The role of Imaging in Ewing sarcoma

Transcription

1 The role of Imaging in Ewing sarcoma Poster No.: P-0109 Congress: ESSR 2014 Type: Educational Poster Authors: D. Beomonte Zobel, C. Dell'atti, M. Bartocci, V. Martinelli, N Magarelli, L. Bonomo ; Roma/IT, Rome/IT Keywords: Education and training, Efficacy studies, PET, MR-Diffusion/ Perfusion, Conventional radiography, Oncology, Musculoskeletal bone, Bones DOI: /essr2014/P-0109 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 17

2 Learning objectives To describe the role of Imaging in diagnosis, staging, treatment, monitoring and surveillance of Ewing sarcomas, a tumor first described by James Ewing in Background The Ewing sarcoma family of tumors represents a group of high-grade, small blue round cell tumors, including Ewing sarcoma of bone, extraskeletal Ewing sarcoma, peripheral primitive neuroectodermal tumor (PNET) and Askin tumor (Thoracopulmonary PNET) [1]. Originally, it was thought that this tumors was derived from primitive neuroectodermal cells; substantial research indicate that mesenchymal stem cells may be the original progenitor of Ewing tumor proliferation and Ewing tumors most often harbor nonrandom balanced chromosomal translocation. The most common translocation involves chromosomes 11 and 22 [2]. Ewing sarcoma of bone represents the second most common primary malignant tumor of bone in children and adolescents, exceeded in prevalence only by osteosarcoma. Overall, it is the fourth most frequent primary malignant tumor of bone after multiple myeloma, osteosarcoma, and chondrosarcoma. Ewing sarcoma is most frequent in the first 3 decades of life, with 95% of cases reported between the ages of 4 and 25 years [3]. In contrast, half or more of primary adult cases are extraskeletal [4]. The annual incidence of Ewing sarcoma, in the United States, is 200 cases, with a rate of one to three cases per 1 million inhabitants (Fig. 1) [3], with a peak prevalence between the ages of 10 and 15 years (Fig. 2) [5]. The clinical presentation of Ewing sarcoma is nonspecific, with local pain in the affected sites (Fig. 3) [3, 5], often erroneously attributed to trauma or to bone development, followed by a mass or swelling and, seldom, by fever, malaise and increased erythrocyte sedimentation rate. Symptoms are often present for more than 6 months before diagnosis. Between 20% and 25% of the patients have already metastatic disease (10% lung, 10% bones/bone marrow, 5% combination or others site) at the time of diagnosis [2]. Images for this section: Page 2 of 17

3 Fig. 1: See text. Page 3 of 17

4 Fig. 2: See text. Page 4 of 17

5 Fig. 3: See text. Page 5 of 17

6 Imaging findings OR Procedure Details The radiographic osseous appearance of Ewing sarcoma reveals aggressive features, reflecting the high-grade nature of this malignant lesion. Ewing sarcoma is characterized by bone destruction with a moth-eaten to permeative pattern in 76%-82% of lesions, and a wide zone of transition (poor margination) in 96% of lesions [3]. Cortical destruction (19%-42%) with an associated soft-tissue mass (56%-80%) is also common [3]. Periosteal reaction is frequent (58%-84%) and usually aggressive in appearance (94%), either lamellated (onionskin) or spiculated (sunburst or hair-on-end) [3]. Sclerotic components are seen in 32%-40% of cases. [3]. Less common radiographic features of Ewing sarcoma of bone include cortical thickening, pathologic fracture, and expansile bone remodeling. The major differential diagnoses to be considered on the basis of the plain radiographic findings in Ewing sarcoma are osteomyelitis,osteosarcoma and lymphoma of bone. Long tubular bone involvement is more common proximally than distally. While a diaphyseal location of osseous Ewing sarcoma is often emphasized, the majority of long-bone lesions are actually meta-diaphyseal (44%-59%). Diaphyseal lesions account for 33%-35% of cases, while a Ewing sarcoma confined to the metaphysis represents 5%-15% of lesions. Epiphyseal extension may be seen in up to 10% of cases, although lesions centered in the epiphysis are rare (0.5%-2%). The most common affected sites are the femur, ilium, tibia, humerus, fibula, ribs and sacrum (Fig. 4a, b). Other less frequently involved skeletal locations include mobile portion of the spine, scapula, hand or foot, radius or ulna, mandible or maxilla, sternum, calvaria, facial bones and clavicle (Fig. 5). Computed Tomography (CT) and FDG-PET are useful for staging, to be more precise CT is performed to evaluate pulmonary and bone metastases (Fig. 6), FDG-PET is superior to bone scintigraphy in detecting osseous metastases (sensitivity 88% vs 37%)[6] (Fig. 7a,b,c)and in primary bone sarcomas in general (18% not evident at bone scintigraphy in comparison with FDG-PET)[6, 7]. The appearance of Ewing sarcoma at CT is similar to that at radiography, with aggressive bone destruction and a large associated soft- tissue mass (96% of cases). The soft-tissue component is commonly homogeneous and similar in attenuation to that of muscle (98% of cases). The soft- tissue mass is frequently circumferential but asymmetric considering the osseous involvement. Large areas of focal cortical destruction and continuity between the intraosseous and soft- tissue components are common (53% of cases) (Fig. 8a,b). Page 6 of 17

