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Primary synovial sarcomas in the paediatric and young adult population: A pictorial review
European Journal of Radiology 133 (2020) 109376
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Primary synovial sarcomas in the paediatric and young adult population: A pictorial review Melissa Hickson a, *, Kieran McHugh b, Beth McCarville c a
The Whittington Hospital, Magdala Avenue, London N19 5NF, UK Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK c St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA b
A R T I C L E I N F O
A B S T R A C T
Keywords: Primary synovial sacroma Paediatric Imaging Malignancy
Purpose: To present a pictorial essay of paediatric primary synovial sarcomas from common and less documented anatomical locations. To review the literature for the imaging characteristics and prognostic factors of this rare but important childhood malignancy. Method: 24 primary synovial sarcoma cases (17 male, 7 female with an age range 4–21 years) were reviewed in a collaborative effort between St Jude Children’s Research Hospital and Great Ormond Street Hospital for Children. Images from 19 cases were selected for inclusion, to demonstrate the spectrum of appearances across imaging modalities, in a range of different anatomical locations (upper limb, lower limb, chest/abdomen/pelvis, and head and neck). A literature review depicting the typical radiological features and the prognostic significance of these features, was also conducted. Results and conclusions: Primary synovial sarcoma can occur in any anatomical location, but typically within the extremities and often in close association with joints. Rarer anatomical locations described in our essay include the gastrohepatic ligament and femoral nerve sheath. We detail the salient imaging characteristics, including the T2 ‘triple signal’ pattern which is believed to be highly specific for this particular sarcoma and in many cases predicts a poor outcome. Other poor prognostic factors include haemorrhage, lack of calcification and tumour size >10 cm. A broad range of radiological appearances are described, and in some cases related to anatomical position and size, however the presence of a soft tissue mass close to a joint in a young patient are suggestive of this diagnosis.
1. Introduction Primary synovial sarcomas (SS) are rare malignant tumours, with an estimated incidence of 2.75 in 100,000 [1]. A subset of the malignant small round cell tumours, they account for 10 % of all soft-tissue sar comas, and are the fourth most common soft tissue sarcoma following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma [2]. Malignant small round cell tumour is a term used for tumours composed of cells which are slightly larger or double the size of red blood cells in air-dried smears [2]. SS were first described in 1865 by Simon [3], and are characterized cytogenetically by a recurring chro mosomal translocation, t(X;18)(p11.2;q11.2) in >95 % of cases [4],
whereby the SS18 gene on chromosome 18 is fused to one of 3 SSX genes found on the x chromosome (SSX1, SSX2 or SSX4). A study examining the transcriptional consequences of these SS18-SSx fusion proteins, found that the SS18-SSX2 fusion protein downregulated downstream target genes, supporting the proposal that SS18-SSX fusion proteins act as an “activator-repressor” through epigenetic mechanisms [5]. They most commonly occur in adolescents and young adults, be tween the ages of 15− 30years. Despite their name they do not commonly occur within a joint, but in the extremities with a close relation to joint spaces, particularly around the knee and lower thigh region. However, they can occur anywhere, even at locations distant from joint spaces. Examples include SS of the lung, an extremely rare and aggressive tumour with a poor prognosis [6], of the kidney [7] and
* Corresponding author at Imaging Department, The Whittington Hospital, Magdala Avenue, London N19 5NF, UK. E-mail addresses: [email protected] (M. Hickson), [email protected] (K. McHugh), [email protected] (B. McCarville). https://doi.org/10.1016/j.ejrad.2020.109376 Received 9 April 2020; Received in revised form 14 October 2020; Accepted 21 October 2020 Available online 28 October 2020 0720-048X/Crown Copyright © 2020 Published by Elsevier B.V. All rights reserved.
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Table 1 Anatomical sites of synovial sarcoma in 24 young adults and children. Anatomical site Head and Neck Upper extremity Chest Abdominal Pelvic Lower extremity
Number of Cases Elbow Forearm/wrist
Groin/Proximal thigh Knee Foot
2 3 3 2 1 2 4 4 3
even of the orbit [8]. SS usually occur in the extremities, with the lower limb accounting for the majority of cases. The most frequent site of involvement is the popliteal fossa [9]. It is the most common paediatric malignancy of the soft tissues involving the foot and ankle [10]. Less commonly affected sites include the head and neck (7%), trunk, thorax and chest wall (7%), retroperitoneum (0.3 %), and pelvis (8%) [9]. SS is a rare malignancy, and therefore patients who were imaged and treated at one of two tertiary centers dating back to 2004 (Great Ormond Street Hospital and St Jude Children’s Research Hospital), were com bined and reviewed. A total of 24 cases were reviewed (17 male, 7 fe male, ranging in age from 4 to 21 years with a mean age of 13 years) from this combined institutional cohort, describing tumours arising in a variety of different anatomical locations (Table 1). Images from 19 cases were selected for inclusion in the pictorial review. 2. Imaging of synovial sarcoma Baseline imaging encompasses ultrasound (US), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomographycomputed tomography (FDG PET-CT), and in some instances plain film radiographs. About half of radiographs, and particularly those associated with smaller lesions, can appear normal [9]. Calcification is seen in up to 30 % of SS on radiography and are often eccentric or peripheral within the soft tissue mass and fairly non-specific in appearance. The imaging findings although not pathognomonic, are frequently enough to suggest the diagnosis [9]. Calcification is also seen in SS metastatic deposits, particularly those which metastasize to the lung. Enhancement of secondary deposits is most often heterogenous, sometimes nodular. 3. Lower limb SS most commonly present in adolescent and young adults, and the majority of cases occur in the lower limb. Because these tumours typi cally present as a soft tissue swelling, ultrasound is often the first mo dality used for assessment. Typical findings on US are of a focal nodular hypoechoic well circumscribed soft tissue lesion, usually with internal vascularity and sometimes with calcific foci (Fig. 1), however US find ings are non-specific and there is no single US feature which is patho gnomonic for SS. Large serpentine vascular channels have been described in approximately one-third of SS, a feature which is not commonly seen in other soft tissue neoplasms [9]. A retrospective study of 35 cases in adults revealed that in 66 % of cases, SS can appear on US as an indolent rather than aggressive process [11]. The findings of a soft-tissue mass near but not in a joint (particu larly the knee joint) in a young patient (15–40 years old), particularly in association with calcification, is very suggestive of a SS (Fig. 1a). Pre sentation is often non-specific, commonly with a chronic history of intermittent joint pain and possibly with a limp. On the rare occasion that a SS is seen to involve/invade the joint and occur intra-articularly, previous studies show this commonly occurs in the Hoffa fat pad [9]. Fig. 3 demonstrates SS with intra-articular
Fig. 1. Ultrasound features of synovial sarcomas are often of a focal nodular, but sometimes smooth, contoured mass with complex internal architecture. Ultrasound images, using a linear array transducer, of synovial sarcomas in the (a) popliteal fossa demonstrating internal vascularity and a focus of calcifica tion with some posterior acoustic shadowing, and (b) forearm, shows a well circumscribed mass with a smooth contour.
invasion via Hoffa’s fat pad. Other manifestations of SS arising in the lower limb include an exophytic, frequently avidly enhancing mass. Fig. 4 demonstrates SS arising from the dorsum of the foot in a teenage boy, who had previously had excision of a small mass that was believed to be a benign schwan noma. The mass recurred with ulceration and rupture and was diag nosed as SS. For assessing the extent and intrinsic features of the tumour MRI, with its superior contrast resolution, is performed. Tumours are usually 2
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Fig. 2. Synovial sarcoma arising close to the right popliteal fossa in a 9 yo Caucasian male who presented with chronic history of a slow growing painless mass. Axial T1W image through the popliteal fossa shows a lobulated well circumscribed lesion (a) displacing the vessels anteriorly, with (b) central focal enhancement post gadolinium. The corresponding DWI/ADC map shows that the solid components of the mass demonstrate restricted diffusion on DWI (c) and ADC (d) images. The same lesion demonstrates the ‘triple signal’ pattern (e) on T2W (high, intermediate, and low signal on T2 weighted images).
