Patients who underwent surgery for 99 histologically proven synovial sarcomas of the extremities were included in this study. Of the 99 patients, we excluded 9 patients, including 6 with less than 2 years of follow-up and 3 with insufficient medical records; thus, 90 patients were eventually examined. All data were obtained retrospectively using medical records and radiographs after approval by the relevant Institutional Review Board.

Of the 90 patients, 34 were female and 56 were male. The mean age at diagnosis was 32.7 years (range, 5 to 80 years), including 20 patients (22%) younger than 20 years. The mean follow-up period was 6 years (range, 2 to 23 years). The lower limbs including the pelvis (n = 73, 81%) were more commonly involved than the upper limbs (n = 17, 19%). For analytical purposes, patients were divided into 2 groups: the planned excision (PE) group (n = 52, 58%), who received standard treatments for synovial sarcomas with no previous unplanned procedures, or the UPE group (n = 38, 42%), who underwent surgical treatments and in whom the possibility of sarcoma was not considered initially. Thirty-three patients (87%) of the UPE group were referred to our institutions after UPEs at other hospitals.

The medical records and magnetic resonance imaging (MRI) scans of patients in the UPE group, documented at the time of initial UPEs, were reviewed to identify the initially presumed diagnoses made at referring hospitals. We regarded pain, presence of swelling, tenderness and an enlarging mass as symptoms. Histopathology specimens obtained at the time of UPEs were examined by musculoskeletal pathologists of our institution. The verified tumor characteristics included the nature of tumor contents, size, anatomical location, depth, histological subtype, and histological grade. Histological grading was performed using the Federation Nationale des Centres de Lutte Contre le Cancer grading.10) For UPE, histological grading was performed by using specimens obtained at the time of UPEs or residual tumors detected during re-excisions. Out of 90 patients, MRI scans done prior to initial surgery were available for 73 patients (81%). Every patient in the UPE group had MRI scans prior to re-excision at our institute. Tumor size was defined by the maximal dimensions reported by pathological or MRI examinations. Tumor depth was graded as superficial or deep; tumors located exclusively above the superficial fascia without invasion of the fascia were defined as superficial.11)

Treatment principles comprised wide excision with or without adjuvant chemotherapy or radiotherapy. Surgery was performed to achieve wide margins by removing the cuff of normal tissues surrounding the tumors. Limb-sparing operations were primarily performed, if possible. All patients of the UPE group underwent re-excision to achieve wide resection margins. Adjuvant chemotherapy or radiotherapy was administered postoperatively when a higher risk of recurrence was believed to exist based on the clinical information, including histological grade, tumor size, presence of metastasis, and surgical margins. However, no prospectively determined criteria were used for patient selection. Adjuvant chemotherapy and radiation therapy were administered for 18 patients (47%) and 24 patients (63%), respectively. Disease-specific survival, metastasis-free survival, or local recurrence-free survival was assessed for documenting oncological outcomes. Specific deaths due to synovial sarcomas were documented as end points for disease-specific survival. Deaths by other causes were documented as censored. Local recurrence was defined as the first recurrence of disease at the primary tumor site after resection.

Overall survival, metastasis-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier estimator. Survival curves for both groups were evaluated using the log-rank testing for univariate factors and Cox's stepwise regression for multivariate factors. Relative risks were calculated using a proportional-hazards model. Comparison of the categorical variables between the PE and UPE groups was performed using the Fisher exact test and Pearson chi-square test. Statistical analyses were performed using the PASW ver. 18.0 (SPSS Inc., Chicago, IL, USA).

Among the clinical characteristics, the duration of symptoms before diagnosis was significantly longer in the PE group than that in the UPE group (p = 0.023) (Table 1). UPEs were more often performed for small (< 5 cm) and superficially located lesions (p = 0.001 and p = 0.049, respectively). Of the 20 upper-limb lesions, UPEs were performed for 12 (60%), compared to 26 (36%) of the 73 lesions located in the lower limb (p = 0.037). Initial metastases were detected in 13 patients (14%). The proportion of patients presenting with metastasis at diagnosis was not significantly different between the PE group (10 patients, 19%) and UPE group (3 patients, 8%; p = 0.112).

MRI scans prior to initial UPEs were available for 26 patients (68%) in the UPE group. Gadolinium enhancement was used in only 8% of cases in the UPE group compared to 96% in the PE group (p < 0.01). When the initial MRI reports of the 26 UPE patients were analyzed, a misdiagnosis pattern was observed with regard to tumor location (Table 2). In the lower limbs, almost half (8/17, 47%) of synovial sarcomas were misdiagnosed as cystic masses (popliteal cysts or meniscal cysts) around the knee (Fig. 1), whereas synovial sarcomas were most commonly misdiagnosed as neurogenic tumors (5/9, 56%) in the upper limbs (Fig. 2).

At the time of analysis, 26 patients (33%) had died of causes associated with synovial sarcoma and 2 patients had died of other causes. Five-year oncological outcomes, including disease-specific survival (64% vs. 73%, p = 0.159), metastasis-free survival (65% vs. 73%, p = 0.444), or local recurrence-free survival (77% vs. 79%, p = 0.335), were not significantly different between the PE and UPE groups, respectively (Fig. 3).

The number of UPEs prior to definitive re-excision ranged from 1 to 4 (mean, 1.36). Patients with a multiple number of UPEs (n = 8) had significantly higher rates of local recurrence than patients (n = 30) with single-excision operations (p = 0.012). The median interval between UPEs to re-excisions was 6 weeks (range, 1 to 132 weeks). Patients with intervals longer than 4 weeks (n = 19) to re-excision had significantly higher rates of local recurrence than patients with intervals shorter than 4 weeks (n = 19) to re-excision (p = 0.038). Of the 38 patients in the UPE group, residual tumors were detected in re-excised specimens in 31 patients (82%), including 29 with macroscopic residual tumors. However, the local recurrence rate did not significantly differ between the patients with residual tumors and patients without residual tumors (19% vs. 14%, p = 0.617).