The mediastinum is a host for a variety of primary and secondary malignancies. Metastatic carcinomas, lymphomas, and thymomas are the most commonly encountered tumors. Synovial sarcoma (SS), though very rarely encountered, could also arise in this location [
Around 80% of synovial sarcomas arise in the extremities [
In the current paper, we attempt to provide a descriptive analysis of mediastinal SS and the patterns of failure following therapy. Furthermore, we analyze factors that may be prognostic for survival.
A comprehensive PubMed search was conducted in July 2013. The following search terms were used: “synovial,” “sarcoma,” and "mediastinum.” No restrictions were applied to the date of publication; however, this search was limited to papers in English language. Reports describing mediastinal SS cases were considered. Furthermore, reference lists of included studies were hand-searched to identify relevant missing publications. Full text articles of eligible abstracts were reviewed. Data pertaining to the age at diagnosis, gender, extent of disease at initial presentation (localized, locally advanced, or metastatic), location of the tumor inside the mediastinum (posterior, middle, and anterior), maximum tumor dimension, histologic subtype (monophasic or biphasic), presence of pericardial effusion, therapeutic modalities (surgery, chemotherapy, and radiotherapy), and completeness of surgical resection were extracted using a predefined datasheet. In addition, the status of patient at last follow-up and sites of any recurrence or progression (if any) were accurately documented. Overall, twenty-two studies—which included 40 patients—form the basis of this review [
Overall and event-free survival (EFS) were defined as surviving and surviving without any recurrence or progression, respectively. The influence of possible prognostic factors on survival was assessed and compared through the Log-Rank test. Survival curves were plotted through the Kaplan-Meier method. A
Statistical testing for heterogeneity was not performed since it requires studies with larger sample size and is therefore not applicable to the included studies in this review (a small number of patients in each individual paper).
The characteristics of the 40 reviewed patients including demographic patient data, clinical and pathological disease variables, and the mode of presentation are outlined in Table
Characteristics of the forty cases of mediastinal synovial sarcoma reported in the literature.
Variable | Result (range) |
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Median age | 30.5 years (3–83 years) |
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Male : female ratio | 2.9 : 1 |
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Median size | 11 cm (5–20 cm) |
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Status at presentation | |
Localized resectable | 22 (55%) |
Locally advanced, unresectable | 16 (40%) |
Metastatic | 2 (5%) |
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Location | |
Anterior/middle mediastinum | 28 (70%) |
Posterior mediastinum | 8 (20%) |
Uncertain | 4 (10%) |
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Histologic subtype | |
Monophasic | 18 (45%) |
Biphasic | 13 (33%) |
Uncertain | 9 (22%) |
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Surgical resection | |
Complete resection | 23 (58%) |
No resection or partial resection | 17 (42%) |
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Presenting symptoms and signs* | |
Chest or shoulder pain | 22/32 (69%) |
Shortness of breath | 20/32 (63 %) |
Cough | 5/32 (16%) |
Pericardial effusion | 7/32 (22%) |
Pleural effusion | 3/32 (9%) |
Weakness and fatigue | 4/32 (13%) |
Fever | 4/32 (13%) |
Weight loss | 3/32 (9%) |
SVC obstruction | 1/32 (3%) |
SVC: superior vena cava.
Although a wide spectrum of presenting symptoms and signs were noted (chest symptoms, fever, fatigue and weight loss), more than three-quarters of patients presented with chest or shoulder pain with or without shortness of breath.
Follow-up data was available for 30 of the 40 included patients, and was included in the survival analysis.
Complete resection was the most commonly applied therapeutic strategy (23 patients; 57.5%); in 8 of those patients the surgery was part of multimodality treatment including chemotherapy and/or external beam radiotherapy (EBRT). The other 17 patients (42.5%) were treated by incomplete resections or with chemotherapy and radiotherapy secondary to the advanced stage of disease at presentation as outlined in Table
Therapeutic modalities for the 40 cases of mediastinal synovial sarcoma reported in the literature.
Treatment modality | Number of patients (%) |
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Complete resection only | 15 (37.5%) |
Complete resection + CTX + EBRT | 4 (10%) |
Complete resection + CTX | 2 (5%) |
Complete resection + EBRT | 2 (5%) |
Partial resection + EBRT | 3 (7.5%) |
Partial resection + EBRT + CTX | 1 (3%) |
CTX only | 4 (10%) |
EBRT only | 4 (10%) |
CTX and EBRT only | 3 (7.5%) |
BSC only | 2 (5%) |
CTX: chemotherapy; EBRT: external beam radiotherapy; BSC: best supportive care.
Of the 30 patients with available follow-up data, 20 (67%) had progression of disease (PD) following the primary therapy: nine of 17 patients with localized disease and 11 of 13 of patients with advanced disease. The median time to progression was 18 months for patients with completely resected tumors and 6 months for patients who did not have complete resection.
The most common site of progression was locally within the mediastinum. Of 15 patients with available data on sites of progression, 6 (40%) had isolated progression in the primary mediastinal tumor site. Other sites of progression included isolated progression in the lungs (3 patients), multiple metastatic sites (3 patients), liver (1 patient), lungs and the primary mediastinal tumor site (1 patient), and dural metastases (1 patient).
