Intriguing Tumor, Synovial Sarcoma: Hard to Diagnose, Harder to Treat

doi:10.21203/rs.3.rs-3562062/v1

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Intriguing Tumor, Synovial Sarcoma: Hard to Diagnose, Harder to Treat

https://doi.org/10.21203/rs.3.rs-3562062/v1

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This study comprehensively assessed synovial sarcoma (SS), a highly aggressive soft tissue sarcoma, focusing on diagnostic and treatment challenges.

Data from 63 patients diagnosed with SS between 2005 and 2020 were analyzed in the single center retrospective study. Patients with comprehensive records of pathology, radiology and surgery with at least 12 months of follow-up were included.

There were 63 patients (49% female, 51% male) with an average age of 37.55±17.08 years. Neither age nor gender significantly affected survival. SS primarily affected extremities (96.92%), with a predilection for the lower limbs (75.38%). Tumor volume, averaging 109.71±176.25 cm3, emerged as a key factor. Tumors >30 cm3 were prone to metastasis (p=0.0077) and reduced survival (p=0.0163). Histologically, 38.46% were monophasic, 36.92% biphasic, and 24.62% poorly differentiated, with lower survival in the latter. Immunohistochemistry revealed high positivity rates for Bcl-2 (89.47%) and EMA (88.14%). TLE1 showed positivity in 86.67% of cases (13/15), and FISH detected SS18-SSX fusion genes in 72.72% (8/11). 41.54% had metastases, 36.92% recurred, and 23.08% succumbed to the disease.

Accurate SS identification is crucial. Consider negative predictive factors (tumor volume >30 cm3, poor histologic differentiation) when making treatment decisions and ensure extended follow-up due to the risk of late recurrence.

Biological sciences/Cancer/Sarcoma

Health sciences/Oncology/Cancer/Bone cancer

synovial sarcoma

soft tissue sarcoma

FISH

SS18

SS is an intriguing tumor to diagnose and to treat.
Recognition of SS is crucial to prevent inappropriate interventions.
Negative predictive factors include tumor volume >30cm³, unplanned excision, and poorly differentiated histologic type.
Th effect of chemotherapy and radiotherapy remain a subject of debate.
Prolonged follow-up is essential due the persistent risk of late recurrence.

Synovial sarcoma (SS) is classified as an aggressive high-grade soft tissue sarcoma, comprising 5-10% of all soft tissue sarcomas.^1-3 This malignancy primarily affects young demographic without showing any predilection for either gender.^3,4 Approximately 80% of cases involve extremities, mainly being lower ones.^1,2,4

The spectrum of symptomology associated is wide-ranging; however, the most prevalent symptoms are pain and the presence of a progressively enlarging lump.⁴ While radiologic features can provide valuable insights, they lack stereotypical characteristics. Consequently, the diagnosis heavily relies on pathological examination, which, in itself, can be quite challenging.^1,5 Although it was initially characterized as a biphasic neoplasm comprising both epithelial and uniform spindle cell components, synovial sarcoma is now recognized to exist in two primary types: monophasic and biphasic.^3,6

Immunohistochemistry assumes a pivotal role in diagnosis, as routine hematoxylin and eosin (H&E) staining fails to distinguish synovial sarcoma from other types of sarcomas. The most frequently employed markers in this context are epithelial markers, including pankeratin, CAM 5.2, and EMA.¹ Bcl-2, while positive in synovial sarcoma (SS), lacks specificity. The presence of CD99, with a 60% positivity rate, can lead to confusion with Ewing sarcoma, while S100, exhibiting a 40% positivity rate, may be misleading in differentiating from malignant peripheral nerve sheath tumors. At the genetic level, primary synovial sarcoma is associated with X-18 translocation in approximately 90% of cases, leading to the formation of the fusion gene SS18-SSX, which can be detected via fluorescence in situ hybridization (FISH).^5,7

