DOCSLIB.ORG

Immunophenotype of Desmoplastic Small Round Cell Tumors As Detected in Cases with EWS-WT1 Gene Fusion Product Paul J

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immunophenotype of Desmoplastic Small Round Cell Tumors As Detected in Cases with EWS-WT1 Gene Fusion Product Paul J Immunophenotype of Desmoplastic Small Round Cell Tumors as Detected in Cases with EWS-WT1 Gene Fusion Product Paul J. Zhang, M.D., John R. Goldblum, M.D., Bruce R. Pawel, M.D., Cyril Fisher, M.D., Teresa L. Pasha, B.S., Frederic G. Barr, M.D., Ph.D. University of Pennsylvania Medical Center (PJZ, TLP, FGB), Philadelphia, Pennsylvania; Cleveland Clinic Foundation, Cleveland, Ohio (JRG); Children’s Hospital of Philadelphia (BRP), Philadelphia, Pennsylvania; Royal Marsden Hospital, London, United Kingdom (CF) immunoreactivity was present in 29% of desmoplastic Desmoplastic small round cell tumor is a rare tumor small round cell tumors. HER2/neu overexpression -typically involving peritoneum. Although the histo- (3؉) and c-kit expression are uncommon in desmo genesis of desmoplastic small round cell tumor has yet plastic small round cell tumors. A panel of myogenic to be elucidated, immunophenotypical and morpho- and epithelial markers should be used to detect the logical analysis shows a characteristic divergent phe- divergent phenotype in desmoplastic small round cell notype overlapping with other round cell tumors such tumors, a key feature in the differential diagnosis. as Ewing’s sarcoma/primitive neuroectodermal tu- Detection of EWS-WT1 fusion becomes critical for the mor, rhabdomyosarcoma, small cell mesothelioma, diagnosis when the characteristic divergent pheno- and carcinoma. Detection of the EWS-WT1 gene fu- type cannot be detected immunohistochemically. sion is characteristic of desmoplastic small round cell tumor and has been used reliably in tumor diagnosis. In this study, we evaluated the immunophenotype of KEY WORDS: Desmoplastic small round cell tumor, 23 desmoplastic small round cell tumor cases with the EWS-WT1 fusion product, HER2/neu, Immun- EWS-WT1 gene fusion product identified by reverse ophenotype. transcription-polymerase chain reaction. Paraffin sec- Mod Pathol 2003;16(3):229–235 tions were stained with antibodies against calretinin, WT1 (C19), desmin, myoglobin, MyoD, Myf5, myoge- Desmoplastic small round cell tumor is a rare but nin, placental alkaline phosphatase, cytokeratins, distinct entity with aggressive clinical behavior (1, MIC2, HER2/neu and c-kit using standard immuno- 2). It was originally described as a tumor primarily histochemical methods. Immunoreactivity was evalu- involving the abdominal peritoneum, with charac- ated semiquantitively by light microscopy. Desmo- teristic small round cell morphology (1, 3–5). Al- plastic small round cell tumors showed reactivity with though the histogenesis of desmoplastic small calretinin in 4/21, desmin in 21/23, myoglobin in 5/17, round cell tumor has yet to be elucidated, immu- placental alkaline phosphatase in 17/21, HER2/neu in nophenotypical analysis shows a polyphenotypic 3؉ in 1 and 1؉ in 6), c-kit in 2/14, MIC2 in 13/23, differentiation overlapping with other round cell) 7/18 WT1 in 16/23, CAM5.2 in 21/23, and AE1/3 in 16/23 tumors such as Ewing’s sarcoma/peripheral neuro- cases. The most sensitive myogenic