Abstract
INTRODUCTION: Nasopharyngeal carcinoma (NPC) rarely presents with extensive osseous metastases and intracranial involvement as initial manifestations, posing diagnostic challenges. This report details an unusual case, highlighting its unique clinical course and the importance of considering NPC in atypical metastatic presentations, particularly when an association with Epstein-Barr virus (EBV) is identified. CASE PRESENTATION: An approximately 60-year-old female presented with a progressively enlarging forehead lesion, headaches, and subsequent findings of calvarial lytic lesions with intracranial extension. Comprehensive imaging (MRI, computed tomography [CT], PET/CT) revealed extensive fluorodeoxyglucose-avid osseous metastases and identified a hypermetabolic primary mass in the nasopharynx. Histopathology of a calvarial lesion confirmed poorly differentiated squamous cell carcinoma, with EBV in situ hybridization positivity, leading to the diagnosis of metastatic EBV-associated NPC. Treatment involved surgical excision of the symptomatic calvarial lesion, palliative radiation to thoracic spine metastases, and systemic therapy with pembrolizumab and denosumab, chosen by the patient over chemotherapy. Despite initial partial symptomatic relief, the patient's condition deteriorated, and she transitioned to hospice care. CONCLUSION: This case underscores the diagnostic complexities of NPC with an atypical metastatic pattern. It emphasizes the critical role of comprehensive diagnostic workup, including EBV testing, and multidisciplinary management. While advanced NPC carries a poor prognosis, this report contributes to understanding its diverse presentations and reinforces the need for patient-centered therapeutic decisions.