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Fig. 3. Synovial sarcoma in a 12 yo Caucasian boy who presented with a 2 year history of intermittent left knee pain following a trampoline accident, during which time the knee became progressively more swollen and painful.(a) Sagittal T1W post gadolinium image of the distal femur, shows a lobulated, heterogeneous enhancing lesion with no involvement of the underlying bone. (b) coronal T1W post gadolinium image of the same lesion showing similar enhancement of the solid components of the lesion. (c) Axial T2W of the same lesion demonstrating another ‘triple signal’ pattern.
well-circumscribed and appear bright on STIR sequences. On T1weighted images SS typically appear as heterogeneous multi-lobulated soft tissue masses with signal similar to muscle [10] (Figs. 5 and 6), with internal foci of high signal consistent with hemorrhage [12]. They are often cystic and solid lesions, with avid post contrast enhancement of the solid components (Fig.7). Less common patterns of enhancement include diffuse homogenous enhancement of predominantly solid
lesions (Fig.8). On T2W imaging, they appear as heterogeneous masses with pre dominant high signal. A ‘triple signal’ pattern has been described con sisting of areas that are of high signal consistent with fluid, areas that are iso-to slightly hyperintense relative to fat, and areas of slightly lower signal intensity, suggesting fibrous tissue [12] (Figs. 2 and 3). This heterogeneity/triple signal sign on T2W sequences is thought to be the 4
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Fig. 4. Case of synovial sarcoma in the foot. (a) Sagittal T1W and (b) sagittal post gadolinium images of sarcoma in the foot of a 14 yo Black male presenting with a 2 year history of foot pain, with gradual onset of swelling and numbness. Images show well-circumscribed homogeneously avid enhancing mass on the dorsum of the right foot.
Fig. 5. Synovial sarcoma of the left femoral sheath in a 16 yo Caucasian boy, who presented with a 2 year history of left groin pain. (a) Axial T1 shows well circumscribed lesion (arrow) with (b) mainly peripheral enhancement post gadolinium.
result of the mixture of solid cellular elements (intermediate signal), calcified/fibrotic areas (low signal) and haemorrhage or necrosis (high signal). Although the ‘triple signal’ pattern has been described as occurring in 35–57 % of cases [12,13] it should be noted that this pattern can be seen in other soft-tissue neoplasms, and therefore this finding alone, particularly without the clinical findings, is not specific enough to be diagnostic. The multi-lobulated appearance of SS, with multiple internal septa, is also typically a feature seen on T2W imaging and more frequently seen in larger lesions. The decision on where to target for biopsy usually involves a review and discussion of all imaging, between the radiologists, pathologists and surgeons, in an MDT setting. A representative high quality tissue sample for histological diagnosis can be obtained by selectively targeting at biopsy the solid, enhancing components of the tumour. These may show variable levels of enhancement post contrast, depending on the degree of internal vascularity. Areas to be avoided when considering biopsy include necrotic foci [14], which are predominantly high on T2W and low on T1W sequences. This also applies more generally to predominantly cystic areas. In addition, areas of calcification and fibrosis (typically low on T1W and T2W) should also be avoided.
Smaller lesions (<5 cm) typically have a more homogeneous appearance (Fig. 9d) whereas larger lesions show heterogeneous inter nal features including post contrast enhancement of solid components. Larger lesions may also be predominantly cystic, with fluid-fluid levels (Fig. 10b and d) which, when large and associated with promi nent haemorrhagic foci, can manifest with a ‘bunch of grapes’ appear ance [10]. These lesions often have a solid enhancing nodular component (Fig. 10). 5. Trunk (chest/abdomen/pelvis) SS of the chest is rare and often presents symptomatically, sometimes with dyspnoea secondary to a pleural effusion. In such cases, radio graphs can play a role in the diagnosis (Fig. 11). When SS occur in the abdomen they tend to be large, and often have a more solid component when compared to their extremity counterparts. The solid components typically show early enhancement (within 7 s) on dynamic MR contrast studies, with rapidly progressive increase in signal intensity, followed by either wash out or a late sustained increase in enhancement after an initial rapid enhancement [15]. The early enhancement patterns described are diffuse (40 %) (Fig. 12), hetero geneous (40 %) (Fig. 13) or peripheral (20 %) (Fig. 5) [15]. Diffuse enhancement is often seen if tumour is viable, whereas largely necrotic tumours demonstrate peripheral or nodular enhancement. Diffusion weighted imaging is often useful as there is often evidence of restricted diffusion of the solid components (Fig. 2c and d). Enhancement of solid nodular foci, representing viable non-necrotic
4. Upper limb Imaging characteristics of SS in the upper arm are similar to cases seen in other parts of the body. They also commonly present as a soft tissue swelling, again often in close proximity to a joint. This most often occurs anterior to the antecubital fossa (Figs. 9 and 10). 5
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Fig. 6. Predominantly solid synovial sarcoma presenting as a painful right gluteal mass in a 21 yo Caucasian woman. (a) axial and (b) coronal T1W imaging showing mass (arrowed) with similar signal as adjacent musculature. (c) STIR axial image of the same patient shows the well circumscribed lesion passing through the right greater sciatic foramen.
tumour, is particularly important when the tumour is predominantly cystic on T1W and T2W imaging, since this helps guide potential areas to target for tissue biopsy. Although CT is rarely used to characterize SS, it typically appears as a well circumscribed, heterogeneous, soft tissue mass with non-enhancing necrotic and cystic areas, acute haemorrhagic foci, enhancing solid components and attenuation similar to or slightly lower than muscle post contrast (Figs.14 and 15) [11,13,15–19]. When closely opposed to bone, the underlying bony cortex is not typically affected (Fig. 15). Head and Neck On MRI, about 50%–90% of SS of the head and neck present as small, homogeneous, well circumscribed masses that may be mistaken for a less aggressive, seemingly indolent process (Fig. 16). Whilst these smaller lesions are often well circumscribed [13], on CT they may contain low attenuation regions, in keeping with cystic foci, or high attenuation regions consistent with acute haemorrhage or calcification
[10]. Calcific foci are low signal on all MR sequences, but are more conspicuous on radiographs and CT. Continuity with or invasion of adjacent bone is seen on MRI in up to 21 % of head and neck SS [20,12, 21] (Fig. 16b). Typically, there is no underlying bony involvement, although there may be mild bone marrow oedema. Case studies of SS in the neck report neurovascular involvement in 17–24 % cases, likely because these tumors originate in an inter muscular site near the neurovascular bundle [20,12,21]. The neuro vascular bundle is surrounded by fat, therefore masses arising in this region maintain a rim of fat around them as they enlarge, resulting in the ‘split fat sign’ [9]. A rim of preserved fat adjacent to a neurovascular bundle can also be appreciated on CT (Fig. 17a). Like the ‘triple signal’ pattern, the ‘split fat sign’ is not specific to SS, since any mass which arises in an intermuscular location can have a similar appearance. SS in the neck most often cause displacement rather than invasion of the adjacent neurovascular bundle (Fig. 17b). 6
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Fig. 8. (a) axial T1W, (b) axial T1 post gadolinium enhancement of another synovial sarcoma presenting anterior to the proximal femur in a 17 yo Cauca sian female with a 2-3 week history of increasing leg pain and limp. In contrast to the cystic variety of synovial sarcoma this tumour was predominantly solid with homogeneous/diffuse enhancement post gadolinium.
Fig. 7. Synovial sarcoma involving the proximal thigh. (a) coronal T2 fat sat and (b) axial post gadolinium images of a sarcoma abutting (but not invading) the proximal left femur in a 14 y Caucasian girl who presented with a chronic history of intermittent hip pain. MRI showed a cystic/solid lesion, with avid enhancement of the solid components.
6. Differential diagnosis of SS The non-specific imaging features of SS and the unfamiliarity of some reporting radiologists with these rare entities may mean they are mis diagnosed or even dismissed as benign lesions which could potentially result in a delay to biopsy, and therefore to a diagnosis. 7
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Fig. 9. Synovial sarcoma at the elbow. Case one (a) radiograph of right upper arm showing soft tissue density but no underlying bony abnormality (b) Coronal T1W and, axial T2W (c) and axial FS post gadolinium (d) of the same lesion on MRI showing a heterogeneous well circumscribed lesion.
