Sarcoma, Synovial

Description

Synovial sarcomas, which represent approximately 10% of all soft tissue sarcomas, are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18)(p11.2;q11.2), which usually represents either of 2 gene fusions, SYT (600192)-SSX1 (312820) or SYT-SSX2 (300192), encoding putative transcriptional proteins differing at 13 amino acid positions (summary by Ladanyi et al., 2002).

Synovial sarcoma, according to the experience of Enzinger and Weiss (1983), is the fourth most common type of soft tissue sarcoma. It usually develops in adolescents and young adults, is more common in males than in females, and has no racial predilection.

The patient described by Griffin and Emanuel (1987) was a 12-year-old black female with an unremarkable previous medical history, who presented with a 3-month history of right calf pain and swelling following a fall onto the right leg. Physical examination was unremarkable except for a large palpable mass in the posterior aspect of the right lower leg. Biopsy of the mass, performed to rule out hematoma, showed a spindle cell soft tissue malignancy, probably monophasic synovial sarcoma. CT scan of the leg showed that the mass encompassed more than one-half of the soft tissue of the leg. No metastasis was detected. An above-the-knee amputation was performed.

Ueda et al. (1988) studied a 13-year old Japanese girl with synovial sarcoma who presented with a very large (15 x 12 cm), hard mass on her right buttock. She had no personal or family history of malignancy. After resection of the tumor, adjuvant chemotherapy was administered. Metastasis to the lung had occurred. Histologically the tumor was composed mainly of solidly packed plump oval or short-spindle cells with a pronounced hemangiopericytomatous pattern and a small portion of pseudoglandular or epithelial arrangement. Tumor cells showed the translocation t(X;18)(p11.2;q11.2).

Synovial sarcoma is an uncommon soft tissue sarcoma that usually occurs in adolescents and young adults. Histologically, synovial sarcoma shows 2 patterns of proliferation: biphasic pattern and monophasic pattern. In the former type, it is easy to make a definite diagnosis. It is difficult and sometimes impossible to distinguish clearly monophasic synovial sarcoma from fibrosarcoma or malignant Schwannoma by routine histology alone. Immunoperoxidase procedures provide a convincing clue to differentiate these conditions; the positive staining of plump cells by anti-human keratin sera is sufficiently characteristic to make a diagnosis of synovial sarcoma (summary by Ueda et al., 1988).

Turc-Carel et al. (1987) found a translocation involving chromosome X (band p11.2) and chromosome 18 (band q11.2) in short-term cultures of cells from 5 synovial sarcomas and 1 malignant fibrous histiocytoma. In 4 of the tumors, the translocation t(X;18)(p11.2;q11.2) was reciprocal. The 2 other tumors had complex translocations, which, however, always involved chromosomes X and 18 at the 2 sites mentioned. The X;18 translocation was not detected in other histologic types of soft tissue sarcoma. This was the first description of a sex chromosome abnormality in a human solid tumor.

Griffin and Emanuel (1987) confirmed the original findings of Turc-Carel et al. (1987). The karyotype of the tumor in their patient was 46,XX,t(X;18)(p11;q11). It may be significant that the ARAF1 oncogene (311010) maps to the same region. Inactivation of the normal X chromosome in cells carrying the X/autosome translocation may result in loss of expression of the normal allele and allow expression of the altered gene at the breakpoint on the X chromosome. This phenomenon permitted localization of the gene for Duchenne muscular dystrophy (DMD; 300377) and a number of other autosomal recessive disorders that have been observed in females with X/autosome translocations.

Smith et al. (1987) identified the translocation t(X;18)(p11.2;q11.2) in every cell analyzed from each of 3 synovial sarcomas. Karakousis et al. (1987) found a specific translocation between the X chromosome and chromosome 18 in 6 cases of synovial sarcoma. Wang-Wuu et al. (1987) likewise found t(X;18) in a case of synovial sarcoma.

In a 13-year-old Japanese girl, Ueda et al. (1988) found t(X;18) in a synovial sarcoma, together with an insertion of chromosome 11q material into 15q. Knight et al. (1989) noted that the oncogene ARAF1 is not directly involved in the X;18 translocation. Miozzo et al. (1992) reported the instructive case of a patient with the Turner syndrome in whom the only X chromosome was involved in a translocation of typical form: t(X;18)(p11;q11).

Knight et al. (1992) examined a hybrid cell line by Southern analysis using 13 additional markers located at Xp11.3-cen. The location of the breakpoint was further confirmed by fluorescence in situ hybridization. Two YAC probes of 300 kb and 450 kb, containing the OATL2 locus (258870), hybridized to both derivative chromosomes, indicating that these YACs span the translocation breakpoint. Similar results were obtained with 2 independent cell lines carrying the translocation. Sinke et al. (1993) concluded that the translocation breakpoint in Xp11.2 that is associated with synovial sarcoma is different from the translocation breakpoint in Xp11.2 associated with renal adenocarcinoma (see 314310).

The SYT-SSX1 form of synovial sarcoma, compared to the SYT-SSX2 form, has a significantly unfavorable prognosis (Kawai et al., 1998; Ladanyi et al., 2002). This suggests that the SYT-SSX fusion genes may influence molecular mechanisms involved in tumor growth and progression and that SYT-SSX1 has a stronger influence on these mechanisms than SYT-SSX2. Xie et al. (2002) used Western blot analysis on 74 fresh, fusion variant-typed tumor samples from localized synovial sarcoma and found a significant correlation between SYT-SSX1 and high expression of cyclin A1 (CCNA1; 604036) and cyclin D1 (CCND1; 168461); P = 0.003 and P = 0.025, respectively. The data suggested that SYT-SSX may influence the cell cycle machinery, and that the more aggressive phenotype of the SYT-SSX1 variant is due to an accelerated tumor cell proliferation.