AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Background

Synovial sarcoma constitutes 8-10% of all sarcomas and most commonly affects adults in the third to fifth decades of life. This malignancy usually involves the extremities, especially the lower extremities around the knees. Synovial sarcoma is frequently misdiagnosed as a benign condition because of its often small size, slow growth, and well-defined appearance.^{1, 2}

Pathophysiology

Gross specimens are usually well-demarcated, pink, fleshy masses with a heterogeneous appearance and may display solid, hemorrhagic, or cystic components on sectioning. Calcification foci are occasionally noted; heavy calcification tends to indicate less aggressive lesions and offers a more favorable prognosis.

Synovial sarcoma is named for its resemblance to developing synovial tissue under light microscopy. It arises from the pluripotential mesenchymal cells near joint surfaces, tendons, tendon sheaths, juxta-articular membranes, and fascial aponeuroses. The histologic appearance is that of large polygonal cells (epithelioid) that secrete hyaluronic acid and show an organization that is suggestive of microscopic joint spaces. These cells are surrounded by spindle cells that simulate subsynovial mesenchymal cells.

The typical morphology is that of 2 strikingly distinct, well-differentiated cell populations. Depending on which cell type predominates, the overall histologic appearances can be described as biphasic (epithelioid and spindle cell), monophasic spindle cell, or monophasic epithelioid. Marked cellular pleomorphism and atypia are uncommon,  but when they are present, their appearance overlaps with that of a high-grade malignant fibrous histiocytoma and fibrosarcoma.

Specific cytogenetic abnormalities have been identified. More than 90% of patients have a t(X;18) translocation mutation, which is not associated with other sarcomas. The translocation involves the SYT gene on chromosome 18 (at 18q11) and the SSX1 or SSX2 gene on the X chromosome (at Xp11).^{3, 4} These genes appear to be transcription regulators, whose functions occur primarily through protein-protein interactions. Subtypes of these translocations have been shown to correlate with distinct histologic subtypes.

Frequency

United States

Synovial sarcoma is the fourth most commonly occurring sarcoma,¹ accounting for 8-10% of all sarcomas. Approximately 800 new cases of synovial sarcoma are diagnosed per year.

Mortality/Morbidity

• Overall, survival rates are 36-76% at 5 years and 20-63% at 10 years.
• Synovial sarcoma of the head and neck region has a better prognosis than that of sarcoma involving the extremities, with 5-year survival rates of 47-82%.

Sex

Although different studies have cited a slight male or female predominance, a study including 672 cases at the Armed Forces Institute of Pathology (AFIP) demonstrated no significant sex or ethnic predilection for synovial sarcoma.¹

Age

Synovial sarcoma can occur in patients with a wide age range, but it is most common in patients in the third to fifth decades of life. In a series of 121 cases, 83.6% of tumors occurred in patients aged 10-50 years, with a median age of 31.3 years. Another large study included patients with ages ranging from 5 to 87 years.⁵

Anatomy

Synovial sarcoma is the most common sarcoma that involves the upper extremity, hip, groin, and buttocks in patients aged 16-25 years. In patients aged 6-45 years, synovial sarcoma is the most common sarcoma in the foot and ankle.

Most synovial sarcomas are found within 5 cm of a joint. Despite the misnomer, only 10% of cases are intra-articular. The tumors are usually well circumscribed, but in unusual cases, they may interdigitate between muscles and tendons or encase neurovascular structures. Invasion of the adjacent bone is seen in 11-20% of patients, a feature that is uncommon in other sarcomas.

The region around the knee is the most common site of involvement. In a large study, 73% of synovial sarcomas occurred in the lower limb; 34% in the upper limb; and 16% in the chest/abdominal wall. Tumors that occur in the upper extremity tend to affect the distal extremity rather than the elbow or shoulder. Less common sites of involvement include the retroperitoneum, mediastinum, and head and neck regions. The most common site in the head and neck is the hypopharynx. Other head and neck locations include the cervical or parapharyngeal regions, masticator space, soft palate, tongue, suboccipital and infratemporal fossa regions, and sinonasal space.

Clinical Details

Clinical features

The clinical features of synovial sarcoma are nonspecific. No one feature distinguishes synovial sarcoma from other sarcomas. Most commonly, patients notice a slowly enlarging, deep-seated mass, which is painful in slightly more than 50% of affected patients.

The mass may be present for an extended period before medical evaluation is sought, with an average time lapse of approximately 2.5 years before presentation (range, several months to 20 y). Deep-seated tumors tend to be evaluated later than superficial tumors.

