Complete Metabolic Response Following VAC/IE and CRT in a PD-L1-High, TMB-High Undifferentiated Round Cell Tumor of the Mediastinum: A Case Report with NGS Insights

Introduction: Undifferentiated malignant round blue cell tumors, though rare, present a formidable challenge in oncology due to their aggressiveness and high fatality rates. Among them, undifferentiated small round cell sarcomas (USRCS) originating from mesodermal tissue carry a particularly poor prognosis. The World Health Organization’s 2020 redefinition of sarcomas introduced USRCS as a distinct entity, emphasizing their molecular diversity. Accurate diagnosis involving morphological, immunohistochemical, and molecular profiling analyses is a key for tailoring effective management strategies, especially in resource-constrained settings. Case presentation: A 33-year-old Asian woman presented to our tertiary care hospital with bilateral neck swelling and shortness of breath. Imaging revealed an anterior mediastinal mass, and the biopsy confirmed an undifferentiated malignant round blue cell tumor resembling undifferentiated round cell sarcoma. Next-generation sequencing (NGS) revealed genomic alterations consistent with high-grade malignancy, along with a PD-L1 tumor proportion score (TPS) of 80%. Despite ineligibility for clinical trials, she responded well to multiagent chemotherapy, achieving a complete metabolic response (CMR). Sustained CMR was documented after concurrent chemo-radiation therapy to the primary mass. Emphasizing the complexity of treatment decisions in managing undifferentiated malignant round blue cell tumors, she was advised to continue with the multiagent systemic chemotherapy with the palliative intent. Conclusion: Rare and difficult to treat, undifferentiated round blue cell tumors require a comprehensive and individualized approach for successful management. This case highlights the importance of multidisciplinary care and focused treatment plans, reflecting advancements in oncology. Continuous monitoring and a collaborative approach are crucial for addressing complications and optimizing patient outcomes.