As previously described, most SS occur in the extremities, particu larly around the knee. There are many benign entities associated with this anatomical site, some of which may mimic SS. Haemangiomas, or venous malformations, are benign abnormal proliferations of blood vessels and are one of the most common soft tissue tumours in children [22]. True haemangiomas occur in infancy at an earlier age than SS. Synovial haemangiomas are rare vascular malformations of the joints which, like SS, can present with non-specific joint pain and swelling. Associated with episodes of spontaneous haemarthrosis, these intra-articular lesions can demonstrate fluid-fluid levels similar to SS with marked hyperintensity on T2W due to pooling of blood within vascular spaces [23]. However unlike SS, they classically show intra-articular dilated tortuous vessels, with variable enhancement post contrast. Synovial chondromatosis is a benign neoplasm which can occur at any age, most commonly in the knee, and may be confused with SS. Their appearance on MRI depends on the degree of synovial membrane
proliferation and the formation of cartilaginous or osseous bodies [24], where cartilaginous bodies may form conglomerate masses which may resemble SS on T1W and T2W imaging. However these bodies (carti laginous or osseous) do not enhance although there may be enhance ment of the hyperplastic synovium. Pigmented villonodular synovitis (PVNS) is a rare monoarticular disease of the joints, most frequently of the knee, and similar to synovial chondromatosis demonstrates proliferation of synovial cells. Like SS they can be present as large lobulated masses, but more typically show homogeneous/inhomogenous low signal on all pulse sequences [25], with characteristic blooming artefact on gradient-echo sequences, sec ondary to haemosiderin from chronic haemorrhage [24]. Peripheral nerve sheath tumours (PNST), including schwannomas and neurofibromas, can occur anywhere in the body, usually superfi cially, and may occur in the atypical SS locations whilst sharing similar imaging characteristics. Like SS they can show avid or variable enhancement post contrast and are associated with the ‘split fat’ sign on 8
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Fig. 10. Synovial sarcoma in an 11 yo Black male who presented with a 5 month history of a right arm mass which started as a small ‘knot’ but continued to enlarge. (a) lateral radiograph showing soft tissue mass (arrow) anterior to the antecubital fossa. (b) axial T2W fat sat through the same region showing a predominantly cystic lesion with a solid nodule, and fluid-fluid levels in keeping with layered haemorrhage components. (c) axial T1W post gadolinium shows this solid nodule to enhance and (d) and coronal T2W shows this nodular component to have a further small cystic component (dashed arrow). The coronal T2W also shows there are multiple solid nodules within the same cystic mass lesion.
T1W images [26]. Unlike SS, PNSTs originate along a major nerve and therefore the visualisation of the nerve entering and exiting the tumour means the diagnosis of PNST can be made. Malignant PNST are usually large ill-defined fusiform masses, arising from medium to large deep nerves such as the sciatic nerve or brachial plexus. They are complex lesions on MR with surrounding oedema due to infiltration of adjacent tissues, and typically with increased heterogeneous enhancement, pe ripheral nodular enhancement and central necrosis [27]. Since SS may be composed of fluid filled spaces, particularly when large, they may also be mistaken for cysts. While some peripheral enhancement of the cyst wall may be seen post contrast, simple cysts lack the internal complexity and soft tissue component seen in SS. Para-articular cystic lesions which may mimic SS, particularly if they demonstrate atypical features, include ganglion cysts and synovial cysts
e.g. Bakers cysts of the knee. Ganglion cysts may present as a multi loculated fluid signal masses adjacent to a joint, with internal foci of T1W hyperintensity if they haemorrhage or contain high proteinaceous content. However unlike SS, they commonly occur on the dorsal surface of the wrist and typically show peripheral enhancement post contrast [24]. In other rare locations where SS may be found, for example the head, neck or abdomen, it is important to differentiate SS from other cystic lesions such as lymphatic malformations, which are benign lesions of vascular origin which show lymphatic differentiation. Most (95 %) of lymphatic malformations occur in the neck and axilla, whilst the remaining 5% can be found in the retroperitoneum, abdominal viscera, mesentery, lung and mediastinum [28] and usually present within the first two years of life. Typically anaechoic multilocular cystic masses, 9
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Fig. 11. High grade synovial sarcoma in a 20 yo Hispanic male who presented to their local hospital with a several month history of shortness of breath. (a) CXR shows a large left sided pleural effusion with contralateral mediastinal shift, (b) CT demonstrates a pleural effusion with a pleurally based soft tissue mass (arrow) at the left lung base, which (c) enhances post gadolinium.
like SS they may also show areas of T1W hyperintensity due to hae morrhage or proteinaceous fluid. However they can be distinguished from SS clinically by their location, their tendency to wax and wane in size, and radiologically by thin internal septa that may enhance in cases of superimposed inflammation and by the lack of soft tissue component [29]. When comparing SS with many soft tissue sarcomas, there is argu ably more overlap in the range of non-specific imaging features between
malignant lesions. Rhabdomyosarcoma is the most common soft tissue sarcoma in children, is associated with neurofibromatosis 1 and Beckwith-Wiedemann syndrome and mostly occur in the head and neck or genitourinary area [30]. About 10 % of rhabdomyosarcomas occur in an extremity, usually in children younger than 10 years of age. Congenital-infantile fibrosarcoma is a rare malignancy, making up for less than 1 % of all childhood cancers [31] and tend to be much larger tumours (up to 16 cm) than SS, occurring in young children less than 10
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Fig. 13. Large synovial sarcoma within the left gluteal region in a 14 yo Caucasian girl, with extension into the pelvis via the left greater sciatic fora men, showing heterogeneous enhancement post-gadolinium.
However they are more likely to show peripheral enhancement in a rimlike fashion [34], whereas SS is more likely to have central solid nodular enhancement.
Fig. 12. Synovial sarcoma arising from the right chest wall and extending into the right supraclavicular fossa in a 17 yo Caucasian male. (a) T1W shows a well circumscribed homogeneous mass (arrowed) (b) which displays homogeneous and diffuse enhancement.
7. Prognostic factors The prognostic significance of radiological findings was examined in a study by Tateishi et al., which included 30 patients 10–61 years of age, with pathologically confirmed SS. They compared the image findings with the histopathological features of the tumour, including tumour grade. Imaging features which favoured the diagnosis of a high-grade tumour included proximal distribution, tumour size over 10 cm, absence of calcification, the presence of haemorrhage and the ‘triple signal’ pattern [13]. Those investigators found that the 5-year disease-free survival rate (DFS) for patients with tumors containing calcification (n = 22; p < 0.01) was 100 %, compared to DFS rate of 0 for patients with haemorrhage (n = 16; p < 0.05) and triple signal pattern (n = 13; p < 0.05) [13]. SS is frequently associated with local recurrence and distant metas tases. The most common metastatic route is haematogenous, occurring in 50–70 % of patients, followed by regional nodal spread in 10–20 % [35]. A recent study of SS in children and adolescents found that the risk of metastases was 32 times higher for subjects whose tumours >5 cm in size [36]. Fortunately, in the paediatric population SS are typically < 5 cm and, therefore, the incidence of metastases in this population is far lower than in adults. Disseminated disease to the lung has also been shown to be the most common site for metastatic disease from other extremity soft tissue
three years of age typically. On imaging however, differentiation rhabdomyosarcoma and fibro sarcoma from SS can be difficult, given the similar non-specific MR characteristics that these three malignant entities share, predominantly iso- to hyperintense T1W signal and variable or heterogeneous enhancement post contrast. Unlike SS, the T2W ‘triple signal’ pattern has not been described in rhabdomyosarcoma or congenital-infant fi brosarcomas, where they typically show T2W hyperintensity compared to skeletal muscle [32]. Rhabdomyosarcomas are also associated with bone destruction or remodelling, whereas SS is not. Undifferentiated pleomorphic sarcomas (UPS) typically occur in the lower extremity and, although these typically present in adulthood, may share many features on MR with SS. For example low-intermediate signal on T1W and intermediate-high signal on T2W [33]. Unlike SS they may erode or invade the bone and may have peripheral ossification, however differentiating between the two based purely on imaging is often impossible. SS of the abdomen is extremely rare, and when they do occur they tend to be large, predominantly solid and may have cystic and hae morrhagic foci (Fig. 14). Abdominopelvic leiomyosarcomas are also predominantly large, heterogeneous masses (average 11 cm) with low density areas on CT due to cysts, necrosis or haemorrhage. Like SS they are relative isointense to muscle on T1W, hyperintense on T2W. 11
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Fig. 15. Synovial sarcoma in a 4 yo Caucasian girl who presented with an enlarging right groin nodule. (a) CT with contrast shows this lesion abuts the right ilium and extends (b) inferiorly into the right proximal thigh. No under lying bony destruction is seen.
value) predicts a poor overall survival [39]. Following treatment (chemotherapy or radiotherapy) increasing signal may be seen on T2W sequences, corresponding to progressive necrosis of the tumour. The size of the tumour may decrease, and sur rounding oedema may develop. FDG-PET/CT may also be used to assess the efficacy of chemotherapy, by showing a reduction in subjective FDG avidity in lesions that have been treated [33]. More recently a genomic study looked at the prognostic value of the number of chromosomal alterations in patients under the age of 25 years with localized disease and found that high tumor genomic complexity was associated with a significantly increased risk of metastasis and decreased probability of event free survival (defined as progression during chemotherapy relapse after complete remission or death from any cause) [40].
