Synovial Sarcoma: Imaging Features of Common and Uncommon Primary Sites, Metastatic Patterns, and Treatment Response
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1 Musculoskeletal Imaging Pictorial Essay akri et al. Synovial Sarcoma Musculoskeletal Imaging Pictorial Essay mit akri 1,2 tul. Shinagare 1 Katherine M. Krajewski 1 Stephanie. Howard 1 Jyothi P. Jagannathan 1 Jason L. Hornick 3 Nikhil H. Ramaiya 1 akri, Shinagare, Krajewski KM, et al. Keywords: CT, MRI, PET/CT, synovial sarcoma DOI: /JR Received October 7, 2011; accepted after revision November 18, Department of Imaging, Dana-Farber Cancer Institute, 450 rookline ve, oston, M ddress correspondence to.. Shinagare (ashinagare@partners.org). 2 Department of Radiology, righam and Women s Hospital, oston, M. 3 Department of Pathology, righam and Women s Hospital, Harvard Medical School, oston, M. WE This is a Web exclusive article. JR 2012; 199:W208 W X/12/1992 W208 merican Roentgen Ray Society Synovial Sarcoma: Imaging Features of Common and Uncommon Primary Sites, Metastatic Patterns, and Treatment Response OJECTIVE. The purpose of this review is to describe the imaging features, common and uncommon sites, metastatic pattern, and treatment response of synovial sarcoma. CONCLUSION. Synovial sarcoma primarily occurs in young adults, most commonly in the lower extremities; presents as a large, noninfiltrative, well-circumscribed mass adjacent to joints, often with punctuate calcifications; and may exhibit a triple signal pattern on T2- weighted images. Small synovial sarcomas can mimic benign lesions. This tumor has a propensity for late local recurrence and metastasis, most commonly to lung. S ynovial sarcoma is the third most common soft-tissue sarcoma in adults, accounting for approximately 10% of soft-tissue sarcomas [1]. Men and women are affected equally, and the mean age at presentation is 32 years [2]. lthough most synovial sarcomas occur in the extremities commonly the lower extremities rare cases originate in the head and neck, thorax, and abdomen [2 5]. Patients present with a palpable, slowly growing, sometimes painful mass. ecause of the insidious onset, there is often a delay in diagnosis. In one study [1], the mean duration of symptoms before the patients sought medical attention was 2.5 years. Lesion size at diagnosis is variable, largely depending on the location. lthough most tumors are larger than 5 cm, peripheral lesions are usually smaller, attributed to earlier discovery, often leading to diagnostic confusion with benign lesions [2, 4, 6]. lthough as many as 50% of synovial sarcomas recur locally within 2 years, late local recurrences and metastasis more than 5 years after initial diagnosis are common, potentially requiring longer follow-up [7]. Various prognostic factors have been reported, including patient age, tumor grade, and histologic subtype, but only tumor size larger than 5 cm is consistently associated with a poor outcome [7]. lthough the name arose owing to resemblance to synovium, synovial sarcoma is thought to originate from primitive (uncommitted) mesenchymal cells that undergo differentiation to resemble synovial cells. Three main histologic variants are described: a classic biphasic type consisting of spindle cells and epithelial cells (usually forming glandular structures), a monophasic type made up of only spindle cells, and a poorly differentiated type consisting of cells that resemble those of small round blue cell tumors. lthough biphasic synovial sarcoma was the first variant to be recognized, monophasic synovial sarcoma is much more common. Synovial sarcoma is highly unusual among mesenchymal neoplasms because it has variable degrees of epithelial differentiation. Synovial sarcoma is associated with a specific t(x;18)(p11;q11) translocation involving SS18 (also known as SYT) and SSX1, SSX2, or SSX4. Other characteristic pathologic features include tumoral calcification or ossification, cystic change, and necrosis [8]. The aim of this review is to summarize the imaging features and show examples of primary synovial sarcoma occurring in both common and uncommon sites. The metastatic patterns of synovial sarcoma are reviewed, and several cases of tumor response to treatment are illustrated. Primary Sites The extremities are the most common primary site of synovial sarcoma. The lower extremities account for approximately 70% of cases. Most synovial sarcomas occur in the popliteal fossa, but this tumor also affects the foot and ankle, upper extremity, hand and wrist, and proximal limb girdle [2]. CT typically shows a noninfiltrative, well-circumscribed mass, often with punctate, peripheral calcifications [9] (Fig. W208 JR:199, ugust 2012