Metastasis occurs in more than 50% of cases, and the five-year mortality rate stands at approximately 60-70%^8-10 Regrettably, survival rates for SS have not shown significant improvement.¹¹ Similar to other sarcomas, the primary objective is the complete surgical resection of the tumor while preserving the affected limb.¹² L Limb-sparing procedures have emerged as the cornerstone of treatment for musculoskeletal tumors in recent years; however, the amputation rate tends to rise in cases of recurrence and is considered a last-resort measure.^13,14 Given SS's classification as a high-grade malignancy, adjuvant radiation therapy is frequently employed.³

SS is a complex ailment characterized by its subtle onset, diverse clinical presentation, and its propensity to mimic other pathologies. It is further compounded by its elevated rates of metastasis, recurrence, and amplified mortality. The primary objective of this study is to present a case series comprising 63 patients, with the aim of scrutinizing the critical facets of diagnosis and assessing the influence of pathological characteristics, tumor volume, and treatment modalities on patient survival.

The study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the University Medical Faculty Human Studies Institutional Ethics Review Board (ID:2021000479).

This study is a single-center retrospective analysis of the patients with synovial sarcoma. All patients diagnosed with synovial sarcoma at the University Hospital between January 2005 and December 2020 were investigated.

The inclusion criteria encompassed patients who had been histologically diagnosed with synovial sarcoma (SS), with available pathology, radiology, and surgical records, and had been under follow-up for a minimum of 12 months. Initially, 84 patients with a diagnosis of synovial sarcoma were identified from the university's registries. However, only 65 tumors, corresponding to 63 patients who met the aforementioned criteria, were ultimately included in the study. The 21 patients who were excluded comprised 6 cases with dissimilar surgical material pathology results, 13 individuals who were lost to follow-up, one patient without pathology records, and one without available imaging results. Patients who had been preoperatively diagnosed as SS but exhibited distinct surgical material pathology results were among those excluded.

Presenting symptoms and location; the pathology results with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH); imaging studies such as ultrasonography (USG), computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and whole-body bone scintigraphy (WBBS); the decided treatment by the multidisciplinary sarcoma team including the surgery, radiotherapy, and chemotherapy; follow-up pattern and metastasis, recurrence, and death during follow-up were investigated. The data was extracted from the patient records, and the patients were called by phone, for the missing data. If written informed consent was not possbiel consent was taken verbally on phone.

Given the retrospective nature of this study, treatment choices were not predicated on a standardized protocol. Instead, the ultimate course of treatment was deliberated and determined by a multidisciplinary musculoskeletal oncology board, comprising specialists in orthopedics, radiology, oncology, radiation oncology, and pathology. Generally, for primary localized tumors that were deemed resectable, surgery was conducted without neoadjuvant chemotherapy or radiotherapy. In cases where the tumor exhibited a substantial volume or resection posed risks to neurovascular structures, neoadjuvant radiotherapy was recommended. When the tumor was found to be adherent to the synovium, extraarticular resection was favored, whereas if the tumor was located within soft tissue and sufficient bone remained to preserve joint function, excision was the preferred approach. Neoadjuvant chemotherapy was more commonly advised when the disease presented with systemic involvement. Amputation as the primary surgical intervention was considered a challenging decision and was only pursued if it was not feasible to perform an extremity-sparing surgery, typically due to the involvement of the neurovascular structures supplying the limb.

Tumor volume is calculated form the MRI using the formula V = π/6 x L x W x H where V is the volume, L is the length, W is the width, and H is the height.¹⁵ In cases of recurrent patients, the volume was computed based on the MRIs acquired at the time of diagnosis, even if these scans were conducted at different medical facilities. T Subsequently, tumors were categorized into three groups: <30cm³, 30-130cm³ and >130cm³, cut off analysis was performed for the cutt of values. While the literature provides diverse cut-off values for various tumors, we made the decision to employ tumor volume, considering that we had comprehensive three-dimensional size data for all tumors, some of which exhibited irregular shapes. This approach was favored over the utilization of a unidimensional variable.

In our clinical practice, the initial postoperative outpatient clinic visit for follow-up occurs during the second week for upper extremity surgeries and the third week for lower extremity surgeries. Subsequent follow-up appointments are scheduled at one month and are continued on a monthly basis for the first six months. Afterward, the frequency shifts to once every three months until the second year post-operation, and subsequently transitions to once every six months.

