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From the Archives of the AFIP

Imaging of Synovial Sarcoma with Radiologic-Pathologic Correlation¹

¹ From the Departments of Radiologic Pathology (M.D.M., M.S.G., B.T.J.) and Soft Tissue Pathology (J.F.S.), Armed Forces Institute of Pathology, 6825 16th St NW, Building 54, Room M-133A, Washington, DC 20306; Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (M.D.M.); Department of Radiology, National Naval Medical Center, Bethesda, Md (M.S.G.); Department of Radiology, Hospital Universitario Miguel Servet, Zaragoza, Spain (A.M.C.R.); and Departments of Radiology (M.D.M.) and Orthopedic Surgery (D.A.G.), Walter Reed Army Medical Center, Washington, DC. Received May 2, 2006; revision requested May 19 and; received June 9; accepted June 9. All authors have no financial relationships to disclose. Address correspondence to M.D.M. (e-mail: murphey{at}afip.osd.mil).

	Abstract

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Clinical Characteristics Pathologic Features Imaging Features Treatment and Prognosis Summary References

 
Synovial sarcoma is the fourth most common type of soft-tissue sarcoma, accounting for 2.5%–10.5% of all primary soft-tissue malignancies worldwide. Synovial sarcoma most often affects the extremities (80%–95% of cases), particularly the knee in the popliteal fossa, of adolescents and young adults (15–40 years of age). Despite its name, the lesion does not commonly arise in an intraarticular location but usually occurs near joints. Histologic subtypes include monophasic, biphasic, and poorly differentiated; the cytogenetic aberration of the t(X;18) translocation is highly specific for synovial sarcoma. Although radiographic features of these tumors are not pathognomonic, findings of a soft-tissue mass, particularly if calcified (30%), near but not in a joint of a young patient, are very suggestive of the diagnosis. Cross-sectional imaging features are vital for staging tumor extent and planning surgical resection; they also frequently reveal suggestive appearances of multilobulation and marked heterogeneity (creating the "triple sign") with hemorrhage, fluid levels, and septa (creating the "bowl of grapes" sign). Two features associated with synovial sarcoma that may lead to an initial mistaken diagnosis of a benign indolent process are slow growth (average time to diagnosis, 2–4 years) and small size (< 5 cm at initial presentation); in addition, these lesions may demonstrate well-defined margins and homogeneous appearance on cross-sectional images. Synovial sarcoma is an intermediate- to high-grade lesion, and, despite initial aggressive wide surgical resection, local recurrence and metastatic disease are common and prognosis is guarded. Understanding and recognizing the spectrum of appearances of synovial sarcoma, which reflect the underlying pathologic characteristics, improve radiologic assessment and are important for optimal patient management.

	LEARNING OBJECTIVES FOR TEST 6

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Clinical Characteristics Pathologic Features Imaging Features Treatment and Prognosis Summary References

 
After reading this article and taking the test, the reader will be able to:

• Describe the radiologic manifestations of synovial sarcoma.
  
• Recognize the pathologic basis of the radiologic features of synovial sarcoma.
  
• Discuss the pathologic spectrum of synovial sarcoma as well as the treatment options and prognosis.
  

	Introduction

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Clinical Characteristics Pathologic Features Imaging Features Treatment and Prognosis Summary References

 
Synovial sarcoma was first reported in 1893 and represents a relatively common type of primary soft-tissue malignancy (1–5). Synovial sarcoma accounts for 2.5%–10.5% of all primary malignant soft-tissue neoplasms (6–13). Previous terminology for this lesion includes tendosynovial sarcoma, synovial cell sarcoma, synovioma, synovial endothelioma, malignant synovioma, and synovioblastic sarcoma (2,4). Despite this nomenclature, these lesions do not arise in an intra-articular location but usually occur near joints. Synovial sarcomas typically affect adolescents and young adults. The extremities, particularly the knee in the popliteal fossa, are most frequently affected. Synovial sarcoma is an intermediate- to high-grade neoplasm with extensive metastatic potential.

Because of the aggressive potential behavior of synovial sarcoma, pathologic and radiologic assessment is important for staging and evaluating lesion extent to direct appropriate therapy. Imaging findings, although not pathognomonic, frequently suggest the diagnosis. Radiographic findings of a soft-tissue mass near but not in a joint in a young patient (15–40 years old), particularly if calcification is present, are very suggestive of synovial sarcoma. Cross-sectional imaging appearances often seen with synovial sarcoma include multilobulated morphology and marked heterogeneity (creating the "triple sign") with hemorrhage, fluid levels, and septa (creating the "bowl of grapes" sign). In this article, the clinical features, pathologic characteristics, spectrum of radiologic appearances, and treatment and prognosis of synovial sarcoma are discussed and illustrated.

	Clinical Characteristics

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Clinical Characteristics Pathologic Features Imaging Features Treatment and Prognosis Summary References

 
Synovial sarcoma is the fourth most common soft-tissue sarcoma in the material from the Armed Forces Institute of Pathology (AFIP), following malignant fibrous histiocytoma (currently known as undifferentiated high-grade pleomorphic sarcoma), liposarcoma, and rhabdomyosarcoma (1–10). In the United States, the prevalence of synovial sarcoma ranges from 2.5% to 10% of all soft-tissue sarcomas as reported by several institutions (6–10). Similar rates have been reported in population-based studies from Japan (8.3%) (11), Sweden (7%) (12), and France (10.5%) (13).

Synovial sarcoma occurs most frequently in adolescents and young adults, with the majority of patients presenting at 15–40 years of age (2,9). In the study by Cadman et al (8), 84% of patients with synovial sarcoma were 10–50 years old. The median age at presentation in several recent large series ranged from 30 to 38 years (13–18). However, as with most neoplastic processes, there is a broad age range and cases have been reported in newborns and the elderly (6,19). In the pediatric population, synovial sarcoma is the most common nonrhabdomyosarcomatous soft-tissue sarcoma (20). A mild male predominance (1.2:1 ratio) has been described by some authors (15). In contradistinction, other reports have indicated a slight female predominance (13,17). In the largest single group reported, a series of 672 cases seen in consultation over a 10-year period at the AFIP, there was no significant difference in gender distribution (9). No race or ethnic predilection has been reported.

