When germ cell tumors defy gender: three cases of primary mediastinal presentation in women

Primary mediastinal germ cell tumors represent approximately 10% of all mediastinal tumors and occur predominantly in men; their presentation in women is exceptionally rare. We describe three female patients illustrating the clinical, radiologic, and pathological spectra. Two patients with large anterior mediastinal mature teratomas underwent complete surgical resection and remain disease-free after long-term follow-up, confirming the curative potential of surgery. The third patient presented with a mixed nonseminomatous germ cell tumor composed of yolk sac tumor, mature teratoma, and immature teratoma. After multiple resections and platinum-based chemotherapy regimens, she developed recurrent intrathoracic and central nervous system metastases and died of progressive disease seven and a half years after diagnosis. These cases underscore the curability of completely resected mature teratomas and highlight that nonseminomatous mediastinal germ cell tumors require complex multidisciplinary management but can achieve prolonged survival in selected patients, although outcomes remain historically poor, with 5-year survival rates of 30-50%. Systematic reporting of female primary mediastinal germ cell tumors is critical to refine prognosis and guide management.