Synovial sarcoma is a unique entity that accounts for 5-10% of all sarcomas. It typically affects patients between 15-40 years, with an average age of 34 [4], and forms a circumscribed, slow-growing, deep soft tissue mass near large joints of the extremities. Synovial sarcoma first appeared in medical literature in 1893, when Stuer described an ‘adenosarcoma’ of the elbow [5-6]. Reports of synovial sarcoma in other locations, such as the pulmonary system, have increased with the use of FISH and immunohistochemical (IHC) techniques [7].

Synovial sarcoma can display different morphologic patterns. Monophasic fibrotic synovial sarcoma is most common (50-60%), with clusters or fascicles of nearly overlapping, small delicate uniform spindled cells with ovoid bland nuclei with inconspicuous nucleoli and scant cytoplasm. Biphasic synovial sarcoma accounts for 20-30% of all synovial sarcoma cases and shows both spindled cells and small cuboidal epithelioid cells forming nests, cords, or simple glands with occasional mucoid material. Rare cases can show a predominantly epithelioid component, but focal fibrotic areas are usually present; thus, these are classified as biphasic. Poorly differentiated synovial sarcoma displays nuclear atypia, high mitotic activity (>6 mitoses/mm2), hypercellularity and a worse prognosis. While uncommon in most sarcomas, fine calcifications can be seen in 20-33% of synovial sarcomas and suggest a better prognosis [8]. Rarely, squamous metaplasia can also be observed [4].

Strong diffuse EMA and keratin staining is unusual in most sarcomas, although it is characteristic of synovial sarcoma, particularly the epithelioid component. Other sarcomas with strong keratin staining include epithelioid sarcoma, desmoplastic small round cell tumor, and extrarenal rhabdoid tumor. Focal weak patchy keratin staining has also been reported in malignant peripheral nerve sheath tumors, epithelioid angiosarcomas, leiomyosarcomas and rhabdomyosarcomas, among others.

Additional stains that may be observed to be positive in synovial sarcoma include PAS-D positivity in mucoid secretions, BCL-2 staining in spindled cells, and variable staining for CD99, beta-catenin, and S100 [9]. Reduced expression of INI-1 staining has also been described [10]. Pertinent negative markers include muscle markers such as desmin, h-caldesmon, myogenin, and MyoD1. Lack of CD34, FLI1, and WT1 staining is also observed. SOX10 typically is negative, but rare positive cases have been reported [11].

Synovial sarcoma typically expresses strong cytoplasmic and nuclear positivity for TLE-1. This marker is highly sensitive for synovial sarcoma and was initially thought to be highly specific as well. However, subsequent reports described a patchy TLE-1 staining pattern in solitary fibrous tumor, myxoinflammatory fibroblastic sarcoma, epithelioid angiosarcoma, rhabdomyosarcoma, mesothelioma, and malignant peripheral nerve sheath tumors [12]. Rare expression has also been reported in some carcinomas (esophageal, prostate, ovarian, adrenocortical, basal cell, and small cell) [13]. Thus, experts [9] recommend confirmatory FISH testing for the characteristic translocation t(X;18)(p11;q11), which can be observed in >95% of cases. This translocation fuses SS18 (also known as SYT or SSXT) and SSX1 (66%), SSX2 (33%), or SSX4 (1%). SSX1 is more common in biphasic synovial sarcoma, but both SSX1 and SSX2 are seen in monophasic synovial sarcoma [9].

Standard therapy involves wide local excision of the lesion and needle tract, with radiation and possibly chemotherapy for high-risk or advanced disease. Other therapies currently under investigation include receptor tyrosine kinase inhibitors, epigenetic modulators, compounds that interfere with the DNA damage response, and immunotherapy [14].

Synovial sarcoma is very aggressive, and 50-70% of cases undergo metastasis [15]. The three most frequent sites of metastasis for synovial sarcoma are the lungs (80%), bone (9.9%) and liver (4.5%) [16]. Lymph node metastasis is rare in most sarcomas but has been reported in approximately 4.2% of synovial sarcomas [17]. Other sarcomas known to metastasize to lymph nodes include rhabdomyosarcoma, clear cell sarcoma, epithelioid sarcoma, and myxoid/round cell liposarcoma [17]. Late recurrences of synovial sarcoma can also occur.

Features associated with a better prognosis includes size <5 cm [18], <10 mitoses/10 HPFs, no necrosis or poorly differentiated component, location on extremities, and younger age [19]. Five-year survival is 83% for patients younger than 19 years, and 62% for older patients [12]. In addition, some studies have suggested that SSX1 fusions are associated with a higher risk of metastasis and a lower survival rate compared to fusions involving SSX2, though other studies have found no such associations [16].

In summary, synovial sarcoma is an uncommon sarcoma that classically involves the knee of young adults. It often displays a biphasic morphologic pattern, with keratin positivity in the epithelial component and diffuse TLE-1 staining. A predominantly epithelioid pattern is unusual and may create diagnostic pitfalls. Confirmatory FISH testing for characteristic rearrangements of SSX is a useful aid in diagnosing unusual synovial sarcoma patterns.