Patients with synovial sarcoma usually present with a palpable soft-tissue mass or swelling (6,8). These lesions are often slow growing initially. Duration of symptoms before diagnosis varies widely, from weeks to decades (8); however, the average duration of symptoms is 2–4 years (2). There are reported cases with as long as a 20-year history of symptoms. The long duration of symptoms and initial slow growth of synovial sarcomas may simulate those of or give a false impression of a benign process. This unusual manifestation is important to recognize, because diagnosis may be significantly delayed otherwise. Pain and tenderness at the site of the mass are frequent, and some patients present with pain but no palpable mass (8). This symptom is unusual compared with other soft-tissue sarcomas that typically manifest as painless masses. Symptoms of sensory and motor dysfunction distal to the lesion, caused by primary or secondary involvement of adjacent nerves, have been reported (8). Weight loss and constitutional symptoms are unusual, but when present usually indicate a poorly differentiated tumor (2). Although synovial sarcoma has occasionally been cited in association with trauma in the literature (2), most cases with this history are likely coincidental. Local trauma may cause hemorrhage in a soft-tissue mass or may bring the mass to the attention of the patient or examining physician.

The majority of synovial sarcomas (80%–95%) occur in the extremities (Fig 1). The lower extremity is most often affected, accounting for 60%–71% of cases, whereas 16%–25% occur in the upper limb (8,9,15,16,18) (Fig 2). The single most frequent site of involvement is the popliteal fossa of the knee (8,9,15,16,18). Synovial sarcoma is the most common malignancy of the deep soft tissues of the foot and ankle in patients 6–45 years of age and the most common malignancy of the lower extremity in patients 6–35 years of age (9). In the AFIP series, 18% of all synovial sarcomas occurred in the foot and ankle. Other less commonly affected sites include the head and neck (5% of cases); trunk, thorax, and chest wall (7%; Fig 3); retroperitoneum (0.3%); and pelvis (8%) (8,9,15,16,21–23). However, synovial sarcoma has also been reported in almost all anatomic locations, with rare involvement of the skin, viscera (kidney, lung, prostate, esophagus, heart), central nervous system, pleura, peripheral nerve, and bone (2–5,21–23). Despite its name, synovial sarcoma infrequently (estimated 5%–10% of cases) originates within a joint (8,14) (Fig 4). The majority of tumors occur either adjacent to (40%–50% of cases) or within 5 cm of (60%–75%) a joint (24). In the study by Jones and colleagues (25), 63% of lesions were within 7 cm of a joint. When intraarticular involvement does occur, it is more commonly because the juxtaarticular neoplasm extended into the joint rather than the tumor arose there (Fig 5).

View larger version (91K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Synovial sarcoma with an intermuscular origin adjacent to the hip of an 18-year-old man who noticed an enlarging soft-tissue mass. (a, b) Axial T1-weighted (a, repetition time msec/echo time msec = 690/25) and T2-weighted (b, 2301/95) magnetic resonance (MR) images show a large juxtaarticular heterogeneous soft-tissue mass (M) with signal intensity slightly higher than that of muscle with T1 weighting and intermediate signal intensity with T2 weighting. The lesion is centered between the rectus (arrow), tensor fascia lata (T), and sartorius (S) muscles, which are displaced. A small amount of intermuscular fat is seen posteriorly (arrowhead). (c) Photograph of the axially sectioned gross specimen reveals similar features with a septated, multilobulated soft-tissue mass (*) arising between the rectus (arrow), tenor fascia lata (T), and sartorius (S) muscles.

View larger version (88K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Synovial sarcoma with an intermuscular origin adjacent to the hip of an 18-year-old man who noticed an enlarging soft-tissue mass. (a, b) Axial T1-weighted (a, repetition time msec/echo time msec = 690/25) and T2-weighted (b, 2301/95) magnetic resonance (MR) images show a large juxtaarticular heterogeneous soft-tissue mass (M) with signal intensity slightly higher than that of muscle with T1 weighting and intermediate signal intensity with T2 weighting. The lesion is centered between the rectus (arrow), tensor fascia lata (T), and sartorius (S) muscles, which are displaced. A small amount of intermuscular fat is seen posteriorly (arrowhead). (c) Photograph of the axially sectioned gross specimen reveals similar features with a septated, multilobulated soft-tissue mass (*) arising between the rectus (arrow), tenor fascia lata (T), and sartorius (S) muscles.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  Synovial sarcoma with an intermuscular origin adjacent to the hip of an 18-year-old man who noticed an enlarging soft-tissue mass. (a, b) Axial T1-weighted (a, repetition time msec/echo time msec = 690/25) and T2-weighted (b, 2301/95) magnetic resonance (MR) images show a large juxtaarticular heterogeneous soft-tissue mass (M) with signal intensity slightly higher than that of muscle with T1 weighting and intermediate signal intensity with T2 weighting. The lesion is centered between the rectus (arrow), tensor fascia lata (T), and sartorius (S) muscles, which are displaced. A small amount of intermuscular fat is seen posteriorly (arrowhead). (c) Photograph of the axially sectioned gross specimen reveals similar features with a septated, multilobulated soft-tissue mass (*) arising between the rectus (arrow), tenor fascia lata (T), and sartorius (S) muscles.

