Underlying Ossification Phenotype in a Murine Model of Metastatic Synovial Sarcoma.

Synovial sarcoma, an uncommon cancer, typically affects young adults. Survival rates range from 36% to 76%, decreasing significantly when metastases are present. Synovial sarcomas form in soft tissues, often near bones, with about 10% demonstrating ossification in the tumor. The literature is inconclusive on whether the presence of ossification portends a worse prognosis. To this end, we analyzed our genetic mouse models of synovial sarcoma to determine the extent of ossification in the tumors and its relationship with morbidity. We noted higher ossification within our metastatic mouse model of synovial sarcoma. Not only did we observe ossification within the tumors at a frequency of 7%, but an even higher frequency, 72%, of bone reactivity was detected by radiography. An enrichment of bone development genes was associated with primary tumors, even in the absence of an ossification phenotype. In spite of the ossification being intricately linked with the metastatic model, the presence of ossification was not associated with a faster or worse morbidity in the mice. Our conclusion is that both metastasis and ossification are dependent on time, but that they are independent of one another.

Primary pulmonary synovial sarcoma with calcification: A case report.

The lung is the organ most commonly affected by primary synovial sarcoma. Intratumoral calcification is less common in this organ versus soft tissue. Meanwhile, the presence of calcification in a lung nodule reduces the risk of lung cancer. Here, we report a case of pulmonary synovial sarcoma which manifested as a nodule with calcification, depicted on computed tomography (CT). A 52-year-old asymptomatic male was referred to Saitama Medical University International Medical Center and CT revealed a well-defined nodule (1.8 cm), with punctate and eccentric calcification in the right lower lobe. Enhanced CT and 18F-fluorodeoxyglucose positron-emission tomography suggested a malignant tumor, and surgery was performed. Histology provided a preliminary diagnosis of monophasic spindle-cell synovial sarcoma with hyalinized collagen bands and calcifications. Genetically, the presence of the SYT-SSX2 fusion gene was consistent with the features of this disease. We conclude that primary pulmonary synovial sarcoma should be listed as a differential diagnosis for solitary pulmonary nodules with calcification.

Systemic Interferon-γ Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors: Results of a Phase 0 Clinical Trial.

Interferon-γ (IFNγ) has been studied as a cancer treatment with limited evidence of clinical benefit. However, it could play a role in cancer immunotherapy combination treatments. Despite high expression of immunogenic cancer-testis antigens, synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) have a cold tumor microenvironment (TME), with few infiltrating T cells and low expression of major histocompatibility complex class I (MHC-I). We hypothesized that IFNγ treatment could drive inflammation in a cold TME, facilitating further immunotherapy. We conducted a phase 0 clinical trial treating 8 SS or MRCL patients with weekly systemic IFNγ. We performed pre- and posttreatment biopsies. IFNγ changed the SS and MRCL TME, inducing tumor-surface MHC-I expression and significant T-cell infiltration (P < 0.05). Gene-expression analysis suggested increased tumor antigen presentation and less exhausted phenotypes of the tumor-infiltrating T cells. Newly emergent antigen-specific humoral and/or T-cell responses were found in 3 of 7 evaluable patients. However, increased expression of PD-L1 was observed on tumor-infiltrating myeloid cells and in some cases tumor cells. These findings suggest that systemic IFNγ used to convert SS and MRCL into "hot" tumors will work in concert with anti-PD-1 therapy to provide patient benefit.

The importance of treating by histological subtype in advanced soft tissue sarcoma.

While surgical resection (±radiotherapy) is standard treatment for localized soft tissue sarcomas (STS), chemotherapy is the mainstay for managing locally advanced and metastatic disease. Expanding knowledge of the biologies and sensitivities of STS histotypes, in conjunction with results from a growing collection of retrospective reviews and prospective randomized studies, point to the importance of treating in consideration of histological subtype. Doxorubicin ± ifosfamide continues to be standard first-line therapy for most STS subtypes. Main options for second- or later-line therapy include trabectedin, dacarbazine, gemcitabine combinations, pazopanib and, most recently, eribulin. Using illustrative case studies, treatment options are reviewed for three of the more common STS subtypes - uterine leiomyosarcoma, liposarcoma and synovial sarcoma - with a focus on use of trabectedin.

Synovial Sarcoma Associated With Indwelling Intramedullary Pin in a Peach-Faced Lovebird (Agapornis roseicollis).

