Unknown Primary Undifferentiated Carcinoma with Good Response to Immune Checkpoint Inhibitor: A Case Report

Abstract Cancer of unknown primary (CUP) is a metastatic malignancy with an unidentified origin and poor prognosis. We report a 60-year-old male with extensive supraclavicular and para-aortic lymphadenopathy who progressed on multiple lines of empiric chemotherapy. Biomarker re-evaluation revealed high programmed death-ligand 1 (PD-L1) expression, prompting treatment with the PD-1 inhibitor pembrolizumab. The patient achieved a near-complete radiographic response after four cycles of pembrolizumab, accompanied by the development of vitiligo – a recognized immune-related adverse event. He maintained a durable response 1 year after discontinuing immunotherapy. This case underscores the efficacy of immune checkpoint inhibitors in CUP with a high expression of PD-L1 involving only the lymph nodes and the clinical importance of biomarker profiling.