Fig. 14. Synovial sarcoma originating from the gastrocolic ligament, in a 15 yo Caucasian boy who presented with a large RUQ mass following a football injury, thought to be a haematoma. (a) Abdominal radiograph showing large right-sided mass (arrow), with displacement of the bowel loops. (b) CT showing a heterogeneous mass with areas of acute haemorrhage (arrow), and displace ment of the adjacent bowel, IVC, right renal artery and vein. Free fluid noted in the right abdomen.
sarcomas, particularly in cases of large (>5 cm) intermediate or high grade lesions. For this reason CT of the chest is necessary for staging [37]. Whilst CT and MRI are most commonly used for detection of distant metastases and loco-regional nodal spread respectively, some centres use FDG-PET/CT for staging of synovial sarcomas and other soft tissue sarcomas, particularly for large and high grade tumours. One study which looked at the most common soft tissue tumours, including SS, found the negative predictive value of PET to be 89 % with a specificity of 96 % [38]. In addition to staging, recent studies have investigated the value of the SUVmax of the primary tumor on pre-treatment FDG-PET/CT in predicting disease progression and overall survival, and found that a higher per-treatment SUVmax (SUVmax of 6.1 was determined as cutoff
8. Conclusion Our pictorial essay demonstrates how SS can occur in any anatomical location, but typically within the extremities and in close association with (but not within) joints. They can take on a range of different enhancement patterns, from diffusely homogeneous to heterogeneous, and can be predominantly cystic (sometimes with fluid-fluid levels) or solid. The ‘triple signal’ pattern seen on T2W images is a feature of SS, but is not pathognomonic, and can be seen in other neoplasms. How ever, when seen as a feature in SS it may predict a poor outcome. Other features which are indicative of poor outcome include presence of 12
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Fig. 17. Synovial sarcoma in 8 yo Caucasian boy who presented with a right neck mass. (a) axial CT post contrast shows a rim of fat surrounding this well circumscribed lesion with (b) posterior displacement of the neuro vascular bundle.
Fig. 16. High grade synovial sarcoma on the right parietal region of an 8 yo Caucasian boy, who presented with a pea sized bump originally believed to be a sebaceous cyst. (a) Axial T2W image shows solitary a well circumscribed lesion (arrow), which (b) homogeneously enhances post gadolinium and involves the inner and outer tables of the calvarium (arrow).
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haemorrhage, absence of calcification, proximal distribution, and large tumour size (>10 cm). Synovial sarcoma usually present as a well circumscribed mass and, despite their size, displace adjacent structures rather than invade them. Radiological findings are relatively non-specific, and in some instances SS may even mimic benign lesions, however the findings of a mixed solid/cystic soft-tissue mass in a young patient, close to a joint and possibly with calcification, are suggestive of this diagnosis.
[18] A.S. Rangheard, D. Vanel, J. Viala, G. Schwaab, O. Casiraghi, R. Sigal, Synovial sarcomas of the head and neck: CT and MR imaging findings of eight patients, AJNR Am. J. Neuroradiol. 22 (2001) 851–857. [19] C.A. Meyer, M.J. Kransdorf, R.P. Moser Jr, J.S. Jelinek, Case report 716: soft-tissue metastasis in synovial sarcoma, Skeletal Radiol. 21 (1992) 128–131, https://doi. org/10.1007/bf00241841. [20] M.D. Murphey, J.S. Jelinek, M.J. Kransdorf, D.J. Flemming, H.T. Temple, S. E. Smith, Imaging of synovial sarcoma (abstract), Radiology 209 (1998) 421, https://doi.org/10.1148/rg.265065084. [21] M.J. Morton, T.H. Berquist, R.A. McLeod, K.K. Unni, F.H. Sim, MR imaging of synovial sarcoma, Am. J. Roentgenol. 156 (1991) 337–340, https://doi.org/ 10.2214/ajr.156.2.1846054. [22] F.M. Enzinger, S.W. Weiss, Soft Tissue Tumors, third ed., Mosby, St. Louis, 1995. [23] P.J. Sheldon, D.M. Forrester, T.J. Learch, Imaging of intraarticular masses, Radiographics 25 (2005) 105–119, https://doi.org/10.1148/rg.251045050. [24] Z. Weissberg, R. Sebro, Distinguishing synovial sarcoma from benign and malignant mimics: MR Imaging indicators, Appl. Radiol. 47 (2018) 15–21. [25] R.H. Dorwart, H.K. Genant, W.H. Johnston, J.M. Morris, Pigmented villonodular synovitis of synovial joints: clinical, pathologic, and radiologic features, Am. J. Roentgenol. 143 (1984) 877–885. [26] C. Kakkar, C.M. Shetty, P. Koteshwara, S. Bajpai, Telltale signs of peripheral neurogenic tumors on magnetic resonance imaging, Indian J. Radiol. Imaging 25 (2015) 453–458, https://doi.org/10.4103/0971-3026.169447. [27] V. Rafailidis, T. Kaziani, C. Theocharides, A. Papanikolaou, D. Rafailidis, Imaging of the malignant peripheral nerve sheath tumour with emphasis on ultrasonography: correlation with MRI, J. Ultrasound 17 (2014) 219–223, https:// doi.org/10.1007/s40477-014-0097-2. [28] C.H. Lugo-Olivieri, G.A. Taylor, CT differentiation of large abdominal lymphangioma from ascites, Paediatr. Radiol. 23 (1993) 129–130, https://doi.org/ 10.2214/ajr.182.6.1821485. [29] J. Dubois, F. Thomas-Chausse, G. Soulez, Common (Cystic) lymphatic malformations: current knowledge and management, Tech. Vasc. Interv. Radiol. 22 (2019) 100631, https://doi.org/10.1016/j.tvir.2019.100631. [30] R. Stein-Wexler, Pediatric soft tissue sarcomas, Semin. Ultrasound CT MR 32 (2011) 470–488, https://doi.org/10.1053/j.sult.2011.03.006. [31] A.H. Al-Salem, Congential-infantile fibrosarcoma masquerading as sacrococcygeal teratoma, J. Pediatr. Surg. 46 (2011) 2177–2180. [32] K.E. Ainsworth, G.B. Chavhan, A.A. Gupta, S. Hopyan, G. Taylor, Congenital infantile fibrosarcoma: review of imaging features, Pediatr. Radiol. 44 (2014) 1124–1129, https://doi.org/10.1007/s00247-014-2957-5. [33] J.F. Eary, E.U. Conrad, Imaging in sarcoma, J. Nucl. Med. 52 (2011) 1903–1913, https://doi.org/10.2967/jnumed.111.092999. [34] R. Stramare, G. Orsatti, S. Attar, M. Rastrelli, A. Brunello, C. Bortolanza, P. Ortolan, A. Coran, Imaging features, differential diagnosis and management of leiomyosarcomas: case series and review of the literature, J. Cancer Sci. Ther. 8 (2016) 84–91, https://doi.org/10.4172/1948-5956.1000397. [35] J.N. Cormier, R.E. Pollock, Soft tissue sarcomas, CA Cancer J. Clin. 54 (2004) 94–109. [36] A. Ferrari, G.L. DeSalvo, O. Oberlin, M. Casanova, A. De Paoli, A. Rey, V. Minard, D. Orbach, M. Carli, B. Brennan, M.M. Vannoesel, C. Morosi, M.C. Stevens, G. Bisogno, Synovial sarcoma in children and adolescents: a critical reappraisal of staging investigations in relation to the rate of metastatic involvement at diagnosis, Eur. J. Cancer 48 (2012) 1370–1375, https://doi.org/10.1016/j.ejca.2012.01.013. [37] NCCN Clinical Practice Guidelines in Oncology, National comprehensive cancer network web site. Soft Tissue Sarcoma, 2020. https://www.nccn.org/store/login/ login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/sa rcoma.pdf. [38] D. Roberge, S. Vakilian, Y.Z. Alabed, R.E. Turcotte, C.R. Freeman, M. Hickeson, FDG PET/CT in initial staging of adult soft-tissue sarcoma, Sarcoma (2012) 960194, https://doi.org/10.1155/2012/960194. [39] K.J. Chang, I. Lim, J.Y. Park, et al., The role of (18)F-FDG PET/CT as a prognostic factor in patients with synovial sarcoma, Nucl. Med. Mol. Imaging 49 (2015) 33–41, https://doi.org/10.1007/s13139-014-0301-5. [40] D. Orbach, V. Mosseri, D. Pissaloux, B. Brennan, A. Ferrari, F. Chibon, G. Bisogno, G.L. de Salvo, C. Chakiba, N. Corradini, V. Minard-Colin, A. Kelsey, D. Ranch` ereVince, Genomic complexity in pediatric synovial sarcomas (Synobio study): the European pediatric soft tissue sarcoma group (EpSSG) experience, Cancer Med. 7 (2018) 1384–1393, https://doi.org/10.1002/cam4.1415.
