Pembrolizumab Failure in an Aggressive, Platinum-Resistant Primary Mediastinal Yolk Sac Tumor With Rapid Metastatic...

Primary mediastinal yolk sac tumors are rare, aggressive extragonadal nonseminomatous germ cell tumors that carry a poorer prognosis than their gonadal counterparts. Outcomes are particularly dismal in platinum-resistant disease, and the role of immune checkpoint inhibitors in this setting remains poorly defined. We report the case of a 26-year-old man with a primary mediastinal yolk sac tumor who progressed despite multimodal therapy, including etoposide, ifosfamide, and cisplatin chemotherapy, high-dose carboplatin and etoposide with autologous stem cell transplantation, gemcitabine and paclitaxel, surgical debulking, and radiation therapy. Pembrolizumab was initiated for progressive disease; however, treatment was associated with rapid biochemical progression, with alpha-fetoprotein doubling from 44,053 to 90,123 ng/mL over two months, accompanied by radiographic worsening of mediastinal, chest wall, and osseous metastases. Shortly thereafter, he developed acute bilateral lower extremity weakness and urinary retention. Magnetic resonance imaging demonstrated new and enlarging multifocal spinal metastases with severe epidural extension and spinal canal stenosis, including recurrence within a prior laminectomy bed and new cervical involvement. Despite palliative radiation, he remained paraplegic and experienced continued systemic progression with central nervous system dissemination. No further disease-directed therapies were available, and he ultimately died from progressive metastatic disease. This case highlights the aggressive biology of platinum-resistant primary mediastinal yolk sac tumors, illustrates primary resistance to programmed death-1 inhibition, and underscores the urgent need for more effective salvage strategies in this high-risk population.