Aggressive somatic-type malignant transformation in primary mediastinal immature teratoma despite multimodal therapy: a case report

Background Immature mediastinal teratomas with somatic-type malignant transformation (SMT) represent an exceptionally rare and aggressive subset of extragonadal germ cell tumors (GCT). The development of SMT occurs in a minority of cases, but it is associated with markedly worse outcomes especially when sarcomatous or neuroectodermal elements are present. Due to their rarity, chemo-radiation-resistant nature, and rapid progression, guideline-directed treatment strategies remain limited. Case presentation A 32-year-old male with no prior oncologic history presented with progressive dyspnea, cough, and fever. Imaging revealed a large anterior mediastinal mass, and biopsy confirmed the diagnosis of immature teratoma. The tumor was initially treated with platinum-based chemotherapy (VIP) with multiple surgical resections. The tumor recurred two years later with SMT to a high-grade undifferentiated sarcoma. Genomic testing revealed BRCA2 and TP53 pathogenic variants as well as a PIK3CD alteration. These findings guided subsequent targeted therapy, including olaparib, which achieved modest effect. The treatment course was further complicated by therapy-related myelodysplastic syndrome (t-MDS). Salvage regimens with pembrolizumab and pazopanib were later attempted. In addition, other paraneoplastic syndromes including hemophagocytic lymphohistiocytosis (HLH) and Sweet syndrome further complicated the patient’s treatment trajectory. Despite multiple additional interventions including surgery, radiation, chemotherapy, immunotherapy, and targeted therapy, the disease continued to progress. The patient ultimately developed acute on chronic respiratory failure secondary to progressive thoracic malignancy and died following transition to comfort-focused care. Conclusion This case highlights the aggressive nature and therapeutic challenges of rare immature mediastinal teratomas with SMT. Conventional germ cell tumor–directed chemotherapy, radiation and surgical interventions offer limited and often temporary benefit once transformation occurs. Molecular profiling provided valuable guidance for targeted therapy, although clinical benefit remained limited by disease progression and therapy related complications. Unlike prior reports, our case demonstrated a prolonged disease course with approximately 55 months of survival from initial diagnosis which is well beyond published outcomes despite multiple recurrences and paraneoplastic syndromes. This case provides valuable insights into how molecular-guided therapy and vigilant longitudinal care can offer hope in a historically challenging and rare disease.