Challenging Diagnosis of Occult Nasopharyngeal Carcinoma by EBER-ISH Test on Cervical Lymph Node Biopsy without Primary Tumor Biopsy: Successful Concurrent Chemoradiotherapy

Abstract

Nasopharyngeal carcinoma (NPC) is usually confirmed by primary tumor biopsy which can be challenging if the lesion is occult or inaccessible. This report aims to present a clinical diagnosis of occult NPC without primary tumor biopsy. A 38-year-old male with a 2-month history of painless left neck swelling revealed a 4.5 cm left cervical lymph node on physical examination with normal nasopharyngeal endoscopy. Fine-needle aspiration (FNA) of the node demonstrated undifferentiated metastatic squamous cell carcinoma and the Epstein-Barr virus-encoded RNA in situ hybridization (EBER-ISH) test was positive. Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) imaging revealed a hypermetabolic lesion in the left nasopharynx with maximum standardized uptake value (SUVmax: 11.43). The patient refused to undergo nasopharyngeal biopsy. Based on the American Joint Committee on Cancer (AJCC) 8^th edition, a T1N1M0 stage of NPC was established. He completed concurrent chemoradiotherapy and achieved a complete metabolic response at the 6-month follow-up. In conclusion, a positive EBER-ISH test from a cervical node biopsy combined with a hypermetabolic nasopharyngeal lesion on PET-CT imaging provides definitive clinical evidence of occult NPC. This approach gives a reliable diagnostic alternative when a primary tumor biopsy is not possible and ensures timely definitive treatment.