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Synovial Sarcoma

Synoviomas

Synovial sarcoma is a rare but highly malignant soft tissue tumor most frequently diagnosed in young adults. It develops in close proximity to the joints of upper and lower limbs but does not originate from synovial cells, contrary to what its name might suggest.


Presentation

Symptoms vary depending on the precise location of the tumor. Typical SS develop in close proximity to the joints of upper and lower limbs, and patients may claim a feeling of fullness and joint pain. The latter may be transient, i.e., induced by physical loads or pressure, or permanent. As the tumor grows, motion ranges diminish. It may be possible to palpate the SS, yet the primary tumor may also develop as an intraosseous neoplasm that causes similar complaints but remains unrecognizable during simple physical examination. Unfortunately, such tumors may grow to a considerable size, may even metastasize before triggering any local mass effects, and thus may go unnoticed until advanced stages. Any slow-growing mass detected close to knees, hand and feet, should prompt a specific workup in order to avoid unnecessary delays in diagnosis of SS.

In rare case, SS develop in other parts of the human body and here, they are associated with distinct symptoms. Intravascular SS, for instance, have been related to deep vein thrombosis and thromboembolism, and - if situated in close proximity to the heart - to pericardial effusion and cardiac failure. If tumors grow in the neck region, they may interfere with respiration and food intake. Similarly, mass effects may be observed at any other location in the body.

SS patients may develop paraneoplastic syndrome, but this is rather uncommon.

Hunting
  • Hunt , Primary Sarcomas of the Lung , Textbook of Uncommon Cancer , (248-265) , (2017) .[doi.org]
  • Hunt, Primary Sarcomas of the Lung, Textbook of Uncommon Cancer, (248-265), (2017).[doi.org]
  • Barco R, Hunt LB, Frump AL, Garcia CB, Benesh A, Caldwell RL, Eid JE. Mol Biol Cell. 2007 Oct;18(10):4003-12. Epub 2007 Aug 8. PMID 17686994 Molecular characterization of synovial sarcoma in children and adolescents: evidence of akt activation.[atlasgeneticsoncology.org]
Recurrent Pleural Effusion
  • We report a case of primary synovial cell sarcoma of the diaphragm presenting as a recurrent pleural effusion and pain in the left hypochondrium managed with multimodality approach.[ncbi.nlm.nih.gov]
Low Fever
  • A 10-year-old boy was admitted with a 1-month history of progressive back pain and low fever for 7 days as well as sudden onset of paraplegia for 1 day.[ncbi.nlm.nih.gov]
Thyroid Nodule
  • FNA of the thyroid nodule showed a cellular smear composed of loosely cohesive oval to spindle-shaped cells with irregular nuclear borders, finely granular chromatin, and inconspicuous nucleoli.[ncbi.nlm.nih.gov]
Constitutional Symptom
  • Primary cardiac sarcomas are exceedingly rare, and they commonly result in nonspecific constitutional symptoms such as shortness of breath, weight loss, and anaemia-related fatigue and malaise.[ncbi.nlm.nih.gov]
Hoarseness
  • Case of a 16 years old female is presented with hoarseness of voice and mass in supraglottic region. Lateral pharangotomy and excision of mass revealed synovial sarcoma. She had been treated with adjuvant radiotherapy in September 2012.[ncbi.nlm.nih.gov]
  • They presented with hoarseness of voice and hemoptysis. Endoscopy detected a mass in the supraglottic region. The biopsy concluded a synovial sarcoma. Immunohistochemistry conveyed diagnostic certainty.[ncbi.nlm.nih.gov]
  • This report describes the case of a 35 year old male patient who presented with acute symptoms of dyspnoea, facial puffiness, engorged neck veins and hoarseness of voice.[ncbi.nlm.nih.gov]
  • Painless mass, hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma.[casereports.in]
  • Similarly, our patients had a variety of presentations, including presenting with pain at the tumor site, sore throat, dysphagia, hoarseness, and hematemesis, but the most common symptom was the presence of an enlarging mass.[jnsci.org]
Productive Cough
  • However, 10 months postoperation she represented with chest pain, productive cough and a repeat CXR showed multiple left pulmonary nodules.[ncbi.nlm.nih.gov]
Parotid Mass
  • Richards , Synovial sarcoma presenting as a parotid mass: Case report and review of literature , Head & Neck , 30 , 12 , (1654-1659) , (2008) . Constantine Komis, George A. Lagogiannis, Gregory Faratzis and Alexander D.[doi.org]
  • Richards, Synovial sarcoma presenting as a parotid mass: Case report and review of literature, Head & Neck, 30, 12, (1654-1659), (2008). Constantine Komis, George A. Lagogiannis, Gregory Faratzis and Alexander D.[doi.org]
  • Jay A, Hutchison I, Piper K, Farthing PM, Richards PS: Synovial sarcoma presenting as a parotid mass: case report and review of literature. Head Neck 30:1654-9,2008.[orthopaedicsone.com]
Joint Swelling
  • Joint swelling, pain, occasionally joint erosions. No calcifications. Low T1 and T2 synovial signal (hemosiderin deposits). A Rare chronic inflammatory process causing synovial proliferation. Soft tissue Hemangioma features? Phleboliths.[quizlet.com]
Arthralgia
  • Patients usually present with arthralgia, and eventually, the tumor becomes palpable. Pressure pain is common and motion ranges become increasingly limited.[symptoma.com]
Meningism
  • The radiologic survey revealed a 5.5cm 5.8cm contrast enhancing dura-based mass at the right parafalcine region with meningeal enhancement and edema in the surrounding areas.[ncbi.nlm.nih.gov]

