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Ewing's Sarcoma and Primary Osseous Lymphoma

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Ewing's Sarcoma and Primary Osseous Lymphoma 36 Ewing’s Sarcoma and Primary Osseous Lymphoma: Spectrum of Imaging Appearances Marc-André Weber, MD, MSc1 Olympia Papakonstantinou, MD2 Violeta Vasilevska Nikodinovska, MD, PhD3 Filip M. Vanhoenacker, MD, PhD4 1 Institute of Diagnostic and Interventional Radiology, University Address for correspondence Marc-André Weber, MD, MSc, Institute Medical Center Rostock, Rostock, Germany of Diagnostic and Interventional Radiology, University Medical Center 2 Second Department of Radiology, National and Kapodistrian Rostock, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany University of Athens “Attikon” Hospital, Athens, Greece (e-mail: [email protected]). 3 Department of Radiology, University Surgical Clinic “St. Naum Ohridski,” University “Ss. Cyril and Methodius,” Skopje, Macedonia 4 Department of Radiology, AZ Sint-Maarten Mechelen, University Hospital Antwerp, Ghent University, Mechelen, Belgium Semin Musculoskelet Radiol 2019;23:36–57. Abstract Ewing’s sarcoma (ES) is a rare, highly malignant anaplastic stem cell tumor. Histolo- gically, the tumor consists of uniform densely packed small monomorphic cells with round nuclei. The typical appearance at hematoxylin and eosin (H&E) staining is small blue round cells without any matrix formation. On conventional radiography, ES typically presents as a permeative lesion in the diaphysis of a long bone in a child. A Keywords large soft tissue component is another characteristic feature, best depicted by ► Ewing’sSarcoma magnetic resonance imaging. ► primary osseous Primary osseous lymphomas are most commonly highly malignant B-cell lymphomas. lymphoma At H&E histologic staining, the tumor stroma consists of diffuse round-cell infiltrates ► radiography that resembles the appearance of ES. Although there is no typical imaging appearance ► magnetic resonance of an osseous lymphoma, it should be considered in an adult presenting with a Lodwick imaging grade II or III lesion in the metaphysis or diaphysis of a large long bone, the pelvis, or the ► review vertebral column. Histologic confirmation is mandatory. Ewing’sSarcoma population of 80 million. Boys are 1.5 to 2.4 times more often affected than girls.2 In children, ES is the second most Definition common primary malignant bone tumor after osteosarcoma. Ewing’s sarcoma (ES) is a rare, highly malignant anaplastic stem cell tumor of neuroectodermal origin, also classified as Clinical Manifestations round-cell sarcoma, to which the primitive neuroectodermal Symptoms consist of nonspecific, non–exercise-related pain tumors also belong. It mainly arises from the bone.1 in the area of the tumor and swelling. General symptoms This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. such as fever, fatigue, loss of appetite, and weight may appear Demography more frequently than in other malignant bone tumors.1 ES represents 7 to 10% of all malignant bone tumors and affects mainly children and adolescents. The mean age is Localization 15 years, and the age peak is 9 to 25 years. However, rarely ES mainly is localized in the long bones of the extremities and children and elderly people may be affected. In a series of 64 most commonly within the diaphysis close to the metaphysis. patients, patient ages ranged between 7 and 67 years.2 In The most commonly affected bone is thefemur (25%) (►Fig. 1), Germany, the annual incidence is 120 new cases in a general followed by the tibia (11%) (►Fig. 2), humerus (11%), andpelvic Issue Theme Bone and Soft Tissue Copyright © 2019 by Thieme Medical DOI https://doi.org/ Tumors; Guest Editors, Marc-André Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0038-1676125. Weber, MD, MSc and Radhesh Lalam, New York, NY 10001, USA. ISSN 1089-7860. MBBS, MRCS, FRCR Tel: +1(212) 584-4662. Ewing’s Sarcoma and Primary Osseous Lymphoma Weber et al. 37 Fig. 1 Extraskeletal Ewing’ssarcomaina26-year-oldman.(a) Anteroposterior projection and (b) lateral projection radiographs performed after a swelling and increasing painfulness of his right thigh that he had observed for 5 days. No bony erosion is visible, but an increased opacification of the quadriceps femoris muscle is observed. (c, d) MRI axial T2-weighted fat-saturated sequences demonstrate the large soft tissue tumor predominantly within the vastus intermedius muscle. The patient was included in the EURO-EWING 2008 study. bones (11%) (►Fig. 3).1 Other localizations are the fibula (7%) blue round cells without any matrix formation (►Fig. 2). At (►Figs. 4 and 5)andribs(6%)(►Fig. 5). ES can virtually involve immunostaining, an expression of the cellular surface anti- all bones of the body and may also involve extraskeletal sites gen CD99, a product of the MIC-2 gene, is characteristic. The (►Fig. 1). An isolated involvement of the soft tissue (extra- characteristic reciprocal translocation between chromo- skeletal ES) was observed in 1.5% of all cases in a series of 64 some 11 and 22 (t[11;22]), which affects in 85% the EWS patients.2 Compared with osteosarcoma, flat bones are more and FLI1 gene, can be confirmed by using break- apart often affected in ES. Rarely, a bicentric ES or synchronous fluorescence in situ hybridization (►Fig. 2).1,6,7 involvement of multiple bones may be seen (►Fig. 6), whereas transarticular spread can rarely be seen in sacroiliac joints.3 Up Imaging This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. to 15% of all ES cases are localized in the vertebral column, with Conventional radiography (CR) reveals an aggressive osteolytic the lumbar spine and the sacrum as the most commonly lesion with a wide zone of transition and with a moth-eaten or affected; the location of ES tends to follow the distribution permeative pattern in most cases.8 In a series of 64 patients, of red marrow. The mean age at initial clinical presentation is most tumors were mixed lytic-sclerotic (in 75%) and purely 19.3 years, slightly higher than the mean age of ES of the lytic in 25%.2 Complex periosteal reactions like onion-skinned, extremity bones.4 Metastases of ES affecting the vertebral spiculae, “sunburst,” or Codman’s triangle can be seen column are more common than a primary ES of the spine.5 (►Fig. 5) in 27 to 50% of all cases.2 Onion-skinned or multi- lamellated periosteal reactions may be encountered in 25% of Pathology cases. Computed tomography (CT) is more sensitive than CR to Macroscopically, the tumor has the aspect of fish flesh. At detect bony destruction in anatomically complex regions such histology, the tumor consists of uniform densely packed as the vertebral column and the pelvic bones due to the lack of small monomorphic cells with round nuclei that are gen- superimposition. In flat bones such as the pelvic bones, ES may erally larger than in primary osseous lymphoma. The typical have a predominantly sclerotic appearance (►Fig. 3)that appearance at hematoxylin and eosin (H&E) staining is small overall represents 10% of cases. The reason for the sclerotic Seminars in Musculoskeletal Radiology Vol. 23 No. 1/2019 38 Ewing’s Sarcoma and Primary Osseous Lymphoma Weber et al. appearance is mainly necrotic bony changes because tumor- extension (►Figs. 4, 5, 6, 7). The MRI protocol has to cover related formation of new bone is not a histologic feature of ES.1 the entire tumor extent as well as the adjacent joints and the Magnetic resonance imaging (MRI) is the method of choice entire bone where the tumor originates because skip lesions for local staging because it demonstrates the true tumor (►Fig. 5), which when present have great influence on the This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Fig. 2 Predominantly extraosseous Ewing’s sarcoma (ES) with histopathologic correlation in a 25-year-old woman. (a) MRI axial T2-weighted fat-saturated sequence and (b) sagittal T2-weighted sequence illustrate the infiltration of the dorsal tibia (arrows) and the large soft tissue mass ventral to the Achilles tendon. (c) Hematoxylin and eosin (H&E) staining demonstrates monomorphous cells with a relatively small eosinophilic cytoplasm. (d, e) The H&E-stained section with a lesser magnification demonstrates that ES stroma consist mainly of infiltrates of small round blue cells with small amounts of relatively cell-poor connective tissue (asterisk). (f) The slightly higher magnification better illustrates the monomorphous small round blue cells typical of ES in hematoxylin-eosin staining. (g) The MIB-1 immunostaining of Ki-67 illustrates mitotic activity of 20%. (h) There was a homogeneous and strong membranous expression of CD99, a p30/32 surface antigen, in the CD99 immunostaining. (i) The diagnosis of ES could be confirmed by using break-apart EWS fluorescence in situ hybridization analysis with the EWS gene locus encompassing DNA probes combination. Tumor cell nuclei show besides an orthologous fused another dislocated hybridization pair (arrow) confirming the translocation t(11;22) of the EWS gene locus. Seminars in Musculoskeletal Radiology Vol. 23 No. 1/2019 Ewing’s Sarcoma and Primary Osseous Lymphoma Weber et al. 39 Fig. 2 (Continued) This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Fig. 3 Predominantly sclerotic Ewing’s sarcoma (ES) of the right os ilium (arrows) in a 26-year-old woman that was subsequently treated by polychemotherapy and radiotherapy. Computed tomography in (a)axialand(b) coronal plane. (c) MRI using a coronal T1-weighted and (d)an axial T2-weighted sequence. These predominantly sclerotic types of ES are not uncommon within the pelvis. treatment planning, are frequent. Skip metastases at initial eous and extraosseous components (►Figs. 5, 6, 7). This presentation were present in 14% of all cases in a series of 64 continuity is also commonly seen as subtle channels extending patients.2 The signal intensity of the tumor tissue of the ES is through the cortex at MRI, a finding that reflects the under- hypointense on T1-weighted images and hyperintense on T2- lying pathologic appearance8 because the communication weighted images.
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