A partial response to atezolizumab in alveolar soft part sarcoma with near-complete resolution of extensive pulmonary metastases: a case report.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with high metastatic potential and limited response to systemic therapy. Biomarkers that predict which patients may benefit from emerging immune checkpoint inhibitors (ICIs) continue to surface. We report a case of stage IV ASPS with extensive pulmonary metastases and high PD-L1 expression that exhibited a marked response to atezolizumab, a PD-L1 antagonist. A 35-year-old man presented to an outside institution in October 2023 with a painless, progressively enlarging left thigh mass. Magnetic resonance imaging (MRI) demonstrated a 7.5 × 4.5 × 14 cm heterogeneous intramuscular lesion. Chest computed tomography (CT) revealed innumerable bilateral pulmonary metastases. Transthoracic biopsy of a pulmonary nodule confirmed stage IV ASPS with strong nuclear TFE3 positivity, Cathepsin K positivity, retained INI1 expression, and PD-L1 expression in 90-100% of malignant cells. The primary lesion was not characterized separately. Following transfer to our institution, atezolizumab was initiated in December 2023. At 3 months, chest CT demonstrated a marked regression of pulmonary metastases. Many resolved completely while others showed significant interval decrease in size. At 8 months, chest CT demonstrated further regression in size, number, and density of the pulmonary metastases. Only micronodules remained. At 12 months, chest CT demonstrated that all remaining pulmonary micronodules were stable without new or progressive disease. The primary lesion was treated with neoadjuvant hypofractionated radiotherapy and wide local resection. Post-operative histopathology of the primary lesion demonstrated >99% tumor necrosis with negative margins. This patient achieved a partial response of the primary thigh mass per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and an immune partial response per immune RECIST (iRECIST). Moreover, this patient experienced a near-complete resolution of pulmonary metastatic disease sustained for 27 months despite an extensive metastatic burden. This case illustrates that substantial disease burden does not preclude meaningful, durable response to ICIs. Moreover, it raises the possibility that high PD-L1 expression may contribute to immune evasion. However, this observation was based on a metastatic biopsy. Prospective acquisition of standardized PD-L1 assay data, fusion-variant genotyping, and tumor-infiltrating lymphocyte profiles in future cases could inform individualized prognostication.