Workup

The presence of a space-occupying mass may be confirmed after realizing imaging studies, e.g., plain radiography, computed tomography scans, magnetic resonance imaging or sonography. Although the former are more commonly applied in case of SS affecting the knees, the latter are often indicated to better assess soft tissue infiltration and involvement of lymph nodes. Evaluation of obtained images may prompt a strong suspicion of a neoplasm, but a biopsy needs to be carried out in order to confirm the tentative diagnosis of SS. Specimens obtained by fine-needle biopsy are generally considered unsuited for a safe diagnosis; instead, it is recommended to analyze tissue samples gained by core needle biopsy or open biopsy. Besides the above described histopathological features, samples may be subjected to immunohistochemical staining. SS generally stain positive for Bcl-2, cytokeratin, EMA and vimentin. The diagnosis of SS is further supported by the identification of translocation t(X;18). Such analyses are required in case of ambiguous histopathological findings; their sensitivity is close to 100%.

Upon histopathological and possibly cytogenetic confirmation of the diagnosis, more extensive imaging studies have to be carried out to scan the patient's body for the presence of metastases. Computed tomography of thorax and abdomen, or positron emission tomography of the whole body should be realized to this end.

Of note, diagnostic imaging is also required during follow-ups after completion of SS therapy.

Pulmonary Infiltrate
  • In contrast, 9/10 patients without PD tumors were alive (7 NED) and 1 died at 12 months with pulmonary infiltrates. SSPN is under-recognized clinically and histologically as it mimics benign and malignant PNST.[ncbi.nlm.nih.gov]

Treatment

Therapy mainly consists in surgical removal of the entire neoplasm, of infiltrated, adjacent soft tissues and regional lymph nodes. In severe but typical cases, complete resection can also be achieved by carrying out an amputation. This may become necessary if the tumor affects large parts of the limb skeleton [13]. On the other hand, SS may develop in less readily accessible parts of the body, e.g., in the thoracic cavity affecting heart or lungs, but the fact that incomplete resection is the main risk factor for local recurrence and metastatic growth should be considered when planning surgery.

In general, SS are also susceptible to chemotherapy and irradiation [14]. Some patients are treated with neoadjuvant chemo- or radiotherapy, and these are also frequently applied postsurgically in order to kill possibly remaining tumor cells, to avoid recurrence and the formation of metastases. Furthermore, chemotherapy and irradiation may form part of a palliative therapy and may be prescribed to patients diagnosed with unresectable tumors such as those mentioned above. They have been shown to effectively slow down tumor growth [15]. With regards to chemotherapy, ifosfamide and doxorubicin are most commonly administered.

Due to the high rate of recurrence, it is strongly advised to realize regular follow-ups during years after completion of therapy. Additionally, the lungs should be regularly checked for metastases. According to a large retrospective study involving almost 300 SS patients, a third of whom was diagnosed with primary metastases, virtually all tumors metastasized into the lungs [12].

Prognosis

Prognosis mainly depends on tumor grading and tumor staging at the time of diagnosis [10]. Good differentiation, few mitotic figures, and absence of necrotic areas are favorable prognostic factors. The smaller the primary tumor, the lower the probability of advanced tumor stages and distant metastases. If the tumor is diagnosed early, i.e., when measuring less than 5 cm in diameter, the likelihood of recurrence-free survival for more than 10 years is greater than 80% [11]. In contrast, about 10% of SS patients present with primary metastases and in these cases, 5-year survival rates don't exceed 30% [12] and has even been reported to be as low as 10% [2]. In sum, an early diagnosis is generally related with a good prognosis - unless the location of the tumor renders it unresectable -, while the outcome is usually poor in case of metastasizing SS.

