Synovial sarcoma

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Synovial sarcoma
Other namesMalignant synovioma
Monophasic synovial sarcoma - high mag.jpg
Micrograph of a monophasic synovial sarcoma. The histologic appearance is non-specific and overlaps with MPNST and fibrosarcoma. H&E stain.
Specialty Oncology

A synovial sarcoma (also known as malignant synovioma [1] ) is a rare form of cancer which occurs primarily in the extremities of the arms or legs, often in proximity to joint capsules and tendon sheaths. [2] It is a type of soft-tissue sarcoma.

Contents

The name "synovial sarcoma" was coined early in the 20th century, as some researchers thought that the microscopic similarity of some tumors to synovium, and its propensity to arise adjacent to joints, indicated a synovial origin; however, the actual cells from which the tumor develops are unknown and not necessarily synovial. [3]

Primary synovial sarcomas are most common in the soft tissue near the large joints of the arm and leg but have been documented in most human tissues and organs, including the brain, prostate, and heart.

Synovial sarcoma occurs in about 1–2 per 1,000,000 people a year. [4] They occur most commonly in the third decade of life, with males being affected more often than females (ratio around 1.2:1). [4] [2]

Signs and symptoms

Synovial sarcoma usually presents with an otherwise asymptomatic swelling or mass, although general symptoms related to malignancies can be reported such as fatigue. [5]

Diagnosis

The diagnosis of synovial sarcoma is typically made based on histology and is confirmed by the presence of t(X;18) chromosomal translocation. [6]

Histopathology

Two cell types can be seen microscopically in synovial sarcoma. One fibrous type, known as a spindle or sarcomatous cell, is relatively small and uniform, and found in sheets. The other is epithelial in appearance. Classical synovial sarcoma has a biphasic appearance with both types present. Synovial sarcoma can also appear to be poorly differentiated or to be monophasic fibrous, consisting only of sheets of spindle cells. Some authorities [3] state that, extremely rarely, there can be a monophasic epithelial form which causes difficulty in differential diagnosis. Depending on the site, there is similarity to biphenotypic sinonasal sarcoma, although the genetic findings are distinctive.

Like other soft tissue sarcomas, there is no universal grading system for reporting histopathology results. [7] In Europe, the Trojani or French system is gaining in popularity [8] while the NCI grading system is more common in the United States. The Trojani system scores the sample, depending on tumour differentiation, mitotic index, and tumour necrosis, between 0 and 6 and then converts this into a grade of between 1 and 3, with 1 representing a less aggressive tumour. [7] The NCI system is also a three-grade one, but takes a number of other factors into account.

Immunohistochemistry (IHC): SS18-fusion specific antibody and SSX-CT antibody are highly sensitive and specific for synovial sarcoma and when used together may obviate the need for molecular testing in most cases. [9] [10] Cytokeratin is typically expressed, at least focally. TLE1, BCL2 and CD99 may be positive but lack specificity.

Molecular biology

Most, and perhaps all, cases of synovial sarcoma are associated with a reciprocal translocation t(x;18)(p11.2;q11.2). There is some debate about whether the molecular observation itself is definitive of synovial sarcoma. [11] [12] [13]

The diagnosis of synovial sarcoma is typically made based on histology and is confirmed by the presence of t(X;18). [6] This translocation event between the SS18 gene on chromosome 18 and one of 3 SSX genes (SSX1, SSX2 and SSX4) on chromosome X causes the presence of an SS18-SSX fusion gene. The resulting fusion protein brings together the transcriptional activating domain of SS18 and the transcriptional repressor domains of SSX. It also incorporates into the SWI/SNF chromatin remodeling complex, a well known tumor suppressor. [14] SS18-SSX is thought to underlie synovial sarcoma pathogenesis through dysregulation of gene expression. [3]

There is some association between the SS18-SSX1 or SS18-SSX2 fusion type and both tumour morphology and five-year survival. [15]