and epithelial ectodermal tumors, rhabdomyosarcoma, Wilms’ markers are desmin and CAM 5.2. Although nuclear tumor, small cell mesothelioma, and carcinoma (1– reactivity of the early myogenic regulatory factors 5). Genetic studies revealed a characteristic trans- (MyoD, myogenin, Myf5) was not detected, myoglobin location between the EWS gene on chromosome 22 and the WT1 gene on chromosome 11, resulting in Copyright © 2003 by The United States and Canadian Academy of an EWS-WT1 fusion gene (6–8). Detection of EWS- Pathology, Inc. WT1 fusion transcript by reverse transcription- VOL. 16, NO. 3, P. 229, 2003 Printed in the U.S.A. Date of acceptance: December 7, 2002. polymerase chain reaction (RT-PCR) has been used Funded in part by National Institutes of Health Grants CA89461 and reliably to enhance our ability to diagnose desmo- CA64202 (to FGB). Address reprint requests to: Paul J. Zhang, M.D., Anatomic Pathology, 6 plastic small round cell tumor, particularly for Founders Pavilion, University of Pennsylvania Medical Center, 3400 those arising outside the abdominal cavity and Spruce Street, Philadelphia, PA 19147; fax: 215-349-5910; e-mail: [email protected]. those with unusual morphologic variation (2, 7, 9). DOI: 10.1097/01.MP.0000056630.76035.F3 Comprehensive immunohistochemical analysis has 229 been performed on desmoplastic small round cell of the authors (FGB) and collected from the surgical tumors in several large series, only few of which had pathology files of the authors’ institutions. The molecular confirmation of the diagnosis in the EWS-WT1 gene transcript was previously identified cases studied (2). In the current study, immunohis- in frozen tissue samples of these cases using a RT- tochemical evaluation of various markers related to PCR method as described elsewhere (18). The im- epithelial, myogenic, and mesothelial differentia- munohistochemical panel consisted of antibodies tion was performed on a series of desmoplastic against the mesothelial markers: calretinin and small round cell tumors that showed EWS-WT1 fu- WT1(WT C-19 against the carboxy terminus of the sion transcript by RT-PCR. protein); the myoid/myogenic markers: desmin, Proto-oncoproteins c-kit (CD117) and HER2/neu myoglobin, MyoD, Myf5 and myogenin; cytokera- are both transmembrane tyrosine kinase receptors tins: CAM5.2, AE1/3; proto-oncoproteins: c-kit, that belong to the platelet-derived growth factor HER2/neu and others: placental alkaline phospha- receptor (PDGFR) or epidermal growth factor re- tase and MIC2 (CD99; Table 1). Four-micrometer- ceptor family, respectively (10, 11). Expression of thick paraffin sections were used for standard im- c-kit has been detected in some mesenchymal tu- munohistochemical methods. Sections were mors such as gastrointestinal stromal tumors and pretreated by heating and enzyme digestion ac- Ewing’s sarcomas/primitive neuroectodermal tu- cordingly (Table 1). The heating method involved mors (12–14). Recently, a tyrosine kinase inhibitor a 1100-W microwave oven at 70% power level or a specific for the PDGFR family (STI571) and human- Black & Decker steamer at 95° C with 1ϫ citrate ized monoclonal antibody against HER2/neu (Her- ϫ ceptin) have been reported to have therapeutic ef- buffer at pH 6.0 (Lab Vision) or 1 Target Re- fects in tumors expressing either aberrant