DOCSLIB.ORG

Rare Tumors of Childhood November 10, 2018 • 1:20 – 3:10 P.M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rare Tumors of Childhood November 10, 2018 • 1:20 – 3:10 P.M SELF-ASSESSMENT MODULE REFERENCE SPR 2018 Oncologic Imaging Course – Rare Tumors of Childhood November 10, 2018 • 1:20 – 3:10 p.m. Imaging of Melanoma Sue Kaste, DO 1. Which of the following statements is true regarding pediatric malignant melanoma? A. The main predictor of outcome is the stage of disease at the time of diagnosis B. Melanoma is a disease seen only in Caucasians C. Spitzoid melanomas who lack the TERT promotor mutation have a poorer prognosis D. The majority of congenital melanocytic nevi undergo malignant degeneration to melanoma Correct Answer: A. The main predictor of outcome is the stage of disease at the time of diagnosis Rationale: Disease stage at the time of diagnosis is the main predictor of outcome. The lower the stage, the better the outcome. Option B is not correct. Melanoma is more common in Caucasians but can develop in any race. It is 5-times more common in Caucasians than Hispanics and 20-times more common in Caucasians than African Americans. Option C. is not correct. Spitzoid melanomas who lack the TERT promotor mutation have a much better prognosis than do those with the TERT promotor mutation. The latter mutation is associated with aggressive behavior and a higher tendency for metastasis and death from disease. Option D. is not correct. Only about 5-10% of congenital melanocytic nevi become melanoma. References: 1. Halalsheh H, Kaste SC, Navid F, Bahrami A, Shulkin BL, Rao B, Kunkel M, Artz N, Pappo A. The role of routine imaging in pediatric cutaneous melanoma.Pediatr Blood Cancer. 2018 Aug 19:e27412. doi: 10.1002/pbc.27412. [Epub ahead of print] PMID:30124237 2. Lee S, Barnhill RL, Dummer R, Dalton J, Wu J, Pappo A, Bahrami A. TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms. Sci Rep. 2015 Jun 10;5:11200. doi: 10.1038/srep11200.PMID:26061100 3. Bahrami A, Barnhill RL. Pathology and genomics of pediatric melanoma: A critical reexamination and new insights. Pediatr Blood Cancer. 2018 Feb;65(2). doi: 10.1002/pbc.26792. Epub 2017 Sep 12. PMID:28895292 4. Stefanaki C, Chardalias L, Soura E, Katsarou A, Stratigos A. Paediatric melanoma. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1604-1615. doi: 10.1111/jdv.14299. Epub 2017 May 22.PMID:28449284 Pleuropulmonary Blastoma and DICER1 Syndrome R. Paul Guillerman, MD 2. Which of the following raises the likelihood that a lung cyst in a child represents a cystic congenital lung malformation rather than a cystic pleuropulmonary blastoma (PPB)? A. Cyst multifocality B. Spontaneous pneumothorax C. Presence on mid-2nd-trimester prenatal ultrasound D. Family history of lung cysts Correct Answer: C. Presence on mid-2nd-trimester prenatal ultrasound Rationale: Since cystic PPBs and cystic congenital lung malformations are very similar in appearance on imaging but the decision regarding surgical management of these lesions may differ, particularly in an asymptomatic child, it is important to recognize features that favor one versus the other. Congenital cystic lung malformations are often manifest on mid-2nd-trimester prenatal ultrasound exams, while cystic PPBs are typically first identified postnatally or on third trimester prenatal ultrasound exams. Cyst multifocality, spontaneous pneumothorax, or a family history of lung cysts or other DICER1 syndrome- related conditions increases the likelihood that a lung cyst in a child represents a cystic PPB rather than a cystic congenital lung malformation. References: 1. Priest JR, Williams GM, Hill DA, Dehner LP, Jaffé A. Pulmonary cysts in early childhood and the risk of malignancy. Pediatr Pulmonol. 