M. Beth McCarville 1,2, Sheri L. Spunt 3,4, Stephen X. Skapek 3,4, Alberto S. Pappo 3 5
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1 Downloaded from by on 12/04/17 from IP address Copyright RRS. For personal use only; all rights reserved Synovial Sarcoma in Pediatric Patients M. eth McCarville 1,2, Sheri L. Spunt 3,4, Stephen X. Skapek 3,4, lberto S. Pappo 3 5 lthough rare, synovial sarcoma is the most common malignant nonrhabdomyosarcomatous soft-tissue sarcoma in children and adolescents. Despite its name, synovial sarcoma does not appear to arise from the synovial membrane but rather from primitive mesenchymal cells. Synovial sarcoma has been classically described as occurring in the soft tissues of the extremities, especially near large joints, but it can occur anywhere in the body in locations distant from joint spaces. lthough this tumor typically affects adults in their fourth decade of life, nearly half the reported cases have occurred in children and adolescents [1]. Since 1964, 59 patients from 2 to 22 Received January 21, 2002; accepted after revision February 28, Supported in part by grant C from the National Institutes of Health and by the merican Lebanese Syrian ssociated Charities. Pictorial Essay years old (median, 12.7 years) have been treated at our institution for synovial sarcoma that arose in the following sites: lower extremity (n = 35), upper extremity (n = 11), head and neck (n = 4), groin (n = 2), pelvis (n = 2), and other sites (n = 5). The purpose of this article is to illustrate the common and uncommon presentations of this rare child- Fig year-old boy with synovial sarcoma who presented with palpable pelvic mass., nteroposterior radiograph shows extensively calcified large pelvic mass. Calcifications are seen in approximately one third of all synovial sarcomas., Contrast-enhanced axial CT scan of pelvis shows unusual primary location of synovial sarcoma (arrows). Mixed cystic and solid appearance of tumor is common in synovial sarcoma and may be due to hemorrhage, necrosis, or both. = bladder. 1 Department of Diagnostic Imaging, Mail Stop 210, St. Jude Children s Research Hospital, 332 N. Lauderdale St., Memphis, TN ddress correspondence to M.. McCarville. 2 Department of Radiology, College of Medicine, The University of Tennessee Health Science Center, 800 Madison ve., Memphis, TN Department of Hematology Oncology, St. Jude Children s Research Hospital, Memphis, TN Department of Pediatrics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN Present address: Department of Hematology Oncology, The Hospital for Sick Children, 555 University ve., Toronto, Ontario M5G 1X8, Canada. JR 2002; 179: X/02/ merican Roentgen Ray Society JR:179, September
2 McCarville et al. hood malignancy and to review the clinical features and treatment of this tumor in the pediatric population. Downloaded from by on 12/04/17 from IP address Copyright RRS. For personal use only; all rights reserved Imaging Features pproximately 30% of synovial sarcomas contain calcifications that may be apparent on radiographs or CT scans [2] (Fig. 1). MR imaging is the modality of choice in evaluating synovial sarcoma because it provides greater contrast between tumor and normal tissue, can reveal neurovascular and lymph node involvement, and has multiplanar capabilities. On MR images, synovial sarcomas tend to be sharply Fig year-old boy with synovial sarcoma in left popliteal space. Sagittal proton density weighted MR image (TR/TE, 3000/17) shows 4-cm well-defined cystic soft-tissue mass (M) adjacent to semimembranous tendon (arrows) of left knee. Most synovial sarcomas, like one shown here, arise near large joints in lower extremity and involve tendon sheaths, bursae, or joint capsules. ecause masses are often well defined and frequently have cystic appearance, synovial sarcoma is malignant lesion most commonly misdiagnosed as benign on MR imaging. marginated tumors that may appear to be largely cystic (Fig. 2). Synovial sarcoma may be misdiagnosed as a hematoma, ganglion cyst, aker s cyst, or other benign cystic mass. In a review of the MR imaging features of 34 synovial sarcomas, Jones et al. [3] reported triple signal intensity on T2-weighted images in 35% of patients. This pattern consisted of mixtures of high signal intensity similar to that of fluid, intermediate signal intensity that was iso- or slightly hyperintense to fat, and slightly lower signal intensity that resembled fibrous tissue. They also found that fluid fluid levels were present in 18% of patients and that tumors smaller than 5 cm in diameter had homogeneously low signal intensity on T1-weighted images and marked heterogeneity on T2weighted images. Further, Morton et al. [4] described a heterogenous, multiloculated appearance with various degrees of internal septations, with or