View larger version (47K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Synovial sarcoma near the elbow in a 15-year-old boy who had a small mass there for 9 years that recently rapidly increased in size. (a) Anteroposterior radiograph of the forearm shows a soft-tissue mass (arrowhead) below the elbow with a small focus of amorphous calcification superiorly (large arrow) and extrinsic erosion of the adjacent radius (small arrow). (b, c) Coronal T1-weighted (630/20) (b) and axial T2-weighted (2339/90) (c) MR images reveal the soft-tissue mass (*) with intermediate signal intensity on the short TR image and intermediate to high signal intensity on the long TR image. Low-signal-intensity focus (arrowheads in b) represents the calcification, which is better seen on the radiograph. Extrinsic erosion of the radius is seen on the axial MR image (arrow in c). (d) Photograph of the coronally sectioned gross specimen shows the synovial sarcoma with hemorrhage (H) and focus of calcification (between arrowheads).

View larger version (80K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Synovial sarcoma near the elbow in a 15-year-old boy who had a small mass there for 9 years that recently rapidly increased in size. (a) Anteroposterior radiograph of the forearm shows a soft-tissue mass (arrowhead) below the elbow with a small focus of amorphous calcification superiorly (large arrow) and extrinsic erosion of the adjacent radius (small arrow). (b, c) Coronal T1-weighted (630/20) (b) and axial T2-weighted (2339/90) (c) MR images reveal the soft-tissue mass (*) with intermediate signal intensity on the short TR image and intermediate to high signal intensity on the long TR image. Low-signal-intensity focus (arrowheads in b) represents the calcification, which is better seen on the radiograph. Extrinsic erosion of the radius is seen on the axial MR image (arrow in c). (d) Photograph of the coronally sectioned gross specimen shows the synovial sarcoma with hemorrhage (H) and focus of calcification (between arrowheads).

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 2c.  Synovial sarcoma near the elbow in a 15-year-old boy who had a small mass there for 9 years that recently rapidly increased in size. (a) Anteroposterior radiograph of the forearm shows a soft-tissue mass (arrowhead) below the elbow with a small focus of amorphous calcification superiorly (large arrow) and extrinsic erosion of the adjacent radius (small arrow). (b, c) Coronal T1-weighted (630/20) (b) and axial T2-weighted (2339/90) (c) MR images reveal the soft-tissue mass (*) with intermediate signal intensity on the short TR image and intermediate to high signal intensity on the long TR image. Low-signal-intensity focus (arrowheads in b) represents the calcification, which is better seen on the radiograph. Extrinsic erosion of the radius is seen on the axial MR image (arrow in c). (d) Photograph of the coronally sectioned gross specimen shows the synovial sarcoma with hemorrhage (H) and focus of calcification (between arrowheads).

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 2d.  Synovial sarcoma near the elbow in a 15-year-old boy who had a small mass there for 9 years that recently rapidly increased in size. (a) Anteroposterior radiograph of the forearm shows a soft-tissue mass (arrowhead) below the elbow with a small focus of amorphous calcification superiorly (large arrow) and extrinsic erosion of the adjacent radius (small arrow). (b, c) Coronal T1-weighted (630/20) (b) and axial T2-weighted (2339/90) (c) MR images reveal the soft-tissue mass (*) with intermediate signal intensity on the short TR image and intermediate to high signal intensity on the long TR image. Low-signal-intensity focus (arrowheads in b) represents the calcification, which is better seen on the radiograph. Extrinsic erosion of the radius is seen on the axial MR image (arrow in c). (d) Photograph of the coronally sectioned gross specimen shows the synovial sarcoma with hemorrhage (H) and focus of calcification (between arrowheads).

View larger version (75K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Synovial sarcoma of the posterior chest wall in a 31-year-old man with a nontender, progressively enlarging, soft-tissue mass. (a) Axial postcontrast computed tomographic (CT) scan shows a large posterior chest wall mass with low attenuation centrally (*) resulting from necrosis and a thick nodular wall peripherally (arrows). (b) Photograph of the axially sectioned gross specimen reveals similar features, with necrosis (N) centrally and a thick nodular wall of viable tumor (T) peripherally.

View larger version (80K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Synovial sarcoma of the posterior chest wall in a 31-year-old man with a nontender, progressively enlarging, soft-tissue mass. (a) Axial postcontrast computed tomographic (CT) scan shows a large posterior chest wall mass with low attenuation centrally (*) resulting from necrosis and a thick nodular wall peripherally (arrows). (b) Photograph of the axially sectioned gross specimen reveals similar features, with necrosis (N) centrally and a thick nodular wall of viable tumor (T) peripherally.

View larger version (155K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Synovial sarcoma arising in the knee joint of a 10-year-old girl who developed progressive pain, swelling, and flexion contracture over 2 years after mild trauma. (a) Sagittal short inversion time inversion recovery (STIR) (5000/26/160) MR image shows a large high-signal-intensity soft-tissue mass that appears to originate in the Hoffa fat pad (*) with invasion throughout the joint and the distal femoral (F) and proximal tibial (T) epiphyses. (b) Photograph of the sagittally sectioned gross specimen reveals the intraarticular mass (straight arrows) with hemorrhage (H) and invasion of the distal femoral (arrowhead) and proximal tibial (curved arrow) epiphyses.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Synovial sarcoma arising in the knee joint of a 10-year-old girl who developed progressive pain, swelling, and flexion contracture over 2 years after mild trauma. (a) Sagittal short inversion time inversion recovery (STIR) (5000/26/160) MR image shows a large high-signal-intensity soft-tissue mass that appears to originate in the Hoffa fat pad (*) with invasion throughout the joint and the distal femoral (F) and proximal tibial (T) epiphyses. (b) Photograph of the sagittally sectioned gross specimen reveals the intraarticular mass (straight arrows) with hemorrhage (H) and invasion of the distal femoral (arrowhead) and proximal tibial (curved arrow) epiphyses.

