Primary renal synovial sarcoma with synchronous pulmonary metastases: A rare case report and review of diagnostic and management strategies

Abstract

Primary renal synovial sarcoma (SS) is an exceptionally rare malignancy, often indistinguishable from other renal tumors on imaging. We report a case of a 67-year-old male presenting with hematuria and a renal mass, later diagnosed as monophasic SS with synchronous pulmonary metastases. Diagnosis was confirmed through histopathology, immunohistochemistry, and cytogenetics. The patient underwent cytoreductive nephrectomy followed by adjuvant chemotherapy. This case highlights the diagnostic challenges and underscores the importance of a multidisciplinary approach in managing metastatic renal SS.

Highlights

• •Rare case of primary renal synovial sarcoma with lung metastases.
• •Diagnosis confirmed via histology, immunohistochemistry, and cytogenetics.
• •Imaging mimicked renal cell carcinoma, complicating preoperative diagnosis.
• •Patient underwent cytoreductive nephrectomy for symptom control.
• •Multidisciplinary care guided treatment with surgery and chemotherapy.

1. Introduction

Synovial sarcomas (SS) represent a distinct subset of soft tissue sarcomas, accounting for approximately 5–10 % of all soft tissue sarcoma cases.¹ They most commonly arise in the extremities, with nearly 70 % of cases initially identified in the lower limbs.² Other reported sites include the lungs and mediastinum, while renal involvement is exceedingly rare, with no definitive incidence reported in the literature.^3,4

SS typically affects young adults and is associated with a poor prognosis, particularly when metastases are present at the time of diagnosis. The tumor is characterized by specific oncogenic translocations involving SS18 and SSX genes—namely SS18-SSX1, SS18-SSX2, or, less commonly, SS18-SSX4.⁴

Surgical resection remains the cornerstone of treatment. However, diagnosis is often established postoperatively through histological and cytogenetic evaluation, as the clinical and radiological features of renal SS closely resemble those of renal cell carcinoma and other sarcomas. Currently, there are no definitive imaging characteristics that reliably distinguish this tumor preoperatively, which explains why most cases are diagnosed only after histopathological analysis of the resected specimen.⁵

Following surgery, treatment options may include radiotherapy, chemotherapy, and targeted molecular therapies, either as monotherapy or in combination, depending on the extent of disease and patient-specific factors.⁶

We present a rare case of primary renal SS with synchronous lung metastasis. Diagnosis was established by radiologic, histopathologic, immunohistochemical, and cytogenetic findings. We present the multidisciplinary approach for management of metastatic renal SS.

2. Case presentation

A 67-year-old male presented with a 4-week history of right flank pain and gross hematuria. Past medical history was significant for diabetes and hypertension, and there was no known family history of malignancy. Laboratory investigations showed a serum creatinine level of 1.50 mg/dL. Contrast-enhanced computed tomography (CT) of the abdomen demonstrated a heterogeneous mass measuring 11 × 8.9 cm located in the lower pole of the right kidney. The lesion showed contrast enhancement and infiltration into the central collecting system, without evidence of renal vein invasion (Fig. 1 A).

Fig. 1.

A) Axial contrast-enhanced CT image showing a heterogeneously enhancing mass lesion occupying the lower pole of the right kidney, measuring approximately 11 × 8.9 cm, with evidence of infiltration into the collecting system. B) Coronal CT chest image demonstrating the largest pulmonary nodule in the left lower lobe, measuring approximately 23 × 19 mm (circled).

Staging Chest- CT scan demonstrated multiple solid pulmonary nodules bilaterally, predominantly in the lower lobes. The largest nodule, located in the left lower lobe, measured 23 × 19 mm (Fig. 1B). A CT-guided biopsy of a pulmonary nodule was performed, revealing a high-grade malignant neoplasm. Immunohistochemical staining was positive for synaptophysin, CD99, SS18:SSX, CD56, and BCOR, consistent with a diagnosis of metastatic, poorly differentiated monophasic synovial sarcoma (Fig. 2).

Fig. 2.

