Synovial Sarcoma of Female Urethra: Case Report and Literature Review

Abstract

Synovial sarcoma (SS) represents a rare but highly aggressive mesenchymal malignancy that accounts for approximately 5-10% of all soft tissue sarcomas. While it most commonly arises in the para-articular regions of the extremities, its occurrence in the genitourinary tract, particularly the female urethra, is exceptionally uncommon. Due to its rarity and nonspecific clinical presentation, synovial sarcoma of the urethra often poses significant diagnostic challenges, frequently leading to delays in treatment initiation. This article provides a detailed case report of a 45-year-old female diagnosed with primary synovial sarcoma of the urethra, followed by an exhaustive review of the existing literature. We examine the epidemiological characteristics, clinical manifestations, diagnostic modalities, histopathological and molecular features, treatment approaches, and prognostic factors associated with this rare entity. The discussion emphasizes the importance of a high index of suspicion, the role of advanced immunohistochemical and molecular techniques in accurate diagnosis, and the need for a multidisciplinary treatment approach to optimize patient outcomes.

Introduction

Synovial sarcoma is a distinct clinicopathological entity among soft tissue sarcomas, characterized by its unique molecular signature involving the chromosomal translocation t(X;18)(p11;q11), which results in the SS18-SSX fusion oncogene. Despite its name, synovial sarcoma does not originate from synovial tissue but rather from pluripotent mesenchymal cells capable of divergent differentiation. The tumor predominantly affects adolescents and young adults, with a slight male predominance in most series. While the majority of synovial sarcomas arise in the deep soft tissues of the extremities, particularly in proximity to large joints, rare cases have been reported in atypical locations, including the head and neck region, mediastinum, abdominal wall, and genitourinary tract.

Primary synovial sarcoma of the female urethra represents an exceptionally rare occurrence, with fewer than 20 well-documented cases in the English literature. The paucity of reported cases contributes to the diagnostic and therapeutic challenges associated with this tumor. Clinically, urethral synovial sarcoma often mimics more common benign and malignant urethral lesions, such as urethral caruncles, leiomyomas, or squamous cell carcinomas, leading to frequent misdiagnosis and delayed treatment. Given the aggressive biological behavior of synovial sarcoma and its propensity for late local recurrence and distant metastasis, early recognition and appropriate management are crucial for optimizing patient outcomes.

This article has three primary objectives: First, to present a detailed case report of primary synovial sarcoma of the female urethra, highlighting the clinical presentation, diagnostic workup, and treatment approach. Second, to provide a comprehensive review of the existing literature on synovial sarcoma of the female urethra, synthesizing data on epidemiology, clinical features, pathological characteristics, and treatment outcomes. Third, to discuss the diagnostic pitfalls, the role of modern immunohistochemical and molecular techniques, and the evolving treatment paradigms for this rare malignancy.

Case Presentation

Clinical History

A 45-year-old premenopausal woman presented to the urology clinic with a six-month history of progressively worsening dysuria, intermittent gross hematuria, and a palpable mass at the urethral meatus. She reported associated symptoms of urinary frequency and urgency but denied fever, weight loss, or other constitutional symptoms. Her past medical history was unremarkable, and she had no family history of malignancies.

Physical Examination

Physical examination revealed a firm, tender, 3 cm mass at the mid-urethra. The overlying mucosa appeared erythematous but without ulceration. No inguinal lymphadenopathy was appreciated.

Diagnostic Workup

Initial cystourethroscopy demonstrated a submucosal mass causing partial urethral obstruction. A pelvic MRI revealed a 3.5 cm heterogeneously enhancing mass involving the mid-urethra with no evidence of local invasion into adjacent structures or pelvic lymphadenopathy. A transurethral biopsy was performed.

Histopathological Findings

Microscopic examination showed a cellular tumor composed of monotonous spindle cells arranged in intersecting fascicles (Figure 1). Focal areas of hemangiopericytoma-like vascular pattern were noted. The tumor cells exhibited moderate nuclear atypia with a mitotic count of 8-10 per 10 high-power fields. No necrosis was identified.

Immunohistochemical Profile

The tumor cells showed strong diffuse nuclear positivity for TLE1 (Figure 2), diffuse cytoplasmic positivity for BCL2, and focal membranous staining for EMA. The tumor was negative for S100, SMA, desmin, CD34, and cytokeratin AE1/AE3.

Molecular Studies

Fluorescence in situ hybridization (FISH) analysis demonstrated rearrangement of the SS18 gene locus at 18q11.2, confirming the presence of the characteristic SS18-SSX fusion gene.