View larger version (171K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Synovial sarcoma with secondary joint invasion. (a) Sagittal proton-density-weighted (2450/38.5) MR image of the knee shows a large popliteal soft-tissue mass (*) with invasion of the knee joint, as evidenced by tumor (arrows) surrounding the posterior cruciate ligament (P). The patient, a 47-year-old man with a 2-year history of progressive limitation of joint movement, also had invasion of the femur (arrowheads). (b) Photograph of a sagittally sectioned, whole-mounted specimen (hematoxylineosin [H-E] stain) from a 35-year-old man reveals invasion of the anterior recess of the ankle by a soft-tissue mass (*), which originates adjacent to the joint (arrow). The intraarticular component of the lesion also causes extrinsic erosion of the anterior tibial cortex (arrowhead). The patient presented with clinical symptoms of limited foot dorsiflexion.

View larger version (84K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Synovial sarcoma with secondary joint invasion. (a) Sagittal proton-density-weighted (2450/38.5) MR image of the knee shows a large popliteal soft-tissue mass (*) with invasion of the knee joint, as evidenced by tumor (arrows) surrounding the posterior cruciate ligament (P). The patient, a 47-year-old man with a 2-year history of progressive limitation of joint movement, also had invasion of the femur (arrowheads). (b) Photograph of a sagittally sectioned, whole-mounted specimen (hematoxylineosin [H-E] stain) from a 35-year-old man reveals invasion of the anterior recess of the ankle by a soft-tissue mass (*), which originates adjacent to the joint (arrow). The intraarticular component of the lesion also causes extrinsic erosion of the anterior tibial cortex (arrowhead). The patient presented with clinical symptoms of limited foot dorsiflexion.

	Pathologic Features

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Clinical Characteristics Pathologic Features Imaging Features Treatment and Prognosis Summary References

There are three main histologic subtypes of synovial sarcoma: biphasic, monophasic, and poorly differentiated (28) (Fig 6). Biphasic synovial sarcoma represents 20%–30% of lesions and has both a mesenchymal spindle cell component and an obvious epithelial component as seen at light microscopy (Fig 6a). The epithelial cells usually form glands, but they may also be seen as solid sheets, nests, cords, and papillary structures, and they may show squamous metaplasia. The glandular component may predominate and occasionally obscure the spindle cell elements, an appearance suggestive of adenocarcinoma and that has been referred to as the purely glandular type monophasic synovial sarcoma.

View larger version (162K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Photomicrographs of various histologic types of synovial sarcoma. (a) Biphasic synovial sarcoma (original magnification, x250; H-E stain) has a blue spindle cell mesenchymal component (arrow) and pinker glandular elements (arrowheads). (b) Monophasic synovial sarcoma (original magnification, x200; inset magnification, x400; H-E stain) typically appears with fascicles and sheets of uniform oval cells but without a glandular component. Inset shows scattered mast cells (arrowheads). (c) Monophasic synovial sarcoma with positive keratin stain (original magnification, x300; Kermix stain) shows the brown staining (arrowheads) in individual tumor cells. (d) Poorly differentiated synovial sarcoma (original magnification, x250; H-E stain) has an epithelioid growth pattern and relatively uniform round cells, a characteristic that makes differentiation from other small round blue cell tumors (eg, Ewing sarcoma) difficult without immunohistochemical staining.

View larger version (160K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Photomicrographs of various histologic types of synovial sarcoma. (a) Biphasic synovial sarcoma (original magnification, x250; H-E stain) has a blue spindle cell mesenchymal component (arrow) and pinker glandular elements (arrowheads). (b) Monophasic synovial sarcoma (original magnification, x200; inset magnification, x400; H-E stain) typically appears with fascicles and sheets of uniform oval cells but without a glandular component. Inset shows scattered mast cells (arrowheads). (c) Monophasic synovial sarcoma with positive keratin stain (original magnification, x300; Kermix stain) shows the brown staining (arrowheads) in individual tumor cells. (d) Poorly differentiated synovial sarcoma (original magnification, x250; H-E stain) has an epithelioid growth pattern and relatively uniform round cells, a characteristic that makes differentiation from other small round blue cell tumors (eg, Ewing sarcoma) difficult without immunohistochemical staining.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 6c.  Photomicrographs of various histologic types of synovial sarcoma. (a) Biphasic synovial sarcoma (original magnification, x250; H-E stain) has a blue spindle cell mesenchymal component (arrow) and pinker glandular elements (arrowheads). (b) Monophasic synovial sarcoma (original magnification, x200; inset magnification, x400; H-E stain) typically appears with fascicles and sheets of uniform oval cells but without a glandular component. Inset shows scattered mast cells (arrowheads). (c) Monophasic synovial sarcoma with positive keratin stain (original magnification, x300; Kermix stain) shows the brown staining (arrowheads) in individual tumor cells. (d) Poorly differentiated synovial sarcoma (original magnification, x250; H-E stain) has an epithelioid growth pattern and relatively uniform round cells, a characteristic that makes differentiation from other small round blue cell tumors (eg, Ewing sarcoma) difficult without immunohistochemical staining.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 6d.  Photomicrographs of various histologic types of synovial sarcoma. (a) Biphasic synovial sarcoma (original magnification, x250; H-E stain) has a blue spindle cell mesenchymal component (arrow) and pinker glandular elements (arrowheads). (b) Monophasic synovial sarcoma (original magnification, x200; inset magnification, x400; H-E stain) typically appears with fascicles and sheets of uniform oval cells but without a glandular component. Inset shows scattered mast cells (arrowheads). (c) Monophasic synovial sarcoma with positive keratin stain (original magnification, x300; Kermix stain) shows the brown staining (arrowheads) in individual tumor cells. (d) Poorly differentiated synovial sarcoma (original magnification, x250; H-E stain) has an epithelioid growth pattern and relatively uniform round cells, a characteristic that makes differentiation from other small round blue cell tumors (eg, Ewing sarcoma) difficult without immunohistochemical staining.