forms or trieval Buffer (DAKO, Carpinteria, CA), accord- high quantities of the corresponding target protein ingly (Table 1). Immunohistochemical staining (15–17). Therefore, STI571 or Herceptin might be was performed on an autostainer (DAKO) with effective in treating tumors positive for c-kit or EnVision kit (DAKO) for all antibodies except HER2/neu by immunohistochemistry. Little is MyoD and WT1, for which staining was per- known about the status of HER2/neu and c-kit im- formed on a Techmate autostainer (Biotech/Ven- munoreactivity in DSRCT. In this study, we also tana, Tucson, AZ) with the avidin-biotin complex evaluated the immunoreactivity of HER2 and c-kit method (ChemMate, Biotech/Ventana, Tucson, in desmoplastic small round cell tumors in the AZ). Based on the intensity of the immunoreac- same series of cases with molecular evidence of the tivity and the percentage of positive tumor cells, EWS/WT1 fusion. immunoreactivity was scored semiquantitively as Fϩ (any intensity but Յ20%), 1ϩ (weak intensity Ͼ20% but Յ50%), 2ϩ (weak intensity Ͼ50%, MATERIALS AND METHODS moderate Ͼ20% but Յ75%, or strong Ͼ20% but Twenty-three desmoplastic small round cell tu- Յ50%), and 3ϩ (moderate intensity Ͼ75% or mors were identified in the consultation file of one strong intensity and Ͼ50%). TABLE 1. Antibodies Used in the Study Antibody Clone Source Titer Antigen Retrieval Calretinin Polyclonal ZYMED, So. San Francisco, CA 1:50 Microwave, 8 minutes, 1X Citrate Buffer at pH6.0 WT1 (C-19) Polyclonal Santa Cruz, Fremont, CA 1:400 Microwave, 8 minutes, 1X Citrate Buffer at pH6.0 Desmin Polyclonal DAKO, Carpinteria, CA 1:400 NA Myoglobin Polyclonal DAKO 1:40K NA MyoD 5.8A DAKO 1:25 Steamer, 15 minutes, Target Retrieval Buffer (DAKO) Myogenin F5D DAKO 1:50 Microwave, 8 minutes, Target Retrieval Buffer (DAKO) Myf5 (C20) Polyclonal Santa Cruz 1:50 Microwave, 8 minutes, Target Retrieval Buffer (DAKO) CAM5.2 CAM 5.2 Beck-Dickinson 1:25 Microwave, 8 minutes in 1X Citrate Buffer at pH6.0 AE1/3 AE1 & AE 3 DAKO 1:40 0.01%Trypsin, 15 minutes at 37°C PLAP 8A9 DAKO 1:25 Microwave, 8 minutes, Target Retrieval Buffer (DAKO) MIC 2 12E7 DAKO 1:25 Microwave, 8 minutes in 1X Citrate Buffer at pH6.0 HER2/neu TAB250 ZYMED 1:10 Ficin (ZYMED), 15 minutes at 37°C c-kit Polyclonal DAKO 1:100 Microwave, 8 minutes, 1X Citrate Buffer at pH6.0 230 Modern Pathology TABLE 2. Immunohistochemical phenotype of Desmoplastic Small Round Cell Tumors CAM5.2 AE1/3 DES PLAP MYO MyoD MYG Myf5 CALR MIC2 WT1 HER2 c-kit Nϭ 23 23 23 21 17 20 22 21 21 23 23 18 14 Neg 2 7 2 4 11 20 22 21 15 10 5 11 12 Fϩ 4434100031202* 1ϩ 3766400015240 2ϩ 3476000007320 3ϩ 11 1 5 1 0 0 0 0 0 0 9 1 0 21/23 16/23 21/23 17/21 5/17 4/21 13/23 16/23 7/18 2/14 Totalϩ (91%) (70%) (91%) (81%) (29%) 0 0 0 (19%) (57%) (70%) (39%) (14%) F Յ 20%. 1ϩ. Weak Ͼ20 but Յ 50%. 2ϩ. Weak Ͼ50%. Moderate Ͼ20% but Յ 75%. Strong Ͼ20% but Յ 50%. 3ϩ Moderate Ͼ 75%. Strong Ͼ50%. * Rare cells only. DES ϭ desmin; MYO ϭ myoglobin; MYG ϭ myogenin; CALR ϭ calretinin; PLAP ϭ placental alkaline phosphatase. RESULTS The results of the immunohistochemical analysis on desmoplastic small round cell tumors were sum- marized on Table 2. In addition to a higher fre- quency of positivity than that of AE1/3, CAM5.2 immunoreactivity was always stronger (n ϭ 11) than or equal (n ϭ 5) to that of AE1/3 (Fig.
