Epithelioid sarcoma with SYT-SSX1 fusion gene expression: molecular and cytogenetic analysis

Epithelioid sarcoma is a rare malignant soft tissue tumor of unknown histogenesis, characterized by the epithelioid morphology of tumor cells and co-expression of epithelial and mesenchymal lineage proteins. A common epithelial and mesenchymal immunophenotype is also found in another soft tissue tumor, the biphasic subtype of synovial sarcoma. Furthermore, the presence of a breakpoint at 18q11 in epithelioid sarcoma, similar to that found in synovial sarcoma, has been reported. These facts would support the hypothesis that both tumors may share a common histogenetic background. However, expression of the SYT-SSX fusion genes has been investigated in epithelioid sarcoma with negative results. We report, to our knowledge, the first epithelioid sarcoma in which the presence of SYT-SSX1 fusion gene has been detected by means of conventional RT-PCR analysis and sequencing, real-time RT-PCR and FISH. The SYT-SSX1 gene fusion was identified in a small proportion of tumoral cells. This finding supports a likely common histogenetic background for both epithelioid sarcoma and synovial sarcoma.     

Immunostaining for SYT protein discriminates synovial sarcoma from other soft tissue tumors: analysis of 146 cases.

Synovial sarcoma in its classic biphasic form can be distinguished readily from other soft tissue lesions; however, monophasic and poorly differentiated forms are diagnostically more problematic. For this reason, we assessed the efficacy of immunostaining for SYT and SSX1 proteins, the gene products resulting from unique synovial sarcoma translocation, to distinguish synovial sarcoma from other soft tissue lesions. A total number of 146 cases were analyzed, including 47 synovial sarcoma cases (all of which were verified by FISH to have t(X; 18) translocation and SYT-SSX fusion gene) and 99 soft tissue tumors of various types. A polyclonal IgG antibody against SYT was used to stain formalin-fixed paraffin embedded tissues. Forty-one out of 47 (87%) synovial sarcoma displayed strong positive nuclear staining (ranging from 80 to 90% of the tumor cells) for SYT antibody. Nineteen of 99 (19%) non-synovial sarcoma cases showed variable nuclear and cytoplasmic staining with SYT, which ranged from 20 to 60% of tumor nuclei, and included malignant peripheral nerve sheath tumor (5/25), solitary fibrous tumor (2/14), Ewing sarcoma (2/6), low grade fibromyxoid tumor (2/4), extraskeletal mesenchymal chondrosarcoma (2/6), gastrointestinal tumor (4/17), epithelioid sarcoma (2/2). The remaining non-synovial sarcomas were negative. This is the first study demonstrating SYT protein expression in tissue sections of synovial sarcoma. This method could provide an easy, rapid and widely applicable means of assisting in the diagnosis of synovial sarcoma, particularly when material and/or resources are unavailable for PCR or FISH-based testing. However, as variable weak staining for SYT may be encountered in a small percentage of non-synovial sarcoma sarcomas, a positive interpretation should be made only when the staining is strong, nuclear and present in the majority of cells.     

Monophasic synovial sarcoma arising in the vulva: a case report and review of the literature

Synovial sarcomas most commonly arise in the soft tissue of the extremities. Less commonly, these tumors present in the head and neck, abdominal wall, and other sites. However, synovial sarcoma occurring in the vulvar area is extremely rare. Only 2 previous cases of biphasic synovial sarcoma of the vulva have been reported, but no case of vulvar monophasic synovial sarcoma has been described in the English literature. We report the third case of synovial sarcoma and apparently the first case of monophasic synovial sarcoma arising in soft tissues of the vulva. The patient was a 33-year-old woman who presented for evaluation of a painless vulvar mass. The tumor was located in the deep fibroadipose tissue of the right vulva (6.5 x 4.2 x 3.5 cm). The histology of the lesion was that of a monophasic synovial sarcoma with a hemangiopericytic vascular pattern. A subsequent molecular analysis revealed SYT-SSX2 gene fusion, which confirmed the diagnosis of synovial sarcoma. After an initial wide local excision, the patient developed a recurrence in the right groin and received chemotherapy and additional surgery. The patient is currently disease free, on adjuvant chemotherapy, and being followed up closely.     

Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors

Background

SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized. We analyzed SOX2 protein expression in soft tissue tumors. Alongside we tested Histone H3 expression (H3K27me3) in SOX2 positive cases to investigate this epigenetic mark and its correlation with the SOX2 status and clinicopathological parameters.

Pulmonary synovial sarcoma with polypoid endobronchial growth: a case report, immunohistochemical and cytogenetic study

A rare case of primary pulmonary synovial sarcoma with polypoid endobronchial growth in a 42-year-old Japanese woman is described. Left upper sleeve lobectomy was performed for the polypoid tumor measuring 2.5 cm in the left major bronchus and the patient was treated with adjuvant chemotherapy. Three years later, a recurrent tumor was discovered. Microscopically, this tumor was characterized by a proliferation of oval to spindle-shaped cells arranged in sheets and fascicles and covered by the thin normal bronchial epithelium. Immunohistochemically, tumor cells were positive for vimentin, and focally positive for pancytokeratin recognized by AE1/AE3, cytokeratin 7 and epithelial membrane antigen. A chimera gene, SYT-SSX1, was detected. Recently, primary pulmonary synovial sarcoma is an increasingly recognized clinical entity; however, most of these tumors present as a parenchymal mass. The present case is a unique example of primary synovial sarcoma of endobronchial polypoid type. This case suggests that pulmonary synovial sarcoma might originate from bronchial submucosal stromal tissue.     

