Tumor biology and incidence
- Malignant soft tissue sarcoma that usually involves tendon sheaths, bursae, and joint capsule; rarely invades joint itself
- Joint cavity involvement has been reported to occur in 5-10% of patients
- Commonly found in close proximity to large joints of extremities
- May arise from the pluripotential mesenchyme of the limb bud
- Fourth most common sarcoma (primary three being MFH, liposarcoma, and rhabdomyosarcoma)
- Most common soft tissue sarcoma of foot and second most common malignant soft-tissue tumor in pediatric patients
- Accounts for 5-10% of all soft tissue sarcomas; approximately 800 new cases diagnosed each year in the US
Age
Adolescents and young adults between ages 15 and 40
Gender
M:F = 1.2:1
Presentation
- Roughly >50% of cases present with a palpable, deep swelling or mass; may be associated with pain or tenderness
- Unusual for pain/tenderness to be only presenting symptom
- Radiating or referred pain and paresthesias as secondary symptoms due to local mass effect on nerves
- Typically a delayed presentation, often confused with recent or remote history of injury to extremity
- May be confounded by mechanical symptoms at involved joint (ie, snapping, locking, JLT at knee joint)
Physical findings
- Tenderness or pain associated with a deep tissue mass
- Tissue mass may be mobile or fixed and of variable size
- Masses are generally located in the extremities
- Typically chronic symptoms specific to involved joint
- Mechanical symptoms involving joint not uncommon
- Paresthesias may be involved as well
Plain films
- X-ray essential - roughly 25% of patients present with images containing evidence of calcification of tumor mass, varying from stippling to dense/amorphous deposition
- Tumors may present with lobulated, round, or oval radiographic shadow on X-ray
Site
Knee most common site, followed by ankle/foot, elbow, and upper arm/shoulder
Size
- May grow to >15 cm, but on average measure 3 to 5 cm
- Lesions <1 cm have been reported.
Tumor effect on bone
- Underlying bone tends to be uninvolved, although 15-20% of patients have bone erosion, invasion, or periosteal reaction
- Massive bony destruction uncommon and seen only with large, extensive, poorly differentiated tumors
- Changes in bone are secondary to pressure atrophy
CT scan
Useful to delineate size, calcification, and bony invasion/destruction (if present)
MRI
- Nonspecific; has appearance of a benign lesion
- Seen in extra-articular locations
- Usually shows heterogeneous septated mass of low to intermediate signal on T1-weighted sequences and high signal on T2 images
- High signal on T1 and T2 images has been reported, hemorrhage within tumor may be evident as fluid levels
Differential diagnosis
- Myositis
- Hematoma
- Synovitis
- Tendonitis
- Bursitis
Natural history
- Insidious, slow growth of tumor with potential for metastasis
- Primary location for metastasis is lungs; however, lymph node involvement occurs in 3-27% of patients
- Time to surgery from onset of symptoms generally 2-4 years
- Poor prognosis; some molecular markers can be used to as prognostic indicators to predict course of disease
Pathology
- Initially named due to a similar appearance to normal synovium microscopically; however, the tumor bears no resemblance to synovium, either ultrastructurally or immunohistochemically
- Gross: Yellow to gray-white
- Four distinct histologic types: classic biphasic, monophasic fibrous, monophasic epithelial, and poorly differentiated
- Classic biphasic
- Epithelial cells characterized by large, round, or oval vesicular nuclei and abundant pale-staining cytoplasm with distinctly outlined cellular borders
- Cells present in solid cords, whorls, or nests
- Spaces lined by single layer of epithelial cells bearing close resemblance to normal synovium
- Surrounding component consists mostly of well-oriented, spindle-shaped cells of uniform appearance with small amounts of indistinct cytoplasm and oval dark-staining nuclei
- Generally indistinguishable from fibrosarcoma except for absence of herringbone pattern
- Monophasic fibrous
- Positive immunostaining of spindle cells for keratin and epithelial membrane antigen