Sarcoma developing in association with a metallic orthopedic procedure is an uncommon but well-recognized complication in mammals. We report on a synovial sarcoma that developed at the site of an intramedullary pin after surgery to treat a bone fracture. A 17-year-old female peach-faced lovebird (Agapornis roseicollis) developed a spherical mass on the distal right dorsal wing at a site that was previously fractured and surgically repaired with an indwelling intramedullary pin. The right wing was amputated at the scapulohumeral joint. One year later, the bird died. Postmortem examination revealed metastases in the right lung, left thoracic wall, and proventricular serosa. Histologically, the tumor had a characteristic biphasic pattern. The tumor was immunohistologically and ultrastructurally identified as a synovial sarcoma. This is the first report of a suspected fracture-associated sarcoma in a bird.

Primary synovial sarcoma of the abdominal wall: a case report and literature review.

Synovial sarcoma (SS) is the fourth most common type of soft tissue sarcoma, following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma. It usually occurs in the extremities near the large joints of middle-aged patients. We describe a case of synovial sarcoma of the anterior abdominal wall (SSAW) in an adolescent girl and undertake a review of the literature.

Fine needle aspiration of primary mediastinal synovial sarcoma: cytomorphologic, immunohistochemical, and molecular study.

The cytologic diagnosis of synovial sarcoma (SS) can be difficult when it occurs in unusual locations, atypical age groups, and/or have unusual morphology. We report a case of primary mediastinal SS in a 65-year-old male with a long smoking history who presented with increasing shortness of breath and was found to have a 14.2 cm mediastinal mass. Smears from the endobronchial ultrasound guided fine needle aspiration of the mass were moderately cellular consisting of loosely cohesive clusters, some of which demonstrated nuclear molding, and dispersed single cells. The relatively uniform tumor cells had a high nuclear-to-cytoplasmic ratio, finely granular chromatin, and inconspicuous nucleoli. Some of the single cells had spindled morphology with unipolar wispy tails and naked nuclei. Based on the clinical presentation and the cytomorphologic features, our initial differential diagnoses included atypical carcinoid, small cell carcinoma, basaloid squamous cell carcinoma, sarcoma, and lymphoma. Immunohistochemical studies on the cell block sections revealed that the tumor cells were focally positive for cytokeratin and diffusely positive for CD56, while negative for CD45, synaptophysin and chromogranin. Ultimately, an immunohistochemical stain for TLE-1 demonstrated diffusely strong nuclear positivity and molecular studies showed the presence of the t(X; 18) SYT/SSX1 translocation confirming the diagnosis of SS. In this report, we describe the cytomorphologic features of SS, its diagnostic pitfalls, and potential mimics in the mediastinum.

Radiation-induced synovial sarcoma of the lung diagnosed by gene analysis after the surgical resection of chondrosarcoma arising from the scapula.

The patient was a 62-year-old male who underwent wide resection and radiotherapy for right scapular chondrosarcoma 12 years ago. An abnormal shadow was detected in the right upper lung field included in the irradiated field on chest X-ray. Since the nodule tended to enlarge, a malignant lung tumor was suspected, and surgery was performed. On histological examination, spindle cells densely proliferated in a bundle pattern. Vimentin, bcl-2 protein, and CD99 were positive, and CD34, cytokeratin, AE1/AE3, and EMA were partially positive on immunohistochemical staining. The SYT-SSX (synaptotagmin- synovial sarcoma X) fusion gene was detected employing RT-PCR, based on which primary synovial sarcoma of the lung was diagnosed. The findings also matched the diagnostic criteria of radiation-induced sarcoma, suggesting radiation-induced primary synovial sarcoma of the lung. Primary synovial sarcoma of the lung is a rare tumor. It is difficult to diagnose based on cellular findings, and immunohistochemical and genetic investigations are essential. Radiation-induced sarcoma may develop through a long-term course, as seen in this patient, for which long-term follow-up after radiotherapy is important.

Synovial sarcoma of the lung in a patient who received radioactive iodine therapy for thyroid cancer.

