50 years ago in CORR: Synovial sarcoma. Kirk J. Anderson, MD and Orliss Wildermuth, MD CORR 1961;29:55-70.

Tracing the history of synovial sarcoma, as with most malignant tumors, is difficult: concepts, terminology, diagnostic tools, and diagnostic criteria have changed with time. These changes have made it difficult to know whether alterations in treatment over time have resulted in lower rates of recurrence and higher rates of survival. The problem is compounded by the relative rarity of some musculoskeletal tumors and the associated need to include collections of cases over long periods of time to have sufficient numbers to meaningfully analyze. The earliest described cases of “synovial sarcoma” likely arise from the late 1800s, although according to Jones and Whitman [4], Simon in 1865 described a case of sarcoma arising from the inner side of the knee and described it as “a “hypertrophied sarcomatous synovial fringe.” It is not clear, however, if this tumor arose from the synovial lining. v. Ruediger Rydygier described 10 cases of “primary sarcomas of the knee joint capsule,” nine of which were reported from 1886 until 1904 [13]. From the descriptions, not all of these cases would qualify as synovial sarcomas as we consider them today. Some were localized, stalked lesions that did not recur despite histologic descriptions of sarcoma. Turner, in 1894, described a case of “Primary Sarcoma of the Synovial Membrane” [11], and according to v. Ruediger Rydygier, Lockwood described another case of “Sarcoma of the Synovial Membrane,” in 1902. Thus, the notion that sarcomas (regardless of the type) could arise from the synovial membrane seems to have been established by the early 1900s. Coley, in his article from 1907 [2], detailed 71 cases of sarcoma of the long bones, not one of which he considered arising from the joint, and along with v. Ruediger Rydygier noted the rare nature of these tumors. Jones and Whitman, in 1914, perhaps first used the term “synovial sarcoma,” presuming these tumors arose from a synovial membrane [4]. In reviewing all the reported cases they could find (including those mentioned above), they suggested only 17 were “authentic cases of primary synovial sarcoma,” to which they added one. Whether their case was truly what we now consider a synovial sarcoma is suspect because there were two primary cell types: “In this case we have a tumor containing two types of giant-cells, one type being a true tumor cell, and important as indicating rapid and incomplete division of the cells, hence high malignancy. The tumor is a true giant-cell sarcoma.” Today, however, we consider the tumor has two cell types that differ from those described earlier: fibrous or spindle-shaped and epithelial, with most tumors being containing both cell types (biphasic). Haagensen and Stout, in 1944 [3], recognized the problem of the effect of diagnostic criteria on treatment outcomes: “One might expect that a clear conception of the pathology, degree of malignancy, clinical course and results of treatment could be gained by a perusal of these papers. It is distressing to find that this is not so, chiefly because a very considerable number of cases have been reported as synovial sarcomas which were not such, but, in reality, xanthomatous giant cell tumors, tumor-like hyperplasias of the synovial tissues or other benign lesions curable by simple excision. Thus, the apparent cure rate has been made higher than is in fact the truth.” They described tumors with currently accepted cell types, and in a review of the literature and their own cases, they found 104 cases; they noted, “only three are known to be free from evidence of persistence or metastasis more than five years after treatment.” This is in contrast to a statement by v. Ruediger Rydygier [13], “The prognosis I would say is not too sad, given the slow progression of this disease and the lack of glandular swellings. If in some cases, local recurrences have been observed, for the selected surgical procedure (circumscribed excisions) is to blame.” Perhaps presciently, Haagensen and Stout believed the tissue of mesothelial origin by culturing tissue from three cases and analyzing the cells. They also challenged the notion that the tumors arose from the synovial lining: “…it is very questionable whether or not they are derived from the normal lining cells of joints, tendon sheaths, and bursae, because the tumors are usually outside of these structures although often in close proximity to them.” Anderson and Wildermuth published their review in 1961 in CORR® [1]; they reported 27 patients and used histologic criteria similar to that described by Haagensen and Stout. As with past investigators, they noted the tumor occurred primarily in younger adults (average age, 30 years). They emphasized the malignant nature of the tumor but reported a somewhat better prognosis than did the latter authors: at an average followup of nearly 6 years, 13 patients were alive without “active” disease, 13 had died, and one was alive with metastases (Table 1). That said, 21 of the 27 patients had experienced recurrences, all of which were treated either with reexcision or amputation. Table 1 Survey Resume of 27 Cases of Synovial Sarcoma Lewis et al. [5] in a series of 122 patients reported in 2000 found 5-year local recurrence, distant recurrence, and mortality rates of 12%, 39%, and 25%, respectively. They noted the following risk factors for higher mortality: tumor size greater than 5 cm and bone or neurovascular invasion. Pitcher [9] suggested a 50% to 80% 5-year overall survival, and noted numerous factors related to worse prognosis: older than 20 years, proximal location, larger than 5 cm, poor differentiation and high mitotic rate, high nuclear grade and aneuploidy, monophasic histology, large percentage of necrosis, vascular invasion, and inability to achieve a wide resection. Evidence during the past two decades suggests synovial sarcoma has a genetic basis [6, 7, 9, 10, 12], related to specific fusion proteins. Naka et al. [8] noted synovial sarcoma was characterized by a unique t(X;18)(p11;q11) chromosomal translocation, and suggested this unique sarcoma may arise from mesenchymal stem cells driven to dysregulation by the SS18-SSX fusion protein. There is little doubt our view of synovial sarcoma will continue to evolve as new methods of observation become available. It remains, however, a deadly tumor to many.