StataMP13 (StataCorp. Stata Statistical Software: Release 13) was used for descriptive and inferential analyzes. Shapiro-Wilk test was used to assess normality. Mean with a standard deviation (std) was used to analyze the normally distributed data. Median with 25 and 75 percentiles (p) was calculated for the not normally distributed data. To assess categorical outcomes, we utilized the Chi-square and Fisher exact tests. Parametric data were analyzed using the t-test, whereas non-parametric data were subjected to analysis via the Mann-Whitney U test. Survival analysis was conducted with regard to recurrence, metastasis, and mortality. Notably, 7 patients with metastasis and 2 patients with recurrence (with 1 patient presenting both conditions) at the time of initial evaluation, who were previously treated in other clinics, were excluded from the survival analysis. As a result, the survival analysis encompassed a cohort of 55 patients. A p-value less than 0.05 was considered statistically significant in our analysis.

The patients in our study had a mean age of 37.55 ± 17.08 years, with women constituting 49% of the cohort. Throughout the average follow-up period of 64.42 ± 54.36 months, it was observed that neither age nor gender exerted a significant influence on survival outcomes.

At the time of presentation, 56.9% had the complaint of swelling, 49.2% had pain, and 12.31% specifically mentioned night pain. Other complaints were decreased range of motion, sense of fullness, and tingling distal to the lesion.

When classified based on location, there were 18 knees, 16 thighs, 8 feet, 4 shoulders, 4 forearms, 3 ankles, 3 cruris, 2 elbows, 2 fingers, 1 hand, 1 pelvis, 1 arm, 1 sacrum, and 1 supraclavicular synovial sarcoma. Almost all (96.92%) of the SS were at the extremities, and 75.38% were at the lower ones. 28 (43.01%) were close to joints, but only 6 were intraarticular. 62.50% of the SS were at the right side of the body. At the time of presentation, 7 (10.77%) were found to have lung metastases, and 2 (3.08%) had recurred lesions (1 patient was both metastatic and recurrent). Table 1 summarizes the demographic and tumor specific information of the study group. Figures 1 and 2 are examples from our case series.

Fig 1. AP (A) radiograph of the left leg in a 46 year-old female demonstrates soft tissue opacity adjacent to the proximal femur, coronal and axial MR images in the same patient demonstrate an intramuscular soft tissue mass situated posterior to the femur, in close relation to the sciatic nerve. The mass demonstrates heterogeneously high signal on T1 weighted fat-saturated images (B) and high signal on T2 weighted images (C). The case went to a biopsy as proven for synovial sarcoma.

Fig 2. AP (A) radiograph of the right arm in a 48-year-old female demonstrates lysis at the proximal humerus. Coronal and axial MR images of the same patient demonstrate a soft tissue mass situated at the medial of the proximal humerus in close relation with the axillary vessels and the brachial plexus. The mass demonstrates heterogeneously high signal on T1 weighted fat-saturated images (B) and high signal on T2 weighted fat saturated images (C). The case went to a biopsy as proven for synovial sarcoma.

Mean volume of the tumors in the study group was 109.71±176.25 cm³. Tumors being bigger than 30 cm³ had significantly decreased survival (p=0.0163) and increased metastasis (p=0.0077).

There were 21 fine needle biopsies, 15 tru-cut biopsies, 4 incisional biopsies and 15 paraphine blocks from other centers as preoperative pathology materials. 5 excisional biopsies, 31 surgical and 14 amputation materials and again 15 paraphine blocks from other centers as postoperative pathology materials were analyzed. Figure 3A and 3B shows the macroscopic image of a SS.

Histologically, 38.46% of the cases had monophasic, and 36.92% had biphasic morphology, whereas 24.62% was poorly differentiated (Figures 3C-F). There was a significant difference in survival between the groups, and the post hoc analysis showed no difference between the mono and biphasic forms. In contrast, the survival was significantly less for poorly differentiated and dedifferentiated forms. Necrosis was seen in 44.21%. Surgical margins were positive for seven patients. Of these 7 patients, 1 had lung metastasis at presentation and died 1 year after the surgery and 1 died 5 months after surgery. 1 patient had no recurrence or metastasis during 24 months of follow up. 1 patient had recurrence on postoperative 1^st month and another on postoperative 3^rd month. 2 patients had both recurrences and metastasis, one recurred at 19 years and metastasized at 22 years, other recurred at 5 years and metastasized at 13 years.

