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At least 19 recordsLinked to original sources
PubMed2026

BRD9 Degraders Unleash GBAF Chromatin Remodeling Activity in Synovial Sarcoma.

UNLABELLED: Synovial sarcoma incorporates the SS18::SSX fusion oncoprotein into GLTSCR1-containing BRG1/BRM and associated factors (GBAF) complexes, which confers a dependency on the GBAF subunit BRD9. However, synovial sarcoma clinical trials with multiple BRD9 degraders failed to achieve clinically impactful remissions. In this study, we identified a mechanistic framework to explain these results. BRD9 depletion served to blunt proliferation in synovial sarcoma harboring minimal genomic alterations, rare in trial participants. In cultured cells, xenografts, and recombinant-purified complexes, BRD9 loss did not affect GBAF assembly. Although BRD9 degradation in synovial sarcoma reduced GBAF enrichment at target loci, BRD9-less complexes maintained or increased chromatin accessibility and associated gene transcription. Biochemical assays with purified recombinant GBAF demonstrated increased nucleosome sliding in the absence of BRD9. Together, these findings show that BRD9 restrains GBAF activity, with BRD9 degradation increasing enzymatic remodeling and target gene expression by fusion oncoprotein-distributed GBAFs in synovial sarcoma. This subtle epigenetic disturbance creates a low hurdle for synovial sarcoma to surpass, limiting the therapeutic efficacy of BRD9 degraders. SIGNIFICANCE: BRD9 represses the GBAF chromatin remodeling complex, which causes enhanced rather than disrupted SS18::SSX complex activity following BRD9 degradation and explains the lack of efficacy of pharmacological BRD9 degraders in synovial sarcoma.

Sarcoma, Synovial↗
PubMedDate not supplied

The early clinical presentation of synovial sarcoma.

While synovial sarcoma most commonly presents as a painless mass, occasionally the cancer emerges in a misleading manner resulting in an unfavorable delay or error in diagnosis. A review of the litrature reveals 4 such occult patterns: pretumor phase characterized only by pain or tenderness; the acute inflammatory lesion presenting as a "hot" arthritis or bursitis; the chronic contracture; the post traumatic tumor. These conditions, especially when otherwise unaccounted for, are indications for biopsy. Four avoidable pitfalls in biopsy management also emerged from the review.

Adult↗
PubMed1975

Synovial sarcoma of the laryngopharynx.

Synovial sarcoma of the laryngopharynx is an extremely rare neoplasm. To date, only two such cases have been reported. We describe two additional patients in whom this lesion occurred as a primary neoplasm of the laryngopharynx. Hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma. The difficulties that may be encountered in histologic diagnosis are emphasized. Our findings suggest that an aggressive surgical approach is indicated. Adjuvant therapy with irradiation and the chemotherapeutic agent, doxorubicin (Adriamycin), may contribute to better survival rates.

Adult↗
PubMed1976

Rare tumors of the ear, nose and throat: synovial sarcoma of the head and neck.

Synovial sarcoma is a rare neoplasm of mesenchymal origin. Contrary to earlier beliefs, this tumor does not arise from the synovial lining of joints and bursae, but develops from pluripotential mesenchymal cells through abnormal differentiation into synovial neoplasms. Macroscopically there are no distinguishing features. Microscopically the tumor is characterized by a biphasic pattern of pseudoepithelial cells and a spindle cell element with fibrosarcomatous appearance. To establish a diagnosis both features must be present, yet their relative proportions vary markedly. The tumor occurs most frequently in the extremities and rarely in other areas. Only 19 cases of synovial sarcoma of the head and neck have been reported in the literature. Two additional cases, one of the hypopharynx and one of the cheek, are reported herein.

Child↗
PubMed1975

Synovial sarcoma.

Of 34 cases with synovial sarcoma, the five-year survival rate was 36%. A high local recurrence rate results when local excision is performed. Wide excision which may necessitate amputation is the treatment of choice. Prophylactic and even therapeutic node dissections are ineffective in increasing survival because of the disease. Evaluation of radiation therapy was impossible, although some patients obtained significant paliation. Adriamycin appears to have a tumoricidal effect and provided clinically significant responses in several patients.

Adult↗
PubMedDate not supplied

Synovial sarcoma of the hypopharynx.

Primary synovial sarcoma of the hypopharynx is an extremely rare neoplasm. Only 16 cases could be traced in the literature so far. An additional case, in a 29-year-old male patient, is presented. Progressive disturbance of deglutition and speech, chocking sensation, and mild respiratory distress were his original complaints. Our case differs from those previously reported in that a) the tumor was pedunculated, and the site of its attachment could be very well-defined, and b) unusual intratumoral destructive hemorrhage turned the case into an emergency. The pedicle was radically excised together with part of the grossly uninvolved underlying tissue, and the tumor was removed in toto. The histological findings are described. The patient is under observation. No recurrence has been noticed 11 months after surgery, and there are no signs of metastasis. The origin of the tumor and its treatment are discussed.

