Discussion and Conclusions

Synovial sarcoma (SS) is a rare and aggressive subtype of soft tissue sarcoma (STS), comprising only 5%-10% of all STSs [1,2]. It is a malignant tumour of mesenchymal origin exhibiting variable degrees of epithelial differentiation [2]. Despite its name, SS is in fact a misnomer as it does not arise from synovial tissue [3-5] and is driven by a specific SS18-SSX fusion oncogene resulting from the t(X;18)(p11.2;q11.2) translocation [1-16].

The intravascular presentation of SS (IVSS) is an exceptionally rare entity. To the best of our knowledge, only 14 cases of IVSS [3-6,8-15] have been reported in the global literature, making this the 15th report worldwide.

IVSS is highly aggressive and characterised by tumour growth within vascular structures. Its prognosis is influenced by several factors, including tumour size, depth, anatomical location, invasion into surrounding tissues, and most importantly, achieving a complete surgical resection [1,5,10,13]. The intravascular location of the tumour contributes to a significantly higher risk of distant metastasis [15]. Our patient’s clinical course underscores this aggressive nature, where local recurrence was detected only 5 months after completion of CT.

In our case, the clinical presentation and initial imaging were suggestive of a DVT. However, it was actually the mass exerting significant extrinsic compressive effects and luminal obstruction of the vein. This resulted in an absence of definite colour flow or a venous spectral waveform, which was initially misinterpreted as a DVT. It can also present as a pulmonary embolism (PE) [4,13], superior vena cava (SVC) syndrome/obstruction (SVCO) [3], pleural effusion [14], and other thromboembolic events depending upon the location of the mass.

This is well illustrated in the case reported by Tong et al. [3], where the IVSS involved the SVC, presenting clinically as a cervical mass with features of SVC syndrome. Similar obstacles have been documented by Schreiner et al. [4] and Schoneveld et al. [13], who reported cases of IVSS initially mimicking common thromboembolic events. This creates a critical diagnostic pitfall where we can mistake a malignant intravascular process for a primary DVT.

To navigate this, a multimodal approach including clinical assessment, imaging, histopathology, IHC, and molecular studies [3-5,10,14,15] is required. Differentiating tumour thrombus from bland thrombus is key, and while Doppler USG is first-line for DVT, advanced imaging is crucial when atypical or malignant features such as internal vascularity and calcific foci are present, as seen in our case [12]. CT venography identified the enhancing mass, and FDG PET CT (Figure 3) confirmed the strong suspicion for a malignant intravascular process. The above-mentioned radiological red flags, along with atypical thrombotic presentations, particularly in young patients with a failure to respond to anticoagulation, should prompt thorough assessment and consideration of intravascular neoplasms to help prevent delay in diagnosis [3,4,10,12].

In our case, histopathological examination and IHC played a crucial role in the diagnostic workup, where the strong expression of SS18 helped in making the diagnosis of SS [17]. SS18 expression is a positive immunoexpression of the SS18::SSX fusion-specific antibody, which is highly specific for SS [18]. IHC also helped rule out neural origin tumours [7], mesothelioma, sex cord-stromal tumours, and carcinomas of the female genital tract [17]. Our case demonstrated significant downregulation of INI1 (SMARCB1) expression. In SS, several studies have reported reduced or mosaic loss of SMARCB1/INI1 protein expression in a large number of cases. This reduction is not due to gene deletion but is attributed to post-transcriptional regulatory mechanisms affecting protein expression within tumour cells. Therefore, the observed downregulation in our sample supports our diagnosis [19]. This IHC profile is consistent with previously published reports. Given the significant morphologic heterogeneity exhibited by SS [2], the use of molecular techniques remains critical for confirming the diagnosis [1-5,10,13-15].

The diagnosis in this case was definitively confirmed by the detection of the SYT-SSX1 gene fusion by FISH, a characteristic molecular alteration unique to this tumour type [1,2,4,5,14]. It is seen approximately in 95% of all cases [4], making it an exceptionally reliable diagnostic marker and also believed to be the cause [1]. This chromosomal reciprocal translocation [5] forms from the fusion of the SS18 gene on chromosome 18 with an SSX gene (SSX1 or SSX2) on the X chromosome [1,2,10,14].

The management of IVSS remains undefined due to the lack of standardized treatment guidelines and presents a significant predicament. Surgical resection remains the cornerstone of treatment [5,13], RT playing a crucial adjunctive role in improving prognosis [13] and reducing the risk of local recurrence. However, the role of CT remains controversial [5,13].

Several reports highlight the need for adapted strategies in IVSS due to its intravascular location and technical surgical challenges. Schreiner et al. [4] utilized a combination of neoadjuvant CT (doxorubicin and ifosfamide) and RT before surgical resection [4]. Maekura et al. [14] reported a case of unresectable pulmonary artery IVSS, in which combined CTRT was utilized as a disease-controlling strategy. Jonathan et al. [10] also reported a case wherein neoadjuvant RT was employed before radical en bloc excision of the tumour, followed by combined arterial and venous reconstruction, resulting in 2 years of disease-free survival. These approaches suggest that in cases where the tumour is large or located in anatomically critical regions, upfront surgery may not be feasible. Hence, preoperative RT or combined chemoradiotherapy (CTRT) may be employed in such cases.

In our case, the patient underwent surgery and was pathologically staged as pT2N0Mx with clear margins. Margin status is recognized as one of the most significant prognostic indicators for local recurrence in STS [16]. Achieving an R0 resection is therefore of paramount importance [5,16], as conservative surgical approaches have been associated with recurrence rates as high as 70% [5]. Additionally, tumour size has also been shown to correlate strongly with both local recurrence and systemic outcomes [10]. Lesions measuring greater than 5 cm in diameter are associated with a significantly increased risk of recurrence [13].

Postoperatively, our patient received five cycles of adjuvant CT with ifosfamide and doxorubicin. Although the role of adjuvant CT in synovial sarcoma remains debated [1,5,13], it was considered appropriate in this case due to the tumour’s size (>5 cm), high-grade histology, localized disease, negative lymph nodes, and the patient’s young age. RT was not administered given the anatomical location and the elevated risk of chronic lymphedema, particularly following extensive lymph node dissection and vascular involvement.

Management strategies are typically extrapolated from conventional synovial sarcoma, and reported cases show variability in therapeutic approaches [4-6,8,10,13-15], reflecting the need for an individualized nature of decision making based on tumour location, size, and extent of vascular involvement. A notable clinical feature is its tendency for late recurrence, frequently occurring beyond 5 years after initial diagnosis and treatment [2,6,16], underscoring the necessity for prolonged follow-up.

What sets our case apart is the unusually early locoregional recurrence within 5 months of receiving adjuvant CT (Figures 1–3) and within a year of surgical resection. This suggests that IVSS may have a more aggressive biology, possibly influenced by factors associated with the tumour microenvironment and mechanisms of vascular spread, and this is a major learning point showing the necessity for stringent monitoring.

A notable limitation of this case is the relatively short surveillance period, as the patient was lost to follow-up shortly after recurrence was documented. Consequently, any further interventions could not be carried out, and the ultimate clinical outcome could not be further evaluated.