Case Report: Anti-PD-1 therapy as a catalyst for the rapid transformation of a hepatic nodule into HCC: a “soil and seed” paradox in metachronous triple primary malignancies?

Multiple primary malignancies (MPMs) are increasingly recognized, yet the impact of immune checkpoint inhibitors (ICIs) on the evolution of metachronous tumors remains poorly understood. Here, we report a rare case of metachronous triple primary malignancies—lung squamous cell carcinoma, gastric adenocarcinoma, and hepatocellular carcinoma (HCC)—in a 68-year-old male with chronic HBV infection and a history of heavy tobacco and alcohol use. Notably, while receiving the PD-1 inhibitor sintilimab for gastric adenocarcinoma, a previously stable hepatic nodule underwent rapid malignant transformation into histologically confirmed HCC. This paradoxical progression occurred despite the patient achieving a partial response in the gastric lesion and sustained remission of the lung malignancy. Given the patient’s high-risk hepatic background, this case raises the hypothesis that ICIs may inadvertently disrupt local immune tolerance in a predisposed “pro-oncogenic soil, ” potentially catalyzing the transition of dormant pre-neoplastic lesions. This report underscores the need for rigorous baseline liver assessment and close radiological surveillance in high-risk patients undergoing immunotherapy, and highlights the importance of further research into the organ-specific effects of ICIs.