Excerpt from Synovial Sarcoma

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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.

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