The mean follow-up time for the patients with reported outcome data was 26.8 months (range: 3–193 months). Eleven of those patients were deceased due to their disease, 9 were alive with evidence of disease, 8 were alive without evidence of disease, and two were alive with unknown disease status. The median EFS was 12 months with a 5-year EFS of 15%. The median overall survival was 36 months with a 5-year overall survival (OS) of 35.7% (Figure
Kaplan-Meier overall survival estimation for the patients with mediastinal synovial sarcoma.
Using univariate analysis (Table
Univariate analysis for the 30 cases of mediastinal synovial sarcoma with available follow-up data.
Variable | Number (%) | MS (months) | 5-year OS | Log-Rank |
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Age | ||||
≥20 years | 24 (80%) | 38 | 39.9% | 0.32 |
<20 years | 6 (20%) | 24 | 31.3% | |
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Gender | ||||
Male | 24 (80%) | Unreached | 56.2% | 0.91 |
Female | 6 (20%) | 36 months | 0% | |
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Pericardial effusion | ||||
Yes | 4 (13%) | Unreached | 67% | 0.83 |
No | 26 (87%) | 36 months | 29% | |
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Histologic subtype | ||||
Monophasic | 10 (33%) | 24 months | 0% | 0.11 |
Biphasic | 10 (33%) | 36 months | 50.0% | |
ND | 10 (33%) | |||
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Size | ||||
<10 cm | 8 (26%) | Unreached | 75% | 0.36 |
≥10 cm | 11 (37%) | 36 months | 26% | |
ND | 11 (37%) | |||
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Surgery | ||||
Complete resection | 17 (57%) | Unreached | 63% | 0.003 |
Incomplete | 13 (43%) | 13 months | 0% | |
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Chemotherapy | ||||
Yes | 14 (47%) | 36 months | 46% | 0.31 |
No | 16 (53%) | 24 months | 24% | |
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Radiotherapy | ||||
Yes | 14 (47%) | 36 months | 21% | 0.89 |
No | 16 (53%) | unreached | 53% | |
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Location in mediastinum | ||||
Anterior/middle | 22 (74%) | 36 months | 39% | 0.93 |
Posterior | 4 (13%) | 6 months | 50% | |
ND | 4 (13%) |
MS: median survival; OS: overall survival; ND: no data.
Kaplan-Meier overall survival estimation for patients with mediastinal synovial sarcoma according to completeness of surgical resection.
Less than 10–20% of SS arise in extra-extremity locations [
Morphologically, synovial sarcomas are divided into monophasic and biphasic subtypes. The biphasic variant consists of proliferation of bland looking spindle-shaped cells, along with evidence of epithelial differentiation. Monophasic subtypes on the other hand can show either spindle cells only or occasionally epithelial component only [
SS is characterized by unique t(X; 18)(p11.2; q11.2) translocation resulting in the fusion of the SYT gene on chromosome 18 to either of two closely related genes: SSX1 and SSX2 on chromosome X [
The current review demonstrated important differences in the characteristics of these mediastinal tumors when compared to cohorts of SS of the extremities. Firstly, the median tumor size in the current analysis is 11 cm and none of the reported cases had a tumor size <5 cm. This size is well above the 5–7 cm median size reported in studies of SS where all or most patients have tumors in the extremities [
Unexpectedly, and as opposed to SS in other locations, we failed to reveal any prognostic significance based on tumor size in this analysis. This is probably because all patients in the current cohort had tumor size above the cutoff value (5 cm) which was most consistently identified as prognostic indicator for this tumor.
We emphasize the importance of complete resection of these tumors as completeness of resection was the only identified factor that is associated with improved survival. Other factors, including the location within the mediastinum, the presence of pericardial effusion, and the histologic subtype had no influence on survival. For that reason, patients should not be denied curative resection based on these factors as long as the tumor can be resected without residual disease.
Patients who present with unresectable nonmetastatic disease should also be managed with the aim of cure as those tumors are highly responsive to radiotherapy and chemotherapy and since obtaining adequate response may allow subsequent surgical resection [
The high proportion of patients who have subsequent local progression may suggest that adjuvant radiotherapy should be considered as part of a multimodality therapeutic approach for all patients. The role of chemotherapy remains elusive; however, some studies have suggested that adjuvant ifosfamide-based therapy improves survival of high risk SS of the extremities particularly those with tumor size of >5 cm [
An important limitation of our analysis is that it was performed for patients whose outcomes were reported from different studies; each one includes a limited number of patients, and as such, statistical tests of heterogeneity could not be performed to ensure the lack of heterogeneity among patients included from different studies. In addition, we cannot reliably exclude the possibility of publication biases with the tendency to report the patients who survived longer and to underreport those with suboptimal outcomes. Nevertheless, and given the rarity of mediastinal SS, no other formal attempt to analyze the influence of disease related factors on survival is realistically possible. Consequently, the current analysis can be utilized with caution as a guidance emphasizing the importance of complete resection of those tumors, the possible need for multimodality adjuvant therapy, and as an approximate estimation of recurrence and survival outcomes.
Mediastinal SS have poor prognosis as they tend to present with large tumors and with advanced stage. Completeness of resection is the only identified factor that influences survival and can result in outcomes similar to the outcomes following resection of SS arising primarily in the extremities.
The authors declare that there is no conflict of interests.