- Shares identical morphological features to spindle-cell portion of the biphasic type
- Monophasic epithelial
- Exhibits glandular structures lined with epithelial cells
- Differential diagnosis includes metastatic and adnexal carcinoma, malignant melanoma, malignant epithelioid schwannoma, and epithelioid sarcoma
- Poorly differentiated
- Solidly packed oval or spindle-shaped cells of small size that seem to be intermediate in appearance between epithelial and spindle cells
- Less-differentiated variants grow more rapidly and tend to be poorly circumscribed, with multiple areas of hemorrhage, necrosis, and cystic formation
- Implies a worse prognosis; however, large studies have not shown that the histologic analysis of synovial sarcoma has a significant prognostic or therapeutic importance
- Distinguishing feature from other sarcomas is potential presence of two distinct cell types: epithelial (seen in carcinoma) and fibrosarcoma-like spindle cells
Immunohistochemistry and cytogenetics
- Both cellular elements show reactivity for cytokeratins and, less intensely, for epithelial membrane antigen
- Positive immunostaining for keratin seen in nearly all biphasic synovial sarcomas and many of the monophasic fibrous type
- Other positive stains include desmoplakin, Leu-7, and S-100 protein
- Characteristic balanced translocation between chromosomes X and 18, t(X;18)(p11.2;q11.2) in most cases
- Translocation fuses the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1, or SSX2
- SYT-SSX1 and SYT-SSX2 function in aberrant transcriptional regulation.
- Translocation occurs in all histological variants
Diagnosis and treatment
- Most commonly misdiagnosed soft tissue tumor, due to variable size, slow growth, benign appearance on imaging studies, and similarity of pain symptoms seen with simple trauma
- Imaging relatively non-specific; biopsy needed to confirm diagnosis
- Diagnosis based on clinical and imaging information such as patient age, symptoms, location of the tumor, presence of calcification or ossification, and MRI appearance
- Treatment is includes surgical wide resection
- No minimal acceptable margin has been established
- However, there is susceptibility for microscopic infiltration of tumor cells into pseudocapsule of tumor
- Suggested margins include 1-3 cm in adults (may be impossible in most children and in deep-seated tumors adjacent to bone or important neurovascular structures)
- Adjuvant chemotherapy controversial, not standard practice
- However, preoperative systemic or isolated limb perfusion chemotherapy may enable limb-sparing surgery in most patients
- Local control may be improved with perioperative radiation, especially in patients with marginal rather than wide-resection
- Recommendations for radiation depend on primary site and size of tumor, histology, patient age, and extent of disease before and after surgical resection
- In general, with conventional fractionation (1×1.8 to 2 Gy/day), radiotherapy doses between 50 and 70 Gy should be administered
- In most cases, the radiation field includes the initial tumor plus 2- to 3-cm margins
- Chemotherapy and/or radiation typically reserved for high risk patients
Prognosis
- Factors determining high risk and associated with a worse prognosis include:
- Size >5 cm
- Deep seated
- Inadequate surgical resection
- Local recurrence
- Patient age >20 years
- Monophasic subtype
- Mitotic activity of >10 per high power field
- Variant of translocation may imply prognostic value: Two studies with cohorts of 104 and 243 synovial sarcoma patients showed the overall 5-year metastasis-free survival for patients with SYT-SSX1 ranged from 42% to 53%, versus 73% to 89% for those with SYT-SSX2.
- Non-metastatic synovial sarcoma: 5-year disease-specific survival rate was 62.9% in one study of 128 patient . 5-year overall survival and the 5-year metastatic-free survival rate in another study of 271 patients was 71% and 51%, respectively.
Recommended reading
Siegel HJ, et al. Synovial sarcoma: clinicopathologic features, treatment, and prognosis. Orthopedics. 2007 Dec;30(12):1020-5.
Schwartz HS. OKU- Musculoskeletal Tumors 2. 2007.
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