Poorly differentiated synovial sarcomas are generally epithelioid in morphology and have high mitotic activity (usually > 15–20/10 high-power field) with geographic necrosis (18,31–33) (Fig 6d). This subtype represents up to 15%–25% of all synovial sarcomas. A very distinctive low-power microscopic pattern for poorly differentiated synovial sarcoma is perivascular tissue sparing, in which rings of tumor form around vessels, with large areas of adjacent geographic necrosis. Poorly differentiated synovial sarcomas can be confused with round cell tumors, such as Ewing sarcoma, although differentiation can be accomplished with immunohistochemical staining and molecular methods.

Grading of synovial sarcoma is achieved by applying the highly reproducible, widely accepted grading scheme for all sarcomas, the FNCLCC (French Federation Nationale des Centres de Lutte Contre le Cancer) scheme, which uses a combined score from three separate parameters, including degree of differentiation, mitotic activity, and necrosis (34,35). Both biphasic and monophasic synovial sarcomas are usually intermediate grade (grade 2/3); however, both types can be high grade (grade 3/3). Poorly differentiated synovial sarcomas are high-grade tumors.

The presence of keratin (epithelial marker) positivity (approximately 90% of cases), measured with immunohistochemical staining in correlation with the histologic appearance, is diagnostic for synovial sarcoma (37,38) (Fig 6c). Both the glandular component (diffusely) and the spindle cell component (focally) demonstrate single cells (monophasic and poorly differentiated subtypes) or clusters of cells (biphasic subtype) that are positive for epithelial markers, most notably pankeratins, EMA, and CK7. CK7 is generally absent from malignant peripheral nerve sheath tumor (as well as pankeratins in this tumor) and Ewing sarcoma, and this finding can aid in diagnosis of synovial sarcoma (39). CD99, which is found as a cytoplasmic membrane marker in Ewing and primitive neuroectodermal tumors, can also be positive in synovial sarcoma (62% of cases). CD34, which is diffusely positive in hemangiopericytoma and solitary fibrous tumor, is negative in synovial sarcoma. Epithelial-type and neural-type cadherins can be found in biphasic synovial sarcoma and to a lesser degree in monophasic and poorly differentiated synovial sarcoma, but they may be useful, in combination with other markers, to separate biphasic synovial sarcoma from mesotheliomas or other tumors (40).

Cytogenetic studies can be performed on formalin-fixed paraffin embedded tissues. The hallmarks for synovial sarcoma are the t(X;18) translocation and SYT-SSX gene fusion products, which can be identified by using FISH (fluorescence in situ hybridization) or RT-PCR (reverse transcription polymerase chain reaction) studies, respectively. This genetic aberration has been identified in greater than 90% of synovial sarcomas and is highly specific, since it has not been identified to date in any other tumors, to the best of our knowledge. Molecular testing is usually performed when there is very little tissue, when the immunohistochemical stains are not diagnostic for synovial sarcoma, or when the tumor is poorly differentiated and mimics Ewing sarcoma. Several variations of the t(X;18) translocation leading to two different gene fusions have been described and associated with the vast majority of synovial sarcomas. These are the SYT-SSX1 and SYT-SSX2 types that account for 67% and 33% of gene fusions, respectively (2–5,42,43). Although much controversy exists in the literature, there is no definite prognostic difference between these two gene fusion types (41). However, biphasic tumors are generally SSX1, and monophasic tumors are either SSX1 or SSX2 (42).

The pathologic differential diagnosis for synovial sarcoma includes the following: carcinosarcoma; other biphasic tumors of the gynecologic tract; teratoma; mixed tumor; malignant mesothelioma; fibrosarcoma; solitary fibrous tumor or hemangiopericytoma; cellular schwannoma; leiomyosarcoma; malignant peripheral nerve sheath tumor (36); Ewing sarcoma or primitive neuroectodermal tumor; and other small round cell tumors, depending on whether biphasic, monophasic, or poorly differentiated. These lesions can all be distinguished by the specific morphologic features of synovial sarcoma (such as stromal collagen, scattered mast cells, and bland cytology of ovoid tumor cells in fascicles; soft tissue or specific organ location; patient age; and immunohistochemical findings of EMA, keratins, and CK7) and particularly by molecular methods in difficult cases or those with scant material.

	Imaging Features

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Clinical Characteristics Pathologic Features Imaging Features Treatment and Prognosis Summary References

 
Radiographs appear normal in approximately 50% of cases of synovial sarcoma, particularly those with small lesions (1,43). Larger legions that are deeply seated or that occur in areas of complex anatomy such as the pelvis may also be occult at radiography. Synovial sarcomas detected at radiography typically appear as nonspecific, round to oval juxtaarticular soft-tissue masses. Calcification is identified in up to 30% of synovial sarcomas at radiography (1, 43) (Figs 2, 7).

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Largely cystic synovial sarcoma in the popliteal region in a 12-year-old boy with a painless soft-tissue mass first noted 4 years ago. (a) Lateral radiograph shows soft-tissue fullness in the popliteal fossa (*) with a small, nonspecific calcification superiorly (arrow). (b–d) Axial T1-weighted (b, 700/16), sagittal T1-weighted fat suppressed postcontrast (c, 800/20), and coronal STIR (d, 2550/30/150) MR images reveal a largely cystic, popliteal soft-tissue mass (C) with a focal nodular area of solid tissue anteriorly (arrowheads). The lesion is intermuscular as demonstrated by the surrounding fat (split fat sign) (arrows). The cystic component (C) demonstrates thin peripheral enhancement and is low signal intensity with T1 weighting (b) and very high signal intensity with the STIR sequence (d), an appearance simulating that of a ganglion or popliteal cyst. However, the solid component (S) reveals diffuse enhancement and is higher signal intensity with T1 weighting (b) and lower signal intensity with the STIR sequence (d). (e) Transverse sonogram of the solid component shows a heterogeneous intermediate echogenicity, ovoid soft-tissue mass. Note the foci of increased echogenicity (arrows), which correspond to calcifications on the radiographs. (f) Photograph of the sectioned gross specimen reveals the solid component (S) and smooth walls of the collapsed cyst cavity (*), corresponding to the imaging findings.

