Answer: Renal synovial sarcoma

Histology: This cellular neoplasm is composed of non pleomorphic, plump spindle cells arranged in short fascicles which intercept abruptly. The cells have ill-defined clear cytoplasm, and uniform “rice-grain” nuclei. Mitotic activity is abundant. Foci of necrosis and collagen deposition are present. This neoplasm demonstrated the SYT-SSX2 gene fusion typical of synovial sarcoma, monophasic spindle cell type.

Discussion: None of the entities in the differential diagnosis would demonstrate the characteristic SYT-SSX2 gene fusion of synovial sarcoma. Monophasic spindle cell Wilms tumor is uncommon, and when seen usually affects younger patients and demonstrates rhabdomyoblastic differentiation. Congenital mesoblastic nephroma essentially does not occur above the age of 3 years. Leiomyosarcoma would feature pleomorphic spindle cells with dense eosinophilic cytoplasm.

Primary renal synovial sarcoma is a novel, distinctive clinicopathologic entity that has been confirmed by demonstration of the characteristic SYT-SSX gene fusion that results from the t(X;18)(p11.2;q11) of synovial sarcoma in these neoplasms. Prior to their recognition, many of these tumors had been classified under the term “embryonal sarcoma of the kidney,” a term used to describe otherwise unclassifiable primitive renal sarcomas with an often prominent cystic component. The latter entity appeared however to be heterogeneous at the clinical, pathologic, and immunohistochemical levels. The observation that one such neoplasm demonstrated a t(X;18) on cytogenetic analysis suggested that a subset of these tumors might be synovial sarcomas, a postulate which was subsequently confirmed by molecular analysis.

All molecularly confirmed primary renal synovial sarcomas have presented in young adults (ages 26-49). Tumors are frequently large (mean diameter 11cm) and often grossly cystic. They tend to present at advanced stage, and while outcome data is incomplete, the prognosis appears to be poor. A number of tumors have recurred and several patients have died of these tumors.

The morphology of the majority of these tumors is best conceptualized as that of a monophasic spindle cell synovial sarcoma encircling native renal elements. The tumors are highly cellular and composed of plump, embryonal-appearing, spindle cells with indistinct cytoplasm growing in short, intersecting fascicles. Mitoses are frequent, and necrosis is common and often extensive. Intratumoral cysts are lined by mitotically-inactive polygonal cells with extensive eosinophilic cytoplasm and apically-oriented nuclei, giving rise to a hobnail appearance. The cyst lining cells represent native collecting ducts that are entrapped and obstructed by the tumor and cystically dilate. Many tumors are dominantly cystic, and have a sieve-like appearance at low power. Most of the cyst walls contain primitive tumor cells, but some may be hypocellular and fibrous, simulating the wall of a cystic nephroma. In fact, some primary renal synovial sarcomas have likely been classified a primitive sarcomas arising in cystic nephroma for this reason. Other monophasic renal synovial sarcomas have likely been classified as adult cellular CMN, or adult blastemal or sarcomatous Wilms tumors. Rarely, primary renal synovial sarcomas may be genuinely biphasic (P. Argani, M. Ladanyi, unpublished observations), and therefore mimic biphasic stromal-epithelial Wilms tumor. It is possible that inclusion of primary renal synovial sarcomas in “adult Wilms tumors” accounts for some of the adverse prognosis ascribed to the latter by many oncologists. It remains to be seen if treatment with more intensive chemotherapy suitable for synovial sarcoma (as opposed to Wilms tumor) will improve the prognosis.

Primary renal synovial sarcomas are typically immunoreactive for vimentin, but nonreactive for S100 protein, CD34, or desmin. Cytokeratin may be focally positive or completely negative, with EMA more frequently showing focal positivity. Bcl2 positivity in the face of CD34 negativity may suggest the diagnosis. CD99 (MIC2) has been reported to be positive in at least 2 molecularly confirmed cases.

Molecularly-confirmed primary renal synovial sarcomas have demonstrated the characteristic SYT-SSX gene fusion using reverse transcriptase polymerase chain reaction (RT-PCR) assays performed upon RNA extracted from formalin-fixed, paraffin-embedded tissue blocks. Interestingly, while the SYT-SSX1 fusion predominates in soft tissue synovial sarcoma, the majority of renal synovial sarcomas (68%) have demonstrated the SYT-SSX2 gene fusion. The SYT-SSX2 fusion type has been correlated in soft tissue synovial sarcoma with monophasic histology; this tendency is consistent with the predominance of monophasic spindled morphology of these tumors in the kidney. While it is intriguing that the SYT-SSX2 fusion may be more common in the kidney, it is possible that synovial sarcomas with the SYT-SSX1 fusion exist in greater numbers but are underdiagnosed in the kidney, since they more frequently are biphasic and are more easily confused with a biphasic adult Wilms tumor.

Reference(s):
– Am J Surg Pathol 2000;24: 1087-1096.