without fluid fluid levels (Fig. 3). Jones et al. reported that 71% of synovial sarcomas were intimately related to bone, with 50% abutting bone and 21% showing cortical thinning or medullary invasion (Fig. 4). Clinical ehavior lthough 85% of synovial sarcomas arise in the extremities, sites in the head, neck, and trunk can be involved [1, 5] (Figs. 5 8). Nonetheless, most lesions are extremity tumors that are paraarticular in location and Fig year-old girl with synovial sarcoma originating near right hip., Contrast-enhanced T1-weighted axial MR image (TR/TE, 710/15) shows inhomogeneously enhancing mass (arrows) adjacent to right hip. Many synovial sarcomas, like this one, appear as heterogenous multiloculated masses with internal septations and may contain fluid fluid levels. Note well-defined margins of mass, characteristic of synovial sarcoma seen on MR images., Contrast-enhanced axial CT scan of upper abdomen obtained 6 years after original diagnosis shows recurrent synovial sarcoma (arrows) in massively enlarged and necrotic retroperitoneal nodes. Regional nodal spread is not unusual in synovial sarcoma; however, in this patient no other nodes were involved between primary site (right hip) and upper retroperitoneum. Case illustrates unpredictable nature of malignancy. 798 JR:179, September 2002
3 Downloaded from by on 12/04/17 from IP address Copyright RRS. For personal use only; all rights reserved Synovial Sarcoma in Pediatric Patients may arise from tendon sheaths, bursae, or joint capsules but seldom involve the articular surface [1]. The most common presenting symptom is a painless mass that has been present for several weeks to years in the soft tissues of the lower extremity [1]. Four other patterns of presentation also exist: a pretumor phase of pain and tenderness without a mass, acute arthritis or bursitis, a chronic contracture, and a tumor noted after an episode of trauma [1]. Synovial sarcoma most commonly metastasizes to the lung (74 81%), lymph nodes (12 23%), and bone (10 20%) [2]. Chest CT is used to detect pulmonary metastases, and 99m Tc-labeled methyl diphosphonate nuclear bone scanning is used to detect bony metastatic disease. MR imaging is useful in assessing regional lymphadenopathy. Pathology and Molecular iology Synovial sarcoma occurs in two histologic subtypes: the biphasic type containing epithelial and spindle cell elements and the monophasic type containing only spindle cells [1]. Much insight into the molecular biology of synovial sarcoma has come from cytogenetic studies [6]. Synovial sarcoma cells are characterized by the presence of a translocation involving chromosomes X and 18 [t(x,18) (p11,q11)]. Molecular genetic studies have shown that this translocation fuses two normal genes, SYT and SSX1 (or the related SSX2) to create an abnormal fusion protein. The mechanism by which the SYT SSX fusion protein confers malignant potential to the cells is unknown. Recently, retrospective studies have shown that the presence of the SYT SSX1 fusion transcript is correlated with biphasic histology, a higher proliferative rate, and a shortened metastasis-free survival [6]. Prognostic Features Patients with localized synovial sarcoma have a good prognosis and most become long-term survivors. In contrast, those who have metastatic disease have a dismal outlook and only a minority survive. The prognostic features most frequently associated Fig year-old girl with metastatic synovial sarcoma., Coronal T1-weighted MR image (TR/TE, 500/9.9) of left knee shows soft-tissue mass (arrows) interposed between cortex of distal left femur and iliotibial tract. In one series, 50% of synovial sarcomas abutted bone, and 21% caused cortical thinning or showed medullary invasion [3]., Coronal short tau inversion recovery MR image (3825/30; flip angle, 140 ) obtained after surgical resection and radiotherapy of primary tumor shows genu valgus deformity caused by effects of therapeutic radiation. lthough radiation therapy provides excellent local control of microscopic residual disease, it may result in substantial growth disturbance when applied near physeal plate of growing bone. Note also bright signal in bones of knee, likely due to radiation-induced ischemia, osteonecrosis, or both. C, 99m Tc-labeled methyl diphosphonate nuclear bone scan of skull shows metastatic focus involving left frontal bone (arrow). Synovial sarcoma metastasizes to bone in 10 20% of cases. C JR:179, September