 

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Largely cystic synovial sarcoma in the popliteal region in a 12-year-old boy with a painless soft-tissue mass first noted 4 years ago. (a) Lateral radiograph shows soft-tissue fullness in the popliteal fossa (*) with a small, nonspecific calcification superiorly (arrow). (b–d) Axial T1-weighted (b, 700/16), sagittal T1-weighted fat suppressed postcontrast (c, 800/20), and coronal STIR (d, 2550/30/150) MR images reveal a largely cystic, popliteal soft-tissue mass (C) with a focal nodular area of solid tissue anteriorly (arrowheads). The lesion is intermuscular as demonstrated by the surrounding fat (split fat sign) (arrows). The cystic component (C) demonstrates thin peripheral enhancement and is low signal intensity with T1 weighting (b) and very high signal intensity with the STIR sequence (d), an appearance simulating that of a ganglion or popliteal cyst. However, the solid component (S) reveals diffuse enhancement and is higher signal intensity with T1 weighting (b) and lower signal intensity with the STIR sequence (d). (e) Transverse sonogram of the solid component shows a heterogeneous intermediate echogenicity, ovoid soft-tissue mass. Note the foci of increased echogenicity (arrows), which correspond to calcifications on the radiographs. (f) Photograph of the sectioned gross specimen reveals the solid component (S) and smooth walls of the collapsed cyst cavity (*), corresponding to the imaging findings.

 

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 7c.  Largely cystic synovial sarcoma in the popliteal region in a 12-year-old boy with a painless soft-tissue mass first noted 4 years ago. (a) Lateral radiograph shows soft-tissue fullness in the popliteal fossa (*) with a small, nonspecific calcification superiorly (arrow). (b–d) Axial T1-weighted (b, 700/16), sagittal T1-weighted fat suppressed postcontrast (c, 800/20), and coronal STIR (d, 2550/30/150) MR images reveal a largely cystic, popliteal soft-tissue mass (C) with a focal nodular area of solid tissue anteriorly (arrowheads). The lesion is intermuscular as demonstrated by the surrounding fat (split fat sign) (arrows). The cystic component (C) demonstrates thin peripheral enhancement and is low signal intensity with T1 weighting (b) and very high signal intensity with the STIR sequence (d), an appearance simulating that of a ganglion or popliteal cyst. However, the solid component (S) reveals diffuse enhancement and is higher signal intensity with T1 weighting (b) and lower signal intensity with the STIR sequence (d). (e) Transverse sonogram of the solid component shows a heterogeneous intermediate echogenicity, ovoid soft-tissue mass. Note the foci of increased echogenicity (arrows), which correspond to calcifications on the radiographs. (f) Photograph of the sectioned gross specimen reveals the solid component (S) and smooth walls of the collapsed cyst cavity (*), corresponding to the imaging findings.

 

View larger version (91K): [in this window] [in a new window] [Download PPT slide]   Figure 7d.  Largely cystic synovial sarcoma in the popliteal region in a 12-year-old boy with a painless soft-tissue mass first noted 4 years ago. (a) Lateral radiograph shows soft-tissue fullness in the popliteal fossa (*) with a small, nonspecific calcification superiorly (arrow). (b–d) Axial T1-weighted (b, 700/16), sagittal T1-weighted fat suppressed postcontrast (c, 800/20), and coronal STIR (d, 2550/30/150) MR images reveal a largely cystic, popliteal soft-tissue mass (C) with a focal nodular area of solid tissue anteriorly (arrowheads). The lesion is intermuscular as demonstrated by the surrounding fat (split fat sign) (arrows). The cystic component (C) demonstrates thin peripheral enhancement and is low signal intensity with T1 weighting (b) and very high signal intensity with the STIR sequence (d), an appearance simulating that of a ganglion or popliteal cyst. However, the solid component (S) reveals diffuse enhancement and is higher signal intensity with T1 weighting (b) and lower signal intensity with the STIR sequence (d). (e) Transverse sonogram of the solid component shows a heterogeneous intermediate echogenicity, ovoid soft-tissue mass. Note the foci of increased echogenicity (arrows), which correspond to calcifications on the radiographs. (f) Photograph of the sectioned gross specimen reveals the solid component (S) and smooth walls of the collapsed cyst cavity (*), corresponding to the imaging findings.

 

View larger version (163K): [in this window] [in a new window] [Download PPT slide]   Figure 7e.  Largely cystic synovial sarcoma in the popliteal region in a 12-year-old boy with a painless soft-tissue mass first noted 4 years ago. (a) Lateral radiograph shows soft-tissue fullness in the popliteal fossa (*) with a small, nonspecific calcification superiorly (arrow). (b–d) Axial T1-weighted (b, 700/16), sagittal T1-weighted fat suppressed postcontrast (c, 800/20), and coronal STIR (d, 2550/30/150) MR images reveal a largely cystic, popliteal soft-tissue mass (C) with a focal nodular area of solid tissue anteriorly (arrowheads). The lesion is intermuscular as demonstrated by the surrounding fat (split fat sign) (arrows). The cystic component (C) demonstrates thin peripheral enhancement and is low signal intensity with T1 weighting (b) and very high signal intensity with the STIR sequence (d), an appearance simulating that of a ganglion or popliteal cyst. However, the solid component (S) reveals diffuse enhancement and is higher signal intensity with T1 weighting (b) and lower signal intensity with the STIR sequence (d). (e) Transverse sonogram of the solid component shows a heterogeneous intermediate echogenicity, ovoid soft-tissue mass. Note the foci of increased echogenicity (arrows), which correspond to calcifications on the radiographs. (f) Photograph of the sectioned gross specimen reveals the solid component (S) and smooth walls of the collapsed cyst cavity (*), corresponding to the imaging findings.