Fig 3. (A) In this case, tumor is well circumscribed and contains cystic areas. Cut surface is tan and grey. (B) This tumor is well circumscribed and solid. Cut surface is tan and grey. (C) A case of monophasic synovial sarcoma. Tumor cells are monotonous cells with scant amphophilic cytoplasm, ovoid to spindled vesicular nuclei, and in fascicules (H&E x 100) . (D) A case of biphasic synovial sarcoma. Tumor has two components: spindle cells and gland-like epithelial structures (H&E x 100). (E) Biphasic synovial sarcoma. Tumor has two components: spindle cells and gland-like epithelial structures (H&E x 200). (F) A case of poorly differentiated synovial sarcoma. Tumor is highly cellular and has frequent mitotic activity. Tumor cells are round hyperchromatic nuclei and prominent nucleoli (H&E x 400). (G) Epithelial component is positive with PANCK (cocktail). Spindle cells are scarcely positive (x200). (H) Epithelial component is positive with EMA. Spindle cells are scarcely positive (x200). (İ) Tumor cells are diffuse positive with Bcl2 (x200). (J) Tumor cells are diffuse nuclear positive with TLE1 (x200). (K) SS18 (18q11) translocation signals by fluorescent in-situ hybridization (FISH).

A total of 53 cases of immunohistochemical results were investigated Figure 3G-J are examples. Immunohistochemically, the most commonly positive markers were Bcl-2 (89.47%) and EMA (88.14%). In addition, TLE1 was recently being studied, and it was 86.67% positive (13/15). Other investigated markers were Ki-67, cytokeratins (pan-CK, CK5, CK6, CK8, CK19, CK20), CD31, CD34, CD45, CD56, CD57, CD99, CD117, S100, SMA, desmin, myogenin, vimentin, caldesmon, calponin, FLI1, TTF1, HMB45, Melan-A, synaptophysin, chromogranin A, PAX8, ERG, ER, P63, P40, DOG1, MUC4, WT1, GFAP, and STAT6. (Percentages are given in Figure 4, positive results are presented).

Fig 4. Immunohistochemistry results of the patients.

FISH for the translocation t(18, X) fusion gene SS18-SSX was performed in 11 cases, and SS18 gene rearrangement was present in 8 (72.72%), 50% being female and 50% being monophasic (Figure 3K).

The most common surgery was resection (marginal, wide or radical). 17 patients were amputated at some point during treatment due recurrence. Amputation was the first-line treatment for 8 patients, where it is the second surgery for 3 patients, third for 3 patients, fourth for 2 patients, and tenth for 1 patient. 7 of the amputations were transfemoral, and 5 were transtibial. There was also 1 hip disarticulation, 1 Lisfranc amputation, 1 finger amputation, 1 radiocarpal disarticulation, and 1 scapulothoracic disarticulation. Out of 9 patients where amputation was not the first surgery, 7 had history of unplanned resection or excision. Extraarticular resection was performed for 4 patients, due synovial involvement. 10 patients required some soft tissue reconstruction.

Forty patients (61.54%) had chemotherapy, and 35 patients (53.85%) had radiotherapy at some point. 21.54% had neoadjuvant, and 53.85% had adjuvant chemotherapy. 10.77% had preoperative, and 44.62% had postoperative radiotherapy. In addition, ten patients had metastasectomy surgeries.

During the follow-up time, 27 patients (41.54%) had metastases, 24 patients (36.92%) had recurrences and 15 patients (23.08%) have died. 19 patients in the study group had history of unplanned resection or excision surgery from other centers where oncologic surgery is not common. Also, although being statistically unsignificant rate of recurrence is higher in the margin positive group (57.14% vs 35.71%, p=0.271).