Treatment

Treatment is usually multimodal, involving surgery, chemotherapy and radiotherapy: [16]

Afamitresgene autoleucel (Tecelra) was approved for medical use in the United States in August 2024. [19] [20]

Related Research Articles

<span class="mw-page-title-main">Soft-tissue sarcoma</span> Malignant tumor that develops in soft tissue

A soft-tissue sarcoma (STS) is a malignant tumor, a type of cancer, that develops in soft tissue. A soft-tissue sarcoma is often a painless mass that grows slowly over months or years. They may be superficial or deep-seated. Any such unexplained mass must be diagnosed by biopsy. Treatment may include surgery, radiotherapy, chemotherapy, and targeted drug therapy. Bone sarcomas are the other class of sarcomas.

<span class="mw-page-title-main">Sarcoma</span> Cancer originating in connective tissue

A sarcoma is a malignant tumor, a type of cancer that arises from cells of mesenchymal origin. Connective tissue is a broad term that includes bone, cartilage, muscle, fat, vascular, or other structural tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates.

<span class="mw-page-title-main">Chondrosarcoma</span> Malignant tumor originating in cartilage

Chondrosarcoma is a bone sarcoma, a primary cancer composed of cells derived from transformed cells that produce cartilage. A chondrosarcoma is a member of a category of tumors of bone and soft tissue known as sarcomas. About 30% of bone sarcomas are chondrosarcomas. It is resistant to chemotherapy and radiotherapy. Unlike other primary bone sarcomas that mainly affect children and adolescents, a chondrosarcoma can present at any age. It more often affects the axial skeleton than the appendicular skeleton.

<span class="mw-page-title-main">Liposarcoma</span> Medical condition

Liposarcomas are the most common subtype of soft tissue sarcomas, accounting for at least 20% of all sarcomas in adults. Soft tissue sarcomas are rare neoplasms with over 150 different histological subtypes or forms. Liposarcomas arise from the precursor lipoblasts of the adipocytes in adipose tissues. Adipose tissues are distributed throughout the body, including such sites as the deep and more superficial layers of subcutaneous tissues as well as in less surgically accessible sites like the retroperitoneum and visceral fat inside the abdominal cavity.

<span class="mw-page-title-main">Desmoplastic small-round-cell tumor</span> Aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones. It is characterized by the EWS-WT1 fusion protein.

<span class="mw-page-title-main">Hemangiopericytoma</span> Medical condition

A hemangiopericytoma is a type of soft-tissue sarcoma that originates in the pericytes in the walls of capillaries. When inside the nervous system, although not strictly a meningioma tumor, it is a meningeal tumor with a special aggressive behavior. It was first characterized in 1942.

<span class="mw-page-title-main">Nodular fasciitis</span> Medical condition

Nodular fasciitis (NF) is a benign, soft tissue tumor composed of myofibroblasts that typically occurs in subcutaneous tissue, fascia, and/or muscles. The literature sometimes titles rare NF variants according to their tissue locations. The most frequently used and important of these are cranial fasciitis and intravascular fasciitis. In 2020, the World Health Organization classified nodular fasciitis as in the category of benign fibroblastic/myofibroblastic tumors. NF is the most common of the benign fibroblastic proliferative tumors of soft tissue.

<span class="mw-page-title-main">Undifferentiated pleomorphic sarcoma</span> Medical condition

Undifferentiated pleomorphic sarcoma (UPS), also termed pleomorphic myofibrosarcoma, high-grade myofibroblastic sarcoma, and high-grade myofibrosarcoma, is characterized by the World Health Organization (WHO) as a rare, poorly differentiated neoplasm. WHO classified it as one of the undifferentiated/unclassified sarcomas in the category of tumors of uncertain differentiation. Sarcomas are cancers derived mesenchymal stem cells that typically develop in bone, muscle, fat, blood vessels, lymphatic vessels, tendons, and ligaments. More than 70 sarcoma subtypes have been described. The UPS subtype of these sarcomas consists of tumor cells that are poorly differentiated and may appear as spindle-shaped cells, histiocytes, and giant cells. UPS is considered a diagnosis that defies formal sub-classification after thorough histologic, immunohistochemical, and ultrastructural examinations fail to identify the type of cells involved.