7 However, subtle cortical involvement, which allows communication between the intraosseous and soft-tissue components, appears as low-attenuation linear channels extending through the high-attenuation cortex, and represents tumor extending along neurovascular channels and haversian canals, is also common. In 17% of cases, the cortex appears intact at CT without apparent connection between the medullary canal and soft- tissue components [3]. Owing to its superior contrast resolution, Magnetic Resonance imaging (MR) is the optimal imaging modality in evaluation of bone and soft-tissue tumors, including Ewing sarcoma. MR evaluate the extent of primary tumor, the efficacy of neoadjuvant chemotherapy and is extremely helpful in the surgical planning [8, 9]. MR imaging of Ewing sarcoma of bone reveals marrow replacement (100%) and cortical destruction (92%), with an associated soft-tissue mass in 96% of cases. The signal intensity is usually homogeneous (73%) and intermediate (95%) on T1-weighted images. On T2-weighted images, Ewing sarcoma is typically homogeneous (86%) and low to intermediate in signal intensity (68%)(Fig. 9a,b). High signal intensity predominates in 32% of Ewing sarcomas of bone on T2-weighted images[3].this signal intensity and homogeneity are likely related to the high degree of cellularity in Ewing sarcoma. Heterogeneity is more common in larger lesions and represent areas of hemorrhage or necrosis[3, 8, 9].Fluid levels may also be seen as a result of hemorrhage, although this is more common after treatment. Contrast enhancement is seen in all cases at MR imaging of Ewing sarcoma and is usually either diffuse or peripheral nodular in pattern(fig. 10). Diffusion technique showed, by the ADC, a good ability to distinguish malignancies, such as Ewing sarcoma, from benign lesions, such as osteomyelitis [10]. Only for skeletal metastases, the whole-body MRI showed a higher diagnostic accuracy than bone scintigraphy [11]. The biopsy, better if surgical, is mandatory to obtain a definitive diagnosis. Neoadjuvant chemotherapy is the standard of care, before a large surgical resection, with or without a radiation treatment. MRI helps in evaluating patients undergoing surgical resection and guides the preoperative planning. Factors that should be considered to determine whether surgery can be performed for local control are primarily those related to lesion staging. These include: patient age; tumor location; tumor extent, size, and volume; involvement of vital soft tissues; relationship to the neurovascular bundle and whether the tumor can be removed Page 7 of 17

8 completely with acceptable margins, particularly in expendable and reconstructable locations. Advances techniques, that preserve or restore limb function (limb salvage techniques) is now the preferred surgical treatment for Ewing sarcoma, as opposed to amputation, which was commonly employed in the past. Dynamic-diffusion MRI with PET are used to monitor the treatment and for the surveillance (Fig. 11a,b,c; Fig. 12a,b). Common findings that are associated with a favorable response to therapy of osseous Ewing sarcoma are: the reduction in size of the neoplasm, the reduction of the signal in T2 "weighted" images, the presence of a ring at low signal intensity around the lesion, the increase of the necrotic areas (> 90%) [8, 9].The dynamic MRI identifies areas of still viable tumor, which show a steeper slope in the time / intensity curve. In 30%-40% of cases, patients experience a recurrence of the tumor, local or at distance, and the prognosis become poor[2]. Images for this section: Fig. 4: a) Pelvis radiograph: mainly sclerotic lesion (arrow) involving left iliac bone in a 31 years old man. b) Femur radiograph: mainly high density lesion in the left femur (green arrow) with an associated malignant periosteal reaction (red arrow) in another 31 years old man. Page 8 of 17

9 Fig. 5: Ewing sarcoma of right clavicle in a 54 years old man. Fig 5a Lytic lesion in proximal meta-epiphysial location. Fig. 5b CT shows irregular sclerosis of a part of the cortical bone with a solid surrounding mass (red arrow). Fig. 5c MR T1 «weighted» image demonstrates neoplastic components both inside (green arrow) and outside the bone (red arrow). Fig 5d The right clavicle after the surgical removal. Note part of the extraosseus component of the tumor (red arrow). Fig. 6: Multiple lung metastases in a 31 years old man with Ewing sarcoma of left iliac wing. Page 9 of 17