Load more

Recommended publications
  • 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]
  • 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]
  • Pediatric Sarcomas
    Pediatric Sarcomas a, b Regan F. Williams, MD *, Israel Fernandez-Pineda, MD , a Ankush Gosain, MD, PhD KEYWORDS Rhabdomyosarcoma Osteosarcoma Ewing’s sarcoma Nonrhabdomyosarcoma soft tissue sarcoma KEY POINTS Pediatric sarcomas are best treated with a multidisciplinary team to include surgery, radi- ation, and oncology. Rhabdomyosarcomas (RMS) often occur in young children, whereas nonrhabdomyosar- comas occur in infants and teenagers. All patients with RMS receive chemotherapy. Low-grade osteosarcomas and low risk nonrhabdomyosarcomas are treated with surgery alone. Pediatric sarcomas are a heterogeneous group of tumors and account for approxi- mately 10% of childhood solid tumors.1 Treatment is focused on multimodality ther- apy, which has improved the prognosis over the past 2 decades. Current regimens focus on decreasing treatment for low-risk patients to decrease the long-term side ef- fects of chemotherapy and radiation while maximizing therapy for patients with met- astatic disease in an attempt to improve survival. Pediatric sarcomas can be divided into soft tissue sarcomas and osseous tumors. Soft tissue sarcomas are further delineated into rhabdomyosarcoma (RMS), which affect young children and nonrhabdomyosarcoma, which are most common in adolescents. The most common bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). RHABDOMYOSARCOMA Epidemiology RMS is the most common soft tissue sarcoma in children and adolescents, accounting for nearly 250 cases of childhood cancer in the United States each year.2 RMS is a The authors have nothing to disclose. a Department of Surgery, University of Tennessee Health Science Center, 49 North Dunlap Avenue, Second Floor, Memphis, TN 38105, USA; b Department of Surgery, St Jude Children’s Research Hospital, MS133, Room B3019, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA * Corresponding author.
    [Show full text]
  • A Case of Dedifferentiated Leiomyosarcoma of the Uterus Kanae Nosaka1,2, Hiroaki Komatsu3, Tetsuro Oishi3, Yasushi Horie2, Tasuku Harada3 and Yoshihisa Umekita1*
    Nosaka et al. Int J Pathol Clin Res 2016, 2:049 Volume 2 | Issue 4 International Journal of ISSN: 2469-5807 Pathology and Clinical Research Case Report: Open Access A Case of Dedifferentiated Leiomyosarcoma of the Uterus Kanae Nosaka1,2, Hiroaki Komatsu3, Tetsuro Oishi3, Yasushi Horie2, Tasuku Harada3 and Yoshihisa Umekita1* 1Division of Organ Pathology, Department of Pathology, Tottori University, Japan 2Division of Anatomic Pathology, Tottori University Hospital, Japan 3Division of Reproductive - Perinatal Medicine and Gynecologic Oncology, Department of surgery, Tottori University, Japan *Corresponding author: Yoshihisa Umekita, MD, PhD, Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori 683-8503, Japan, E-mail: [email protected] Abstract Case Report Dedifferentiation of leiomyosarcoma is a rare phenomenon that Clinical history associates pleomorphic histology and loss of smooth muscle differentiation. Although the leiomyosarcoma is well known A 63-year-old multiparous female presented with bloody vaginal sarcoma in the uterus, and the dedifferentiated leiomyosarcoma discharge lasting for 2 months. She had no particular medical history is well recognized in the soft parts, there are only a few reports except for the uterine leioimyoma discovered 13 years before. Her of dedifferentiation of leiomyosarcoma in the uterus. Herein we cervical cytology was negative while endometrial cytology detected present a case of dedifferentiated uterine leiomyosarcoma and atypical cells. There was no elevation of tumor markers (CEA and discuss its relation to the undifferentiated uterine sarcoma. CA19-9) in her serum. Hysteroscopy revealed a smooth-surfaced Keywords massive tumor occupying the uterine cavity. Abdominal MRI revealed 7.7 × 9.4 × 12.4 cm of round mass in the anterior uterine Uterine leiomyosarcoma, Dedifferentiation, Undifferentiated uterine corpus.
