What is the best course of treatment for a young adult with synovial carcinoma and tumor fever, and no significant past medical history?

Management of Synovial Sarcoma with Tumor Fever

For a young adult with synovial sarcoma presenting with tumor fever, the primary treatment is wide surgical excision with negative margins followed by adjuvant radiation therapy (50-60 Gy), with strong consideration for neoadjuvant or adjuvant chemotherapy using doxorubicin plus ifosfamide given the chemotherapy-sensitive nature of synovial sarcoma. 1

Immediate Assessment and Fever Management

Tumor fever (paraneoplastic fever) must be distinguished from infectious causes before proceeding with definitive oncologic treatment. 2

• Tumor fever in synovial sarcoma results from tumor necrosis and cytokine release, presenting as temperature >37.8°C without antipyretic use 2
• Rule out life-threatening infectious causes first: febrile neutropenia (if post-chemotherapy), healthcare-associated infections, catheter-related infections 2
• Consider venous thromboembolic disease as an alternative fever source 2
• Once infection is excluded, tumor fever itself is not a contraindication to proceeding with standard oncologic treatment 2

Diagnostic Workup

All patients require histopathological confirmation with molecular testing to identify the characteristic SS18 gene rearrangement. 1

• Core needle biopsy with multiple cores is the standard diagnostic procedure 1
• The biopsy must be performed by the surgeon who will perform definitive resection, with incision placement in an area that will be excised during definitive surgery 3
• MRI of the primary site is mandatory for surgical planning 1
• Chest CT with thin cuts (1 cm) is mandatory for staging, as pulmonary metastases are common 3, 1
• Regional lymph node assessment is critical for synovial sarcoma specifically, as it has higher nodal involvement risk compared to other soft tissue sarcomas 3, 1

Surgical Management

Wide surgical excision with negative margins (R0) is the cornerstone of treatment and must be performed by a surgeon specifically trained in sarcoma surgery. 1

• The standard procedure removes the tumor with a rim of normal tissue around it 3, 1
• Margins can be minimal (<1 cm) when resistant anatomical barriers (muscular fasciae, periosteum, perineurium) are present 3, 1
• The biopsy scar must be resected en bloc with the tumor 3
• Re-operation should be considered if previous resection achieved only marginal or intralesional margins 1

Radiation Therapy

Adjuvant radiation therapy is standard for high-grade, deep tumors >5 cm following wide excision. 3, 1

• Dose: 50-60 Gy in 1.8-2 Gy fractions, with possible boost to 66 Gy depending on presentation and surgical quality 3, 1
• Can be delivered postoperatively (standard) or preoperatively at 50 Gy 1
• Radiation improves local control but not overall survival 3

Chemotherapy Strategy

Synovial sarcoma is relatively chemotherapy-sensitive compared to other soft tissue sarcomas, making chemotherapy consideration particularly important in this histologic subtype. 3

Neoadjuvant/Adjuvant Chemotherapy:

• Preoperative chemotherapy should be considered for synovial sarcoma given its chemotherapy-sensitive nature and documented response rates with anthracycline- and ifosfamide-based treatment 3
• Standard regimen: Doxorubicin plus ifosfamide for fit patients with good performance status 3, 1
• While definitive histology-specific randomized trials have not been performed for synovial sarcoma, the chemotherapy-sensitive nature justifies consideration of adjuvant treatment 3
• Monitor cumulative doxorubicin dose to minimize cardiotoxicity 1
• Consider prophylactic G-CSF in older patients (>65 years) or those with comorbidities 1

Advanced/Metastatic Disease:

• First-line: Anthracycline-based chemotherapy (doxorubicin) 3, 1
• For synovial sarcoma specifically: High-dose ifosfamide (12-14 g/m²/cycle) or trabectedin are preferential second-line options 3
• Pazopanib is an option after progression on standard chemotherapy 3

Multidisciplinary Team Approach

All treatment decisions must be made by a specialist Sarcoma Multidisciplinary Team (MDT). 1

• Decisions regarding surgery, chemotherapy, radiotherapy timing and sequencing require MDT discussion 1
• Referral to a specialist sarcoma center should occur as soon as synovial sarcoma is suspected 4

Follow-up Protocol

High-risk patients (high-grade tumors) typically relapse within 2-3 years, requiring intensive early surveillance. 1

• Clinical examination every 3-4 months for the first 2-3 years 1
• MRI of primary site twice yearly for 2-3 years, then annually 1
• Chest imaging (X-ray or CT) every 3-4 months for 2-3 years, twice yearly up to 5 years, then annually 1

Critical Pitfalls to Avoid

• Do not delay treatment to "observe" tumor fever—once infection is excluded, proceed with definitive oncologic management 2
• Do not perform biopsy without involving the definitive surgeon, as improper biopsy placement can compromise subsequent resection 3
• Do not omit lymph node assessment in synovial sarcoma, unlike other soft tissue sarcomas 3, 1
• Do not dismiss chemotherapy consideration in synovial sarcoma based on general soft tissue sarcoma data—this histologic subtype is more chemotherapy-sensitive 3