Adult↗
PubMed1976

[Course and outcome of treatment of synovial sarcoma].

The results of exploration of 126 patients with synovial sarcoma are reported; males -- 70, females -- 54, aged from 4 to 74 years old. The tumor was found to be localized as follows: the extremities -- 117 (upper -- 33, lower -- 84), and the body -- 9 patients. Seven structural variants of synovial sarcoma were differentiated: 1) alveolar -- 19, 2) adenomatous -- 10, 3) histioid -- 65, 4) perithelial --3, 5) fibrous -- 6, 6) gigantic-cell -- 3 and 7) mixed -- 20 patients. The patients were treated surgically (56 patients) and using the combined technics (70 patients). The most favourable results were noted in treatment of patients with adenomatous and fibrous types of synovial sarcoma, worse issues -- in patients with gigantic-cell and perithelial forms. Synovial sarcomas of histioid and mixed types occupy the intermediate place. The most malignant character of the neoplasm was observed in patients with alveolar tumor.

Adolescent↗
PubMed1975

Cervical synovial sarcoma at the bifurcation of the carotid artery.

Cervical synovial sarcoma has been reported in only 15 cases; in none of these was there any association with a vascular structure. A patient with cervical synovial sarcoma encompassing the bifurcation of the left carotid artery underwent a left radical neck dissection, including excision of the left external carotid artery and the hypoglossal nerve. The tumor was dissected away from the common carotid and internal carotid arteries. Although the fibrous pseudocapsule of the tumor had not involved the fibrous adventitia of the carotid arteries. Radiation therapy with 6000 rads tumor dose was administered to a wide local field. There is no evidence of recurrence 1 year postoperatively. Histologic and ultrastructural findings were similar to those reported previously in a case of synovial sarcoma of an extremity.

Adult↗
PubMed1976

[Synovial sarcoma in the region of the head and neck].

A young woman with primary cervical synovial sarcoma above the collar-bone is described. Synovial sarcomas of the head and neck are infrequently reported. The pathology, treatment and progress appear to be very similar to that of synovial sarcomas situated elsewhere. It appears that primary lesions occur in younger people and that the survival rate is better than that for synovial sarcoma elsewhere.

Adult↗
PubMed1977

Monophasic synovial sarcoma--a histological entity?

Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed.

Collagen↗
PubMed1978

Synovial sarcoma of the neck associated with previous head and neck radiation therapy.

Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem.

Acne Vulgaris↗
PubMed1976

Poorly differentiated synovial sarcoma. A light and electron microscopic study.

Few studies of the ultrastructural features of synovial sarcoma have appeared in the literature. The case under study represented a poorly differentiated synovial sarcoma with a predominant fibrosarcomatous component and a few areas with epithelioid and pseudoacinar patterns. Ultrastructurally, the cellular elements of the varied histologic patterns were similar. Basement membranes and desmosomes were absent, and the cell surfaces facing the acinar lumen exhibited multiple microvilli. It appears from a comparison of our studies with the previous reports that the fine structure of this tumor varies according to the degree of histologic differentiation.

Adult↗
PubMed1976

Synovial sarcoma of the neck: report of case.

Synovial sarcoma is an uncommon neoplasm that usually arises in the extremities and rarely in the head and neck. A case arising in the neck has been reported herein. The tumor is composed of two intimately associated cellular patterns; one resembles synovial structures and the other resembles fibrosarcoma. The tumor is fairly slow growing and is fairly well circumscribed but not actually encapsulated. There is a predilection for males; most occur in the third through fifth decades of life. Recurrence follows inadequate therapy. Although local excision was the therapy used in this case, the patient is alive and free of disease 30 months postoperatively.

Adult↗
PubMedDate not supplied

Synovial sarcoma diagnosed by fine-needle aspiration biopsy. A case report.

The cytologic findings of a synovial sarcoma are described. A 60 year old male had felt a slowly growing tumor in his right sole for three years. From the first fine-needle aspiration biopsy a fibrosarcoma or other mesenchymal tumor was suggested; but the second biopsy showed both fibrosarcoma and mesothelial-like cells in contact with each other, and the diagnosis of synovial sarcoma was made. Histologic and electron microscopic sections confirmed the diagnosis. In the differential diagnosis of this case, fibrosarcoma and other malignant mesenchymal tumors were considered. The applicability of fine-needle aspiration biopsy in mesenchymal lesions is discussed.

Biopsy, Needle↗