Declaration of Competing Interest The authors reported no declarations of interest. References [1] R. Deshmukh, H.J. Mankin, S. Singer, Synovial sarcoma: the importance of size and location for survival, Clin. Orthop. Relat. Res. 419 (2004) 155–161. [2] A. Rajwanshi, R. Srinivas, G. Upasana, Malignant small round cell tumors, J. Cytol. / Indian Acad. Cytolo. 26 (2009) 1–10, https://doi.org/10.4103/09709371.54861. [3] C. Fisher, Synovial sarcoma: ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors, Hum. Pathol. 17 (1986) 996–1008, https://doi.org/10.1016/S0046-8177(86)80083-1. [4] A.A. Sandberg, J.A. Bridge, Updates on the cytogenetics and molecular genetics of bone and soft tissue tumours. Synovial sarcoma, Cancer Genet. Cytog. 133 (2002) 1–23, https://doi.org/10.1016/s0165-4608(01)00626-4. [5] D.R.H. de Bruijn, S.V. Allander, A.H.A. van Dijk, M.P. Willemse, J. Thijssen, J.J. M. van Groningen, P.S. Meltzer, A.G. van Kessel, The synovial sarcoma–Associated SS18-SSX2 fusion protein induces epigenetic gene (De)Regulation, Cancer Res. 66 (2006) 9474–9482, https://doi.org/10.1158/0008-5472.CAN-05-3726. [6] D. Cabuk, B. Ustuner, A.G. Akgul, et al., Primary synovial sarcoma of lung, Korean J. Thorac. Cardiovasc. Surg. 47 (2014) 306–309, https://doi.org/10.5090/ kjtcs.2014.47.3.306. [7] M. Vedana, M. Fuenfschilling, A. Tzankov, T. Zellweger, Primary synovial cell sarcoma of the kidney: case report and review of the literature, Case Rep. Oncol. 8 (2015) 128–132, https://doi.org/10.1159/000379740. [8] M.E. Harstein, F.-L. Silver, O.J. Ludwig, D.M. O’Connor, Primary synovial sarcoma, Ophthalmology 113 (2006) 2093–2096, https://doi.org/10.1016/j. ophtha.2006.04.037. [9] M.D. Murphey, M.S. Gibson, B.T. Jennings, A.M. Crespo-Rodríguez, J. FanburgSmith, D.A. Gajewski, Imaging of synovial sarcoma with radiologic-pathologic correlation, RadioGraphics 26 (2006) 1543–1565, https://doi.org/10.1148/ rg.265065084. [10] M.J. Kransdorf, Malignant soft-tissue tumors in a large referral population: distribution of diagnoses by age, sex, and location, AJR Am. J. Roentgenol. 164 (1995) 129–134, https://doi.org/10.2214/ajr.164.2.7839977. [11] L. Marzano, S. Failoni, M. Gallazzi, P. Garbagna, The role of diagnostic imaging in synovial sarcoma: our experience, Radiol. Med. 107 (2004) 533–540. [12] B.C. Jones, M. Sundaram, M.J. Kransdorf, Synovial sarcoma: MR imaging findings in 34 patients, AJR Am. J. Roentgenol. 161 (1993) 827–830, https://doi.org/ 10.2214/ajr.161.4.8396848. [13] U. Tateishi, T. Hasegawa, Y. Beppu, M. Satake, N. Moriyama, Synovial sarcoma of the soft tissues: prognostic significance of imaging features, J. Comput. Assist. Tomogr. 28 (2004) 140–148, https://doi.org/10.1097/00004728-20040100000024. [14] A. Leithner, W. Maurer-Ertl, R. Windhager, Biopsy of bone and soft tissue tumours: hints and hazards, Recent Results Cancer Res. 179 (2009) 3–10. [15] C.S. van Rijswijk, P.C. Hogendoorn, A.H. Taminiau, J.L. Bloem, Synovial sarcoma: dynamic contrast- enhanced MR imaging features, Skeletal Radiol. 30 (2001) 25–30, https://doi.org/10.1007/s002560000295. [16] M.J. Kransdorf, M.D. Murphey, Imaging of Soft Tissue Tumors, second ed., Lippincott William & Wilkins, Philadelphia, 2006. [17] S.J. Israels, H.S. Chan, A. Daneman, S.S. Weitzman, Synovial sarcoma in childhood, AJR Am. J. Roentgenol. 142 (1984) 803–806, https://doi.org/10.2214/ ajr.142.4.803.
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Primary synovial sarcomas in the paediatric and young adult population: A pictorial review Melissa Hickson a, *, Kieran McHugh b, Beth McCarville c a
The Whittington Hospital, Magdala Avenue, London N19 5NF, UK Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK c St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA b
A R T I C L E I N F O
A B S T R A C T
Keywords: Primary synovial sacroma Paediatric Imaging Malignancy
Purpose: To present a pictorial essay of paediatric primary synovial sarcomas from common and less documented anatomical locations. To review the literature for the imaging characteristics and prognostic factors of this rare but important childhood malignancy. Method: 24 primary synovial sarcoma cases (17 male, 7 female with an age range 4–21 years) were reviewed in a collaborative effort between St Jude Children’s Research Hospital and Great Ormond Street Hospital for Children. Images from 19 cases were selected for inclusion, to demonstrate the spectrum of appearances across imaging modalities, in a range of different anatomical locations (upper limb, lower limb, chest/abdomen/pelvis, and head and neck). A literature review depicting the typical radiological features and the prognostic significance of these features, was also conducted. Results and conclusions: Primary synovial sarcoma can occur in any anatomical location, but typically within the extremities and often in close association with joints. Rarer anatomical locations described in our essay include the gastrohepatic ligament and femoral nerve sheath. We detail the salient imaging characteristics, including the T2 ‘triple signal’ pattern which is believed to be highly specific for this particular sarcoma and in many cases predicts a poor outcome. Other poor prognostic factors include haemorrhage, lack of calcification and tumour size >10 cm. A broad range of radiological appearances are described, and in some cases related to anatomical position and size, however the presence of a soft tissue mass close to a joint in a young patient are suggestive of this diagnosis.
1. Introduction Primary synovial sarcomas (SS) are rare malignant tumours, with an estimated incidence of 2.75 in 100,000 [1]. A subset of the malignant small round cell tumours, they account for 10 % of all soft-tissue sar comas, and are the fourth most common soft tissue sarcoma following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma [2]. Malignant small round cell tumour is a term used for tumours composed of cells which are slightly larger or double the size of red blood cells in air-dried smears [2]. SS were first described in 1865 by Simon [3], and are characterized cytogenetically by a recurring chro mosomal translocation, t(X;18)(p11.2;q11.2) in >95 % of cases [4],
whereby the SS18 gene on chromosome 18 is fused to one of 3 SSX genes found on the x chromosome (SSX1, SSX2 or SSX4). A study examining the transcriptional consequences of these SS18-SSx fusion proteins, found that the SS18-SSX2 fusion protein downregulated downstream target genes, supporting the proposal that SS18-SSX fusion proteins act as an “activator-repressor” through epigenetic mechanisms [5]. They most commonly occur in adolescents and young adults, be tween the ages of 15− 30years. Despite their name they do not commonly occur within a joint, but in the extremities with a close relation to joint spaces, particularly around the knee and lower thigh region. However, they can occur anywhere, even at locations distant from joint spaces. Examples include SS of the lung, an extremely rare and aggressive tumour with a poor prognosis [6], of the kidney [7] and
* Corresponding author at Imaging Department, The Whittington Hospital, Magdala Avenue, London N19 5NF, UK. E-mail addresses: [email protected] (M. Hickson), [email protected] (K. McHugh), [email protected] (B. McCarville). https://doi.org/10.1016/j.ejrad.2020.109376 Received 9 April 2020; Received in revised form 14 October 2020; Accepted 21 October 2020 Available online 28 October 2020 0720-048X/Crown Copyright © 2020 Published by Elsevier B.V. All rights reserved.