2 Synovial Sarcoma 1). MRI is the modality of choice for the diagnosis and initial staging of synovial sarcoma because of the information provided by intrinsic signal characteristics and superior soft-tissue contrast [10]. Typical MRI findings include a mass larger than 5 cm near a joint, deep in the tissue, and in contact with bone [6, 11] (Figs. 1 3). In addition, a triple signal pattern on T2- weighted images consisting of areas that are hypointense, isointense, and hyperintense to fat is often seen [6] (Fig. 1). lthough most synovial sarcomas are large (> 5 cm) at diagnosis, smaller lesions do occur. The smaller lesions are often superficial and more peripheral and tend to have benign features, such as smooth contours, homogeneous signal characteristics, and lack of invasion into adjacent structures [12] (Figs. 1, 3, and 4). ggressive features such as involvement of adjacent bone, neurovascular encasement, and muscular invasion can be optimally assessed with MRI. previous study of dynamic gadolinium-enhanced MRI of synovial sarcoma [13] showed that the only feature highly associated with malignancy was early enhancement, that is, within 7 seconds after arterial enhancement. Gadolinium-enhanced sequences are helpful for differentiating primary cystic synovial sarcoma from periarticular cysts and hematomas by showing a solid nodular enhancing component [14]. The pretherapy maximum standardized uptake value of the tumor was predictive of overall survival and progression-free survival. FDG PET may be helpful for prognosis because pretreatment FDG avidity greater than 4.4 is reportedly associated with increased risk of local recurrence and metastatic disease, probably secondary to higher cellularity and mitotic rate [15] (Fig. 5). Primary intraabdominal synovial sarcoma is rare, retroperitoneal lesions accounting for fewer than 1% of all cases of primary synovial sarcoma [2]. The typical imaging features of extremity primary tumors are heterogeneous T2 signal intensity, fluid-fluid levels, and areas of high T1 signal intensity suggestive of hemorrhage. The lesions may be larger than extremity primary lesions at presentation, resulting in displacement of adjacent structures such as the kidney [5] (Fig. 6). Retroperitoneal organs can also be sites of primary disease [16]. Fewer than 50 cases of primary renal synovial sarcoma have been reported in the literature. CT and MRI may show the lesion as primarily cystic with a peripheral nodular component; however, a rapid growth pattern may be most suggestive of a more aggressive primary lesion than renal cell carcinoma [3] (Fig. 7). Pleuropulmonary synovial sarcoma can originate in the chest wall, heart, mediastinum, pleura, or lung. On contrast-enhanced CT images, these tumors are well-circumscribed heterogeneously enhancing lesions that do not involve adjacent bone or calcifications [17]. Often, it is unclear whether the lesion originates from the pleura or lung parenchyma. Ipsilateral pleural effusions are common, and associated lymphadenopathy is not usually seen, which may help in differentiation from primary bronchogenic neoplasms. MRI depiction of nodular soft tissue and multilocular fluidfilled components is excellent [17] (Fig. 8). Primary pericardial synovial sarcoma is rare, previously reported to account for approximately 5% of primary pericardial neoplasms [18]. Pericardial primary lesions can be predominantly low in attenuation on CT images with some peripheral areas of intense enhancement. diffusely infiltrative appearance with encasement of mediastinal structures and blood vessels can also be seen. MRI reveals an appearance similar to that of extremity synovial sarcoma, that is, a heterogeneously T2 hyperintense lesion