Rapid metastatic progression of primary pulmonary synovial sarcoma despite guideline-concordant multimodal therapy: a...

Soft tissue synovial sarcoma is a rare mesenchymal tumor that mainly affects deep soft tissues of the extremities in young adults, but it is also recognized as a primary pulmonary neoplasm. Primary pulmonary synovial sarcoma (PPSS) accounts for less than 0.5% of all primary lung malignancies. Unlike other primary lung malignancies, PPSS has no known association with tobacco exposure and environmental carcinogens. It is characterized by an aggressive clinical course and a defining chromosomal translocation, t(X,18)(p11;q11), resulting in the fusion of the SYT gene on chromosome 18 with SSX1 or SSX2 on chromosome X. A 60-year-old woman with a 50-pack-per-year smoking history presented with gross hematuria and was incidentally found to have a right lower lobe lung mass on chest radiography. Positron emission tomography (PET) and computed tomography (CT) demonstrated a 7.1 x 6.6 cm supradiaphragmatic pulmonary mass without lymphadenopathy or distant metastases. Biopsy confirmed synovial sarcoma. Due to borderline pulmonary function, she was initially deemed a poor surgical candidate and referred to a sarcoma specialty center, where neoadjuvant chemotherapy with Adriamycin, Ifosfamide, and Mesna was initiated locally. After four cycles, follow-up imaging showed tumor reduction greater than 30% and no evidence of metastatic disease. Her lung function improved following smoking cessation, and she subsequently underwent a right lower lobectomy, with pathology revealing a largely necrotic synovial sarcoma with peripheral residual tumor, negative margins, and negative lymph nodes. Then, 4 months postoperatively, surveillance imaging revealed widespread metastatic sarcoma with innumerable pulmonary metastases, a large omental mass, and invasion of the right supraspinatus and scapula. Palliative management was initiated, but subsequent imaging demonstrated metastatic disease progression, showing more than 50 metabolically active pulmonary nodules, omental carcinomatosis, peritoneal metastases, and abdominopelvic ascites. This case highlights the aggressive clinical course of PPSS despite optimal multimodal therapy including neoadjuvant chemotherapy and complete surgical resection. Recurrence and metastasis remain common even following apparent initial response to therapy, underscoring the need for improved targeted systemic therapies and broader access to clinical trials for this rare malignancy.