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Table 1 Anatomical sites of synovial sarcoma in 24 young adults and children. Anatomical site Head and Neck Upper extremity Chest Abdominal Pelvic Lower extremity
Number of Cases Elbow Forearm/wrist
Groin/Proximal thigh Knee Foot
2 3 3 2 1 2 4 4 3
even of the orbit [8]. SS usually occur in the extremities, with the lower limb accounting for the majority of cases. The most frequent site of involvement is the popliteal fossa [9]. It is the most common paediatric malignancy of the soft tissues involving the foot and ankle [10]. Less commonly affected sites include the head and neck (7%), trunk, thorax and chest wall (7%), retroperitoneum (0.3 %), and pelvis (8%) [9]. SS is a rare malignancy, and therefore patients who were imaged and treated at one of two tertiary centers dating back to 2004 (Great Ormond Street Hospital and St Jude Children’s Research Hospital), were com bined and reviewed. A total of 24 cases were reviewed (17 male, 7 fe male, ranging in age from 4 to 21 years with a mean age of 13 years) from this combined institutional cohort, describing tumours arising in a variety of different anatomical locations (Table 1). Images from 19 cases were selected for inclusion in the pictorial review. 2. Imaging of synovial sarcoma Baseline imaging encompasses ultrasound (US), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomographycomputed tomography (FDG PET-CT), and in some instances plain film radiographs. About half of radiographs, and particularly those associated with smaller lesions, can appear normal [9]. Calcification is seen in up to 30 % of SS on radiography and are often eccentric or peripheral within the soft tissue mass and fairly non-specific in appearance. The imaging findings although not pathognomonic, are frequently enough to suggest the diagnosis [9]. Calcification is also seen in SS metastatic deposits, particularly those which metastasize to the lung. Enhancement of secondary deposits is most often heterogenous, sometimes nodular. 3. Lower limb SS most commonly present in adolescent and young adults, and the majority of cases occur in the lower limb. Because these tumours typi cally present as a soft tissue swelling, ultrasound is often the first mo dality used for assessment. Typical findings on US are of a focal nodular hypoechoic well circumscribed soft tissue lesion, usually with internal vascularity and sometimes with calcific foci (Fig. 1), however US find ings are non-specific and there is no single US feature which is patho gnomonic for SS. Large serpentine vascular channels have been described in approximately one-third of SS, a feature which is not commonly seen in other soft tissue neoplasms [9]. A retrospective study of 35 cases in adults revealed that in 66 % of cases, SS can appear on US as an indolent rather than aggressive process [11]. The findings of a soft-tissue mass near but not in a joint (particu larly the knee joint) in a young patient (15–40 years old), particularly in association with calcification, is very suggestive of a SS (Fig. 1a). Pre sentation is often non-specific, commonly with a chronic history of intermittent joint pain and possibly with a limp. On the rare occasion that a SS is seen to involve/invade the joint and occur intra-articularly, previous studies show this commonly occurs in the Hoffa fat pad [9]. Fig. 3 demonstrates SS with intra-articular
Fig. 1. Ultrasound features of synovial sarcomas are often of a focal nodular, but sometimes smooth, contoured mass with complex internal architecture. Ultrasound images, using a linear array transducer, of synovial sarcomas in the (a) popliteal fossa demonstrating internal vascularity and a focus of calcifica tion with some posterior acoustic shadowing, and (b) forearm, shows a well circumscribed mass with a smooth contour.
invasion via Hoffa’s fat pad. Other manifestations of SS arising in the lower limb include an exophytic, frequently avidly enhancing mass. Fig. 4 demonstrates SS arising from the dorsum of the foot in a teenage boy, who had previously had excision of a small mass that was believed to be a benign schwan noma. The mass recurred with ulceration and rupture and was diag nosed as SS. For assessing the extent and intrinsic features of the tumour MRI, with its superior contrast resolution, is performed. Tumours are usually 2
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Fig. 2. Synovial sarcoma arising close to the right popliteal fossa in a 9 yo Caucasian male who presented with chronic history of a slow growing painless mass. Axial T1W image through the popliteal fossa shows a lobulated well circumscribed lesion (a) displacing the vessels anteriorly, with (b) central focal enhancement post gadolinium. The corresponding DWI/ADC map shows that the solid components of the mass demonstrate restricted diffusion on DWI (c) and ADC (d) images. The same lesion demonstrates the ‘triple signal’ pattern (e) on T2W (high, intermediate, and low signal on T2 weighted images).
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Fig. 3. Synovial sarcoma in a 12 yo Caucasian boy who presented with a 2 year history of intermittent left knee pain following a trampoline accident, during which time the knee became progressively more swollen and painful.(a) Sagittal T1W post gadolinium image of the distal femur, shows a lobulated, heterogeneous enhancing lesion with no involvement of the underlying bone. (b) coronal T1W post gadolinium image of the same lesion showing similar enhancement of the solid components of the lesion. (c) Axial T2W of the same lesion demonstrating another ‘triple signal’ pattern.
well-circumscribed and appear bright on STIR sequences. On T1weighted images SS typically appear as heterogeneous multi-lobulated soft tissue masses with signal similar to muscle [10] (Figs. 5 and 6), with internal foci of high signal consistent with hemorrhage [12]. They are often cystic and solid lesions, with avid post contrast enhancement of the solid components (Fig.7). Less common patterns of enhancement include diffuse homogenous enhancement of predominantly solid
lesions (Fig.8). On T2W imaging, they appear as heterogeneous masses with pre dominant high signal. A ‘triple signal’ pattern has been described con sisting of areas that are of high signal consistent with fluid, areas that are iso-to slightly hyperintense relative to fat, and areas of slightly lower signal intensity, suggesting fibrous tissue [12] (Figs. 2 and 3). This heterogeneity/triple signal sign on T2W sequences is thought to be the 4
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Fig. 4. Case of synovial sarcoma in the foot. (a) Sagittal T1W and (b) sagittal post gadolinium images of sarcoma in the foot of a 14 yo Black male presenting with a 2 year history of foot pain, with gradual onset of swelling and numbness. Images show well-circumscribed homogeneously avid enhancing mass on the dorsum of the right foot.
Fig. 5. Synovial sarcoma of the left femoral sheath in a 16 yo Caucasian boy, who presented with a 2 year history of left groin pain. (a) Axial T1 shows well circumscribed lesion (arrow) with (b) mainly peripheral enhancement post gadolinium.
result of the mixture of solid cellular elements (intermediate signal), calcified/fibrotic areas (low signal) and haemorrhage or necrosis (high signal). Although the ‘triple signal’ pattern has been described as occurring in 35–57 % of cases [12,13] it should be noted that this pattern can be seen in other soft-tissue neoplasms, and therefore this finding alone, particularly without the clinical findings, is not specific enough to be diagnostic. The multi-lobulated appearance of SS, with multiple internal septa, is also typically a feature seen on T2W imaging and more frequently seen in larger lesions. The decision on where to target for biopsy usually involves a review and discussion of all imaging, between the radiologists, pathologists and surgeons, in an MDT setting. A representative high quality tissue sample for histological diagnosis can be obtained by selectively targeting at biopsy the solid, enhancing components of the tumour. These may show variable levels of enhancement post contrast, depending on the degree of internal vascularity. Areas to be avoided when considering biopsy include necrotic foci [14], which are predominantly high on T2W and low on T1W sequences. This also applies more generally to predominantly cystic areas. In addition, areas of calcification and fibrosis (typically low on T1W and T2W) should also be avoided.