containing septations and fluid levels (Fig. 9). Primary lung involvement may be seen with or without internal calcification (Fig. 10). Distant Metastasis Like other soft-tissue sarcomas, synovial sarcoma metastasizes mainly to the lung. Unlike most other soft-tissue sarcomas, however, synovial sarcoma carries a small risk of spread to lymph nodes (Fig. 11). Soft-tissue sarcomas originating from extremities rarely metastasize to the liver. One study [19] showed a 75:1 ratio of lung to liver as sites of distant spread; however, the subset of patients with hepatic metastasis and primary disease of the abdomen was an unusually high at 22%. Similarly, metastasis to the brain is also rare, even in widely disseminated disease (Fig. 3). There is also a high incidence of late metastasis. One prospective study showed almost 50% of deaths occurred within 5 10 years of diagnosis, emphasizing the importance of long-term follow-up [20] (Fig. 1). Like primary lesions, locally recurrent and metastatic lesions tend to calcify, a noteworthy characteristic from an imaging standpoint. Treatment For tumors that can be completely excised, surgical resection with or without radiotherapy has been found effective in establishing local control. Metastatic disease is more difficult to treat. Certainly, tumor response has occurred with first-line chemotherapy regimens consisting of ifosfamide-based chemotherapy (with or without doxorubicin), however, whether there is a substantial effect on long-term survival is uncertain, and toxicity and side effects must be weighed against potential benefits [8]. Cross-sectional imaging can be useful in assessing tumor response of both the primary lesion (Fig. 8) and distant metastasis (Fig. 11) by showing decreased size and, in our experience, cystic changes after treatment. t our institution, CT is mainly used for initial staging and follow-up and MRI for presurgical planning. FDG PET has been found useful in assessing the efficacy of chemotherapy in the care of sarcoma patients by showing reduction in FDG avidity in treated lesions [21]. Conclusion In the care of adults years old with a large juxtaarticular mass containing calcifications, the diagnosis of synovial sarcoma should be considered in addition to other sarcomas, such as Ewing sarcoma and rhabdomyosarcoma. The diagnosis of synovial sarcoma should also be considered when small periarticular masses are found and should be differentiated from other cystic lesions. It is important to be aware that primary intrathoracic and intraabdominal tumors can occur, suggested by imaging features more typical of sarcoma than common primary tumors in those locations. Finally, in addition to early metastasis, delayed metastasis is more typical of synovial sarcoma than of many other sarcomas and should be considered in determining the appropriate frequency and duration of follow-up imaging. References 1. rennan MF, Singer S, Maki RG, et al. Sarcomas of the soft tissues and bone. In: DeVita VT, Hellmann S, Rosenberg S, eds. Cancer: principles and practice of oncology, vol. 35. Philadelphia, P: Lippincott Williams & Wilkins, 2005: Kransdorf MJ. Malignant soft-tissue tumors in a large referral population: distribution of diagnoses by age, sex, and location. JR 1995; 164: Perlmutter E, Saunders SE, Zaslau S, Chang WW, Farivar-Mohseni H. Primary synovial sarcoma of the kidney. Int J Urol 2005; 12: O Sullivan PJ, Harris C, Munk PL. Radiological features of synovial cell sarcoma. r J Radiol 2008; 81: Ulusan S. Radiological findings of primary retro- JR:199, ugust 2012 W209
3 akri et al. peritoneal synovial sarcoma. r J Radiol 2005; 78: Jones C, Sundaram M, Kransdorf MJ. Synovial sarcoma: MR imaging findings in 34 patients. JR 1993; 161: Krieg H, Hefti F, Speth M, et al. Synovial sarcomas usually metastasize after > 5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors. nn Oncol 2011; 22: Eilber FC, Dry SM. Diagnosis and management of synovial sarcoma. J Surg Oncol 2008; 97: Nakanishi H, raki N, Sawai Y, et al. Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation. Skeletal Radiol 2003; 32: Kransdorf MJ, Murphey MD. Radiologic evaluation of soft-tissue masses: a current perspective. JR 2011; 175: C 11. Morton MJ, erquist TH, McLeod R, Unni KK, Sim FH. MR imaging of synovial sarcoma. JR 1991; 156: ixby SD, Hettmer S, Taylor G, Voss SD. Synovial sarcoma in children: imaging features and common benign mimics. JR 2010; 195: van Rijswijk CS, Hogendoorn PC, Taminiau H, loem JL. Synovial sarcoma: dynamic contrastenhanced MR imaging features. Skeletal Radiol 2001; 30: Murphey MD, Gibson MS, Jennings T, Crespo- Rodríguez M, Fanburg-Smith J, Gajewski D. Imaging of synovial sarcoma with radiologicpathologic correlation. RadioGraphics 2006; 26: Lisle JW, Eary JF, O Sullivan J, Conrad EU. Risk assessment based on FDG-PET imaging in patients with synovial sarcoma. Clin Orthop Relat Res 2008; 467: Miyashita T, Imamura T, Ishikawa Y, et al. Primary retroperitoneal synovial sarcoma. Intern Med 1994; 33: Frazier, Franks TJ, Pugatch RD, Galvin JR. From the rchives of the FIP: pleuropulmonary synovial sarcoma. RadioGraphics 2006; 26: urke, Virmani R. Primary cardiac sarcomas. In: Tumors of the heart and great vessels. Washington, DC: rmed Forces Institute of Pathology, Jaques DP, Coit DG, Casper ES, rennan MF. Hepatic metastases from soft-tissue sarcoma. nn Surg 1995; 221: Singer S, aldini EH, Demetri GD, Fletcher J, Corson JM. Synovial sarcoma: prognostic significance of tumor size, margin of resection, and mitotic activity for survival. J Clin Oncol 1996; 14: Eary JF, Conrad EU. Imaging in sarcoma. J Nucl Med 2011; 52: Fig year-old man with synovial sarcoma of right hip in whom biopsy-proven pleuropulmonary and osseous metastatic disease developed more than 7 years after initial diagnosis., xial contrast-enhanced CT image shows partially calcified primary mass (arrow) anterior to right gluteus maximus muscle and inseparable from obturator externus and quadratus femoris., xial T2-weighted fast spin-echo MR image slightly superior to shows well-circumscribed ovoid mass anterior to gluteus maximus muscle and posterior to obturator internus tendon and pyriformis muscle with characteristic T2 triple signal pattern: hyperintensity (curved arrow), intermediate intensity (straight arrow), and hypointensity (arrowhead). C, Coronal unenhanced CT image of chest 7 years after and shows 7-cm left pleural-based mass (arrow) and partially calcified pulmonary nodule (arrowhead) in left lower lobe that proved to be metastatic synovial sarcoma at biopsy. W210 JR:199, ugust 2012
4 Synovial Sarcoma C Fig year-old man with synovial sarcoma of popliteal fossa., Sagittal proton density weighted MR image shows primary ovoid popliteal fossa mass (arrow), which is slightly hyperintense to adjacent muscle., Sagittal proton density weighted fat-suppressed MR image shows inhomogeneous hyperintense mass (arrow). C, xial contrast-enhanced fat-suppressed T1-weighted MR image shows heterogeneous enhancement of mass (straight arrow) encasing popliteal artery (curved arrow). Fig year-old woman with primary synovial sarcoma of left forearm metastatic to lung (not shown) and brain., Coronal contrast-enhanced fat-suppressed T1-weighted MR image of left forearm shows ovoid enhancing mass (arrow)., xial contrast-enhanced T1-weighted MR image of brain more than 3 years after primary diagnosis shows enhancing intraaxial mass (arrow) in right occipital lobe abutting dura. Pathologic finding was metastatic lesion. Fig year-old man with large left axillary mass initially thought to be desmoid fibromatosis, but biopsy finding was synovial sarcoma. Coronal proton density weighted fat-suppressed MR image of left shoulder shows well-circumscribed 15-cm left axillary mass (arrow). JR:199, ugust 2012 W211
5 akri et al. Fig year-old woman with history of primary ovarian synovial sarcoma in whom peritoneal and hepatic metastases developed 3 years after initial diagnosis., xial fused FDG PET/CT image shows several FDG-avid (maximum standardized uptake value, 9.8) perihepatic metastatic lesions (arrows). Normal physiologic radiotracer accumulation is present in liver, left kidney, and stomach., xial fused FDG PET/CT image through pelvis shows FDG-avid pelvic (arrow). Fig year-old woman with primary retroperitoneal synovial sarcoma., xial T2-weighted fast spin-echo MR image shows lobulated heterogeneous retroperitoneal mass (arrow) with triple signal characteristics of hyperintensity, intermediate intensity, and hypointensity relative to fat. Mass displaces left kidney and invades adjacent paraspinal muscles., xial gadolinium-enhanced fat-suppressed T1-weighted MR image shows avid enhancement through most of mass (arrow) with nonenhancing lateral area. Findings are consistent with cystic change. W212 JR:199, ugust 2012