<span class="mw-page-title-main">Ewing sarcoma</span> Type of cancer

Ewing sarcoma is a type of pediatric cancer that forms in bone or soft tissue. Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. The most common areas where it begins are the legs, pelvis, and chest wall. In about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis. Complications may include a pleural effusion or paraplegia.

<span class="mw-page-title-main">Mesoblastic nephroma</span> Medical condition

Congenital mesoblastic nephroma, while rare, is the most common kidney neoplasm diagnosed in the first three months of life and accounts for 3-5% of all childhood renal neoplasms. This neoplasm is generally non-aggressive and amenable to surgical removal. However, a readily identifiable subset of these kidney tumors has a more malignant potential and is capable of causing life-threatening metastases. Congenital mesoblastic nephroma was first named as such in 1967 but was recognized decades before this as fetal renal hamartoma or leiomyomatous renal hamartoma.

<span class="mw-page-title-main">SSX2</span> Mammalian protein found in Homo sapiens

Protein SSX2 is a protein that in humans is encoded by the SSX2 gene.

<span class="mw-page-title-main">SS18</span> Protein-coding gene in the species Homo sapiens

Protein SSXT is a protein that in humans is encoded by the SS18 gene.

<span class="mw-page-title-main">SSX1</span> Protein-coding gene in the species Homo sapiens

Protein SSX1 is a protein that in humans is encoded by the SSX1 gene.

<span class="mw-page-title-main">SSX4 (gene)</span> Protein-coding gene in the species Homo sapiens

Protein SSX4 is a protein that in humans is encoded by the SSX4 gene.

<span class="mw-page-title-main">Clear cell sarcoma</span> Rare form of cancer

Clear cell sarcoma is a sub-type of a rare form of cancer called a sarcoma. It is known to occur mainly in the soft tissues and dermis. Rare forms were thought to occur in the gastrointestinal tract before they were discovered to be different and redesignated as gastrointestinal neuroectodermal tumors.

Myxofibrosarcoma (MFS), although a rare type of tumor, is one of the most common soft tissue sarcomas, i.e. cancerous tumors, that develop in the soft tissues of elderly individuals. Initially considered to be a type of histiocytoma termed fibrous histiocytoma or myxoid variant of malignant fibrous histiocytoma, Angervall et al. termed this tumor myxofibrosarcoma in 1977. In 2020, the World Health Organization reclassified MFS as a separate and distinct tumor in the category of malignant fibroblastic and myofibroblastic tumors.

Sclerosing epithelioid fibrosarcoma (SEF) is a very rare malignant tumor of soft tissues that on microscopic examination consists of small round or ovoid neoplastic epithelioid fibroblast-like cells, i.e. cells that have features resembling both epithelioid cells and fibroblasts. In 2020, the World Health Organization classified SEF as a distinct tumor type in the category of malignant fibroblastic and myofibroblastic tumors. However, current studies have reported that low-grade fibromyxoid sarcoma (LGFMS) has many clinically and pathologically important features characteristic of SEF; these studies suggest that LGSFMS may be an early form of, and over time progress to become, a SEF. Since the World Health Organization has classified LGFMS as one of the malignant fibroblastic and myofibroblastic tumors that is distinctly different than SEF, SEF and LGFMS are here regarded as different tumor forms.