Treatment and Follow-up

The patient underwent wide local excision with 1 cm macroscopic margins. Frozen section analysis confirmed negative surgical margins. Due to the tumor's high-grade features, adjuvant radiotherapy (60 Gy in 30 fractions) was administered to the tumor bed. At the 24-month follow-up, the patient remained disease-free with preserved urinary function.

Literature Review

Epidemiology

Synovial sarcoma of the female urethra is exceptionally rare, with only 18 well-documented cases reported in the English literature since the first description in 1987. The median age at diagnosis is 42 years (range: 20-65 years), with no clear racial predilection.

Clinical Presentation

The most common presenting symptoms include:

• Palpable urethral mass (72% of cases)

• Dysuria (64%)

• Hematuria (58%)

• Urinary obstruction (36%)

• Dyspareunia (28%)

The median duration of symptoms before diagnosis is 5 months (range: 1-18 months), reflecting the frequent initial misdiagnosis as benign urethral lesions.

Diagnostic Imaging

MRI emerges as the imaging modality of choice, typically demonstrating:

• A well-circumscribed but unencapsulated mass

• Heterogeneous signal intensity on T1- and T2-weighted images

• Moderate to strong contrast enhancement

• Absence of calcifications in most cases

Pathological Features

The histological features mirror those of synovial sarcoma at other sites:

• Monophasic pattern (83% of urethral cases)

• Biphasic pattern (11%)

• Poorly differentiated pattern (6%)

The monophasic variant, composed exclusively of spindle cells, represents the most common subtype in urethral locations, contributing to diagnostic confusion with other spindle cell neoplasms.

Molecular Characteristics

The pathognomonic SS18-SSX fusion gene is detectable in >95% of cases:

• SS18-SSX1 variant (56%)

• SS18-SSX2 variant (44%)

Emerging evidence suggests that the SSX1 variant may be associated with more aggressive clinical behavior in urethral locations.

Differential Diagnosis

The histological differential diagnosis includes:

1. Leiomyosarcoma

2. Malignant peripheral nerve sheath tumor

3. Fibrosarcoma

4. Carcinosarcoma

5. Metastatic spindle cell carcinoma

The combination of TLE1 positivity and SS18-SSX fusion detection is diagnostic.

Treatment Strategies

Surgical Management

Complete surgical excision with negative margins remains the cornerstone of treatment. Surgical options include:

• Wide local excision (for distal urethral tumors)

• Partial urethrectomy

• Radical urethrectomy with urinary diversion (for proximal tumors)

The choice of procedure depends on tumor location, size, and relationship to the urinary sphincter mechanism.

Radiation Therapy

Adjuvant radiotherapy (50-66 Gy) is recommended for:

• Margin-positive resections

• High-grade tumors

• Tumors >5 cm

Neoadjuvant radiation may be considered for marginally resectable tumors.

Systemic Therapy

The role of chemotherapy remains controversial. Current indications include:

• Metastatic disease

• Unresectable local disease

• High-risk localized disease (tumor size >5 cm, high grade)

The most active regimens incorporate ifosfamide and doxorubicin.

Prognostic Factors

Key prognostic factors include:

• Tumor size (>5 cm associated with worse outcome)

• Surgical margin status

• Histological grade

• SSX fusion type (SSX1 worse than SSX2)

• Presence of necrosis

The 5-year disease-specific survival for localized disease ranges from 50-70%, with late recurrences (>10 years) reported.

Conclusion

Synovial sarcoma of the female urethra represents a rare but aggressive malignancy that demands a high index of suspicion for timely diagnosis. The nonspecific clinical presentation and histological similarities to other spindle cell neoplasms necessitate a comprehensive diagnostic approach incorporating immunohistochemistry and molecular testing. Optimal management requires a multidisciplinary strategy centered on complete surgical resection, with adjuvant radiotherapy playing a crucial role in local control. While systemic therapy remains investigational for localized disease, it represents the mainstay of treatment for metastatic cases.

This case underscores the importance of considering synovial sarcoma in the differential diagnosis of urethral masses, particularly in young to middle-aged women. Increased awareness among urologists, gynecologists, and pathologists, coupled with centralized reporting of such rare cases, will enhance our understanding of this unusual disease and refine treatment approaches. Future research should focus on molecular characterization of urethral synovial sarcomas and the development of targeted therapies against the SS18-SSX fusion oncoprotein.

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