4 Downloaded from by on 12/04/17 from IP address Copyright RRS. For personal use only; all rights reserved McCarville et al. with an unfavorable outcome include tumor size greater than 5 cm, invasion into bone or neurovascular structures, and high histologic grade [7, 8]. Older age, nonextremity primary site, and the biphasic histologic pattern have also been associated with a less favorable outcome. Treatment The optimal approach to the treatment of synovial sarcoma remains undefined because no prospective clinical trials have compared differing therapeutic approaches [7, 8]. Complete surgical resection of the primary tumor is the mainstay of treatment. djuvant radiotherapy to treat microscopic residual disease after surgery provides excellent local control and obviates amputation for most patients with extremity tumors. The role of adjuvant chemotherapy remains controversial, and the small number of randomized prospective tri- Fig year-old boy with synovial sarcoma who presented with vomiting and dull chest pain. Contrast-enhanced axial CT scan of chest shows huge, predominantly cystic mass (M) arising from mediastinum that proved to be synovial sarcoma at biopsy. Cystic and septate appearance of tumor is common for synovial sarcoma. als complicates interpretation of results. Most regimens that have shown activity in patients with measurable disease include doxorubicin used with or without an alkylating agent (cyclophosphamide or ifosfamide). Despite the chemosensitivity of synovial sarcoma, some series have failed to show a significant improvement in survival with the addition of chemotherapy. Chemotherapy is probably beneficial only for those with high-risk fea- Fig year-old boy with synovial sarcoma who presented with right pneumothorax. Preoperative contrast-enhanced axial CT scan of chest shows right pleural thickening or fluid (arrows). fter unsuccessful treatment of right pneumothorax with thoracostomy tube placement, patient underwent parietal pleurectomy that revealed synovial sarcoma originating from pleura. Case shows that tumor may arise nearly anywhere in body. Fig year-old boy with synovial sarcoma of right cheek., Photograph shows patient with protuberant mass in right face (arrows)., T2-weighted axial MR image (TR/TE, 3500/120) shows well-circumscribed cystic mass (arrows) with internal septations, abutting right maxilla. Cheek is unusual primary location. Synovial sarcoma has also been reported to occur in infratemporal fossa, external temporal fossa, posterior neck, parotid region, tongue, and other parts of neck. 800 JR:179, September 2002
5 Synovial Sarcoma in Pediatric Patients Downloaded from by on 12/04/17 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old girl with synovial sarcoma who presented with neck pain., Contrast-enhanced T1-weighted axial MR image (TR/TE, 975/20) shows soft-tissue mass (arrows) in right prevertebral space obtained at level of first cervical vertebra. In neck, synovial sarcoma has predilection for prevertebral soft tissues, as in this patient., Unenhanced axial CT scan of upper neck shows destruction (arrow) of right anterior arch of first cervical vertebra, which was not evident on MR image. lthough most synovial sarcomas have well-defined margins on MR imaging, they may invade bone, as shown here. tures of distant disease recurrence, such as large tumor size, invasiveness, and high histologic grade. Prospective clinical trials to evaluate the benefit of adjuvant chemotherapy in the treatment of synovial sarcoma are needed. Conclusion fter rhabdomyosarcoma, synovial sarcoma is the most common soft-tissue sarcoma in children. The tumor does not appear to arise from the synovium and has the potential to develop almost anywhere in the body. It is characterized by a consistent molecular genetic abnormality that offers insight into its biology. Prognosis is good when the tumor is smaller than 5 cm, noninvasive, and of low or intermediate histologic grade. References 1. Coffin CM. Synovial-based tumors and synovial sarcoma. In: Coffin CM, O Shea P, Dehner LP, eds. Pediatric soft tissue tumors: a clinical, pathological, and therapeutic approach, 1st ed. altimore: Williams & Wilkins, 1997: Cadman NL, Soule EH, Kelly PJ. Synovial sarcoma: an analysis of 134 tumors. Cancer 1965;18: Jones C, Sundaram M, Karansdorf MJ. Synovial sarcoma: MR imaging findings in 34 patients. JR 1993;161: Morton MJ, erquist TH, McLeod R, Unni KK, Sim FH. MR imaging of synovial sarcoma. JR 1991;156: Hirsch RJ, Yousem DM, Loevner L, et al. Synovial sarcomas of the head and neck: MR findings. JR 1997;169: Skapek SX, Chui CH. Cytogenetics and the biological basis of sarcomas. Curr Opin Oncol 2000;12: Miser JS, Triche TJ, Kinsella TJ, Pritchard DJ. Other soft tissue sarcomas of childhood. In: Pizzo P, Poplack DG, eds. Principles and practice of pediatric oncology, 3rd ed. Philadelphia: Lippincott-Raven, 1997: rennan MF, lektiar KM, Maki RG. Sarcomas of the soft tissues and bones. In: DeVita VT Jr, Hellman S, Rosenberg S, eds. Cancer: principles and practice of oncology, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001: JR:179, September
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