In larger joints such as the knee, vague symptoms of pain may occur for months without an appreciable mass. If they grow sufficiently large, tumors near joint spaces may cause limitation of movement.

Involvement at sites other than the extremities occasionally presents as a painful mass or with symptoms related to a mass effect on the adjacent structures. In head and neck involvement, patients complain of symptoms such as dyspnea, dysphagia, hoarseness, and headache.

Rarely, a patient may present with symptoms secondary to pulmonary metastases, such as hemoptysis.

Disease progression

Synovial sarcomas are slow growing, but they can be locally aggressive. Approximately 25% of synovial sarcomas are associated with pulmonary metastases at the time of the initial presentation. The natural history of synovial sarcoma includes local recurrence, especially when the resection margins demonstrate positive results on pathology¹; this recurrence usually appears within 2 years of the initial treatment. However, recurrences that are delayed for as long as 10 years are not uncommon.

Although local control of sarcomas has improved with curative resection and adjuvant irradiation, metastases develop in many patients—in approximately 41% of patients in one large study. The sites most commonly involved are the lung (94%), lymph nodes (4-18%), and bones (8-11%).

Tumor staging

Tumors are staged according to the American Joint Committee on Cancer staging classification for soft-tissue sarcomas.⁶ This system considers the size of the tumor, invasion of adjacent structures (bone, major vessels, major nerves), lymph node involvement, histologic grade, and presence of distant metastases.

Prognostic predictors

Some studies have identified important prognostic predictors for synovial sarcoma; for example, younger age, a smaller tumor size, a distal limb location, and negative resection margins have been correlated with improved outcomes. Adjuvant radiation therapy has also been associated with improved outcomes.

Controversy exists over the prognostic implications of histologic subtypes. Some study results have suggested that lesions in which the histology is primarily epithelioid or those that are heavily calcified are associated with lower risks of early metastasis and improved long-term survival rates.

Invasion of bone and neurovascular structures, marked cellular atypia, and distant metastases are associated with a poor prognosis.⁷

Preferred Examination

As with all sarcomas, magnetic resonance imaging (MRI) is the modality of choice because of its excellent tissue contrast and ability to depict the lesion in multiple planes. MRI is useful for evaluating the extent of the tumor and its involvement with adjacent soft-tissue structures. For instance, MRI is helpful in the differentiation of tumor from muscle tissue and in depicting the involvement of neurovascular structures, tendons, fascial/fat planes, and bone marrow. MRI is also helpful for the differentiation of recurrent soft-tissue tumors from postsurgical or postirradiation changes.

Computed tomography (CT) scanning can be used in lieu of MRI in patients who have contraindications (eg, claustrophobia, pacemakers, aneurysm clips) to MRI. As with MRI, CT scanning can be useful for determining the gross anatomic extent of the tumor, and this modality is also especially useful for depicting calcifications, bone invasion, or periosteal reaction.

Limitations of Techniques

MRI has proven to be valuable for the detection and staging of soft-tissue tumors, but MRI signal intensity characteristics are usually nonspecific for a histologic diagnosis, with some exceptions (eg, lipomas, some liposarcomas, pigmented villonodular synovitis). Although certain signs can suggest synovial sarcoma in the differential diagnosis, MRI findings are by no means pathognomonic, and histologic analysis of the involved tissue is usually required for definitive diagnosis.

DIFFERENTIALS

Section 3 of 12  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

RADIOGRAPH

Section 4 of 12  

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• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Radiography is often the initial study obtained for the evaluation of synovial sarcoma. In 50% of patients with synovial sarcoma, radiographic findings are interpreted as normal (see Image 7). If an abnormality is present, the radiograph may reveal a well-defined, round or lobulated soft-tissue mass that averages approximately 8 cm in its largest dimension.

Approximately 30% of patients have calcifications that are detectable radiographically (see Images 1 and 4). The calcifications may be focal or spread throughout most of the tumor, and they may appear fine, stippled, or opaque.

Uncommonly, tumors can erode bone. Adjacent periosteal reaction can be seen in as many as 20% of patients. Distant metastases to bone are usually of the lytic and/or mixed variety.

When the neoplasm is near a joint and causes limitation of movement, periarticular osteoporosis may be seen.

CT SCAN

Section 5 of 12  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

CT scan findings are nonspecific and usually demonstrate a single round or lobulated mass with a soft-tissue density. The lesions measure approximately 3-12 cm in their largest dimension and are usually found near a joint. Masses in the head and neck or distal extremities are smaller at presentation, presumably secondary to an early mass effect.