For the survival analysis, 7 metastatic and 2 recurrent patients (1 having both) at the time of presentation (secondary cases treated in other clinics) were excluded and the survival analysis was performed with 55 patients. The median survival is 120 months for the rest of the study group. Metastasis occurred after a mean of 96 months (36-264). Local recurrence occurred after a mean of 61 months (36-204).

Median survival for death and metastasis was lower for the patients who had chemotherapy at some point (p=0.0253 and p=0.0106). Also, survival for metastasis and recurrence is lower for the patients who had radiotherapy at some point (p=0.002, 0.046).

Local recurrence occurred after a mean of 24 months for the neoadjuvant radiotherapy group, and 61 months for adjuvant radiotherapy group. Distant metastasis occurred after a mean of 36 months for the neoadjuvant chemotherapy group, and 42 months for adjuvant chemotherapy group (Table 2). Kaplan Meier survival curves are given in figure 5.

Fig 5. Survival analysis & Kaplan Meier curves for death, metastasis and recurrence.

There are 16 patients in the study group without history of radiotherapy or chemotherapy. 3 (18.75%) of these had recurrence and 2 (12.50%) had distant metastasis. 13 of these 16 patients had neither recurrence nor metastasis, irrelevant of the tumor size. The survival is calculated separately for the excluded 8 patients and the median survival is 96 months (36-96).

SS presents as a complex and challenging disease characterized by diagnostic and treatment hurdles. Its clinical presentation is notably heterogeneous, often mirroring other pathological conditions. Moreover, SS exhibits elevated rates of recurrence, metastasis, and mortality. In this comprehensive study, we have compiled a case series encompassing 65 instances of synovial sarcoma, involving 63 patients. Through a meticulous retrospective analysis, we have delved into the intricacies of diagnosis, treatment, and the subsequent follow-up process.

The results of the study are consistent with the current literature. SS has no gender predilection, and there were 65 tumors from 32 males vs. 31 females in the study.⁴ SS is more common in the young population, and the mean age was 37.57.³ SS is most commonly seen in extremities, and in this study, 96.92% were at extremities, 75.38% being at the lower ones.² According to the study of Vlenterie et al, the survival of synovial sarcoma is better for age under 18; but there was significant age relevance in our study.¹⁶

The mean tumor size in the study, 109.71 cm³, was similar to the data in the literature. Although one dimension is given as 5.9 cm and 5 cm respectively in the studies of Minami et al. and Gronchi et al., calculated volume is similar.^17,18 ¹⁹ The volume of the tumors in the study of Terra et al. and Ortega et al. were a bit bigger where average being 13.5 cm and 12.5 cm respectively.^20,21 Although the idea that the increase in size having poor prognosis is accepted, the cut-off was different in different studies. The cut-off is 10 cm in the studies of Guo et al. and Singer et al., whereas it is 5 cm for Heuvel et al., Cheng et al.²² and Siegel et al.^10,23-25. Our study's cut-off was 30 cm³; the analysis was done according to the volume. Our results are consistent with the literature as size is an important predictive value despite the changing cut off.

The distribution of the subtypes (monophasic, biphasic, dedifferentiated) differed from the previous studies. There were 38.46% monophasic and 36.92% biphasic SS in our study; whereas the numbers were 33% biphasic to 31% monophasic in Wright et al. study and 17% biphasic to 33% monophasic in the Study of Jami et al.²⁶ ²⁷ In our study survival was not significantly differed between mono and biphasic SS, similar to the study of Campbell et al. whereas it is the opposite of the Xiong et al. study where biphasic SS had better prognosis.²⁸ ²⁹

Immunophenotypic results were also consistent, with high EMA and bcl-2 positivity.¹ In the literature, there are case series of synovial sarcoma primarily based on the diagnosis at the molecular level and differentiation from other sarcomas. For instance, the study of Rooper et al. discusses the differential diagnosis of Ewing sarcoma and SS without FISH.³⁰ Studies suggest IHC, specifically TLE-1, for distinction from other soft tissue sarcomas.^31-33 Knösel et al. investigated 319 spindle cell sarcomas and compared results of IHC and FISH for SS diagnosis.³⁴

In our study, FISH for the translocation t(18, X) fusion gene SS18-SSX was performed in 11 cases, and SS18 gene rearrangement was present in 8 (72.72%). The ratio is lower than the literature; mainly when some studies accept FISH as the definitive diagnostic modality for SS. ^35,36 Also, our study lacks the subtype analysis for SS18 translocation.

