Supplemental Material for: EBV-Negative MSI-High Nasopharyngeal Carcinoma Treated With Toripalimab and Radiation: A Case Report

Hypermutated phenotypes defined by microsatellite instability-high (MSI-high) status and high tumor mutational burden (TMB) are rare in NPC, and their therapeutic implications remain incompletely defined.</p><p dir="ltr">Case Presentation: An 82-year-old woman with no prior tobacco history presented with recurrent epistaxis and progressive right-sided nasal obstruction and was found to have EBV-negative, p16-negative nonkeratinizing squamous cell carcinoma of the nasopharynx.

Following progression on platinum-based chemotherapy, she was treated with palliative-intent radiation therapy and toripalimab. Comprehensive tumor profiling demonstrated MSI-high status, a TMB of 35.87 mutations/Mb, and alterations involving MSH3, BRCA2, PIK3CA, ATM, CDKN2A, MTAP, and CCND1. Follow-up imaging demonstrated substantial reduction in tumor burden, with resolution of presenting symptoms and continued clinical disease control at last follow-up.</p><p dir="ltr">Conclusion: This case highlights an uncommon EBV-negative NPC molecular phenotype characterized by MSI-high status, markedly elevated TMB, and DNA damage response alterations.