Mammary secretory carcinoma (MSC), also termed secretory carcinoma of the breast, is a rare form of the breast cancers. MSC usually affects women but in a significant percentage of cases also occurs in men and children. Indeed, McDvitt and Stewart first described MSC in 1966 and termed it juvenile breast carcinoma because an increased number of cases were at that time diagnosed in juvenile females. MSC is the most common form of breast cancer in children, representing 80% of childhood breast cancers, although it accounts for less than 0.15% of all breast cancers.

Dermatofibrosarcoma protuberans, fibrosarcomatous (DFSP-FS), also termed fibrosarcomatous dermatofibrosarcoma protuberans, is a rare type of tumor located in the dermis. DFSP-FS tumors have been viewed as: 1) a more aggressive form of the dermatofibrosarcoma protuberans (DFSP) tumors because they have areas that resemble and tend to behave like malignant fibrosarcomas or 2) as a distinctly different tumor than DFSP. DFSP-FS tumors are related to DFSP. For example, surgically removed DFSP tumors often recur with newly developed fibrobosarcoma-like areas. Nonetheless, the World Health Organization (WHO), 2020, classified DFSP and DFSP-FS as different tumors with DFSP being in the category of benign and DFSP-FS in the category of rarely metastasizing fibroblastic and myofibroblastic tumors. This article follows the WHO classification: the 5-15% of DFSP tumors that have any areas of fibrosarcomatous microscopic histopathology are here considered DFSP-FS rather than DFSP tumors.

Afamitresgene autoleucel, sold under the brand name Tecelra is a T cell immunotherapy used for the treatment of synovial sarcoma.