Metastasis is more than 50%, and the mortality is about 60-70% in five years in the literature, but in the study group, the metastasis rate is 41.54%, the recurrence rate is 36.92%, and the mortality is 23.08% which are more optimistic.^8-10 By increasing the minimum follow-up period from 5 months to 5 years will make the results closer to the literature. In this study only 18 (32.73%) patients had follow up longer than 5 years.

The survival for death, metastasis, and recurrence was lower for the groups who have radiotherapy or chemotherapy, which is against the literature as previous studies showed the effect of chemo and radiotherapy. In the study of Guo et al., both chemo and radiotherapy significantly affect survival in uni and multivariant analysis.²³ Also, the Wu et al. study showed that chemotherapy could increase survival and control distant metastasis.³⁷ Recurrence or the systemic disease significantly decrease survival rather than the chemo or radiotherapy.

A few studies discuss the molecular targets of synovial sarcoma, but there is no real improvement in survival yet. Abe et al. suggests glycogen synthase kinase 3b as a target, Sekita et al. points out Traf2- and Nck-interacting kinase (TNIK), and Wang et al. mentions Skp2 knockdown for treatment.^38-40

Surgery is still the backbone of the non-systemic SS and literature supports surgery-only approaches. Adequately resected SS smaller than 5 cm, regardless of grade, can be safely treated with a surgery-only approach and the definitive treatment by trained oncologic surgeons decreases the risk of local recurrence and metastasis.^41,42 In our study, out of 16 patients without history of radiotherapy and chemotherapy, 50% had a volume smaller than 30cm³. Additionally, more studies are needed to assess the efficacies of the different surgical methods.^13,14,27 For instance, the study of Jami et al. discusses the extraarticular resection for intraarticular SS.⁴³ As most SS are extraarticular, discussion fot intraarticular SS treatment is still insufficient in the literature.²⁷

This study is subject to several limitations. Firstly, it is a retrospective analysis conducted on a heterogeneous group of patients. Secondly, due to the relative rarity of synovial sarcoma in comparison to more common sarcomas like osteosarcoma or Ewing sarcoma, a non-probabilistic sampling approach was employed. Additionally, the study did not exclude or differentiate patients whose disease progressed systemically or recurred during the follow-up period. Furthermore, the minimum follow-up duration of five months may not be sufficient to accurately assess metastasis and recurrence rates, as well as mortality. A more extended follow-up period, ideally spanning five years, would be necessary to provide a more comprehensive understanding of these outcomes.

Besides its limitations, this study provides literature on a heterogeneous group of synovial sarcomas with different treatment modalities and points out the critical aspects of differential diagnosis, especially with IHC. Future research endeavors could benefit significantly from randomized controlled multicenter studies encompassing larger patient cohorts and extended follow-up periods. Additionally, further investigations focusing on IHC markers, notably TLE1, and their prognostic implications, as well as exploring alternative treatment approaches like extraarticular resection, hold promise for advancing the management of synovial sarcoma.

SS is an intriguing disease and differ from other soft tissue sarcomas due to challenges in diagnosis and treatment. Our results suggest that it is crucial for orthopaedic surgeons to recognize synovial sarcoma and be aware of the negative predictive variables as the tumor volume (>30cm³), unplanned excision and poorly differentiated histologic type. The role of chemotherapy and radiotherapy in high-grade tumors remains a topic of debate, with varying benefits observed. It's also crucial to emphasize the necessity for extended follow-up in SS cases, given the persistent risk of late recurrence.

Acknowledgements: Authors thank to the radiology and pathology departments of the university for their support.