The mass is usually well defined (see Images 6 and 8) but can occasionally appear infiltrative and can be homogeneous and show homogeneous enhancement, particularly in smaller lesions; alternatively, if hemorrhage or necrosis has occurred, the lesion may be multiloculated and show heterogeneous enhancement.^{8, 9}

Calcifications are demonstrated in 30% of patients;¹ typically, diffuse punctate calcifications are revealed. These are often more concentrated at the periphery than at the center. Extensive calcifications can be similar in appearance to osteosarcoma or a calcified chondroid lesion. Densely calcified lesions, when found near a joint, may simulate tumoral calcinosis (see Image 5).

Involvement of the adjacent bone can cause changes, including cortical invasion with a wide zone of transition, bone remodeling from pressure erosion, and/or adjacent periosteal reaction.

MRI

Section 6 of 12  

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• MRI
• Ultrasound
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• References

Findings

Synovial sarcoma tumors tend to be large, averaging approximately 8 cm in their largest dimension, which is usually parallel to the long axis of the body. Approximately 91% of patients have a well-defined ovoid lesion with rounded or gently lobulated margins (see Image 9).⁹ The effect on adjacent structures is usually displacement, rather than invasion or destruction.

Most tumors display a heterogeneous intermediate signal intensity on T1-weighted MRIs. Lesions smaller than 5 cm are more likely to have a predominantly homogeneous signal intensity that is similar to that of the adjacent muscle (see Image 9). Larger lesions are most often heterogeneous secondary to extensive areas of hemorrhage and necrosis (see Image 11).

On T2-weighted images, lesions are usually hyperintense, with a signal intensity similar to or higher than that of fatty tissue (see Image 3). Considerable inhomogeneity is demonstrated in 82% of lesions, with cystic components seen in 77% (see Images 10 and 12).⁹ Cystic components with striking fluid-fluid levels are demonstrated in 18% of tumors.⁹ Approximately one third of lesions demonstrate the "triple signal pattern" on T2-weighted images; this pattern consists of a combination of (1) hyperintense fluid within cystic components, with or without fluid levels, (2) intermediate signal tissue similar in intensity to that of muscle, and (3) slightly hypointense tissue similar in intensity to that of fibrous tissue.

Apposition to bone surfaces without a clear plane of separation is seen in 50-59% of cases (see Image 12), with clear bone erosion or destruction in 22% (see Image 2). Calcifications are not easily seen on MRIs and, when visible, are usually hypointense on all sequences (see Image 3).

The use of gadolinium-based contrast agents has a limited value in the evaluation of synovial sarcomas. On dynamic imaging, malignant soft-tissue masses have been shown to enhance earlier, faster, and more predominantly peripherally than benign lesions.¹⁰ These findings are believed to be secondary to the effects of tumor angiogenesis. Synovial sarcomas usually demonstrate heterogeneous contrast enhancement, with early enhancement of tumor within 7 seconds of arterial enhancement.¹⁰ Gadolinium-based agents may be helpful in posttreatment MRIs, in which mild, diffuse, nonfocal contrast enhancement is a typical finding. With recurrent disease, focal nodules with homogeneous enhancement and high signal intensity without cystic components are typically seen on T2-weighted images.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint  stiffness with trouble  moving  or  straightening  the  arms,  hands,  legs,  or  feet;  pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

False Positives/Negatives

Synovial sarcoma tumors can appear small, especially those in the hands or head and neck regions,^{2, 8, 11} where they come to medical attention earlier. Often, the small size, well-defined margins, and sometimes homogeneous appearance of synovial sarcoma can lead to misdiagnosis as a benign lesion. Berquist et al found that synovial sarcoma was the malignant soft-tissue sarcoma most frequently misdiagnosed as benign.¹² Small, superficial, solid lesions should be approached as a possible sarcoma unless strong signs prove otherwise.^{5, 13}

ULTRASOUND

Section 7 of 12  

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• MRI
• Ultrasound
• Nuclear Medicine
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• References

Findings

Ultrasonography does not play a significant role in the evaluation of synovial sarcomas. The imaging characteristics cannot be used to establish a precise diagnosis. Grossly, sonograms can provide information regarding the size and consistency of a soft-tissue mass (eg, differentiating cystic from solid masses or a localized mass from diffuse edema). Most commonly, a well-circumscribed, heterogeneous mass, with or without cystic components, is seen.