 

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 7f.  Largely cystic synovial sarcoma in the popliteal region in a 12-year-old boy with a painless soft-tissue mass first noted 4 years ago. (a) Lateral radiograph shows soft-tissue fullness in the popliteal fossa (*) with a small, nonspecific calcification superiorly (arrow). (b–d) Axial T1-weighted (b, 700/16), sagittal T1-weighted fat suppressed postcontrast (c, 800/20), and coronal STIR (d, 2550/30/150) MR images reveal a largely cystic, popliteal soft-tissue mass (C) with a focal nodular area of solid tissue anteriorly (arrowheads). The lesion is intermuscular as demonstrated by the surrounding fat (split fat sign) (arrows). The cystic component (C) demonstrates thin peripheral enhancement and is low signal intensity with T1 weighting (b) and very high signal intensity with the STIR sequence (d), an appearance simulating that of a ganglion or popliteal cyst. However, the solid component (S) reveals diffuse enhancement and is higher signal intensity with T1 weighting (b) and lower signal intensity with the STIR sequence (d). (e) Transverse sonogram of the solid component shows a heterogeneous intermediate echogenicity, ovoid soft-tissue mass. Note the foci of increased echogenicity (arrows), which correspond to calcifications on the radiographs. (f) Photograph of the sectioned gross specimen reveals the solid component (S) and smooth walls of the collapsed cyst cavity (*), corresponding to the imaging findings.

 

View larger version (92K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Extensively calcified synovial sarcoma in a 36-year-old woman who presented with a mass anterior to the elbow that had progressively enlarged over 15 months, resulting in a flexion deformity. (a) Lateral elbow radiograph shows a large calcified soft-tissue mass (arrows) anterior to the elbow without evidence of an effusion. (b) Axial CT scan also reveals the extensively calcified soft-tissue mass (arrows). (c, d) Coronal oblique T1-weighted (650/36) (c) and sagittal gradient-echo (1000/13/30°) (d) MR images demonstrate the large heterogeneous soft-tissue mass (arrowheads) with low- to intermediate-signal-intensity areas (*) corresponding to the calcifications seen on radiographs and CT scans. The extent of low to intermediate signal intensity is not as prominent as might be expected from the radiographic or CT appearance, likely related to intermixture with viable tumor cells. The mass is anterior to the anterior recess of the elbow, and lack of joint effusion is consistent with juxtaarticular but not intraarticular origin. (e) Photograph of the coronally sectioned gross specimen shows extensive calcification (*) superiorly.

View larger version (64K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Extensively calcified synovial sarcoma in a 36-year-old woman who presented with a mass anterior to the elbow that had progressively enlarged over 15 months, resulting in a flexion deformity. (a) Lateral elbow radiograph shows a large calcified soft-tissue mass (arrows) anterior to the elbow without evidence of an effusion. (b) Axial CT scan also reveals the extensively calcified soft-tissue mass (arrows). (c, d) Coronal oblique T1-weighted (650/36) (c) and sagittal gradient-echo (1000/13/30°) (d) MR images demonstrate the large heterogeneous soft-tissue mass (arrowheads) with low- to intermediate-signal-intensity areas (*) corresponding to the calcifications seen on radiographs and CT scans. The extent of low to intermediate signal intensity is not as prominent as might be expected from the radiographic or CT appearance, likely related to intermixture with viable tumor cells. The mass is anterior to the anterior recess of the elbow, and lack of joint effusion is consistent with juxtaarticular but not intraarticular origin. (e) Photograph of the coronally sectioned gross specimen shows extensive calcification (*) superiorly.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 8c.  Extensively calcified synovial sarcoma in a 36-year-old woman who presented with a mass anterior to the elbow that had progressively enlarged over 15 months, resulting in a flexion deformity. (a) Lateral elbow radiograph shows a large calcified soft-tissue mass (arrows) anterior to the elbow without evidence of an effusion. (b) Axial CT scan also reveals the extensively calcified soft-tissue mass (arrows). (c, d) Coronal oblique T1-weighted (650/36) (c) and sagittal gradient-echo (1000/13/30°) (d) MR images demonstrate the large heterogeneous soft-tissue mass (arrowheads) with low- to intermediate-signal-intensity areas (*) corresponding to the calcifications seen on radiographs and CT scans. The extent of low to intermediate signal intensity is not as prominent as might be expected from the radiographic or CT appearance, likely related to intermixture with viable tumor cells. The mass is anterior to the anterior recess of the elbow, and lack of joint effusion is consistent with juxtaarticular but not intraarticular origin. (e) Photograph of the coronally sectioned gross specimen shows extensive calcification (*) superiorly.

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 8d.  Extensively calcified synovial sarcoma in a 36-year-old woman who presented with a mass anterior to the elbow that had progressively enlarged over 15 months, resulting in a flexion deformity. (a) Lateral elbow radiograph shows a large calcified soft-tissue mass (arrows) anterior to the elbow without evidence of an effusion. (b) Axial CT scan also reveals the extensively calcified soft-tissue mass (arrows). (c, d) Coronal oblique T1-weighted (650/36) (c) and sagittal gradient-echo (1000/13/30°) (d) MR images demonstrate the large heterogeneous soft-tissue mass (arrowheads) with low- to intermediate-signal-intensity areas (*) corresponding to the calcifications seen on radiographs and CT scans. The extent of low to intermediate signal intensity is not as prominent as might be expected from the radiographic or CT appearance, likely related to intermixture with viable tumor cells. The mass is anterior to the anterior recess of the elbow, and lack of joint effusion is consistent with juxtaarticular but not intraarticular origin. (e) Photograph of the coronally sectioned gross specimen shows extensive calcification (*) superiorly.