BACKGROUND: Synovial sarcomas are uncommon malignancies that mainly affect adolescents and young adults. Most arise from the deep soft tissues of the extremities, but they can occur in other parts of the body such as the lung. Synovial sarcomas after radiation therapy are rare, in contrast with other sarcomas, with only six reported cases. Secondary malignancies after radioactive iodine (RAI) therapy are also uncommon, with the most consistent evidence for hematologic malignancies. PATIENT FINDINGS: We present what we believe to be the first report of a synovial sarcoma of the lung with an SS18/SSX1 translocation after RAI therapy. At age 20, the patient developed papillary thyroid cancer and later had two surgically confirmed recurrences. Over the course of her care, she received a total of about 220 mCi of RAI. At age 34, as part of an evaluation for another suspected recurrence, she had a position emission spectroscopy-computed tomography scan, and a pulmonary mass was detected. SUMMARY AND CONCLUSION: Although not previously reported, this case suggests that synovial sarcomas may be a secondary malignancy after RAI therapy. The latency in this case is reasonable, the dose to the lungs was small, but in the range where radiation-related malignancy may occur, and the somatic chromosomal rearrangement could be a radiation effect.

Synovial cell sarcoma of the larynx.

Synovial cell sarcoma represents a rare group of cancers, particularly in the head and neck region, that typically affects young individuals and has a male preponderance. Prognosis varies with patient age, site and size of the malignancy, degree of necrosis, high level of mitotic activity, and neurovascular invasion. Complete surgical resection of the tumor via partial or total laryngectomy is the first-line treatment in locally invasive disease. CO(2) lasers have been shown to be useful in controlling localized disease. There is also a role for adjuvant radiotherapy. Ifosfamide-based chemotherapy is most useful for malignant disease.

Synovial sarcoma of the buttocks presenting with a non-healing wound and rapid progression after local resection: a case report.

Synovial sarcoma is a malignant mesenchymal neoplasm that is frequently misdiagnosed as a benign condition because of its small size, slow growth, and well-delineated appearance. Rapid spread and early death occur rarely. Here we report a case of synovial sarcoma of the buttocks presenting with a non-healing wound and rapid progression after local resection in a 23-year-old woman. She initially found a slightly painful subcutaneous mass in the left buttock and underwent local excision. Postoperatively, she developed a non-healing wound that did not respond to conventional antibiotic therapy and local wound care, and pitting edema of the lower extremities. A magnetic resonance imaging scan revealed a large heterogeneous, irregular mass in the buttocks with regional lymph node involvement. Histological and immunohistochemical analyses suggested the diagnosis of a poorly differentiated synovial sarcoma. Her condition deteriorated dramatically shortly thereafter; she developed systemic edema and died of respiratory failure. This case suggests that synovial sarcoma may be fatal within months of recognition if improperly managed and stresses the importance of adequate pre-surgical evaluation and postoperative pathological analysis in the management of a subcutaneous mass.

CD133 negatively regulates tumorigenicity via AKT pathway in synovial sarcoma.

Synovial sarcoma (SS) is an aggressive tumor that accounts for almost 10% of all soft tissue sarcomas. In this study, we found the expression of CD133 in human SS specimens, thus, we focused on the function of CD133 in SS. Separation of the CD133-positive and -negative subpopulations in SS cell lines clarified that the CD133-negative subpopulation exhibited enhanced growth and hyperphosphorylation of AKT. Treatment of Akt inhibitor suppressed the cell growth of CD133-negative subpopulation to the levels of CD133-positive cells. These results suggest that CD133 has negative effect on the growth of cells through AKT-dependent signalling pathway.

[Synovial sarcoma in a patient with metal-on-polyethylene total hip replacement. A case report]. / Sarcoma sinovial en un paciente con reemplazo total de cadera metal-plástico. Informe de un caso.

We present the case of a synovial sarcoma five years after primary total hip arthroplasty in a male 65 year-old patient who was surgically treated for left hip pain due to coxarthrosis. A 32 mm uncemented prosthesis with metal-on-polyethylene tribology was placed in the patient. The latter developed synovial sarcoma that caused lung metastasis. The association between total hip arthroplasty and malignancy is discussed, as well as its frequency worldwide.

Synovial sarcoma arising in the foot: case report.