Ultrasonography can be useful as a real-time imaging technique for guiding diagnostic needle biopsy, especially in large heterogeneous tumors.¹⁴ Color-flow Doppler ultrasound imaging reveals blood flow in solid soft-tissue masses.¹⁴

Degree of Confidence

Studies have shown that color-flow Doppler ultrasound findings are not specific for differentiating benign from malignant tumors; however, the technique may be useful for monitoring the regression of tumor neovascularity after the administration of chemotherapy or irradiation.

NUCLEAR MEDICINE

Section 8 of 12  

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Findings

Nuclear medicine does not play a significant role in the workup of synovial sarcoma. Positron emission tomography or bone scanning can be used for the evaluation of skeletal or lung metastases or recurrent disease.

ANGIOGRAPHY

Section 9 of 12  

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Findings

Angiography does not play a significant role in the evaluation of synovial sarcoma. Angiography allows the gross evaluation of the tumor's size and vascularity. The tumor appears as a soft-tissue mass with a fine network of tumor vessels and an inhomogeneous capillary blush. The degree of vascularity may vary according to the histopathology. One study reported that monophasic tumors of synovial sarcoma demonstrate a higher degree of neovascularity than biphasic tumors.¹⁵

INTERVENTION

Section 10 of 12  

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• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Diagnosis

Open biopsy is often difficult to perform, and the procedure is associated with an increased prevalence of complications such as anesthetic complications, unnecessary amputations, poor wound healing and breakdown, fracture, bleeding, and infection. Image-guided biopsy is now commonly performed for the initial histologic diagnosis of soft-tissue tumors^{16, 17} because of the comparative ease, safety, and cost-effectiveness of this less-invasive procedure. Complication rates of percutaneous biopsies are as low as 1%, whereas those of open surgical biopsy are 2-20%.¹⁸

Reported accuracies of percutaneous techniques vary in the literature. One large study of CT-guided needle biopsy of musculoskeletal neoplasms revealed an accuracy of 93% for core-needle biopsy and 80% for fine-needle aspiration.

Because synovial sarcomas cannot be distinguished from other soft-tissue tumors, percutaneous biopsy techniques and considerations are no different from those for other soft-tissue masses. A potential but infrequent complication of biopsy includes intercompartmental contamination along the biopsy path with malignant tumor cells. Thus, the biopsy route should be discussed with the primary orthopedic surgeon to ensure that the needle tract can be easily incorporated in the eventual surgical resection.

Core biopsy can be easily performed by using a 14-gauge Tru-Cut needle (Travenol Laboratories Inc, Morton Grove, Ill) or similar device. Synovial sarcomas do not originate from bone; therefore, bone-cutting trephine-type needles are not needed. Fine-needle aspirations are performed with smaller 20- to 22-gauge needles.

In general, fine-needle aspiration is less accurate than other techniques for the diagnosis of soft-tissue tumors because of the lack of architectural information, smaller amounts of obtained tissue, and the need for specialized pathologic expertise in cytologic interpretation. Some authors report that fine-needle aspiration is adequate for the diagnosis of suspected metastatic disease, in which case the accuracy is high. Other authors advocate the use of both techniques in the percutaneous biopsy of soft-tissue tumors, stating that the information obtained is complementary and that many lesions are diagnosed by means of one and not the other. Accuracy rates for the diagnosis of lesions that are biopsied by both fine-needle aspiration and core biopsy are generally higher than those for either technique alone.

The choice of the imaging modality for biopsy guidance depends on the availability of the equipment, the expertise of the radiologist, and the characteristics of the lesion. CT scanning guidance is optimal for the biopsy of small lesions or those lesions that are near neurovascular bundles or other critical structures. Fluoroscopy is a real-time imaging modality that can be used for the biopsy of larger lesions that are easily seen on 2-dimensional radiographs. Ultrasonography can be used in select cases in which the lesion is more superficial and easily visible on real-time images.

The advantages of ultrasonography over CT scanning include the following: (1) continuous real-time visualization of the needle, (2) the ability to assess regions of viable tissue by using color-flow Doppler imaging, (3) the lack of ionizing radiation, (4) the availability of ultrasound scanners, (5) the reduced procedural time, and (6) overall cost-effectiveness. In some cases in which the tumor is not easily seen on CT scans or in which visualization of the tumor in several planes is desired, MRI-guided biopsy can be performed.