Primary pulmonary sarcoma with morphologic features of biphasic synovial sarcoma: a case report.

We report an unusual primary case of pulmonary sarcoma that developed in the lung of a 36-year-old woman. The tumor had histologic, immunologic and ultrastructural features identical to those of biphasic synovial sarcoma of the soft tissue. It consisted of an intimate admixture of cytokeratin and epithelial membrane antigen(EMA)-positive neoplastic epithelial cells and vimentin-positive fibroblast-like spindle cells with areas of hyalinization. The patient had a lobectomy and showed no evidence of recurrence or tumor at other sites 15 months after surgery. This case is an useful addition to the small number of published reports on pulmonary synovial sarcoma. The distinctive features of this neoplasm allow it to be different from other types of primary and metastatic malignancies in the lung.     

Epithelioid Monophasic Synovial Sarcoma

A 47-year-old man presented with a soft tissue mass of the distal right thigh near the knee. The tumor was highly vascular with epithelioid tumor cells growing in a peritheliomatous pattern, suggesting a soft tissue glomus tumor. Yet many tumor cells contained hemosiderin pigment and formed papillary structures suggestive of pigmented villonodular synovitis. Tumor cells were cytologically bland, and there was minimal mitotic activity. The tumor cells were strongly immunoreactive for cytokeratin, however, and contained true desmosomes, gland lumina, microvilli, tonofilaments, and well-developed basal lamina. These findings plus the absence perinuclear aggregates of intermediate filaments rule out malignant rhabdoid tumor and epithelioid sarcoma. Also, magnetic resonance imaging revealed no other lesions to suggest metastatic carcinoma. Thus this tumor appears to be a predominantly epithelioid form of monophasic synovial sarcoma. Recognition of this variant of synovial sarcoma is important for prognostication and therapeutic decision making because some studies indicate that this variant of synovial sarcoma follows a relatively benign clinical course.     

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.     

Primary retroperitoneal synovial sarcoma: a case report

A case of a 36-yr-old woman with retroperitoneal synovial sarcoma is described. Her presenting symptom was epigastric pain that radiating to the back. On radiologic study, bulky retropancreatic soft tissue mass was detected which showed cystic and solid components. At operation, complete resection of the tumor was not possible because of the adhesion to the vena cava and the liver. During the follow-up, extensive tumor recurrence and liver metastasis were revealed. Primary retroperitoneal synovial sarcoma is a very rare malignant tumor with high mortality and recurrence rates. Retroperitoneal synovial sarcoma usually appears as a nonspecific soft tissue mass that do not have specific imaging features differentiating it from other mesenchymal tumors. However general radiologic findings and anatomic location of the tumor may help the diagnosis. In addition, synovial sarcoma should be included in the differential diagnosis of retroperitoneal soft tissue mass detected in young adults.     

Synovial sarcoma presenting as a lung mass and diagnosed by cytology

Synovial sarcoma is a common soft tissue sarcoma with variable fibrous and epithelial differentiation that rarely arises from other body sites, such as within the lung. A case of a 68‐year‐old male with an extensive smoking history who presented with chest pain and a primary, central, metabolically active lung mass was reported. The mass was biopsied by bronchial brushing, bronchoalveolar lavage (BAL), and transbronchial fine‐needle aspiration (FNA). Cytologic analysis of bronchial brushing, BAL, and FNA revealed single and clusters of atypical spindle cells, oval, or spindle‐shaped nuclei with smooth nuclear membranes, hyperchromatic and granular chromatin, scant to moderate and delicate cytoplasm, a high degree of mitotic figures, and a lack of necrosis. Immunohistochemical studies showed that the tumor cells were positive for CD99, BCL2, and CK7. A diagnosis of synovial sarcoma was rendered. The differential diagnosis of primary pulmonary synovial sarcoma is discussed, including neuroendocrine tumors, squamous cell carcinoma, and various sarcomatous tumors. Diagn. Cytopathol. 2016;44:434–437. © 2016 Wiley Periodicals, Inc.     

SYT-SSX2 variant of primary pulmonary synovial sarcoma with focal expression of CD117 (c-Kit) protein and a poor clinical outcome

Pulmonary synovial sarcoma is a rare neoplasm recently recognized as a distinct entity and characterized by t(X;18) translocation and production of at least 2 fusion genes, SYT-SSX1 and SYT-SSX2. We report a case of primary pulmonary synovial sarcoma with the SYT-SSX2 phenotype and a rapidly progressive downhill course. Previous reports have suggested that the soft tissue synovial sarcomas with SYT-SSX2 phenotype have a favorable clinical outcome. To the best of our knowledge, this is also the first report of CD117 (c-Kit) expression in a pulmonary synovial sarcoma. A 45-year-old woman presented with left chest pain and was found to have a left lower lobe tumor that was originally diagnosed as a sarcomatoid carcinoma. After the patient underwent chemotherapy and brachytherapy, the specimen from a left pneumonectomy showed a large spindle cell tumor, which was reclassified as a synovial sarcoma based on the results of immunophenotyping and molecular genetic studies. Differentiation between sarcoma and carcinosarcoma is crucial for implementing appropriate therapy. Furthermore, if the tumor expresses c-Kit, it may respond to target-based therapy.