2009;44:14-30 2. Oliveira C, Himidan S, Pastor AC, Nasr A, Manson D, Taylor G, et al. Discriminating preoperative features of pleuropulmonary blastomas (PPB) from congenital cystic adenomatoid malformations (CCAM): a retrospective, age-matched study. Eur J Pediatr Surg. 2011;21:2-7 3. Feinberg A, Hall NJ, Williams GM, Schultz KA, Miniati D, Hill DA, et al. Can congenital pulmonary airway malformation be distinguished from Type I pleuropulmonary blastoma based on clinical and radiological features? J Pediatr Surg. 2016;51:33-37 4. Waelti SL, Garel L, Dal Soglio D, Rypens F, Messerli M, Dubois J. Neonatal congenital lung tumors - the importance of mid-second-trimester ultrasound as a diagnostic clue. Pediatr Radiol 2017;47:1766-1775 Desmoplastic Small Round Cell Tumor: What the Radiologist Needs to Know Anita P. Price, MD, FACR 3. Desmoplastic small round cell tumor is associated with which of the following gene fusions: A. EWS - ATF1 B. EWS - WT1 C. TFE3 - ASPL D. SSX1 – SYT Correct Answer: B. EWS - WT1 Rationale: Fusion of the Ewing sarcoma gene (EWS) with Wilms Tumor1 suppressor gene (WT1), resulting from a characteristic translocation (11;22) (p13;q12) translocation. Options A, C and D are incorrect. Clear cell sarcoma is associated with EWS-ATF1 gene fusion. Alveolar soft part sarcoma is associated with TFE3- ASPL gene fusion. Synovial sarcoma is associated with SSX1 – SYT. References: 1. Gerald WL, Rosai J (1989) Case 2. Desmoplastic small cell tumor with divergent differentiation. Pediatr Pathol 9:177–183 2. Ladanyi, M. & Gerald, W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res 54, 2837-2840 (1994). 3. Gerald WL, Ladanyi M, de Alava E et al (1998) Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16: 3028–3036 4. Gerald, W.L., Rosai, J. & Ladanyi, M. Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. Proc Natl Acad Sci U S A 92, 1028-1032 (1995) 5. Abruzzo, L.V., Pollock, R.E. , Lee, S., Czerniak, B., Lazar, A. Molecular Diagnosis of Sarcomas Chromosomal Translocations in Sarcomas. Arch Pathol Lab Med. Volume 130:1199–1207, August 2006. 4. Axial and coronal CT images of a 7 yo male with no previous medical history. Which of the following is the least likely diagnosis? A. Burkitt Lymphoma B. DSRCT C. Nephroblastomosis D. Angiomyolipoma Correct Answer: D. Angiomyolipoma Rationale: Angiomyolipoma is an uncommon benign renal neoplasm in children containing mature adipose tissue, smooth muscle, and abnormal blood vessels. Varying amounts of fat are present. 80% patients with Tuberous Sclerosis have angiomyolipoma. 90% of angiomyolipomas which are not associated with Tuberous Sclerosis present as solitary unilateral lesions. The lesions in this child are bilateral and do not contain fat. The child has no significant prior medical history to suggest tuberous sclerosis. A. Burkitt lymphoma may involve the kidney as multifocal hypodense renal lesions. B. DSRCT can involve the kidney as hypodense lesions. A delayed right nephrogram raises the question of a pelvis mass causing distal ureteral obstruction. Axial image through the pelvis of same patient demonstrates large heterogenous retrovesical pelvic mass with punctate calcification. Patient has pathologically confirmed DSRCT. C. Nephroblastomatosis can present as hypodense peripheral cortical lesions. References: 1. Edward Y. Lee. CT imaging of mass-like renal lesions in children. Pediatric Radiology, 2007, Volume 37, Number 9, Page 896. 2. Wang LL1, Perlman EJ, Vujanic GM, Zuppan C, Brundler MA, Cheung CR, Calicchio ML, Dubois S, Cendron M, Murata-Collins JL, Wenger GD, Strzelecki D, Barr FG, Collins T, Perez-Atayde AR, Kozakewich H.. Desmoplastic small round cell tumor of the kidney in childhood. Am J Surg Pathol. 2007 Apr;31(4):576-84 3. Vandan Caur Arora, Anita P. Price, Stephen Fleming, Michael J. Sohn, Heather Magnan, Michael P. LaQuaglia, Sara Abramson. Characteristic imaging features of desmoplastic small round cell tumour. Pediatric Radiology, 2013, Volume 43, Number 1, Page 93 Ovarian Tumors of Childhood Shailee V. Lala, MD 5. The most common ovarian tumor in children is: A. Sclerosing stromal tumor B. Mature cystic teratoma C. Dysgerminoma D. Serous cystadenoma Correct Answer: B. Mature cystic teratoma References: Brown MF, Hebra A, McGeehin K, Ross AJ III. Ovarian masses in children: a review of 91 cases of malignant and benign masses. J Pediatr Surg 1993; 28:930–933. Epelman M., Chikwava K. R., Chauvin N., Servaes S. Imaging of pediatric ovarian neoplasms. Pediatric Radiology. 2011;41(9):1085–1099. 6. What percentage of ovarian dysgerminomas are bilateral? A. 0-5% B. 10-15% C. 45-50% D. 70-75% Correct Answer: B. 10-15% References: Epelman M1, Chikwava KR,et al.Imaging of pediatric ovarian neoplasms.Pediatr Radiol. 2011 Sep;41(9):1085-99 .