Synovial sarcomas occur primarily in the soft tissue structures adjacent to the joints and tendons of the extremities. A diagnostic dilemma exists when the clinical presentation is similar to that of an infection or soft tissue trauma. We report a case of soft tissue sarcoma of the foot in a previously healthy 19-year-old male who presented after hitting his right foot against a refrigerator. Initial radiographs were negative; however, 6 weeks later plain radiographs revealed destruction of the metatarsals. Histologic analysis on a specimen obtained via fine-needle aspiration confirmed the diagnosis of primary synovial sarcoma. Further workup revealed metastases to the lungs. An amputation at Chopart's joint was performed. Primary synovial sarcoma in the foot can mimic infection or edema from a traumatic event. Clinicians should always be suspicious of soft tissue masses and keep neoplastic processes in the list of differentials.

Paraspinal synovial sarcoma as an unusual postradiation complication in pediatric abdominal neuroblastoma.

SUMMARY: The development of a soft-tissue sarcoma is an infrequent but well-known long-term complication of radiotherapy. Malignant fibrous histiocytomas, extraskeletal osteosarcomas, fibrosarcomas, malignant peripheral nerve sheath tumors, and angiosarcomas are most frequently encountered. Radiation-associated synovial sarcomas are uncommon and exceedingly rare in pediatric patients. We report an unusual case of paraspinal synovial sarcoma presenting in an adolescent female 13 years after radiation therapy for her neuroblastoma.

Imaging of benign and malignant soft tissue masses of the foot.

The foot is a relatively uncommon site of neoplastic and non-neoplastic soft tissue tumors. Although it contains a relatively small amount of somatic soft tissue elements, the foot is considerably rich in tendons, fasciae, retinaculae, and synovium. Corresponding to this distribution of soft tissue elements, some soft tissue lesions, such as giant cell tumor of tendon sheath, fibromatosis, and synovial sarcoma, are commonly seen in this location. Vascular tumors represent common soft tissue masses of the foot as well. Magnetic resonance imaging is the modality of choice in the assessment of soft tissue tumors. The presence of a suspected lesion can be confirmed and tumor margins can be defined accurately. In general, MRI does not provide histologic specificity, but considering some MR features may often help in correctly distinguishing benign from malignant lesions. In addition, characteristic features of the most common benign tumors (i.e., fibromatosis, cavernous hemangioma) and reactive processes of the foot (ganglion cyst, Morton's neuroma) often suggest a specific diagnosis.

Reduced risk of synovial sarcoma in females: X-chromosome inactivation?

Synovial sarcoma shows a characteristic t(X;18) translocation but not the expected female predominance in incidence. We speculate that, among females, one X-chromosome is inactivated and that only the translocation to an active X-chromosome leads to development of synovial sarcoma. Population-based cancer registry data from the SEER program support this hypothesis.

Molecular mechanisms underlying human synovial sarcoma development.

Synovial sarcomas are rather common among soft-tissue tumors, occurring at any age but affecting mainly young adults. The vast majority of synovial sarcomas carries a t(X;18)(p11.2;q11.2) chromosomal translocation, in about one-third of the cases as the sole cytogenetic anomaly. Several studies have indicated that the t(X;18) translocation arises exclusively in synovial sarcomas, therefore being an excellent tool to diagnose this malignancy. The breakpoint-associated genes were recently isolated: SYT, from chromosome 18, and SSX1 and SSX2, both from the X chromosome. This discovery enabled the detection of SYT-SSX fusion transcripts by specific reverse transcriptase-polymerase chain reactions. This molecular genetics methodology has now been applied to numerous tumor samples and has led to the finding that, in contrast to tumors carrying SYT-SSX2 fusions, SYT-SSX1-positive tumors more often exhibit a biphasic histology, show a higher proliferation rate, and are associated with a poorer clinical outcome. It has also been shown that the SYT and SSX proteins are localized in the nucleus, where they appear to play a role in transcriptional regulation, SYT as an activator of transcription and the SSX proteins as transcriptional repressors. It was also found that SYT interacts and colocalizes in the nucleus with the BRM protein, a transcriptional coactivator, and that the SSX proteins colocalize in the nucleus with polycomb group proteins, which are transcriptional corepressors. Together, these studies have provided mechanistic clues about how the SYT-SSX fusion proteins may trigger synovial sarcoma development.

Synovial sarcoma arising in association with a popliteal cyst.

Synovial sarcoma is a relatively common soft tissue sarcoma particularly in the adolescent and young adult. We report an unusual case of a synovial sarcoma arising within a popliteal cyst in a 13-year-old female presenting with bilateral popliteal cysts. MR imaging demonstrated the cyst with evidence of subacute haemorrhage and a discrete nodule of tumour.