Smaller lesions (<5 cm) typically have a more homogeneous appearance (Fig. 9d) whereas larger lesions show heterogeneous inter nal features including post contrast enhancement of solid components. Larger lesions may also be predominantly cystic, with fluid-fluid levels (Fig. 10b and d) which, when large and associated with promi nent haemorrhagic foci, can manifest with a ‘bunch of grapes’ appear ance [10]. These lesions often have a solid enhancing nodular component (Fig. 10). 5. Trunk (chest/abdomen/pelvis) SS of the chest is rare and often presents symptomatically, sometimes with dyspnoea secondary to a pleural effusion. In such cases, radio graphs can play a role in the diagnosis (Fig. 11). When SS occur in the abdomen they tend to be large, and often have a more solid component when compared to their extremity counterparts. The solid components typically show early enhancement (within 7 s) on dynamic MR contrast studies, with rapidly progressive increase in signal intensity, followed by either wash out or a late sustained increase in enhancement after an initial rapid enhancement [15]. The early enhancement patterns described are diffuse (40 %) (Fig. 12), hetero geneous (40 %) (Fig. 13) or peripheral (20 %) (Fig. 5) [15]. Diffuse enhancement is often seen if tumour is viable, whereas largely necrotic tumours demonstrate peripheral or nodular enhancement. Diffusion weighted imaging is often useful as there is often evidence of restricted diffusion of the solid components (Fig. 2c and d). Enhancement of solid nodular foci, representing viable non-necrotic
4. Upper limb Imaging characteristics of SS in the upper arm are similar to cases seen in other parts of the body. They also commonly present as a soft tissue swelling, again often in close proximity to a joint. This most often occurs anterior to the antecubital fossa (Figs. 9 and 10). 5
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Fig. 6. Predominantly solid synovial sarcoma presenting as a painful right gluteal mass in a 21 yo Caucasian woman. (a) axial and (b) coronal T1W imaging showing mass (arrowed) with similar signal as adjacent musculature. (c) STIR axial image of the same patient shows the well circumscribed lesion passing through the right greater sciatic foramen.
tumour, is particularly important when the tumour is predominantly cystic on T1W and T2W imaging, since this helps guide potential areas to target for tissue biopsy. Although CT is rarely used to characterize SS, it typically appears as a well circumscribed, heterogeneous, soft tissue mass with non-enhancing necrotic and cystic areas, acute haemorrhagic foci, enhancing solid components and attenuation similar to or slightly lower than muscle post contrast (Figs.14 and 15) [11,13,15–19]. When closely opposed to bone, the underlying bony cortex is not typically affected (Fig. 15). Head and Neck On MRI, about 50%–90% of SS of the head and neck present as small, homogeneous, well circumscribed masses that may be mistaken for a less aggressive, seemingly indolent process (Fig. 16). Whilst these smaller lesions are often well circumscribed [13], on CT they may contain low attenuation regions, in keeping with cystic foci, or high attenuation regions consistent with acute haemorrhage or calcification
[10]. Calcific foci are low signal on all MR sequences, but are more conspicuous on radiographs and CT. Continuity with or invasion of adjacent bone is seen on MRI in up to 21 % of head and neck SS [20,12, 21] (Fig. 16b). Typically, there is no underlying bony involvement, although there may be mild bone marrow oedema. Case studies of SS in the neck report neurovascular involvement in 17–24 % cases, likely because these tumors originate in an inter muscular site near the neurovascular bundle [20,12,21]. The neuro vascular bundle is surrounded by fat, therefore masses arising in this region maintain a rim of fat around them as they enlarge, resulting in the ‘split fat sign’ [9]. A rim of preserved fat adjacent to a neurovascular bundle can also be appreciated on CT (Fig. 17a). Like the ‘triple signal’ pattern, the ‘split fat sign’ is not specific to SS, since any mass which arises in an intermuscular location can have a similar appearance. SS in the neck most often cause displacement rather than invasion of the adjacent neurovascular bundle (Fig. 17b). 6
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Fig. 8. (a) axial T1W, (b) axial T1 post gadolinium enhancement of another synovial sarcoma presenting anterior to the proximal femur in a 17 yo Cauca sian female with a 2-3 week history of increasing leg pain and limp. In contrast to the cystic variety of synovial sarcoma this tumour was predominantly solid with homogeneous/diffuse enhancement post gadolinium.
Fig. 7. Synovial sarcoma involving the proximal thigh. (a) coronal T2 fat sat and (b) axial post gadolinium images of a sarcoma abutting (but not invading) the proximal left femur in a 14 y Caucasian girl who presented with a chronic history of intermittent hip pain. MRI showed a cystic/solid lesion, with avid enhancement of the solid components.
6. Differential diagnosis of SS The non-specific imaging features of SS and the unfamiliarity of some reporting radiologists with these rare entities may mean they are mis diagnosed or even dismissed as benign lesions which could potentially result in a delay to biopsy, and therefore to a diagnosis. 7
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Fig. 9. Synovial sarcoma at the elbow. Case one (a) radiograph of right upper arm showing soft tissue density but no underlying bony abnormality (b) Coronal T1W and, axial T2W (c) and axial FS post gadolinium (d) of the same lesion on MRI showing a heterogeneous well circumscribed lesion.
As previously described, most SS occur in the extremities, particu larly around the knee. There are many benign entities associated with this anatomical site, some of which may mimic SS. Haemangiomas, or venous malformations, are benign abnormal proliferations of blood vessels and are one of the most common soft tissue tumours in children [22]. True haemangiomas occur in infancy at an earlier age than SS. Synovial haemangiomas are rare vascular malformations of the joints which, like SS, can present with non-specific joint pain and swelling. Associated with episodes of spontaneous haemarthrosis, these intra-articular lesions can demonstrate fluid-fluid levels similar to SS with marked hyperintensity on T2W due to pooling of blood within vascular spaces [23]. However unlike SS, they classically show intra-articular dilated tortuous vessels, with variable enhancement post contrast. Synovial chondromatosis is a benign neoplasm which can occur at any age, most commonly in the knee, and may be confused with SS. Their appearance on MRI depends on the degree of synovial membrane
proliferation and the formation of cartilaginous or osseous bodies [24], where cartilaginous bodies may form conglomerate masses which may resemble SS on T1W and T2W imaging. However these bodies (carti laginous or osseous) do not enhance although there may be enhance ment of the hyperplastic synovium. Pigmented villonodular synovitis (PVNS) is a rare monoarticular disease of the joints, most frequently of the knee, and similar to synovial chondromatosis demonstrates proliferation of synovial cells. Like SS they can be present as large lobulated masses, but more typically show homogeneous/inhomogenous low signal on all pulse sequences [25], with characteristic blooming artefact on gradient-echo sequences, sec ondary to haemosiderin from chronic haemorrhage [24]. Peripheral nerve sheath tumours (PNST), including schwannomas and neurofibromas, can occur anywhere in the body, usually superfi cially, and may occur in the atypical SS locations whilst sharing similar imaging characteristics. Like SS they can show avid or variable enhancement post contrast and are associated with the ‘split fat’ sign on 8
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Fig. 10. Synovial sarcoma in an 11 yo Black male who presented with a 5 month history of a right arm mass which started as a small ‘knot’ but continued to enlarge. (a) lateral radiograph showing soft tissue mass (arrow) anterior to the antecubital fossa. (b) axial T2W fat sat through the same region showing a predominantly cystic lesion with a solid nodule, and fluid-fluid levels in keeping with layered haemorrhage components. (c) axial T1W post gadolinium shows this solid nodule to enhance and (d) and coronal T2W shows this nodular component to have a further small cystic component (dashed arrow). The coronal T2W also shows there are multiple solid nodules within the same cystic mass lesion.