    [Show full text]
  • Pathology and Genetics of Tumours of Soft Tissue and Bone
    bb5_1.qxd 13.9.2006 14:05 Page 3 World Health Organization Classification of Tumours WHO OMS International Agency for Research on Cancer (IARC) Pathology and Genetics of Tumours of Soft Tissue and Bone Edited by Christopher D.M. Fletcher K. Krishnan Unni Fredrik Mertens IARCPress Lyon, 2002 bb5_1.qxd 13.9.2006 14:05 Page 4 World Health Organization Classification of Tumours Series Editors Paul Kleihues, M.D. Leslie H. Sobin, M.D. Pathology and Genetics of Tumours of Soft Tissue and Bone Editors Christopher D.M. Fletcher, M.D. K. Krishnan Unni, M.D. Fredrik Mertens, M.D. Coordinating Editor Wojciech Biernat, M.D. Layout Lauren A. Hunter Illustrations Lauren A. Hunter Georges Mollon Printed by LIPS 69009 Lyon, France Publisher IARCPress International Agency for Research on Cancer (IARC) 69008 Lyon, France bb5_1.qxd 13.9.2006 14:05 Page 5 This volume was produced in collaboration with the International Academy of Pathology (IAP) The WHO Classification of Tumours of Soft Tissue and Bone presented in this book reflects the views of a Working Group that convened for an Editorial and Consensus Conference in Lyon, France, April 24-28, 2002. Members of the Working Group are indicated in the List of Contributors on page 369. bb5_1.qxd 22.9.2006 9:03 Page 6 Published by IARC Press, International Agency for Research on Cancer, 150 cours Albert Thomas, F-69008 Lyon, France © International Agency for Research on Cancer, 2002, reprinted 2006 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention.
    [Show full text]
  • Wilms Tumor, Medulloblastoma, and Rhabdomyosarcoma in Adult Patients: Lessons Learned from the Pediatric Experience
    Cancer and Metastasis Reviews (2019) 38:683–694 https://doi.org/10.1007/s10555-019-09831-3 Wilms tumor, medulloblastoma, and rhabdomyosarcoma in adult patients: lessons learned from the pediatric experience Filippo Spreafico1 & Andrea Ferrari1 & Maurizio Mascarin2 & Paola Collini3 & Carlo Morosi4 & Davide Biasoni5 & Veronica Biassoni1 & Elisabetta Schiavello1 & Lorenza Gandola 6 & Giovanna Gattuso1 & Stefano Chiaravalli1 & Maura Massimino1 Published online: 3 December 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Wilms tumor (or nephroblastoma), rhabdomyosarcoma, and medulloblastoma, common embryonal tumors in children, can occasionally occur in adults, for whom survival is significantly inferior than pediatric patients. Available data on adults with Wilms tumor consist of case or case series reports. Among other factors, the unfamiliarity of adult oncologists and pathologists with nephroblastoma and consequent delays in initiating the appropriate risk-adapted chemotherapy may negatively influence outcomes. The survival decrement in adults with rhabdomyosarcoma has been attributed to the lack of centralized care, the inconsistent use of standard protocol-driven multimodal therapy, and lower chemotherapy tolerance in adult patients. In children with medulloblastoma, evidence from randomized clinical trials has led to risk-tailored therapies tuned on histology, extent of initial disease, and biological features. Such refinements are still missing for adults due to the lack of similar trials and studies that might provide the same or a different understanding regarding patients’ individual prognosis, treatment morbidity, and quality of life. Recent experiences have suggested that applying or adjusting pediatric protocols to adult patients with these tumors is feasible and can improve survival. Here, we provide an evaluation of the current evidence for the management of Wilms tumor, rhabdomyosarcoma, and medulloblastoma arising in adults.
    [Show full text]
  • FAK Signaling in Rhabdomyosarcoma
    International Journal of Molecular Sciences Review FAK Signaling in Rhabdomyosarcoma 1,2, 1, 1, 3, Clara Perrone y , Silvia Pomella y , Matteo Cassandri y, Maria Rita Braghini z, 1,2, 1,4 1, Michele Pezzella z, Franco Locatelli and Rossella Rota * 1 Department of Oncohematology, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] (C.P.); [email protected] (S.P.); [email protected] (M.C.); [email protected] (M.P.); [email protected] (F.L.) 2 Department of Science, University of Rome ‘Roma Tre’, 00146 Rome, Italy 3 Molecular Genetics of Complex Phenotype Unit, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; [email protected] 4 Department of Pediatrics, Sapienza University of Rome, 00185 Rome, Italy * Correspondence: [email protected]; Tel.: +39-06-68592648 Equal contribution. y Equal contribution. z Received: 12 October 2020; Accepted: 8 November 2020; Published: 10 November 2020 Abstract: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges.