Etiology

Etiology and pathogenesis of most types of sarcoma are only poorly understood, and this also applies to SS. Accordingly, the World Health Organization classifies SS as malignant soft tissue tumors of uncertain differentiation [4]. Studies have been conducted to ascertain possible causal relations between genetic factors, pathogens or environmental influences and development of SS, yet conclusive findings have not been provided so far.

But although the trigger of malignant transformation could not yet be identified, its nature has been described repeatedly: More than 95% of SS are characterized by the chromosomal translocation t(X;18). This translocation yields a unique fusion oncogene, currently considered to be specific for SS. It has been proposed that the SS18-SSX fusion protein triggers chromatin remodeling and may serve as a transcriptional regulator [5]. Genes encoding for insulin-like growth factor 2 and early growth response protein 1 are possible targets of SS18-SSX and are involved in the regulation of cell division, growth and differentiation.

Additional mutations have been identified in SS as well, e.g., Dutch researchers analyzed eight tumor samples and detected eight distinct somatic mutations [6]. Those results stress the genetic heterogeneity of SS which is paralleled by a considerable variation in tumor behavior and clinical presentation.

Epidemiology

Up to 10% of soft tissue sarcomas are SS [1]. The latter is a rare entity and, according to a Taiwanese study, its annual incidence is only about 0.08 per 100,000 person-years [7]. In the United States, an average of 800 cases are diagnosed annually [8], which corresponds to an incidence rate of the same magnitude.

SS is typically diagnosed in adolescents and young adults, with a mean age of 36 years at the time of diagnosis and about a third of SS patients being younger than 20 years [1] [8]. However, age is no exclusion criterion for SS and this type of tumor has been encountered in young children as well as in the elderly.

Men and women seem to be equally affected by SS: Some studies report a slight preference for females [7], while males are overrepresented in others [9]. According to the aforecited work, the disease is related to a worse outcome in blacks.

Sex distribution
Age distribution

Pathophysiology

Upon histopathological analyses of SS specimens, distinct morphological patterns may be encountered. The most common one is generally referred to as biphasic SS, and this designation originates from the tumor being composed of two components: spindle cells as well as epithelial structures, possibly including gland-like patterns. On the other hand, there are monophasic SS that don't include epithelial cells but merely consist of monomorphic spindle cells. In very rare occasions, monophasic epithelial SS have been described. Some SS are very poorly differentiated and consist of spindle cells, epithelial cells and other, non-assignable cell types; they also grow faster than the other forms. It is strongly recommended to assure a tentative diagnosis of SS by means of cytogenetic analyses, particularly if the tumor's morphology differs from the classical, biphasic pattern. If diagnoses are based on microscopic observation alone, SS may easily be confounded with adenocarcinoma.

Prevention

Since the disease's etiology is only poorly understood, no specific measures can be recommended to prevent SS.

Summary

Synovial sarcoma (SS) is a rare type of neoplasm and accounts for 5%–10% of soft tissue cancers [1]. Although its name implies an origin from synovial cells, this designation is merely based on morphological similarities between tumor cells and synovial cells. In fact, the cellular origin of SS remains largely unknown. In the vast majority of cases, it develops in close proximity to the joints of upper and lower limbs. Knees, hands and feet are affected in decreasing order of incidence. SS are considered highly malignant tumors and local recurrence as well as distant metastases are common, but the tumors grow slowly. Indeed, years may pass between initial malignant transformation and symptom onset. There is an average time gap of more than three years between treatment of the primary tumor and local recurrence, and of almost six years between diagnosis and detection of metastases.

Patients usually present with arthralgia, and eventually, the tumor becomes palpable. Pressure pain is common and motion ranges become increasingly limited. Diagnosis is based on imaging techniques, which primarily serve to precisely localize the tumor and to assess its extension, and histopathological analyses of biopsy samples. Determined immunohistochemical properties support a tentative diagnosis of SS, which can be confirmed by cytogenetic studies.

Treatment consists in surgical resection of the tumor and regional lymph nodes. Patients may benefit from adjuvant radio- and chemotherapy. Unfortunately, in some cases, there is not therapeutic alternative to amputation [2] [3]. The patient's prognosis is favorable if metastases are not present at the time of diagnosis. Metastasizing SS are generally associated with a poor outcome, though.

Patient Information

Synovial sarcoma (SS) is a rare type of cancer; less than five cases per million inhabitants are diagnosed each year. Usually, SS develop in close proximity to the joints of legs and arms, with knees, hands and feet being the most common sites of tumor growth. SS are considered highly malignant neoplasms and although they grow slowly, the risk of local recurrence after treatment of the primary tumor and the likelihood of the formation of metastases is rather high. To date, it is not known which cell types SS originate from. Their name indicates joint tissue as possible origin, but this designation has a mere descriptive character.

