A synovial sarcoma (also known as malignant synovioma) is a rare form of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

which occurs primarily in the extremities of the arms or legs, often in proximity to joint capsules and

tendon sheath A tendon sheath is a layer of synovial membrane around a tendon. It permits the tendon to stretch and not adhere to the surrounding fascia. It has two layers: * synovial sheath A synovial sheath is one of the two membranes of a tendon sheath wh ...

s. It is a type of

soft-tissue sarcoma A soft-tissue sarcoma (STS) is a malignant tumour, 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 unexplaine ...

. The name "synovial sarcoma" was coined early in the 20th century, as some researchers thought that the microscopic similarity of some tumors to

synovium The synovial membrane (also known as the synovial stratum, synovium or stratum synoviale) is a specialized connective tissue that lines the inner surface of capsules of synovial joints and tendon sheath. It makes direct contact with the fibrous ...

, 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. Primary synovial sarcomas are most common in the

soft tissue Soft tissue is all the tissue in the body that is not hardened by the processes of ossification or calcification such as bones and teeth. Soft tissue connects, surrounds or supports internal organs and bones, and includes muscle, tendons, ...

near the large joints of the arm and leg but have been documented in most human tissues and organs, including the

brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...

, prostate, and

heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...

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

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.

Diagnosis

The diagnosis of synovial sarcoma is typically made based on

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures v ...

and is confirmed by the presence of t(X;18)

chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal transl ...

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 Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

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 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 sarcoma A soft-tissue sarcoma (STS) is a malignant tumour, 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 ...

s, there is no universal grading system for reporting histopathology results. In Europe, the Trojani or French system is gaining in popularity 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. 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. Cytokeratin is typically expressed, at least focally. TLE1,

BCL2 Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis ...

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. The diagnosis of synovial sarcoma is typically made based on

and is confirmed by the presence of t(X;18). This translocation event between the SS18 gene on chromosome 18 and one of 3

SSX ''SSX'' is a series of snowboarding and skiing video games published by EA Sports. It is an arcade-style racing game with larger-than-life courses, characters, and tricks. While the general focus of the series is racing and performing tricks on ...

genes (

SSX1 Protein SSX1 is a protein that in humans is encoded by the ''SSX1'' gene. The product of this gene belongs to the family of highly homologous synovial sarcoma, X (SSX) breakpoint proteins. These proteins may function as transcriptional represso ...

SSX2 Protein SSX2 is a protein that in humans is encoded by the ''SSX2'' gene. The product of this gene belongs to the family of highly homologous synovial sarcoma, X (SSX) breakpoint proteins. These proteins may function as transcriptional represso ...

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. SS18-SSX is thought to underlie synovial sarcoma pathogenesis through dysregulation of gene expression. There is some association between the SS18-SSX1 or SS18-SSX2 fusion type and both tumour morphology and five-year survival.

Treatment

Treatment is usually multimodal, involving

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

and

radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...

: *

Surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...

, to remove the tumor and a safety margin of healthy tissue. This is the mainstay of synovial sarcoma treatment and is curative in approximately 20–70% of patients, depending on the particular study being quoted. *Conventional

, (for example, doxorubicin hydrochloride and

ifosfamide Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, ce ...

), to reduce the number of remaining microscopic

metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...

. The benefit of chemotherapy in synovial sarcoma to overall survival remains unclear, although a recent study has shown that survival of patients with advanced, poorly differentiated disease marginally improves with doxorubicin/ifosfamide treatment. *

Radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...

to reduce the chance of local recurrence. The benefit of radiotherapy in this disease is less clear than for chemotherapy.

References

External links

*
Sarcoma Help: What is Synovial Sarcoma?

WebMD: Synovial Sarcoma Overview
{{Chromosomal abnormalities Musculoskeletal disorders Sarcoma