T1W images [26]. Unlike SS, PNSTs originate along a major nerve and therefore the visualisation of the nerve entering and exiting the tumour means the diagnosis of PNST can be made. Malignant PNST are usually large ill-defined fusiform masses, arising from medium to large deep nerves such as the sciatic nerve or brachial plexus. They are complex lesions on MR with surrounding oedema due to infiltration of adjacent tissues, and typically with increased heterogeneous enhancement, pe ripheral nodular enhancement and central necrosis [27]. Since SS may be composed of fluid filled spaces, particularly when large, they may also be mistaken for cysts. While some peripheral enhancement of the cyst wall may be seen post contrast, simple cysts lack the internal complexity and soft tissue component seen in SS. Para-articular cystic lesions which may mimic SS, particularly if they demonstrate atypical features, include ganglion cysts and synovial cysts
e.g. Bakers cysts of the knee. Ganglion cysts may present as a multi loculated fluid signal masses adjacent to a joint, with internal foci of T1W hyperintensity if they haemorrhage or contain high proteinaceous content. However unlike SS, they commonly occur on the dorsal surface of the wrist and typically show peripheral enhancement post contrast [24]. In other rare locations where SS may be found, for example the head, neck or abdomen, it is important to differentiate SS from other cystic lesions such as lymphatic malformations, which are benign lesions of vascular origin which show lymphatic differentiation. Most (95 %) of lymphatic malformations occur in the neck and axilla, whilst the remaining 5% can be found in the retroperitoneum, abdominal viscera, mesentery, lung and mediastinum [28] and usually present within the first two years of life. Typically anaechoic multilocular cystic masses, 9
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Fig. 11. High grade synovial sarcoma in a 20 yo Hispanic male who presented to their local hospital with a several month history of shortness of breath. (a) CXR shows a large left sided pleural effusion with contralateral mediastinal shift, (b) CT demonstrates a pleural effusion with a pleurally based soft tissue mass (arrow) at the left lung base, which (c) enhances post gadolinium.
like SS they may also show areas of T1W hyperintensity due to hae morrhage or proteinaceous fluid. However they can be distinguished from SS clinically by their location, their tendency to wax and wane in size, and radiologically by thin internal septa that may enhance in cases of superimposed inflammation and by the lack of soft tissue component [29]. When comparing SS with many soft tissue sarcomas, there is argu ably more overlap in the range of non-specific imaging features between
malignant lesions. Rhabdomyosarcoma is the most common soft tissue sarcoma in children, is associated with neurofibromatosis 1 and Beckwith-Wiedemann syndrome and mostly occur in the head and neck or genitourinary area [30]. About 10 % of rhabdomyosarcomas occur in an extremity, usually in children younger than 10 years of age. Congenital-infantile fibrosarcoma is a rare malignancy, making up for less than 1 % of all childhood cancers [31] and tend to be much larger tumours (up to 16 cm) than SS, occurring in young children less than 10
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Fig. 13. Large synovial sarcoma within the left gluteal region in a 14 yo Caucasian girl, with extension into the pelvis via the left greater sciatic fora men, showing heterogeneous enhancement post-gadolinium.
However they are more likely to show peripheral enhancement in a rimlike fashion [34], whereas SS is more likely to have central solid nodular enhancement.
Fig. 12. Synovial sarcoma arising from the right chest wall and extending into the right supraclavicular fossa in a 17 yo Caucasian male. (a) T1W shows a well circumscribed homogeneous mass (arrowed) (b) which displays homogeneous and diffuse enhancement.
7. Prognostic factors The prognostic significance of radiological findings was examined in a study by Tateishi et al., which included 30 patients 10–61 years of age, with pathologically confirmed SS. They compared the image findings with the histopathological features of the tumour, including tumour grade. Imaging features which favoured the diagnosis of a high-grade tumour included proximal distribution, tumour size over 10 cm, absence of calcification, the presence of haemorrhage and the ‘triple signal’ pattern [13]. Those investigators found that the 5-year disease-free survival rate (DFS) for patients with tumors containing calcification (n = 22; p < 0.01) was 100 %, compared to DFS rate of 0 for patients with haemorrhage (n = 16; p < 0.05) and triple signal pattern (n = 13; p < 0.05) [13]. SS is frequently associated with local recurrence and distant metas tases. The most common metastatic route is haematogenous, occurring in 50–70 % of patients, followed by regional nodal spread in 10–20 % [35]. A recent study of SS in children and adolescents found that the risk of metastases was 32 times higher for subjects whose tumours >5 cm in size [36]. Fortunately, in the paediatric population SS are typically < 5 cm and, therefore, the incidence of metastases in this population is far lower than in adults. Disseminated disease to the lung has also been shown to be the most common site for metastatic disease from other extremity soft tissue
three years of age typically. On imaging however, differentiation rhabdomyosarcoma and fibro sarcoma from SS can be difficult, given the similar non-specific MR characteristics that these three malignant entities share, predominantly iso- to hyperintense T1W signal and variable or heterogeneous enhancement post contrast. Unlike SS, the T2W ‘triple signal’ pattern has not been described in rhabdomyosarcoma or congenital-infant fi brosarcomas, where they typically show T2W hyperintensity compared to skeletal muscle [32]. Rhabdomyosarcomas are also associated with bone destruction or remodelling, whereas SS is not. Undifferentiated pleomorphic sarcomas (UPS) typically occur in the lower extremity and, although these typically present in adulthood, may share many features on MR with SS. For example low-intermediate signal on T1W and intermediate-high signal on T2W [33]. Unlike SS they may erode or invade the bone and may have peripheral ossification, however differentiating between the two based purely on imaging is often impossible. SS of the abdomen is extremely rare, and when they do occur they tend to be large, predominantly solid and may have cystic and hae morrhagic foci (Fig. 14). Abdominopelvic leiomyosarcomas are also predominantly large, heterogeneous masses (average 11 cm) with low density areas on CT due to cysts, necrosis or haemorrhage. Like SS they are relative isointense to muscle on T1W, hyperintense on T2W. 11
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Fig. 15. Synovial sarcoma in a 4 yo Caucasian girl who presented with an enlarging right groin nodule. (a) CT with contrast shows this lesion abuts the right ilium and extends (b) inferiorly into the right proximal thigh. No under lying bony destruction is seen.
value) predicts a poor overall survival [39]. Following treatment (chemotherapy or radiotherapy) increasing signal may be seen on T2W sequences, corresponding to progressive necrosis of the tumour. The size of the tumour may decrease, and sur rounding oedema may develop. FDG-PET/CT may also be used to assess the efficacy of chemotherapy, by showing a reduction in subjective FDG avidity in lesions that have been treated [33]. More recently a genomic study looked at the prognostic value of the number of chromosomal alterations in patients under the age of 25 years with localized disease and found that high tumor genomic complexity was associated with a significantly increased risk of metastasis and decreased probability of event free survival (defined as progression during chemotherapy relapse after complete remission or death from any cause) [40].
Fig. 14. Synovial sarcoma originating from the gastrocolic ligament, in a 15 yo Caucasian boy who presented with a large RUQ mass following a football injury, thought to be a haematoma. (a) Abdominal radiograph showing large right-sided mass (arrow), with displacement of the bowel loops. (b) CT showing a heterogeneous mass with areas of acute haemorrhage (arrow), and displace ment of the adjacent bowel, IVC, right renal artery and vein. Free fluid noted in the right abdomen.
sarcomas, particularly in cases of large (>5 cm) intermediate or high grade lesions. For this reason CT of the chest is necessary for staging [37]. Whilst CT and MRI are most commonly used for detection of distant metastases and loco-regional nodal spread respectively, some centres use FDG-PET/CT for staging of synovial sarcomas and other soft tissue sarcomas, particularly for large and high grade tumours. One study which looked at the most common soft tissue tumours, including SS, found the negative predictive value of PET to be 89 % with a specificity of 96 % [38]. In addition to staging, recent studies have investigated the value of the SUVmax of the primary tumor on pre-treatment FDG-PET/CT in predicting disease progression and overall survival, and found that a higher per-treatment SUVmax (SUVmax of 6.1 was determined as cutoff
8. Conclusion Our pictorial essay demonstrates how SS can occur in any anatomical location, but typically within the extremities and in close association with (but not within) joints. They can take on a range of different enhancement patterns, from diffusely homogeneous to heterogeneous, and can be predominantly cystic (sometimes with fluid-fluid levels) or solid. The ‘triple signal’ pattern seen on T2W images is a feature of SS, but is not pathognomonic, and can be seen in other neoplasms. How ever, when seen as a feature in SS it may predict a poor outcome. Other features which are indicative of poor outcome include presence of 12
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Fig. 17. Synovial sarcoma in 8 yo Caucasian boy who presented with a right neck mass. (a) axial CT post contrast shows a rim of fat surrounding this well circumscribed lesion with (b) posterior displacement of the neuro vascular bundle.
Fig. 16. High grade synovial sarcoma on the right parietal region of an 8 yo Caucasian boy, who presented with a pea sized bump originally believed to be a sebaceous cyst. (a) Axial T2W image shows solitary a well circumscribed lesion (arrow), which (b) homogeneously enhances post gadolinium and involves the inner and outer tables of the calvarium (arrow).
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haemorrhage, absence of calcification, proximal distribution, and large tumour size (>10 cm). Synovial sarcoma usually present as a well circumscribed mass and, despite their size, displace adjacent structures rather than invade them. Radiological findings are relatively non-specific, and in some instances SS may even mimic benign lesions, however the findings of a mixed solid/cystic soft-tissue mass in a young patient, close to a joint and possibly with calcification, are suggestive of this diagnosis.
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