Next-generation Sequencing Helps to Make the Definite Diagnosis of Adenocarcinoma of Unknown Primary Site: A Case Report

Abstract We report the case of a 52-year-old Taiwanese male who presented with a left lower neck mass for 2 months. Computed tomography and positron emission tomography scans revealed malignant lymphadenopathies in the left neck, supraclavicular fossa, mediastinum, and pulmonary hilum, without definite lung lesions. Thoracic lymph node dissection pathologically proved metastatic nonsmall cell carcinoma. Immunohistochemistry markers were positive for CK7, CK20 (focal), TTF-1, and TdT, and negative for CD5, PAX8, and GATA3, suggesting a pulmonary origin. Crucially, an EGFR exon 19 deletion (E746_T751) was identified using next-generation sequencing (NGS)-based assay (TruSight Oncology 500). This pivotal finding confirmed primary lung cancer with lymph node metastasis (T0N3M1, stage IV), and indicated EGFR-targeted therapy. This case underscores the crucial role of NGS in diagnosing adenocarcinoma of unknown primary site and guiding optimal treatment.