6 Synovial Sarcoma C Fig year-old woman with rapidly enlarging cystic left renal mass that proved to be primary synovial sarcoma. Patient was disease free for 2 years after resection, but local recurrence and bone and pleura-based metastases developed., xial contrast-enhanced fat-suppressed T1-weighted MR image shows cystic left renal lesion (arrow) with enhancing internal septations but no clear nodular component., xial contrast-enhanced fat-suppressed T1-weighted MR image obtained 4 months after shows interval enlargement of mass, prominent enhancing soft-tissue component (arrow), and only small cystic component in medial aspect. C, xial T2-weighted HSTE MR image obtained 24 months after shows recurrent ovoid left retroperitoneal mass that is heterogeneously hyperintense to muscle (arrow). Incidental finding is 5-mm cystic pancreatic lesion thought to be side-branch intraductal papillary mucinous neoplasm. D, xial contrast-enhanced fat-suppressed T1-weighted MR image of lung base obtained 27 months after shows left pleura-based multicystic tumor with prominent enhancing septations and nodular components (arrows) that proved to be metastatic synovial sarcoma and right pleural effusion (curved arrow). Enhancing lesion (arrowhead) in thoracic vertebral body was believed to be probable osseous metastatic lesion. D JR:199, ugust 2012 W213
7 akri et al. C Fig year-old woman with multifocal primary synovial sarcoma of right pleural space., Coronal contrast-enhanced fast spoiled gradient-recalled MR image shows multifocal pleura-based mass (straight arrow) extending to chest wall. Inferior mass has cystic (curved arrow) and enhancing solid (arrowhead) components., xial contrast-enhanced fat-suppressed T1-weighted MR image shows enhancing pleura-based mass (arrow). C, xial contrast-enhanced CT image obtained after second cycle of neoadjuvant chemotherapy with doxorubicin and ifosfamide shows decrease in size and reflecting tumor response to treatment. Fig year-old man with pericardial synovial sarcoma., xial contrast-enhanced CT image of chest shows predominantly low-attenuation infiltrative anterior pericardial mass (straight arrows) surrounding ascending aorta and effacing superior vena cava. Small right pleural effusion (curved arrow) with underlying subsegmental atelectasis is present in right lower lobe., xial contrast-enhanced fat-suppressed T1-weighted VIE MR image shows anterior pericardial mass. Lesion has both enhancing nodular components (arrowhead) and thin peripheral enhancement (arrow) surrounding cystic component. Small right pleural effusion (curved arrow) and subsegmental atelectasis are present in right lower lobe. W214 JR:199, ugust 2012
8 Synovial Sarcoma Fig year-old woman with history of primary pulmonary synovial sarcoma. xial unenhanced CT image of chest shows left upper lobe nodule with lobulated margins and central coarse calcification (arrow). Nodule was excised and proved to be synovial sarcoma. C Fig year-old woman with history of primary synovial sarcoma of lower extremity in whom pulmonary and inguinal region metastasis developed 6 months after completion of adjuvant chemotherapy with adriamycin and ifosfamide., xial contrast-enhanced CT image of chest shows large homogeneous right pulmonary mass involving both middle and lower lobes (arrow) presumed to be metastatic synovial sarcoma., xial contrast-enhanced CT image of pelvis shows cystic right inguinal nodal mass (arrow) anterior to right femoral artery and vein. Lesion proved to be metastatic synovial sarcoma. C and D, xial contrast-enhanced CT images of chest (C) and pelvis (D) show marked interval decrease in size of pulmonary and right inguinal masses (arrow) consistent with favorable treatment response. D JR:199, ugust 2012 W215
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