Abstract
Primary mediastinal yolk sac tumor (PMYST) represents an extremely rare and highly aggressive germ cell malignancy with poor prognosis and limited therapeutic options. We report a 55-year-old male who presented with a large anterior mediastinal mass measuring 149 × 73 mm and significantly elevated serum alpha-fetoprotein (AFP) levels (>1210 ng/mL). Histopathological examination and immunohistochemical staining confirmed the diagnosis of PMYST. An interim response was observed after one cycle of etoposide-cisplatin chemotherapy given concurrently with radiotherapy. However, upon completion of the entire chemoradiotherapy course (radiotherapy plus three cycles of chemotherapy), the patient was found to have disease progression with an enlarging tumor burden. Subsequently, sintilimab-based chemo-immunotherapy was initiated, resulting in a partial response achieved after four cycles of treatment. At the most recent follow-up, the patient demonstrates sustained clinical stability with continued disease control. This case highlights the potential efficacy of PD-1 inhibitor-based combination therapy in refractory mediastinal yolk sac tumor (YST), which may provide a novel therapeutic strategy for managing this challenging malignancy.