A) Lung nodule biopsy, showing high-grade malignant spindle cells (Hematoxylin and eosin stain, 600×). B) Immunohistochemical staining of lung nodule biopsy demonstrates positive expression for synaptophysin. Additional markers including CD99, SS18SSX, CD56, and BCOR were also positive. C) Histopathology specimen of resected kidney specimen shows features of synovial sarcoma, monophasic variant, with malignant spindle cells arranged in solid collagenous sheets (Hematoxylin and eosin stain, 400×).

Given the patient's symptoms such as flank pain and gross hematuria and limited burden of metastatic disease, cytoreductive nephrectomy was planned for local control.

The patient subsequently underwent open right radical nephrectomy with regional lymphadenectomy through an anterior subcostal incision. A large renal mass with grossly negative margins was removed (Fig. 3). Oral intake was reinstituted on postoperative day (POD) 1, urinary catheter removed on POD3, and drain was removed on POD4. Due to low hemoglobin levels on POD5, a single unit of packed red blood cells was transfused, and patient was discharged on POD6. His hematuria resolved completely. Histopathological examination confirmed the diagnosis of synovial sarcoma, with an additional tumor deposit identified in the upper pole of the kidney (Fig. 2). All six sampled lymph nodes were negative for metastatic involvement.

Fig. 3.

Nephrectomy specimen showing a large tumor measuring 13.4 × 11.2 cm occupying the middle and lower poles of the kidney.

At the 3-month follow-up, positron emission tomography-CT (PET-CT) demonstrated progression in the size of existing pulmonary nodules and the emergence of new lesions (Fig. 4A and B). Owing to his borderline performance status (ECOG2), patient is receiving single agent doxorubicin chemotherapy of 60mg/m² every three weeks, with planned response assessment CT after 3–4 cycles.

Fig. 4.

A) Coronal sections from a post-operative PET-CT scan in a patient with metastatic synovial sarcoma following radical nephrectomy and lymph node dissection. The original preoperative pulmonary nodule in the left lower lobe remained stable in size, measuring approximately 3.0 × 3.2 cm (yellow circle). B) Coronal and transverse PET-CT images showing a new pulmonary nodule in the lower basal zone of the left lung, measuring approximately 0.6 cm (purple circle).

3. Discussion

Synovial sarcoma (SS) is a malignant soft tissue neoplasm believed to arise from multipotent stem cells capable of differentiating into both epithelial and mesenchymal lineages. It accounts for approximately 5–10 % of all soft tissue sarcomas, with no clear sex predilection, and is associated with a generally poor prognosis.^1,2

Primary renal synovial sarcoma typically presents with nonspecific symptoms such as flank pain, an abdominal mass, and hematuria. Preoperative diagnosis is challenging due to the absence of distinct radiologic features. Imaging modalities such as CT or magnetic resonance imaging (MRI) often reveal large, heterogeneous renal masses with complex architecture and aggressive local invasion. These features, while suggestive of malignancy, are not specific and may overlap with those of renal cell carcinoma.^7,8

At initial presentation, only 8 % of primary renal SS cases exhibit metastatic disease. The lungs (42 %) and liver (24 %) are the most common sites of metastasis. This underscores the importance of comprehensive preoperative staging with chest CT or whole-body PET-CT to detect occult metastases and guide therapeutic planning. In selected cases, CT-guided biopsy of metastatic lesions may aid in confirming the diagnosis and establishing the extent of disease. Such an approach was utilized in our case.⁹

The standard treatment for localized primary renal SS is radical nephrectomy with regional lymphadenectomy. In patients with metastatic disease, cytoreductive nephrectomy followed by adjuvant chemotherapy—typically with ifosfamide and doxorubicin (Adriamycin)—is considered the optimal approach. Doxorubicin-based regimens have demonstrated efficacy in soft tissue sarcomas, as supported by meta-analyses.¹⁰ However, due to the rarity of primary renal SS, there are no universally accepted treatment guidelines, and management is often extrapolated from protocols used for soft tissue synovial sarcomas.⁴

Diagnosis is confirmed through a combination of histopathological evaluation and cytogenetic analysis. Histologically, SS is characterized by spindle cells arranged in short, intersecting fascicles, with pleomorphic, mitotically active nuclei. Immunohistochemical staining typically reveals positivity for epithelial membrane antigen (EMA), synaptophysin, cytokeratin 7 (CK7), CD99, CD56, Ki-67, and vimentin. Negative staining for markers such as MyoD1, S100, PAX8, CD34, Desmin, Wilms tumor protein 1 (WT1), and smooth muscle actin helps exclude other differential diagnoses. Fluorescence in situ hybridization remains the gold standard for detecting the pathognomonic SYT-SSX (SS18SSX) fusion oncogene.11, 12, 13