Treatment

Synovial sarcoma tumors are treated aggressively with limb-sparing therapy when possible. The recommended treatment is wide resection with negative margins, which often includes removing the surrounding muscle groups or total amputation. Resection is commonly followed by localized irradiation.

Multidrug adjuvant chemotherapy is currently recommended for systemic control of the cancer. However, although synovial sarcomas have been shown to be markedly chemosensitive, controversy exists over the actual survival benefit in patients.

MULTIMEDIA

Section 11 of 12  

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• Differentials
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• Ultrasound
• Nuclear Medicine
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• Intervention
• Multimedia
• References

Media file 1:  Lateral radiograph of the foot in a 60-year-old man who presented with a mass on the dorsum of his left foot. The radiograph shows a soft-tissue mass that is anterior to the talus and without obvious underlying bone erosion. Subtle faint calcifications are seen within the mass.
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Media type:  X-RAY

Media file 2:  Coronal T1-weighted magnetic resonance image of the foot in a 60-year-old man who presented with a mass on the dorsum of his left foot (same patient as in Images 1 and 3). A rounded, soft-tissue mass is seen eroding the cortex of the superior talus. The mass is predominantly isointense relative to the muscle, with scattered areas of hyperintensity that are consistent with hemorrhage.
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Media type:  MRI

Media file 3:  Sagittal T2-weighted magnetic resonance image of the foot in a 60-year-old man who presented with a mass on the dorsum of his left foot (same patient as in Images 1-2). The mass shows predominantly high signal intensity that is hyperintense relative to fat. Scattered areas of hypointensity probably represent calcifications.
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Media type:  MRI

Media file 4:  Anteroposterior radiograph of the hip in a patient who presented with a mass in the region of the left hip. Opaque, masslike calcifications overlying the femoral neck and inferior pubic ramus are seen.
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Media type:  X-RAY

Media file 5:  Computed tomography scan of the hip in a patient who presented with a mass in the region of the left hip (same patient as in Image 4). The scan was obtained through the mass and demonstrates masslike areas of calcification within the muscle density in the region of the left obturator externus muscle.
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Media type:  CT

Media file 6:  Computed tomography scan through the right thigh. This image demonstrates a round, noncalcified, well-circumscribed mass that displaces, rather than invades, the surrounding muscles. The mass appears to be separate from the bone.
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Media type:  CT

Media file 7:  Lateral radiograph of the femur in a 45-year-old man who presented with a large, right midthigh mass. This radiograph is remarkable only for a subtle soft-tissue prominence on the anterior aspect of the thigh. No calcifications are depicted.
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Media type:  X-RAY

Media file 8:  Computed tomography scan of the thigh in a 45-year-old man who presented with a large, right midthigh mass (same patient as in Images 7, 9-10). A well-defined mass is seen on the anterior aspect of the thigh and appears to be mostly isodense relative to the muscle, with curvilinear areas of slightly increased density. The mass appears apposed to the underlying bone.
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Media type:  CT

Media file 9:  Axial T1-weighted magnetic resonance image of the thigh in a 45-year-old man who presented with a large, right midthigh mass (same patient as in Images 7-8, 10). The anterior mass is well circumscribed, with mostly homogeneous isointensity relative to the muscle. Scattered, small, hyperintense foci probably represent hemorrhage. The fat plane between the mass and the femur is preserved.
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Media type:  MRI

Media file 10:  Coronal T2-weighted magnetic resonance image of the thigh in a 45-year-old man who presented with a large midthigh mass on the right (same patient as in Images 7-9). On this T2-weighted image, the mass has become markedly heterogeneous, with high signal intensity depicting cystic regions of hemorrhage and necrosis. Note that portions of the mass are hyperintense relative to the subcutaneous fat. The location of the mass is somewhat atypical because it is centered at the level of the midshaft rather than near a joint.
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Media type:  MRI

Media file 11:  Sagittal T1-weighted magnetic resonance image of the thigh in a patient with a mass in the anterior left upper thigh and/or inguinal region. The image shows large areas of hemorrhage and necrosis, with intermediate signal intensity on a background of a muscle-intensity mass.
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Media type:  MRI

Media file 12:  Axial T2-weighted magnetic resonance image of the hip in a patient with a mass in the anterior left upper thigh and/or inguinal region (same patient as in Image 11). The mass is inseparable from the underlying femoral cortex and contains strikingly hyperintense cystic areas with irregular septa of intermediate signal intensity.
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Media type:  MRI

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

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Article Last Updated: Jul 13, 2007