A novel case of synovial sarcoma of the kidney: impact of SS18/SSX analysis of renal hemangiopericytoma-like tumors.

We report a new case of synovial sarcoma of the kidney. The patient underwent nephrectomy because of a large tumor in the right kidney. The histologic diagnosis was hemangiopericytoma. Less than 1 year after primary surgery the patient was reoperated due to massive local recurrence. Histology now revealed a poorly differentiated tumor tissue with hemangiopericytoma-like features. Immunostainings showed immunoreactivity to cytokeratin, epithelial membrane antigen, and vimentin. The tumor was negative to CD34 and factor VIII. The tumor cell proliferation, assessed by Ki-67, was high. RT-PCR analysis and sequence analysis demonstrated the presence of SS18/SSX2 fusion gene. Review of the histologic specimens from the original tumors confirmed hemangiopericytoma-like morphology. The new diagnosis was poorly differentiated synovial sarcoma. At the time of reoperation, lung metastases were detected radiologically, reflecting a very aggressive phenotype. To our knowledge, this is the third case of poorly differentiated synovial sarcoma of the kidney. Common for all these three cases is the hemangiopericytoma-like histology and a very aggressive clinical behavior. These circumstances accentuate the impact of SS18/SSX analysis in diagnosis of renal hemangiopericytoma-like tumors.     

Novel SS18‐NEDD4 gene fusion in a primary renal synovial sarcoma

We report a primary renal synovial sarcoma with a novel gene fusion and unusual morphology. The patient was a 35‐year‐old female who was found to have a 5 cm hypocellular, myxoid spindle cell renal neoplasm that subtly permeated amongst native renal tubules. The tumor cells showed elongated hyperchromatic nuclei with ill‐defined pale cytoplasm, lacking significant mitotic activity or necrosis. Based on its deceptively bland morphology, the differential diagnosis included mainly benign entities, such as metanephric stromal tumor, mixed epithelial stromal tumor (MEST), and myxoid peripheral nerve sheath tumors. A definitive diagnosis of synovial sarcoma was made only subsequently to RNA‐sequencing, which revealed a novel SS18‐NEDD4 gene fusion. These results were further confirmed by fluorescence in situ hybridization using custom design break‐apart probes for both genes. This case illustrates the utility of targeted RNA‐sequencing in the classification of challenging tumors with deceptive morphology and identification of novel gene fusion variants. Apart from the canonical SS18‐SSX fusion, this is only the second alternative gene fusion variant described in synovial sarcoma to date, in addition to two cases harboring the SS18L1‐SSX1 fusion.     

滑膜肉瘤融合基因SYT-SSX的检测及意义分析

目的研究逆转录-聚合酶链反应(RT-PCR)在滑膜肉瘤石蜡包埋组织中检测SYT-SSX融合基因的可行性和意义。方法20例滑膜肉瘤标本均用10％福尔马林固定、石蜡包埋。采用RT-PCR检测SYT-SSX融合基因。看家基因PBGD作为内参照。结果所有标本均可检测到PBGDmRNA的表达。18例(90％)检测到融合基因SYT-SSX的表达。SYT-SSX1型占12例(66．7％)，SYT-SSX2型占6例(33．3％)。结论在经福尔马林固定经石蜡包埋组织的滑膜肉瘤用RT-PCR方法检测SYT-SSX融合基因是可行的，有较高的敏感性。融合基因亚型可能为预后提供重要信息。     

Calcifying/ossifying synovial sarcoma shows t(X;18) with SSX2 involvement and mitochondrial calcifications

AIMS: Synovial sarcoma with extensive calcification and ossification is a rare variant, the ultrastructural, cytogenetic and molecular analysis of which has not been reported previously. METHODS AND RESULTS: A large mass in the shoulder of a 20-year-old male patient led to a deformity of the chest wall, thus supporting the hypothesis that this is a slowly growing variant of synovial sarcoma. Nevertheless, the patient developed metastatic lung disease 7 months after resection. On histology, the monophasic spindle cell proliferation was in several areas obscured by the massive calcification and ossification. Immunohistochemistry showed keratin, epithelial membrane antigen, vimentin and CD99 expression. The cytogenetic analysis revealed a single t(X;18)(p11.2; q11.2), typical for synovial sarcoma. Additional fluorescence in-situ hybridization revealed SSX2 involvement. At the ultrastructural level, prominent needle-shaped intramitochondrial crystals were present, both in the cytoplasm and in the extracellular matrix. CONCLUSION: The presence of the t(X;18) with SSX2 involvement definitively characterizes this tumour as a variant of synovial sarcoma. In addition, the needle-like mitochondrial calcifications give a possible clue to the pathogenesis of the extensive metaplastic ossification and calcification.     

滑膜肉瘤的融合基因检测分析

目的：基于存在染色体易位所致特异的SYT－SSX融合基因,证实可在滑膜肉瘤组织石蜡切片上检测出并探讨其在诊断中的价值。方法：采用逆转录－聚合酶链反应,检测并分析20例滑膜肉瘤（组织学亚型15例单相,5例双相）的SYT－SSX转录物,并对照相应病理学所见,结果：所检20例滑膜肉瘤中,有19例（95％）出现特异SYT－SSX逆转录聚酶链反应产物,其中13例具有SYT－SSX2融合基因的肿瘤有10例呈组织学单相分化。结论：SYT－SSX融合基因转录物可在石蜡切片和组织块中获得满意结果。具有较好的灵敏性,是滑膜肉瘤所特有的诊断标志物,它的亚类分型（SYT－SSX1和SYT－SSX2）,可能成为预后推测指征。     

Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX fusion proteins

Synovial sarcoma is characterized by a prevalent chromosomal translocation, t(X;18)(p11;q11). As a result of this translocation the SYT gene on chromosome 18 fuses to either the SSX1 or the SSX2 gene on the X chromosome. In this study, we generated polyclonal antibodies against the SYT and SSX2 proteins. These antibodies specifically detected both these proteins and the SYT-SSX fusion proteins in transfected COS-1 cell extracts. Indirect immunofluorescence analysis of COS-1 cells expressing tagged or untagged SYT, SSX2, SYT-SSX1 or SYT- SSX2 indicated that all these proteins are localized in the nucleus, excluding the nucleoli. The SSX2 protein exhibited a diffuse staining pattern whereas both the SYT and SYT-SSX proteins appeared in several nuclear dots. Similar nuclear dots were also detected in primary synovial sarcoma cells growing in a short-term in vitro culture. Double immunofluorescence in conjunction with confocal laser-scanning microscopy revealed that the SYT and SYT-SSX nuclear dots do not co- localize with known nuclear structures as e.g. coiled bodies, SC35 interchromatin granules or PML bodies. The similar nuclear localization patterns of SYT and SYT-SSX suggest that the SYT-SSX fusion proteins are directed to SYT-associated nuclear domains where an abnormal function may be exerted.