In our case, the diagnosis was established through a combination of morphologic, immunohistochemical, and cytogenetic findings (Fig. 2A, B and 2C). The characteristic SS18 translocation was confirmed in both the renal primary tumor and pulmonary metastases using immunohistochemistry and FISH.

Primary renal SS can be classified into three histologic subtypes: monophasic (76 %), biphasic (14 %), and poorly differentiated (10 %).⁷ The monophasic variant, as in our case, consists of ovoid or spindle cells with moderate nuclear pleomorphism arranged in solid collagenous sheets. The biphasic subtype contains both spindle and epithelial components, while the poorly differentiated form is composed of undifferentiated round cells with high mitotic activity and is associated with a worse prognosis.¹¹

In total, 95 % of SS are characterized by chromosomal translocation t(X:18) (p11.2: q11.2), which results in multiple chimeric gene variants: SS18-SSX1, SS18-SSX2 and SS18-SS4. The prognostic value of each chimeric gene differs depending on the gene type: SS18-SSX1 is associated with higher mortality and metastasis incidence than SS18-SSX2, but SS18-SSX2-positive patients more frequently develop recurrence in periarticular synovial sarcomas. However, their prognostic role in primary renal SS is less well established.^12,13

Tumor size and histologic grade are key prognostic indicators. While surgery and chemotherapy remain the mainstays of treatment, adjuvant radiotherapy may reduce local recurrence but has not been shown to improve overall survival. A systematic review of 96 primary renal SS cases reported a median overall survival of 34 months and a disease-free survival of 25 months. Patients presenting with metastases had significantly worse outcomes (6 months vs. 37 months; p ≤ 0.01).⁷

More than 90 % of patients with completely resected primary SS may relapse locally. Unfortunately, from published series, it is unclear which tumors will recur after total resection even with negative microscopic margins.¹³ Emerging therapies for SS include Anlotinib, a multi-targeted tyrosine kinase inhibitor that suppresses tumor growth and angiogenesis by inhibiting vascular endothelial and fibroblast growth factor receptor pathways. It has shown efficacy in patients unresponsive to anthracycline-based chemotherapy. Immunotherapy targeting NY-ESO-1, expressed in 80 % of SS cases, also demonstrates promise. Sorafenib, an oral kinase inhibitor, disrupts mitogen-activated protein kinase signaling and insulin-like growth factor −2 transcription driven by SS18-SSX fusion proteins, inducing apoptosis and cell cycle arrest. While preclinical data are encouraging, further clinical trials are necessary to validate Sorafenib's therapeutic role in SS management.^14,15

4. Conclusion

Primary renal SS is a rare and aggressive malignancy with significant diagnostic and therapeutic challenges. Even with complete surgical resection and systemic therapy, long-term survival remains limited. Chemotherapy may offer modest improvements in prognosis, while radiotherapy appears to have limited benefit. This report underscores the importance of a multidisciplinary approach and demonstrates the role of cytoreductive surgery and systemic therapy in the management of metastatic primary renal SS. Given the scarcity of reported cases, continued case reporting and longitudinal data are essential to guide management strategies and improve patient outcomes.

CRediT authorship contribution statement

Sri Saran Manivasagam: Writing – original draft, Visualization, Validation, Software, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation. Max S. Yudovich: Writing – review & editing, Resources, Project administration, Methodology, Investigation, Conceptualization. Guoli Chen: Writing – review & editing, Validation, Supervision, Resources, Methodology, Conceptualization. Eric Cochran: Writing – review & editing, Validation, Resources, Methodology, Conceptualization. Alireza Aminsharifi: Writing – review & editing, Validation, Supervision, Resources, Data curation, Conceptualization.

Consent

Consent was obtained from the patient for publication purposes.

Disclosures

None.

Financial interests

This research is supported by Penn State Department of Urology No Shave November Education and Research Fund.