Author contributions:

Conceived and designed the analysis: MOK, KB, HYY

Collected data: MDS, SY

Contributed data or analysis tools: MOK, MDS, SY, GK

Performed the analysis: MDS, SY, GK

Wrote the paper: MOK, MDS

Literature review: MDS, SY

Review and editing: GK, KB, HYY

Supervision: HYY

Each author has made substantial contribution to the study. All authors have approved the submitted version and have agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

Conflict of Interest: The authors declare that they have no conflict of interest. Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members.

Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding: There is no funding source.

Ethics: The study is approved by the Ethics Committee of Ankara University. (Application number: 2021/479. Decision number: İ11-708-21.)

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Age mean (min-max) years

37.55 (9-84)

Gender n (%)

Male

Female

33 (50.77)

32 (49.23)

Follow up mean (std) months

64.42 (12-456) m

Complaint n (%)

Swelling

Pain

Night pain

Decreased ROM

Sense of fullness

Tingling

37 (56.92)

33 (50.77)

8 (12.31)

1 (1.54)

Location n (%)

Upper extremity

Supraclavicular

Shoulder

Arm

Elbow

Forearm

Hand

Finger

Lower extremity

Thigh

Knee

Cruris

Ankle

Foot

Axial

Pelvis

Sacrum

1 (1.54)

4 (6.15)

1 (1.54)

2 (3.08)

4 (6.15)

1 (1.54)

2 (3.08)

18 (27.69)

3 (4.62)

8 (12.31)

1 (1.54)

At presentation n(%)

Metastatic

Recurrent

7 (10.77)

2 (3.08)

Table 1: Demographic data and complaints at admission of the study, along with the location of the tumor is given.

DEATH

MET

RECURRENCE

Patient number

NUMBER (%)

MEDIAN SURVIVAL (m)

NUMBER (%)

MEDIAN SURVIVAL (m)

NUMBER (%)

MEDIAN SURVIVAL (m)

Gender

Female

Male

5 (17.24)

6 (23.08)

0.0589

0.5742

10 (34.48)

9 (34.62)

0.992

0.5646

9 (31.03)

13 (50.00)

0.152

228

0.6809

Size

0-30cm3

30-130cm3

>130cm3

2 (7.14)

4 (26.67)

5 (41.68)

0.033

102

0.0163

6 (21.43)

6 (40.00)

7 (58.33)

0.070

264

0.0077

13 (46.43)

4 (26.67)

5 (41.67)

0.448

102

0.9615

Chemotherapy

Yes

Neoadjuvant

Yes

Adjuvant

Yes

9 (28.12)

2 (8.70)

0.076

2 (20.00)

9 (19.57)

0.855

8 (28.57)

3 (11.11)

0.106

0.0253

102

0.6639

0.0364

15 (46.88)

4 (17.39

0.023

4 (44.44)

15 (32.61)

0.495

14 (50.00)

5 (18.52)

0.014

0.0106

156

0.3394

0.0051

16 (50.00)

6 (26.09)

0.074

4 (44.44)

18 (39.13)

0.766

14 (50.00)

8 (29.63)

0.123

204

0.0839

102

0.5912

108

0.0929

Radiotherapy

Yes

Neoadjuvant

Yes

Adjuvant

Yes

9 (29.03)

2 (8.33)

0.057

3 (42.86)

8 (16.67)

0.106

6 (24.00)

5 (16.67)

0.498

120

0.2538

0.0652

120

0.9382

16 (51.61)

3 (12.50)

0.002

5 (71.43)

14 (29.17)

0.028

11 (44.00)

8 (26.67)

0.178

0.0732

156

0.0943

264

0.6627

16 (51.61)

6 (25.00)

0.046

4 (57.14)

18 (37.5)

0.322

12 (48.00)

10 (33.33)

0.269

108

0.5663

0.6129

108

0.8688

Amputation

Yes

4 (33.33)

7 (16.29)

0.192

0.1969

5 (41.67)

14 (32.56

0.557

156

0.7977

9 (75.00)

13 (30.23)

0.005

102

0.0000

Table 2. The summary of the survival analysis data for the study group for recurrence, metastasis and death.

No competing interests reported.

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Intriguing Tumor, Synovial Sarcoma: Hard to Diagnose, Harder to Treat

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