ANGIO- 1. Fibrosarcoma SARCOMA) 2. " Canine haemangiopericytoma" C. GLOMUS TUMOUR C. OTHER SARCOMAS D. LYMPHANGIOMA D. EQUINE SARCOID E. LYMPHANGIOSARCOMA (MALIGNANT LYMPH- E. TUMOUR-LIKE LESIONS ANGIOMA) 1. Cutaneous fibrous polyp F. TUMOUR-LIKE LESIONS 2. Keloid and hyperplastic scar V. MESENCHYMAL TUMOURS OF 3. Calcinosis circumscripta PERIPHERAL NERVES II. TUMOURS OF FAT TISSUE VI.
    [Show full text]
  • Undifferentiated Pleomorphic Sarcoma: Diagnosis of Exclusion
    Published online: 2019-04-16 Case Report Undifferentiated pleomorphic sarcoma: Diagnosis of exclusion ABSTRACT Malignant soft‑tissue tumors which were designated as malignant fibrous histiocytoma are regrouped by the WHO (in 2002) under the new entity termed as “undifferentiated pleomorphic sarcoma.”[1] It accounts for less than 5% of all adult soft‑tissue sarcomas. Here, we report the lesion in a 70‑year‑old man who presented with high‑grade undifferentiated pleomorphic sarcoma in the lower extremity. Keywords: Adult soft‑tissue sarcomas, malignant fibrous histiocytoma, soft‑tissue sarcoma of lower extremity, undifferentiated pleomorphic sarcoma INTRODUCTION On gross inspection, soft‑tissue mass measured 12 cm × 5 cm × 4 cm, with tumor mass of about Undifferentiated pleomorphic sarcomas are aggressive 3 cm × 2 cm × 1 cm dimensions. tumors, commonly seen in adults. However histopathological pattern is very much variable in these soft tissue Cut section was gray brown with areas of necrosis in it malignant neoplasms. We detected this case where [Figure 1]. proper clinico‑histomorphological analysis coupled with immunohistochemistry (IHC) helped us to arrive at a Histopathological examination revealed a malignant tumor diagnosis. with pleomorphic bizarre cells. At places, spindled and tadpole like contour cells were seen. Many histiocytic giant CASE REPORT cells were also noted in the sections [Figure 2, 3]. The surgical margins were free of the tumor. A 70‑year‑old male presented with swelling over the posterior aspect of the left thigh. Swelling was gradually increasing Based on these microscopic findings and the site involved, in size. differentials of pleomorphic rhabdomyosarcoma and an undifferentiated pleomorphic sarcoma were kept.
    [Show full text]
  • The Role of Cytogenetics and Molecular Diagnostics in the Diagnosis of Soft-Tissue Tumors Julia a Bridge
    Modern Pathology (2014) 27, S80–S97 S80 & 2014 USCAP, Inc All rights reserved 0893-3952/14 $32.00 The role of cytogenetics and molecular diagnostics in the diagnosis of soft-tissue tumors Julia A Bridge Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA Soft-tissue sarcomas are rare, comprising o1% of all cancer diagnoses. Yet the diversity of histological subtypes is impressive with 4100 benign and malignant soft-tissue tumor entities defined. Not infrequently, these neoplasms exhibit overlapping clinicopathologic features posing significant challenges in rendering a definitive diagnosis and optimal therapy. Advances in cytogenetic and molecular science have led to the discovery of genetic events in soft- tissue tumors that have not only enriched our understanding of the underlying biology of these neoplasms but have also proven to be powerful diagnostic adjuncts and/or indicators of molecular targeted therapy. In particular, many soft-tissue tumors are characterized by recurrent chromosomal rearrangements that produce specific gene fusions. For pathologists, identification of these fusions as well as other characteristic mutational alterations aids in precise subclassification. This review will address known recurrent or tumor-specific genetic events in soft-tissue tumors and discuss the molecular approaches commonly used in clinical practice to identify them. Emphasis is placed on the role of molecular pathology in the management of soft-tissue tumors. Familiarity with these genetic events
    [Show full text]