10 Fig. 7: Ewing sarcoma of right iliac wing. FDG CT-PET shows increased uptake in the right iliac wing: Fig. 7a PET image Fig. 7b CT-PET images in axial and coronal views Fig. 10c CT images in axial and coronal views. Page 10 of 17

11 Fig. 8: Ewing sarcoma of the superior ramus of the right pubis. Fig. 8a CT shows irregular cortical bone with a mass in the soft tissues of pelvis (asterisk). Fig. 8b Follow-up after chemotherapy with a clear progression of the disease. Page 11 of 17

12 Fig. 9: Ewing sarcoma of the proximal meta-epiphysial region of right femur in a 15 years old girl. MRI images Fig. 9a T1 «weighted» coronal scan demonstrates the extension of extraosseus component (arrow) and the permeative aspect of the cortical bone in the neck region;fig. 9b T2 «weighted» fat sat axial scan shows the tumor infiltrating all the surrounding muscles in anterior, medial and posterior compartments with a hypointense disomogeneous signal. Page 12 of 17

13 Fig. 10: Same patients as figure 9 Ewing sarcoma of the proximal meta-epiphysial region of right femur in a 15 years old girl. T1 «weighted» fat sat post-contrast scan allows the real evaluation of the extraosseus infiltration of the neoplasm. Page 13 of 17

14 Fig. 11: Post treatment L4 recurrence of a left iliac wing Ewing sarcoma. MR sagittal scans. Fig. 11a T1 «weighted»;fig. 11b T2 «weighted»; Fig. 11c Fat sat post-contrast T1 «weighted». Page 14 of 17

15 Fig. 12: Same patient as figure 11. Post treatment L4 recurrence of a left iliac wing Ewing sarcoma. Fig 12a CT PET axial images, Fig 12b PET images. Page 15 of 17

16 Conclusion Imaging studies play a vital role for diagnosis, staging and follow-up of Ewing sarcoma patients, that gain a five year survival rate, in localized disease, of %. In presence of bone metastases, the outcome is poorer, with a five year survival rate of less than 20 %. References 1) Ross K. A., Smyth N. A., Murawski C. D., Kennedy J. G. "The biology of Ewing Sarcoma" ISRN Oncology, ID , Epub ) Paulussen M., Bielack S., Jurgens H, Casali P. G. "Ewing's sarcoma of the bone: ESMO clinical recommendations for diagnosis, treatment and follow-up" Annals of Oncology, 20 (4), iv140-iv142, ) Murphey M. D., Senchak L. T., Mambalam P.K. et al. "From the Radiologic Pathology archives: Ewing sarcoma family of tumors: radiologic-pathologic correlation" Radiographics, 33 (3), , ) Javery O., Krajewski K., O'Regan K. et al. "A to Z of extraskeletal Ewing sarcoma family of tumors in adults: imaging features of primary disease, metastatic patterns and treatment responses" AJR, 197, w1015-w1022, ) Var der Woude H. J. e Smithuis R Bone tumor-systematic approach and differential diagnosis; Bone tumors and tumor-like lesions in alphabetic order, 2010 e ) Bestic J. M., Peterson J. J., Bancroft L. W. "Use of FDG-PET in staging, restaging and assessment of therapy response in Ewing sarcoma" Radiographics, 29, , ) Treglia G., Salsano M., Stefanelli A. et al. "Diagnostic accuracy of ¹#F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumors: a systematic review and a metaanalysis" Skeletal Radiology, 41(3), , ) Dyke J. P., Panicek D. M., Healey J. H. et al. "Osteogenic and Ewing sarcomas: estimation of necrotic fraction during induction chemotherapy with dynamic contrast enhanced MR Imaging" Radiology, 228, , ) Neubauer H., Evangelista L., Hassold N. et al. "Diffusion-weighted MRI for detection and differentiation of musculoskeletal tumorous and tumor-like lesions in pediatric patients" World Journal of Pediatrics, doi /s , Epub 2012 Page 16 of 17

17 10) Henninger B., Glodny B., Rudisch A. et al. "Ewing sarcoma versus osteomyelitis: differential diagnosis with magnetic resonance imaging" Skeletal Radiology, doi: / s , Epub ) Siegel J. M., Acharyya S., Hoffer F. A. et al."whole-body MR Imaging for Staging of Malignant Tumors in Pediatric Patients: Results of the American College of Radiology Imaging Network 6660 Trial" Radiology, 266, 2, , 2013 Personal Information Daniela Beomonte Zobel Diagnostic Radiology Department "A.Gemelli" Hospital Chatholic University,Rome Italy Page 17 of 17