Load more

Recommended publications
  • Angiomyolipoma of the Cervix – Report of a Rare Entity
    Internet Journal of Medical Update. 2017 July;12(2):13-15. doi: 10.4314/ijmu.v12i2.4 Internet Journal of Medical Update Journal home page: http://www.akspublication.com/ijmu Case Report Angiomyolipoma of the cervix – report of a rare entity N. Hariharanadha Sarmaᴪ1, Rama Srivastava2, Smriti Agnihotri3 1Consultant Pathologist, Department of Pathology, RDT Hospital, Bathalapalli, Andhra Pradesh, India 2Professor, Department of Pathology, SSR Medical College, Belle Rive, Mauritius 3Professor, Department of Pathology, American University of Antigua College of Medicine, Antigua & Barbuda, WI (Received 22 September 2017 and accepted 04 October 2017) ABSTRACT: Angiomyolipoma (AML) is a mesenchymal neoplasm seen usually in the kidney. Few cases of extra renal AML have been documented in various organs including the female genital tract, where the uterus is the most common site. To the best of our knowledge, only 4 cases of AML in the cervix have been reported in the literature. Association of AML with tuberous sclerosis is well known. Presently AML is included in the spectrum of disease entities called PEComa. We report a case of AML without tuberous sclerosis arising from the uterine cervix, which has to be differentiated from lipoleiomyoma. KEY WORDS: Angiomyolipoma; Uterine cervix; PEComas; Uterine tumor INTRODUCTIONV localization8, and mostly in females over 409. The occurrence of AML in the cervix without Angiomyolipoma (AML) occurs most frequently in concurrent incidence in the kidney is extremely the kidney, where it is closely related to tuberous rare, and only four cases have been reported in the sclerosis complex (TSC)1,2, occasionally in other scientific literature10. We are reporting a case of organs, most commonly the liver, but occurrence at uterine cervix AML without tuberous sclerosis other sites is extremely rare3.
    [Show full text]
  • 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]
  • 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]
  • Non-Wilms Renal Cell Tumors in Children
    PEDIATRIC UROLOGIC ONCOLOGY 0094-0143/00 $15.00 + .OO NON-WILMS’ RENAL TUMORS IN CHILDREN Bruce Broecker, MD Renal tumors other than Wilms’ tumor are tastases occur in 40% to 60% of patients with infrequent in childhood. Wilms’ tumors ac- clear cell sarcoma of the kidney, whereas they count for 6% to 7% of childhood cancer, are found in less than 2% of patients with whereas the remaining renal tumors account Wilms’ tumor.**,26 This distinct clinical behav- for less than l%.27The most common non- ior is one of the features that has led to its Wilms‘ tumors are clear cell sarcoma of the designation as a separate tumor. Other clini- kidney, rhabdoid tumor of the kidney (both cal features include a lack of association with formerly considered unfavorable Wilms’ tu- sporadic aniridia or hemihypertrophy. mor variants but now considered separate tu- Clear cell sarcoma of the kidney has not mors), renal cell carcinoma, mesoblastic been reported to occur bilaterally and is not nephroma, and multilocular cystic nephroma. associated with nephroblastomatosis. It has Collectively, these tumors account for less been reported in infancy and adulthood, but than 10% of the primary renal neoplasms in the peak incidence is between 3 and 5 years childhood. of age. It has an aggressive behavior that responds poorly to treatment with vincristine and actinomycin alone, leading to its original CLEAR CELL SARCOMA designation by Beckwith as an unfavorable histology pattern. The addition of doxorubi- Clear cell sarcoma of the kidney is cur- cin in aggressive chemotherapy regimens has rently considered a separate tumor distinct improved outcome.
