What is the treatment plan for a maxillary mass diagnosed as a spindle cell neoplasm favoring sarcoma after biopsy?

Treatment of Maxillary Spindle Cell Sarcoma

Wide en-bloc surgical resection with negative margins (R0) performed by a specialized sarcoma surgeon is the cornerstone of treatment, followed by multidisciplinary team discussion to determine the need for adjuvant radiotherapy and systemic chemotherapy based on tumor grade and margin status. 1

Immediate Referral Requirements

• All patients with maxillary spindle cell sarcoma must be referred to a specialist sarcoma multidisciplinary team (MDT) before any definitive treatment, as discordance rates between non-specialist and specialist sarcoma pathologists range from 8-11% for major discordance and 16-35% for minor discordance. 2, 1
• The MDT must include pathologists, radiologists, surgeons, radiation oncologists, and medical oncologists who specialize in sarcoma management. 2
• Do not proceed with surgery until the case has been discussed at a sarcoma MDT, as spindle cell sarcomas are diagnostically heterogeneous and can be misidentified even after examining different sections. 1

Diagnostic Confirmation and Staging

Pathology Review

• Mandatory specialist sarcoma pathologist review of the biopsy according to the 2020 WHO Classification of Soft Tissue and Bone. 2, 1
• Molecular genetic testing should be performed using FISH or PCR-based methods, as many spindle cell sarcomas have characteristic genetic aberrations (including potential NTRK fusions that may be targetable). 1, 3
• FNCLCC grading system must be applied (grades I-III based on differentiation, necrosis, and mitotic rate) to guide treatment decisions. 2, 1

Complete Staging Imaging

• MRI of the entire maxilla with adjacent structures to assess local extent and guide surgical planning. 1
• CT chest to evaluate for lung metastases (the most common site of distant spread). 2, 1
• Bone scintigraphy to assess for distant bone involvement. 1
• Consider PET/CT if equivocal findings or clinical concern for additional metastatic sites. 2

Surgical Management

Primary Treatment

• Wide en-bloc resection with negative margins (R0) is mandatory and must be performed by a surgeon with specialized training in sarcoma surgery. 2, 1
• The goal is complete tumor excision surrounded by normal tissue (wide margins). 1
• Mark risk areas and marginal margins with titanium clips during surgery to facilitate postoperative radiotherapy planning if needed. 1
• The surgical approach should consider functional consequences while maintaining oncologic principles—maxillary resections often require reconstructive planning. 2

Margin Assessment

• Inked margins must be assessed by the pathologist in collaboration with the surgeon, documenting the distance between tumor edge and closest margins. 2
• If margins are positive or close (<1 cm), re-excision should be considered if anatomically feasible. 2

Adjuvant Radiotherapy

Postoperative radiotherapy is recommended for:

• High-grade tumors (G2-3). 1
• Deep location (which applies to maxillary sarcomas). 1
• Size >5 cm. 1
• Inadequate surgical margins (positive or close margins). 1

Radiotherapy can be omitted only for:

• G1 tumors with R0 resection, <5 cm, and superficial location (rarely applicable to maxillary sarcomas). 1

For unresectable tumors or incomplete resection, definitive radiotherapy should be considered, though surgery remains the preferred approach when feasible. 1

Systemic Chemotherapy

High-Grade Tumors

• For high-grade spindle cell sarcomas, chemotherapy following osteosarcoma treatment principles is recommended. 1
• Standard regimen: anthracyclines (doxorubicin) plus alkylating agents (ifosfamide). 1
• Neoadjuvant chemotherapy should be considered for borderline resectable disease or to facilitate less morbid surgery. 1

Baseline Assessments Required

• Renal function testing (for ifosfamide). 1
• Cardiac function assessment (for anthracyclines). 1
• Audiogram if platinum derivatives are considered. 1
• Fertility preservation counseling: sperm storage for males, fertility consultation for females of reproductive age. 1

Low-Grade Tumors

• Chemotherapy is generally not indicated for low-grade tumors with complete resection. 2

Molecular-Targeted Therapy

• If NTRK fusion is identified on molecular testing, NTRK inhibitors (larotrectinib) provide an important targeted therapy option, particularly for unresectable, recurrent, or metastatic disease. 3

Follow-Up Protocol

Structured surveillance is essential as late metastases and local recurrence can occur >10 years post-diagnosis. 1

High-Grade Tumors (G2-3)

• Every 2-3 months for the first 2-3 years. 2, 1
• Every 4-6 months for years 3-5. 2
• Every 6-12 months thereafter up to 10+ years. 1

Low-Grade Tumors (G1)

• Every 4-6 months for the first 3-5 years. 2
• Annually thereafter. 2

Surveillance Imaging

• Chest CT at each visit (more sensitive than chest X-ray for detecting lung metastases). 2
• MRI of the primary site to detect local recurrence. 2
• Clinical assessment of the surgical site at each visit. 2

Critical Pitfalls to Avoid

• Never perform definitive surgery before sarcoma MDT discussion—maxillary sarcomas require specialized surgical planning and may benefit from neoadjuvant therapy. 2
• Do not rely on initial biopsy grade alone—core biopsies may underestimate tumor grade due to heterogeneity and underrepresentation of necrosis. 2
• Do not perform incisional biopsy except in exceptional circumstances—percutaneous core needle biopsy is standard, and the biopsy tract must be planned for removal during definitive surgery. 1
• Do not assume benign behavior based on location—spindle cell sarcomas of the maxilla are aggressive despite their rarity, with local recurrence being the primary cause of treatment failure. 4, 5
• Do not neglect long-term follow-up—late recurrences beyond 10 years have been documented, particularly in NTRK-rearranged tumors. 1, 3