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 8e.  Extensively calcified synovial sarcoma in a 36-year-old woman who presented with a mass anterior to the elbow that had progressively enlarged over 15 months, resulting in a flexion deformity. (a) Lateral elbow radiograph shows a large calcified soft-tissue mass (arrows) anterior to the elbow without evidence of an effusion. (b) Axial CT scan also reveals the extensively calcified soft-tissue mass (arrows). (c, d) Coronal oblique T1-weighted (650/36) (c) and sagittal gradient-echo (1000/13/30°) (d) MR images demonstrate the large heterogeneous soft-tissue mass (arrowheads) with low- to intermediate-signal-intensity areas (*) corresponding to the calcifications seen on radiographs and CT scans. The extent of low to intermediate signal intensity is not as prominent as might be expected from the radiographic or CT appearance, likely related to intermixture with viable tumor cells. The mass is anterior to the anterior recess of the elbow, and lack of joint effusion is consistent with juxtaarticular but not intraarticular origin. (e) Photograph of the coronally sectioned gross specimen shows extensive calcification (*) superiorly.

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Synovial sarcoma of the thigh with extensive calcification and metastatic disease to the chest in a 52-year-old woman who presented with an enlarging soft-tissue mass in her thigh. (a) Axial postcontrast CT scan shows a large heterogeneous soft-tissue mass with both solid (arrows) and necrotic (N) regions and extensive calcification (arrowheads). (b) Coronal T2-weighted (2050/90) MR image reveals marked heterogeneity with the triple sign, including areas of high (H), intermediate (I), and low (L) signal intensity in the large soft-tissue mass. (c) Frontal chest radiograph demonstrates multiple pulmonary nodules (arrows) and a mediastinal mass (M). (d) Photograph of the sectioned gross specimen shows the large heterogeneous soft-tissue mass with hemorrhage (H) and large areas of calcification (C) that histologically (not shown) revealed metaplastic bone.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Synovial sarcoma of the thigh with extensive calcification and metastatic disease to the chest in a 52-year-old woman who presented with an enlarging soft-tissue mass in her thigh. (a) Axial postcontrast CT scan shows a large heterogeneous soft-tissue mass with both solid (arrows) and necrotic (N) regions and extensive calcification (arrowheads). (b) Coronal T2-weighted (2050/90) MR image reveals marked heterogeneity with the triple sign, including areas of high (H), intermediate (I), and low (L) signal intensity in the large soft-tissue mass. (c) Frontal chest radiograph demonstrates multiple pulmonary nodules (arrows) and a mediastinal mass (M). (d) Photograph of the sectioned gross specimen shows the large heterogeneous soft-tissue mass with hemorrhage (H) and large areas of calcification (C) that histologically (not shown) revealed metaplastic bone.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Synovial sarcoma of the thigh with extensive calcification and metastatic disease to the chest in a 52-year-old woman who presented with an enlarging soft-tissue mass in her thigh. (a) Axial postcontrast CT scan shows a large heterogeneous soft-tissue mass with both solid (arrows) and necrotic (N) regions and extensive calcification (arrowheads). (b) Coronal T2-weighted (2050/90) MR image reveals marked heterogeneity with the triple sign, including areas of high (H), intermediate (I), and low (L) signal intensity in the large soft-tissue mass. (c) Frontal chest radiograph demonstrates multiple pulmonary nodules (arrows) and a mediastinal mass (M). (d) Photograph of the sectioned gross specimen shows the large heterogeneous soft-tissue mass with hemorrhage (H) and large areas of calcification (C) that histologically (not shown) revealed metaplastic bone.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Synovial sarcoma of the thigh with extensive calcification and metastatic disease to the chest in a 52-year-old woman who presented with an enlarging soft-tissue mass in her thigh. (a) Axial postcontrast CT scan shows a large heterogeneous soft-tissue mass with both solid (arrows) and necrotic (N) regions and extensive calcification (arrowheads). (b) Coronal T2-weighted (2050/90) MR image reveals marked heterogeneity with the triple sign, including areas of high (H), intermediate (I), and low (L) signal intensity in the large soft-tissue mass. (c) Frontal chest radiograph demonstrates multiple pulmonary nodules (arrows) and a mediastinal mass (M). (d) Photograph of the sectioned gross specimen shows the large heterogeneous soft-tissue mass with hemorrhage (H) and large areas of calcification (C) that histologically (not shown) revealed metaplastic bone.

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Synovial sarcoma of the foot with indolent erosion of bone in a 14-year-old girl with an enlarging foot mass. (a) Anteroposterior radiograph of the foot shows indolent extrinsic erosion of the second and third metatarsals (arrowheads). (b) CT scan reveals a small focus of nonspecific calcification (arrow) (not seen on the radiograph) in the soft-tissue mass, which extends between the first to third metatarsals (arrowheads). (c) Short axis T2-weighted (2100/90) MR image shows an intermediate-signal-intensity soft-tissue mass (*) with extension dorsally (white arrow) between the second and third metatarsals that causes the extrinsic erosion of bone (black arrow).

View larger version (71K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Synovial sarcoma of the foot with indolent erosion of bone in a 14-year-old girl with an enlarging foot mass. (a) Anteroposterior radiograph of the foot shows indolent extrinsic erosion of the second and third metatarsals (arrowheads). (b) CT scan reveals a small focus of nonspecific calcification (arrow) (not seen on the radiograph) in the soft-tissue mass, which extends between the first to third metatarsals (arrowheads). (c) Short axis T2-weighted (2100/90) MR image shows an intermediate-signal-intensity soft-tissue mass (*) with extension dorsally (white arrow) between the second and third metatarsals that causes the extrinsic erosion of bone (black arrow).

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 10c.  Synovial sarcoma of the foot with indolent erosion of bone in a 14-year-old girl with an enlarging foot mass. (a) Anteroposterior radiograph of the foot shows indolent extrinsic erosion of the second and third metatarsals (arrowheads). (b) CT scan reveals a small focus of nonspecific calcification (arrow) (not seen on the radiograph) in the soft-tissue mass, which extends between the first to third metatarsals (arrowheads). (c) Short axis T2-weighted (2100/90) MR image shows an intermediate-signal-intensity soft-tissue mass (*) with extension dorsally (white arrow) between the second and third metatarsals that causes the extrinsic erosion of bone (black arrow).

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