References

  1. ↑ "Synovioma". Encyclopædia Britannica Online. Retrieved 20 May 2012.
  2. 1 2 Goldblum, John R.; Folpe, Andrew L.; Weiss, Sharon W. (2001). "33". Enzinger and Weiss's Soft Tissue Tumors (Sixth ed.). St Louis, Missouri: CV Mosby. pp. 1052–1070. ISBN   978-0323088343. LCCN   2013010770.
  3. 1 2 3 Pollock, Raphael E., ed. (2002). Soft Tissue Sarcomas. American Cancer Society Atlas of Clinical Oncology. BC Decker. ISBN   155009128X.
  4. 1 2 Ferrari and Collini (2012). "Synovial Sarcoma". ESUN. 9 (5).
  5. ↑ 楊照彬 (2010). "青少年骨髓性肉瘤初期以背痛呈現: 病例報告". 台灣復健醫學雜誌 (in Chinese). 38 (4): 269–275.
  6. 1 2 Coindre, Jean-Michel; Pelmus, Manuela; Hostein, Isabelle; Lussan, Catherine; Bui, Binh N.; Guillou, Louis (2003). "Should molecular testing be required for diagnosing synovial sarcoma? A prospective study of 204 cases". Cancer . 98 (12): 2700–7. doi:10.1002/cncr.11840. PMID   14669292.
  7. 1 2 Coindre, Jean-Michel (October 2006). "Grading of soft tissue sarcomas: review and update". Archives of Pathology & Laboratory Medicine . 130 (10): 1448–53. doi:10.5858/2006-130-1448-GOSTSR. PMID   17090186.
  8. ↑ Paul, A.S.; Charalambous, C.; Maltby, B.; Whitehouse, R. (April 2003). "The management of soft-tissue sarcomas of the extremities". Current Orthopaedics. 17 (2): 124–133. doi:10.1054/cuor.2002.0314. ISSN   0268-0890.
  9. ↑ Gill, Anthony J.; Zaborowski, Matthew; Vargas, Ana C.; et al. (19 June 2020). "When used together SS18–SSX fusion-specific and SSX C-terminus immunohistochemistry are highly specific and sensitive for the diagnosis of synovial sarcoma and can replace FISH or molecular testing in most cases". Histopathology . 77 (4): 588–600. doi:10.1111/his.14190. PMID   32559341. S2CID   219949018.
  10. ↑ Baranov, Esther; McBride, Matthew J.; Bellizzi, Andrew M.; Ligon, Azra Hadi; Fletcher, Christopher D. M.; Kadoch, Cigall; Hornick, Jason L. (July 2020). "A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma". The American Journal of Surgical Pathology . 44 (7): 922–33. doi:10.1097/PAS.0000000000001447. PMC   7289668 . PMID   32141887.
  11. ↑ Pfeifer, John D.; Hill, D. Ashley; O'Sullivan, Maureen J.; Dehner, Louis P. (4 January 2002). "Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics?". Histopathology . 37 (6): 485–500. doi:10.1046/j.1365-2559.2000.01107.x. PMID   11122430. S2CID   6825413.
  12. ↑ O'Sullivan, Maureen J.; Kyriakos, M.; Zhu, X.; Wick, M.R.; Swanson, P.E.; Dehner, Louis P.; Humphrey, P.A.; Pfeifer, John D. (2000). "Malignant peripheral nerve sheath tumors with t(X;18). A pathologic and molecular genetic study". Modern Pathology . 13 (12): 1336–46. doi: 10.1038/modpathol.3880247 . PMID   11144931.
  13. ↑ Coindre, Jean-Michel; Hostein, Isabelle; Benhattar, Jean; Lussan, Cathy; Rivel, Janine; Guillou, Louis (June 2002). "Malignant Peripheral Nerve Sheath Tumors are t(X;18)-Negative Sarcomas. Molecular Analysis of 25 Cases Occurring in Neurofibromatosis Type 1 Patients, Using Two Different RT-PCR-Based Methods of Detection". Modern Pathology . 15 (6): 589–92. doi: 10.1038/modpathol.3880570 . PMID   12065770.
  14. ↑ Middeljans, Evelien; Wan, Xi; Jansen, Pascal W.; Sharma, Vikram; Stunnenberg, Hendrik G.; Logie, Colin (March 2012). Freitag, Michael (ed.). "SS18 together with animal-specific factors defines human BAF-type SWI/SNF complexes". PLOS One . 7 (3): e33834. Bibcode:2012PLoSO...733834M. doi: 10.1371/journal.pone.0033834 . PMC   3307773 . PMID   22442726.
  15. ↑ Ladanyi, Marc; Antonescu, Christina R.; Leung, Denis H.Y.; et al. (January 2002). "Impact of SS18-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients" (PDF). Cancer Research . 62 (1): 135–40. PMID   11782370. Archived (PDF) from the original on 26 August 2017.
  16. 1 2 3 4 5 Thway, Khin; Fisher, Cyril (December 2014). "Synovial sarcoma: defining features and diagnostic evolution". Annals of Diagnostic Pathology. 18 (6): 369–380. doi:10.1016/j.anndiagpath.2014.09.002. ISSN   1092-9134. PMID   25438927.
  17. ↑ Lewis, Jonathan J.; Antonescu, Cristina R.; Leung, Denis Hy.Y.; Blumberg, David; Healey, John H.; Woodruff, James M.; Brennan, Murray F. (2000). "Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity". Journal of Clinical Oncology . 18 (10): 2087–94. doi:10.1200/JCO.2000.18.10.2087. PMID   10811674.
  18. ↑ Ren, Xiao-Hua; WU, Xiao-Min; JIN, Cheng; CUI, Yong-An (2009). "Advances in the diagnosis and treatment of synovial sarcoma". Journal of Medical Biomechanics (in Chinese). 15 (4): 541–542. Retrieved 7 May 2016.
  19. ↑ "FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma". U.S. Food and Drug Administration (FDA). 2 August 2024. Retrieved 5 August 2024.
  20. ↑ "Adaptimmune Receives U.S. FDA Accelerated Approval of Tecelra (afamitresgene autoleucel), the First Approved Engineered Cell Therapy for a Solid Tumor" (Press release). Adaptimmune. 2 August 2024. Retrieved 5 August 2024– via Business Wire.
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