    [Show full text]
  • Appendix 4 WHO Classification of Soft Tissue Tumours17
    S3.02 The histological type and subtype of the tumour must be documented wherever possible. CS3.02a Accepting the limitations of sampling and with the use of diagnostic common sense, tumour type should be assigned according to the WHO system 17, wherever possible. (See Appendix 4 for full list). CS3.02b If precise tumour typing is not possible, generic descriptions to describe the tumour may be useful (eg myxoid, pleomorphic, spindle cell, round cell etc), together with the growth pattern (eg fascicular, sheet-like, storiform etc). (See G3.01). CS3.02c If the reporting pathologist is unfamiliar or lacks confidence with the myriad possible diagnoses, then at this point a decision to send the case away without delay for an expert opinion would be the most sensible option. Referral to the pathologist at the nearest Regional Sarcoma Service would be appropriate in the first instance. Further International Pathology Review may then be obtained by the treating Regional Sarcoma Multidisciplinary Team if required. Adequate review will require submission of full clinical and imaging information as well as histological sections and paraffin block material. Appendix 4 WHO classification of soft tissue tumours17 ADIPOCYTIC TUMOURS Benign Lipoma 8850/0* Lipomatosis 8850/0 Lipomatosis of nerve 8850/0 Lipoblastoma / Lipoblastomatosis 8881/0 Angiolipoma 8861/0 Myolipoma 8890/0 Chondroid lipoma 8862/0 Extrarenal angiomyolipoma 8860/0 Extra-adrenal myelolipoma 8870/0 Spindle cell/ 8857/0 Pleomorphic lipoma 8854/0 Hibernoma 8880/0 Intermediate (locally
    [Show full text]
  • The Identification of a Girl with Tuberous Sclerosis and an Unexpected Large Sized Renal Angiomyolipoma: a Case Report and Literature Review Study
    Case Report Annals of Clinical Case Reports Published: 24 Aug, 2020 The Identification of a Girl with Tuberous Sclerosis and an Unexpected Large Sized Renal Angiomyolipoma: A Case Report and Literature Review Study Mitra Naseri1, Farah Ashrafzadeh2, Fatemeh Ghalibafan3* and Paria Dehghanian4 1Department of Pediatric Nephrology, Mashhad University of Medical Sciences, Iran 2Department of Pediatric Neurology, Mashhad University of Medical Sciences, Iran 3Department of Medicine, Mashhad University of Medical Sciences, Iran 4Department of Pathology, Mashhad University of Medical Sciences, Iran Abstract Background: The TSC1 mutated gene, hamartin, and the TSC2 gene, tuberin, cause tuberous sclerosis, the autosomal dominant tumor syndrome. The angiomyolipoma of the kidney is a benign tumor that often happens along with tuberous sclerosis. Large renal angiomyolipoma’s associated with tuberous sclerosis are in danger of fatal hemorrhage. This study reported a case with an unexpected large size of renal angiomyolipoma’s associated with tuberous sclerosis. Case Presentation: We report a girl aged 5 years and 9 months old with tuberous sclerosis who referred to nephrology clinic due to abdominal pain. Physical examination revealed a large mass in the right flank. Kidney ultrasound reported a large mass with approximate size of 90 mm × 60 mm in the right kidney, and abdominal CT scan also showed a non-hemogenic solid mass in the right kidney with size of 91 mm × 68 mm × 67 mm, was highly suspected for Wilms' tumor. Since OPEN ACCESS the large size
    [Show full text]
  • Morphological and Immunohistochemical Characteristics of Surgically Removed Paediatric Renal Tumours in Latvia (1997–2010)