    [Show full text]
  • The Immunosuppressive Niche of Soft-Tissue Sarcomas Is Sustained
    Published OnlineFirst April 24, 2020; DOI: 10.1158/1078-0432.CCR-19-3416 CLINICAL CANCER RESEARCH | PRECISION MEDICINE AND IMAGING The Immunosuppressive Niche of Soft-Tissue Sarcomas is Sustained by Tumor-Associated Macrophages and Characterized by Intratumoral Tertiary Lymphoid Structures A C Lingling Chen1, Teniola Oke1, Nicholas Siegel2, Gady Cojocaru3, Ada J. Tam1, Richard L. Blosser1, Jessica Swailes1, John A. Ligon1, Andriana Lebid4, Carol Morris5, Adam Levin5, Daniel S. Rhee6, Fabian M. Johnston7, Jonathan B. Greer7, Christian F. Meyer8, Brian H. Ladle1, Elizabeth D. Thompson9, Elizabeth A. Montgomery10, Woonyoung Choi11, David J. McConkey12, Robert A. Anders13, Drew M. Pardoll4, and Nicolas J. Llosa1 ABSTRACT ◥ Purpose: Clinical trials with immune checkpoint inhibition in bution diverged. UPS specimens demonstrated diffuse intratumoral sarcomas have demonstrated minimal response. Here, we interro- infiltration of T cells, while rhabdomyosarcomas samples revealed gated the tumor microenvironment (TME) of two contrasting soft- intratumoral T cells that clustered with B cells near perivascular tissue sarcomas (STS), rhabdomyosarcomas and undifferentiated beds, forming tertiary lymphoid structures (TLS). T cells in UPS þ pleomorphic sarcomas (UPS), with differing genetic underpinnings specimens were comprised of abundant CD8 T cells exhibiting and responses to immune checkpoint inhibition to understand the high PD-1 expression, which might represent the tumor reactive mechanisms that lead to response. repertoire. In rhabdomyosarcomas, T cells were limited to TLS, but Experimental Design: Utilizing fresh and formalin-fixed, par- expressed immune checkpoints and immunomodulatory molecules affin-embedded tissue from patients diagnosed with UPS and which, if appropriately targeted, could help unleash T cells into the rhabdomyosarcomas, we dissected the TME by using IHC, flow rest of the tumor tissue.
    [Show full text]
  • Soft Tissue Sarcoma: an Insight on Biomarkers at Molecular, Metabolic and Cellular Level
    cancers Review Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level Serena Pillozzi 1,* , Andrea Bernini 2, Ilaria Palchetti 3 , Olivia Crociani 4, Lorenzo Antonuzzo 1,4, Domenico Campanacci 5 and Guido Scoccianti 6 1 Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; lorenzo.antonuzzo@unifi.it 2 Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; [email protected] 3 Department of Chemistry Ugo Schiff, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy; ilaria.palchetti@unifi.it 4 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; olivia.crociani@unifi.it 5 Department of Health Science, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; domenicoandrea.campanacci@unifi.it 6 Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; [email protected] * Correspondence: serena.pillozzi@unifi.it Simple Summary: Soft tissue sarcoma is a rare mesenchymal malignancy. Despite the advancements in the fields of radiology, pathology and surgery, these tumors often recur locally and/or with metastatic disease. STS is considered to be a diagnostic challenge due to the large variety of histologi- Citation: Pillozzi, S.; Bernini, A.; cal subtypes with clinical and histopathological characteristics which are not always distinct. One of Palchetti, I.; Crociani, O.; Antonuzzo, the important clinical problems is a lack of useful biomarkers. Therefore, the discovery of biomarkers L.; Campanacci, D.; Scoccianti, G. Soft that can be used to detect tumors or predict tumor response to chemotherapy or radiotherapy could Tissue Sarcoma: An Insight on help clinicians provide more effective clinical management.
    [Show full text]