Both men and women and people of all races may be diagnosed with SS. Similarly, the patient's age is not an exclusion criterion for SS, but the vast majority of SS patients is younger than 40 years. In fact, about a third of affected individuals are minors. Typically, patients claim a feeling of fullness in their knees or other joints, and joint pain. A mass may become palpable and as the tumor grows, joint mobility is increasingly restricted. Though, as has been implied above, SS may also develop in other regions of the human body. Thus, symptoms may differ largely from those described before: If SS grow in the neck region, they may interfere with respiration and food intake. SS have also been described to grow in the thoracic cavity and here, they may impair pulmonary and cardiac function.

Imaging is usually the first approach to SS diagnosis, and distinct techniques may be applied depending on the location of the tumor. Plain radiography, computed tomography scans and magnetic resonance imaging allow the assessment of tumor size, soft tissue infiltration and involvement of lymph nodes. Additionally, a biopsy needs to be performed to obtain tissue samples for further analysis and confirmation of the tentative diagnosis of SS. The ensuing treatment may comprise surgical resection, chemo- and/or radiotherapy.

The single most important prognostic parameter is the presence of metastases at the time of diagnosis: If the tumor is recognized and treated early, the outcome is usually good. If metastases are present, the patient's prognosis is poor.

References

Article

  1. Krieg AH, Hefti F, Speth BM, et al. Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors. Ann Oncol. 2011; 22(2):458-467.
  2. Palmerini E, Staals EL, Alberghini M, et al. Synovial sarcoma: retrospective analysis of 250 patients treated at a single institution. Cancer. 2009; 115(13):2988-2998.
  3. Steinstraesser L, Agarwal R, Stricker I, Steinau HU, Al-Benna S. Biphasic synovial sarcoma of the extremity: quadruple approach of isolated limb perfusion, surgical ablation, adipofascial perforator flap and radiation to avoid amputation. Case Rep Oncol. 2011; 4(1):222-228.
  4. Fletcher C, Bridge J, Hogendoorn P, Mertens F., eds. World Health Organization classification of tumours of soft tissue and bone: pathology and genetics of tumours of soft tissue and bone. 4 ed. Lyon, France: IARC Press; 2013.
  5. Tamaki S, Fukuta M, Sekiguchi K, et al. SS18-SSX, the Oncogenic Fusion Protein in Synovial Sarcoma, Is a Cellular Context-Dependent Epigenetic Modifier. PLoS One. 2015; 10(11):e0142991.
  6. Vlenterie M, Hillebrandt-Roeffen MH, Flucke UE, et al. Next generation sequencing in synovial sarcoma reveals novel gene mutations. Oncotarget. 2015; 6(33):34680-34690.
  7. Hung GY, Yen CC, Horng JL, et al. Incidences of Primary Soft Tissue Sarcoma Diagnosed on Extremities and Trunk Wall: A Population-Based Study in Taiwan. Medicine (Baltimore). 2015; 94(41):e1696.
  8. Casal D, Ribeiro AI, Mafra M, et al. A 63-year-old woman presenting with a synovial sarcoma of the hand: a case report. J Med Case Rep. 2012; 6:385.
  9. Sultan I, Rodriguez-Galindo C, Saab R, Yasir S, Casanova M, Ferrari A. Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients. Cancer. 2009; 115(15):3537-3547.
  10. Ipach I, Wingert T, Kunze B, Kluba T. Oncological outcome and prognostic factors in the therapy of soft tissue sarcoma of the extremities. Orthop Rev (Pavia). 2012; 4(4):e34.
  11. El Beaino M, Araujo DM, Gopalakrishnan V, Lazar AJ, Lin PP. Prognosis of T1 synovial sarcoma depends upon surgery by oncologic surgeons. J Surg Oncol. 2016.
  12. Scheer M, Dantonello T, Hallmen E, et al. Primary Metastatic Synovial Sarcoma: Experience of the CWS Study Group. Pediatr Blood Cancer. 2016; 63(7):1198-1206.
  13. Beck SE, Nielsen GP, Raskin KA, Schwab JH. Intraosseous synovial sarcoma of the proximal tibia. Int J Surg Oncol. 2011; 2011:184891.
  14. Outani H, Hamada K, Oshima K, et al. Clinical outcomes for patients with synovial sarcoma of the hand. Springerplus. 2014; 3:649.
  15. Maekura T, Shimizu S, Kawaguchi T, et al. Intravascular synovial sarcoma of the pulmonary artery with massive pleural effusion: report of a case with a favorable response to Ifosfamide chemotherapy and palliative radiation therapy. Intern Med. 2015; 54(9):1095-1098.

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Last updated: 2019-07-11 21:46