    DOI: 10.2478/v10163-012-0008-6 ACTA CHIRURGICA LATVIENSIS • 2011 (11) ORIGINAL ARTICLE Morphological and Immunohistochemical Characteristics of Surgically Removed Paediatric Renal Tumours in Latvia (1997–2010) Ivanda Franckeviča*,**, Regīna Kleina*, Ivars Melderis** *Riga Stradins University, Riga, Latvia **Children’s Clinical University Hospital, Riga, Latvia Summary Introduction. Paediatric renal tumours represent 7% of all childhood malignancies. The variable appearances of the tumours and their rarity make them especially challenging group of lesions for the paediatric pathologist. In Latvia diagnostics and treatment of childhood malignancies is concentrated in Children’s Clinical University Hospital. Microscopic evaluation of them is realised in Pathology office of this hospital. Aim of the study is to analyze morphologic spectrum of children kidney tumours in Latvia and to characterise them from modern positions with wide range of immunohistochemical markers using morphological material of Pathology bureau of Children’s Clinical University Hospital. Materials and methods. We have analyzed surgically removed primary renal tumours in Children Clinical University Hospital from the year 1997 till 2010. Samples were fixed in 10% formalin fluid, imbedded in paraffin and haematoxylin-eosin stained slides were re-examined. Immunohistochemical re-investigation was made in 65.91% of cases. For differential diagnostic purposes were used antibodies for the detection of bcl-2, CD34, EMA, actin, desmin, vimentin, CKAE1/AE3, CK7, Ki67, LCA, WT1, CD99, NSE, chromogranin, synaptophyzin, S100, myoglobin, miogenin, MyoD1 (DakoCytomation) and INI1 protein (Santa Cruz Biotechnology). Results. During the revised period there were diagnosed 44 renal tumours. Accordingly of morphological examination data neoplasms were divided: 1) nephroblastoma – 75%, 2) clear cell sarcoma – 2.27%, 3) rhabdoid tumour – 4.55%, 4) angiomyolipoma – 4.55%, 5) embrional rhabdomyosarcoma – 2.27%, 6) mesoblastic nephroma – 4.55%, 7) multicystic nephroma – 4.55%, 8) angiosarcoma – 2.27%.
    [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]
  • 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]
  • Stage I Clear Cell Sarcoma of the Kidney: Is It the Time for a Less Intensive Adjuvant Treatment?
    Editorial Stage I clear cell sarcoma of the kidney: is it the time for a less intensive adjuvant treatment? Filippo Spreafico1, Lorenza Gandola2, Fraia Melchionda3 1Pediatric Oncology Unit, Hematology and Pediatric Onco-Hematology Department, 2Pediatric Radiotherapy Unit, Department of Radiology/ Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; 3Pediatric Oncology and Hematology Unit “Lalla Seràgnoli”, Departement of Pediatrics, University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy Correspondence to: Filippo Spreafico, MD. Fondazione IRCCS Istituto Naizonale dei Tumori, Milano, Italy. Email: [email protected]. Abstract: Clear cell sarcoma of the kidney (CCSK) is a rare type of renal tumor, comprising 2% to 5% of all primary renal tumors in children. Despite the label of “unfavorable” tumor, with recent multimodality treatment schedules, including radiotherapy and multi-agent chemotherapy, disease free survival rates approaching 80% can be achieved. Younger age at tumor diagnosis and advanced-stage disease represent adverse prognostic factors. Of note, as a consequence of oncologic therapies a number of surviving patients have suffered from late sequelae on the musculoskeletal, gastrointestinal, hepatic, endocrine and cardiovascular function, or developed second tumors. Improved survival rates and a deeper knowledge of iatrogenic complications have promoted the awareness of a sequential reduction of treatment intensity, at least for low-stage CCSK, above all focusing on the abolition of flank radiation therapy (RT). It is fundamental to recognize that the rarity of this tumor calls for international cooperation trough controlled clinical trials, and without forgetting the key importance of a correct histological diagnosis and adequate surgical staging. The recent recognition of CCSK specific chromosomal translocation might help to guide targeted therapies complementary to conventional chemotherapy and radiotherapy.
    [Show full text]